the neural correlates of reasoning


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(Updated 4/13/04)

Kosslyn SM.
If neuroimaging is the answer, what is the question?
Philos Trans R Soc Lond B Biol Sci. 1999 Jul 29;354(1387):1283-94.
"It is unclear that we will come to a better understanding of mental processes simply by observing which neural loci are activated while subjects perform a task. Rather, I suggest here that it is better to come armed with a question that directs one to design tasks in ways that take advantage of the strengths of neuroimaging techniques (particularly positron emission tomography and functional magnetic resonance imaging). Here I develop a taxonomy of types of questions that can be easily addressed by such techniques. The first class of questions focuses on how information processing is implemented in the brain; these questions can be posed at a very coarse scale, focusing on the entire system that confers a particular ability, or at increasingly more specific scales, ultimately focusing on individual structures or processes. The second class of questions focuses on specifying when particular processes and structures are invoked; these questions focus on how one can use patterns of activation to infer that specific processes and structures were invoked, and on how processing changes in different circumstances. The use of neuroimaging to address these questions is illustrated with results from experiments on visual cognition, and caveats regarding the logic of inference in each case are noted. Finally, the necessary interplay between neuroimaging and behavioural studies is stressed." [Abstract] [PDF]

Jung-Beeman M, Bowden EM, Haberman J, Frymiare JL, Arambel-Liu S, et al.
Neural Activity When People Solve Verbal Problems with Insight.
PLoS Biol 2(4): e97 DOI:10.1371/journal.pbio.0020097. 2004.
"People sometimes solve problems with a unique process called insight, accompanied by an “Aha!” experience. It has long been unclear whether different cognitive and neural processes lead to insight versus noninsight solutions, or if solutions differ only in subsequent subjective feeling. Recent behavioral studies indicate distinct patterns of performance and suggest differential hemispheric involvement for insight and noninsight solutions. Subjects solved verbal problems, and after each correct solution indicated whether they solved with or without insight. We observed two objective neural correlates of insight. Functional magnetic resonance imaging (Experiment 1) revealed increased activity in the right hemisphere anterior superior temporal gyrus for insight relative to noninsight solutions. The same region was active during initial solving efforts. Scalp electroencephalogram recordings (Experiment 2) revealed a sudden burst of high-frequency (gamma-band) neural activity in the same area beginning 0.3 s prior to insight solutions. This right anterior temporal area is associated with making connections across distantly related information during comprehension. Although all problem solving relies on a largely shared cortical network, the sudden flash of insight occurs when solvers engage distinct neural and cognitive processes that allow them to see connections that previously eluded them."
[Full Text]

Parsons, Lawrence M., Osherson, Daniel
New Evidence for Distinct Right and Left Brain Systems for Deductive versus Probabilistic Reasoning
Cereb. Cortex 2001 11: 954-965
"Deductive and probabilistic reasoning are central to cognition but the functional neuroanatomy underlying them is poorly understood. The present study contrasted these two kinds of reasoning via positron emission tomography. Relying on changes in instruction and psychological ‘set’, deductive versus probabilistic reasoning was induced using identical stimuli. The stimuli were arguments in propositional calculus not readily solved via mental diagrams. Probabilistic reasoning activated mostly left brain areas whereas deductive activated mostly right. Deduction activated areas near right brain homologues of left language areas in middle temporal lobe, inferior frontal cortex and basal ganglia, as well as right amygdala, but not spatial–visual areas. Right hemisphere activations in the deduction task cannot be explained by spill-over from overtaxed, left language areas. Probabilistic reasoning was mostly associated with left hemispheric areas in inferior frontal, posterior cingulate, parahippocampal, medial temporal, and superior and medial prefrontal cortices. The foregoing regions are implicated in recalling and evaluating a range of world knowledge, operations required during probabilistic thought. The findings confirm that deduction and induction are distinct processes, consistent with psychological theories enforcing their partial separation. The results also suggest that, except for statement decoding, deduction is largely independent of language, and that some forms of logical thinking are non-diagrammatic." [Full Text]

Goel V, Dolan RJ.
Differential involvement of left prefrontal cortexin inductive and deductive reasoning.
Cognition. 2004 Oct;93(3):B109-21.
"While inductive and deductive reasoning are considered distinct logical and psychological processes, little is known about their respective neural basis. To address this issue we scanned 16 subjects with fMRI, using an event-related design, while they engaged in inductive and deductive reasoning tasks. Both types of reasoning were characterized by activation of left lateral prefrontal and bilateral dorsal frontal, parietal, and occipital cortices. Neural responses unique to each type of reasoning determined from the Reasoning Type (deduction and induction) by Task (reasoning and baseline) interaction indicated greater involvement of left inferior frontal gyrus (BA 44) in deduction than induction, while left dorsolateral (BA 8/9) prefrontal gyrus showed greater activity during induction than deduction. This pattern suggests a dissociation within prefrontal cortex for deductive and inductive reasoning." [Abstract]

Knauff M, Fangmeier T, Ruff CC, Johnson-Laird PN.
Reasoning, models, and images: behavioral measures and cortical activity.
J Cogn Neurosci. 2003 May 15;15(4):559-73.
"The goal of this study was to investigate the neurocognitive processes of mental imagery in deductive reasoning. Behavioral studies yielded four sorts of verbal relations: (1) visuospatial relations that are easy to envisage both visually and spatially; (2) visual relations that are easy to envisage visually but hard to envisage spatially; (3) spatial relations that are hard to envisage visually but easy to envisage spatially; and (4) control relations that are hard to envisage both visually and spatially. In three experiments, visual relations slowed the process of reasoning in comparison with control relations, whereas visuospatial and spatial relations yielded inferences comparable to those of control relations. An experiment using functional magnetic resonance imaging showed that in the absence of any correlated visual input (problems were presented acoustically via headphones), all types of reasoning problems evoked activity in the left middle temporal gyrus, in the right superior parietal cortex, and bilaterally in the precuneus. In the prefrontal cortex, increased activity was found in the middle and inferior frontal gyri. However, only the problems based on visual relations also activated areas of the visual association cortex corresponding to V2. The results indicate that cortical activity during reasoning depends on the nature of verbal relations. All relations elicit mental models that underlie reasoning, but visual relations in addition elicit visual images. This account resolves inconsistencies in the previous literature." [Abstract] [PDF]

Knauff M, Mulack T, Kassubek J, Salih HR, Greenlee MW.
Spatial imagery in deductive reasoning: a functional MRI study.
Brain Res Cogn Brain Res. 2002 Apr;13(2):203-12.
"Various cognitive theories aim to explain human deductive reasoning: (1) mental logic theories claim syntactic language-based proofs of derivation, (2) the mental model theory proposes cognitive processes of constructing and manipulating spatially organized mental models, and (3) imagery theories postulate that such abilities are based on visual mental images. To explore the neural substrates of human deductive reasoning, we examined BOLD (blood oxygen level dependent) contrasts of twelve healthy participants during relational and conditional reasoning with whole-brain functional magnetic resonance imaging (fMRI). The results indicate that, in the absence of any correlated visual input, reasoning activated an occipitoparietal-frontal network, including parts of the prefrontal cortex (Brodmann's area, BA, 6, 9) and the cingulate gyrus (BA 32), the superior and inferior parietal cortex (BA 7, 40), the precuneus (BA 7), and the visual association cortex (BA 19). In the discussion, we first focus on the activated occipito-parietal pathway that is well known to be involved in spatial perception and spatial working memory. Second, we briefly relate the activation in the prefrontal cortical areas and in the anterior cingulate gyrus to other imaging studies on higher cognitive functions. Finally, we draw some general conclusions and argue that reasoners envisage and inspect spatially organized mental models to solve deductive inference problems." [Abstract]

Zacks JM, Ollinger JM, Sheridan MA, Tversky B.
A parametric study of mental spatial transformations of bodies.
Neuroimage. 2002 Aug;16(4):857-72.
"TWO CLASSES OF MENTAL SPATIAL TRANSFORMATION CAN BE DISTINGUISHED: Object-based spatial transformations are imagined movements of objects; and egocentric perspective transformations are imagined movements of one's point of view. The hypothesis that multiple neural systems contribute to these mental imagery operations was tested with functional MRI. Participants made spatial judgments about pictures of human bodies, and brain activity was analyzed as a function of the judgment required and the time taken to respond. Areas in right temporal, occipital and parietal cortex and the medial superior cerebellum appear to be differentially involved in object-based spatial transformations. Additionally, midline structures and lateral parietal cortex were found to decrease in activity during the spatial reasoning tasks, independently of the judgment required or of the latency of response. The results are discussed in terms of a model of spatial reasoning that postulates specialized subsystems for performing object-based and egocentric perspective image transformations." [Abstract]

Goel V, Gold B, Kapur S, Houle S.
Neuroanatomical correlates of human reasoning.
J Cogn Neurosci. 1998 May;10(3):293-302.
"One of the important questions cognitive theories of reasoning must address is whether logical reasoning is inherently sentential or spatial. A sentential model would exploit nonspatial (linguistic) properties of representations whereas a spatial model would exploit spatial properties of representations. In general terms, the linguistic hypothesis predicts that the language processing regions underwrite human reasoning processes, and the spatial hypothesis suggests that the neural structures for perception and motor control contribute the basic representational building blocks used for high-level logical and linguistic reasoning. We carried out a [(15)O] H(2)O PET imaging study to address this issue. Twelve normal volunteers performed three types of deductive reasoning tasks (categorical syllogisms, three-term spatial relational items, and three-term nonspatial relational items) while their regional cerebral blood flow pattern was recorded using [(15)O] H(2)O PET imaging. In the control condition subjects semantically comprehended sets of three sentences. In the deductive reasoning conditions subjects determined whether the third sentence was entailed by the first two sentences. The areas of activation in each reasoning condition were confined to the left hemisphere and were similar to each other and to activation reported in previous studies. They included the left inferior frontal gyrus (Brodmann area 45, 47), a portion of the left middle frontal gyrus (Brodmann area 46), the left middle temporal gyrus (Brodmann areas 21, 22), a region of the left lateral inferior temporal gyrus and superior temporal gyrus (Brodmann areas 22, 37), and a portion of the left cingulate gyrus (Brodmann areas 32, 24). There was no significant right-hemisphere or parietal activation. These results are consistent with previous neuroimaging studies and raise questions about the level of involvement of classic spatial regions in reasoning about linguistically presented spatial relations." [Abstract] [PDF]

Goel V, Dolan RJ.
Functional neuroanatomy of three-term relational reasoning.
Neuropsychologia. 2001;39(9):901-9.
"In a recent study we demonstrated that reasoning with categorical syllogisms engages two dissociable mechanisms. Reasoning involving concrete sentences engaged a left hemisphere linguistic system while formally identical arguments, involving abstract sentences, recruited a parietal spatial network. The involvement of a parietal visuo-spatial system in abstract syllogism reasoning raised the question whether argument forms involving explicit spatial relations (or relations that can be easily mapped onto spatial relations) are sufficient to engage the parietal system? We addressed this question in an event-related fMRI study of three-term relational reasoning, using sentences with concrete and abstract content. Our findings indicate that both concrete and abstract three-term relational arguments activate a similar bilateral occipital-parietal-frontal network. However, the abstract reasoning condition engendered greater parietal activation than the concrete reasoning condition. We conclude that arguments involving relations that can be easily mapped onto explicit spatial relations engage a visuo-spatial system, irrespective of concrete or abstract content." [Abstract] [PDF]

Goel, V.
Cognitive Neuroscience of Deductive Reasoning.
In Cambridge Handbook of Thinking & Reasoning, Eds. K. Holyoak & R. Morrison. Cambridge UniversityPress. 2003. [PDF]

Goel V, Dolan RJ.
Anatomical segregation of component processes in an inductive inference task.
J Cogn Neurosci. 2000 Jan;12(1):110-9.
"Inductive inference underlies much of human cognition. The essential component of induction is hypothesis selection based on some criterion of relevance. The purpose of this study was to determine the neural substrate of inductive inference, particularly hypothesis selection, using fMRI. Ten volunteers were shown stimuli consisting of novel animals under two task conditions, and asked to judge whether all the animals in the set were the same type of animal. In one condition, subjects were given a rule that specified the criteria for "same type of animal". In the other condition, subjects had to infer the rule without instruction. The two conditions were further factored into easy and difficult components. Rule inference was specifically associated with bilateral hippocampal activation while the task by difficulty interaction was associated with activation in right lateral orbital prefrontal cortex. We interpret the former in terms of semantic encoding of novel stimuli and the latter in terms of hypothesis selection. Thus, we show an anatomical dissociation between task implementation and task difficulty that may correspond to a critical psychological distinction in the processes necessary for inductive inference." [Abstract]

Goel V, Gold B, Kapur S, Houle S.
The seats of reason? An imaging study of deductive and inductive reasoning.
Neuroreport. 1997 Mar 24;8(5):1305-10.
"We carried out a neuroimaging study to test the neurophysiological predictions made by different cognitive models of reasoning. Ten normal volunteers performed deductive and inductive reasoning tasks while their regional cerebral blood flow pattern was recorded using [15O]H2O PET imaging. In the control condition subjects semantically comprehended sets of three sentences. In the deductive reasoning condition subjects determined whether the third sentence was entailed by the first two sentences. In the inductive reasoning condition subjects reported whether the third sentence was plausible given the first two sentences. The deduction condition resulted in activation of the left inferior frontal gyrus (Brodmann areas 45, 47). The induction condition resulted in activation of a large area comprised of the left medial frontal gyrus, the left cingulate gyrus, and the left superior frontal gyrus (Brodmann areas 8, 9, 24, 32). Induction was distinguished from deduction by the involvement of the medial aspect of the left superior frontal gyrus (Brodmann areas 8, 9). These results are consistent with cognitive models of reasoning that postulate different mechanisms for inductive and deductive reasoning and view deduction as a formal rule-based process." [Abstract] [PDF]

Acuna BD, Eliassen JC, Donoghue JP, Sanes JN.
Frontal and parietal lobe activation during transitive inference in humans.
Cereb Cortex. 2002 Dec;12(12):1312-21.
"Cortical areas engaged in knowledge manipulation during reasoning were identified with functional magnetic resonance imaging (MRI) while participants performed transitive inference (TI) on an ordered list of 11 items (e.g. if A < B and B < C, then A < C). Initially, participants learned a list of arbitrarily ordered visual shapes. Learning occurred by exposure to pairs of list items that were adjacent in the sequence. Subsequently, functional MR images were acquired as participants performed TI on non-adjacent sequence items. Control tasks consisted of height comparisons (HT) and passive viewing (VIS). Comparison of the TI task with the HT task identified activation resulting from TI, termed 'reasoning', while controlling for rule application, decision processes, perception, and movement, collectively termed 'support processes'. The HT-VIS comparison revealed activation related to support processes. The TI reasoning network included bilateral prefrontal cortex (PFC), pre-supplementary motor area (preSMA), premotor area (PMA), insula, precuneus, and lateral posterior parietal cortex. By contrast, cortical regions activated by support processes included the bilateral supplementary motor area (SMA), primary motor cortex (M1), somatic sensory cortices, and right PMA. These results emphasize the role of a prefrontal-parietal network in manipulating information to form new knowledge based on familiar facts. The findings also demonstrate PFC activation beyond short-term memory to include mental operations associated with reasoning." [Abstract]

Wharton CM, Grafman J, Flitman SS, Hansen EK, Brauner J, Marks A, Honda M.
Toward neuroanatomical models of analogy: a positron emission tomography study of analogical mapping.
Cognit Psychol. 2000 May;40(3):173-97.
"Several brain regions associated with analogical mapping were identified using (15)O-positron emission tomography with 12 normal, high intelligence adults. Each trial presented during scanning consisted of a source picture of colored geometric shapes, a brief delay, and a target picture of colored geometric shapes. Analogous pictures did not share similar geometric shapes but did share the same system of abstract visuospatial relations. Participants judged whether each source-target pairing was analogous (analogy condition) or identical (literal condition). The results of the analogy-literal comparison showed activation in the dorsomedial frontal cortex and in the left hemisphere; the inferior, middle, and medial frontal cortices; the parietal cortex; and the superior occipital cortex. Based on these results as well as evidence from relevant cognitive neuroscience studies of reasoning and of executive working memory, we hypothesize that analogical mapping is mediated by the left prefrontal and inferior parietal cortices." [Abstract]

Luo Q, Perry C, Peng D, Jin Z, Xu D, Ding G, Xu S.
The neural substrate of analogical reasoning: an fMRI study.
Brain Res Cogn Brain Res. 2003 Oct;17(3):527-34.
"This study investigated the anatomical substrate of analogical reasoning using functional magnetic resonance imaging. In the study, subjects performed a verbal analogy task (e.g., soldier is to army as drummer is to band) and, to control for activation caused by purely semantic access, a semantic judgment task. Significant activation differences between the verbal analogy and the semantic judgment task were found bilaterally in the prefrontal cortex (right BA 11/BA 47 and left BA45), the fusiform gyrus, and the basal ganglia; left lateralized in the postero-superior temporal gyrus (BA 22) and the (para) hippocampal region; and right lateralized in the anterior cingulate. The role of these areas in analogical reasoning is discussed." [Abstract]

Ruff CC, Knauff M, Fangmeier T, Spreer J.
Reasoning and working memory: common and distinct neuronal processes.
Neuropsychologia. 2003;41(9):1241-53.
"The neuronal processes underlying reasoning and the related working memory subsystems were examined with functional magnetic resonance imaging (fMRI). Twelve volunteers solved relational reasoning problems which either supported a single (determinate) or several alternative solutions (indeterminate). In a second condition, participants maintained the identical premises of these problems in working memory without making inferences. Although problems were presented in auditory format, activity was detected for both reasoning and maintenance in a network comprising bilaterally the secondary visual cortex, the posterior cingulate cortex, and the medial anterior frontal cortex. In direct comparisons, reasoning was associated with stronger dorsolateral and medial prefrontal activation than maintenance, whereas maintenance led to stronger lateral parietal activation than reasoning. Participants' visuo-spatial abilities ("Block Design" score) covaried positively with behavioral performance and negatively with activity of the precuneus for reasoning, but not for maintenance. These results support the notion that relational reasoning is based on visuo-spatial mental models, and they help to distinguish the neuronal processes related to reasoning itself versus to the maintenance of problem information in working memory." [Abstract]

Delazer M, Domahs F, Bartha L, Brenneis C, Lochy A, Trieb T, Benke T.
Learning complex arithmetic-an fMRI study.
Brain Res Cogn Brain Res. 2003 Dec;18(1):76-88.
"Aim of the present functional magnet resonance imaging (fMRI) study was to detect modifications of cerebral activation patterns related to learning arithmetic. Thirteen right-handed subjects were extensively trained on a set of 18 complex multiplication problems. In the following fMRI session, trained and untrained problems (closely matched for difficulty) were presented in blocked order alternating with a number matching task and a fact retrieval task. Importantly, left hemispheric activations were dominant in the two contrasts between untrained and trained condition, suggesting that learning processes in arithmetic are predominantly supported by the left hemisphere. Contrasting untrained versus trained condition, the left intraparietal sulcus showed significant activations, as well as the inferior parietal lobule. A further significant activation was found in the left inferior frontal gyrus. This activation may be accounted for by higher working memory demands in the untrained as compared to the trained condition. Contrasting trained versus untrained condition a significant focus of activation was found in the left angular gyrus. Following the triple-code model [Science 284 (1999) 970], the shift of activation within the parietal lobe from the intraparietal sulcus to the left angular gyrus suggests a modification from quantity-based processing to more automatic retrieval. The present study shows that the left angular gyrus is not only involved in arithmetic tasks requiring simple fact retrieval, but may show significant activations as a result of relatively short training of complex calculation." [Abstract]

Menon V, Mackenzie K, Rivera SM, Reiss AL.
Prefrontal cortex involvement in processing incorrect arithmetic equations: evidence from event-related fMRI.
Hum Brain Mapp. 2002 Jun;16(2):119-30.
"The main aim of this study was to investigate the differential processing of correct and incorrect equations to gain further insight into the neural processes involved in arithmetic reasoning. Electrophysiological studies in humans have demonstrated that processing incorrect arithmetic equations (e.g., 2 + 2 = 5) elicits a prominent event-related potential (ERP) compared to processing correct equations (e.g., 2 + 2 = 4). In the present study, we investigated the neural substrates of this process using event-related functional magnetic resonance imaging (fMRI). Subjects were presented with arithmetic equations and asked to indicate whether the solution displayed was correct or incorrect. We found greater activation to incorrect, compared to correct equations, in the left dorsolateral prefrontal cortex (DLPFC, BA 46) and the left ventrolateral prefrontal cortex (VLPFC, BA 47). Our results provide the first brain imaging evidence for differential processing of incorrect vs. correct equations. The prefrontal cortex activation observed in processing incorrect equations overlaps with brain areas known to be involved in working memory and interference processing. The DLPFC region differentially activated by incorrect equations was also involved in overall arithmetic processing, whereas the VLPFC was activated only during the differential processing of incorrect equations. Differential response to correct and incorrect arithmetic equations was not observed in parietal cortex regions such as the angular gyrus and intra-parietal sulcus, which are known to play a specific role in performing arithmetic computations. The pattern of brain response observed is consistent with the hypothesis that processing incorrect equations involves detection of an incorrect answer and resolution of the interference between the internally computed and externally presented incorrect answer. More specifically, greater activation during processing of incorrect equations appears to reflect additional operations involved in maintaining the results in working memory, while subjects attempt to resolve the conflict and select a response. These findings allow us to further delineate and dissociate the contributions of prefrontal and parietal cortices to arithmetic reasoning." [Abstract]

Prabhakaran V, Rypma B, Gabrieli JD.
Neural substrates of mathematical reasoning: a functional magnetic resonance imaging study of neocortical activation during performance of the necessary arithmetic operations test.
Neuropsychology. 2001 Jan;15(1):115-27.
"Brain activation was examined using functional magnetic resonance imaging during mathematical problem solving in 7 young healthy participants. Problems were selected from the Necessary Arithmetic Operations Test (NAOT; R. B. Ekstrom, J. W. French, H. H. Harman, & D. Dermen, 1976). Participants solved 3 types of problems: 2-operation problems requiring mathematical reasoning and text processing, 1-operation problems requiring text processing but minimal mathematical reasoning, and 0-operation problems requiring minimal text processing and controlling sensorimotor demands of the NAOT problems. Two-operation problems yielded major activations in bilateral frontal regions similar to those found in other problem-solving tasks, indicating that the processes mediated by these regions subserve many forms of reasoning. Findings suggest a dissociation in mathematical problem solving between reasoning, mediated by frontal cortex, and text processing, mediated by temporal cortex." [Abstract]

Jacqueline N. Wood & Jordan Grafman
Nature Reviews Neuroscience 4, 139 -147 (2003); doi:10.1038/nrn1033
"Through evolution, humans have acquired 'higher' cognitive skills — such as language, reasoning and planning — and complex social behaviour. Evidence from neuropsychological and neuroimaging research indicates that the prefrontal cortex (PFC) underlies much of this higher cognition. A number of theories have been proposed for how the PFC might achieve this. Although many of these theories focus on the types of 'process' that the PFC carries out, we argue for the validity of a representational approach to understanding PFC function."
[Abstract] [PDF]

Curtis CE, D'Esposito M.
Persistent activity in the prefrontal cortex during working memory.
Trends Cogn Sci. 2003 Sep;7(9):415-423.
"The dorsolateral prefrontal cortex (DLPFC) plays a crucial role in working memory. Notably, persistent activity in the DLPFC is often observed during the retention interval of delayed response tasks. The code carried by the persistent activity remains unclear, however. We critically evaluate how well recent findings from functional magnetic resonance imaging studies are compatible with current models of the role of the DLFPC in working memory. These new findings suggest that the DLPFC aids in the maintenance of information by directing attention to internal representations of sensory stimuli and motor plans that are stored in more posterior regions." [Abstract] [PDF]

Walter H, Bretschneider V, Gron G, Zurowski B, Wunderlich AP, Tomczak R, Spitzer M.
Evidence for quantitative domain dominance for verbal and spatial working memory in frontal and parietal cortex.
Cortex. 2003 Sep-Dec;39(4-5):897-911.
"Neuroimaging studies in humans have shown that different working memory (WM) tasks recruit a common bilateral fronto-parietal cortical network. Animal studies as well as neuroimaging studies in humans have suggested that this network, in particular the prefrontal cortex, is preferentially recruited when material from different domains (e.g. spatial information or verbal/object information) has to be memorized. Early imaging studies have suggested qualitative dissociations in the prefrontal cortex for spatial and object/verbal WM, either in a left-right or a ventral-dorsal dimension. However, results from different studies are inconsistent. Moreover, recent fMRI studies have failed to find evidence for domain dependent dissociations of WM-related activity in prefrontal cortex. Here we present evidence from two independent fMRI studies using physically identical stimuli in a verbal and spatial WM task showing that domain dominance for WM does indeed exist, although only in the form of quantitative differences in activation and not in the form of a dissociation with different prefrontal regions showing mutually exclusive activation in different domains. Our results support a mixed dimension model of domain dominance for WM within the prefrontal cortex, with left ventral prefrontal cortex (PFC) supporting preferentially verbal WM and right dorsal PFC supporting preferentially spatial WM. The concept of domain dominance is discussed in the light of recent theories of prefrontal cortex function." [Abstract]

Reichle ED, Carpenter PA, Just MA.
The neural bases of strategy and skill in sentence-picture verification.
Cognit Psychol. 2000 Jun;40(4):261-95.
"This experiment used functional Magnetic Resonance Imaging to examine the relation between individual differences in cognitive skill and the amount of cortical activation engendered by two strategies (linguistic vs. visual-spatial) in a sentence-picture verification task. The verbal strategy produced more activation in language-related cortical regions (e.g., Broca's area), whereas the visual-spatial strategy produced more activation in regions that have been implicated in visual-spatial reasoning (e.g., parietal cortex). These relations were also modulated by individual differences in cognitive skill: Individuals with better verbal skills (as measured by the reading span test) had less activation in Broca's area when they used the verbal strategy. Similarly, individuals with better visual-spatial skills (as measured by the Vandenberg, 1971, mental rotation test) had less activation in the left parietal cortex when they used the visual-spatial strategy. These results indicate that language and visual-spatial processing are supported by partially separable networks of cortical regions and suggests one basis for strategy selection: the minimization of cognitive workload." [Abstract]

N. F. Ramsey, J. M. Jansma, G. Jager, T. Van Raalten, and R. S. Kahn
Neurophysiological factors in human information processing capacity
Brain Advance Access published on March 1, 2004, DOI 10.1093/brain/awh060.
Brain 127: 517-525.
"What determines how well an individual can manage the complexity of information processing demands when several tasks have to be executed simultaneously? Various theoretical frameworks address the mechanisms of information processing and the changes that take place when processes become automated, and brain regions involved in various types of information processing have been identified, as well as sequences of events in the brain. The neurophysiological substrate of human information processing capacity, i.e. the amount that can be processed simultaneously, is, however, unresolved, as is the basis of inter-individual variability in capacity. Automatization of cognitive functions is known to increase capacity to process additional tasks, but behavioural indices of automatization are poor predictors of processing capacity in individuals. Automatization also leads to a decline of brain activity in the working memory system. In this study, we test the hypothesis that processing capacity is closely related to the way that the brain adjusts to practice of a single cognitive task, i.e. to the changes in neuronal activity that accompany automatization as measured with functional MRI (fMRI). Using a task that taxes the working memory system, and is sensitive to automatization, performance improved while activity in the network declined, as expected. The key finding is that the magnitude of automatization-induced reduction of activity in this system was a strong predictor for the ability to perform two different working memory tasks simultaneously (after scanning). It explained 60% of the variation in information processing capacity across individuals. In contrast, the behavioural measures of automatization did not predict this. We postulate that automatization involves at least two partially independent neurophysiological mechanisms, i.e. (i) streamlining of neuronal communication which improves performance on a single task; and (ii) functional trimming of neuronal ensembles which enhances the capacity to accommodate processing of additional tasks, potentially by facilitating rapid switching of instruction sets or contexts. Finally, this study shows that fMRI can provide information that predicts behavioural output, which is not provided by overt behavioural measures." [Abstract]

Osaka N, Osaka M, Kondo H, Morishita M, Fukuyama H, Shibasaki H.
The neural basis of executive function in working memory: an fMRI study based on individual differences.
Neuroimage. 2004 Feb;21(2):623-31.
"Using fMRI, neural substrates of the executive system were investigated with respect to differences in working memory capacity. To explore the executive control processes, reading span test (RST) and read conditions were performed. Two subject groups were selected: those with large working memory capacities, labeled high-span subjects (HSS) according to the reading span test, and those with small working memory capacities, labeled low-span subjects (LSS). Significant activation was found mainly in three regions in comparison with the control: anterior cingulate cortex (ACC), left inferior frontal gyrus (IFG), visual association cortex (VAC) and superior parietal lobule (SPL). For both groups, the fMRI signal intensity increased in ACC and IFG during the RST condition compared to that under the read condition. A group difference was also found in the ACC and IFG region, specifically a significant increase in signal intensity was observed only for the HSS group but not for the LSS group. Behavioral data also showed that the performance was better in HSS than in LSS. Moreover, the cross correlation of signal change between ACC and IFG was higher in HSS than in LSS, indicating that the network system between ACC and IFG was more activated in HSS compared to that of LSS. These results suggest that executive function, that is, working attention controlling system is more active in HSS than in LSS. Moreover, the results confirmed our hypothesis that there is a general neural basis for the central executive function in both RST and previous LST (listening span test) tasks despite differences in modality-specific buffers." [Abstract]

Gray JR, Chabris CF, Braver TS.
Neural mechanisms of general fluid intelligence.
Nat Neurosci. 2003 Mar;6(3):316-22.
"We used an individual-differences approach to test whether general fluid intelligence (gF) is mediated by brain regions that support attentional (executive) control, including subregions of the prefrontal cortex. Forty-eight participants first completed a standard measure of gF (Raven's Advanced Progressive Matrices). They then performed verbal and nonverbal versions of a challenging working-memory task (three-back) while their brain activity was measured using functional magnetic resonance imaging (fMRI). Trials within the three-back task varied greatly in the demand for attentional control because of differences in trial-to-trial interference. On high-interference trials specifically, participants with higher gF were more accurate and had greater event-related neural activity in several brain regions. Multiple regression analyses indicated that lateral prefrontal and parietal regions may mediate the relation between ability (gF) and performance (accuracy despite interference), providing constraints on the neural mechanisms that support gF." [Abstract] [PDF]

Duncan, John, Seitz, Rudiger J., Kolodny, Jonathan, Bor, Daniel, Herzog, Hans, Ahmed, Ayesha, Newell, Fiona N., Emslie, Hazel
A Neural Basis for General Intelligence
Science 2000 289: 457-460
"Universal positive correlations between different cognitive tests motivate the concept of "general intelligence" or Spearman's g. Here the neural basis for g is investigated by means of positron emission tomography. Spatial, verbal, and perceptuo-motor tasks with high-g involvement are compared with matched low-g control tasks. In contrast to the common view that g reflects a broad sample of major cognitive functions, high-g tasks do not show diffuse recruitment of multiple brain regions. Instead they are associated with selective recruitment of lateral frontal cortex in one or both hemispheres. Despite very different task content in the three high-g-low-g contrasts, lateral frontal recruitment is markedly similar in each case. Many previous experiments have shown these same frontal regions to be recruited by a broad range of different cognitive demands. The results suggest that "general intelligence" derives from a specific frontal system important in the control of diverse forms of behavior." [Full Text]

Prabhakaran V, Smith JA, Desmond JE, Glover GH, Gabrieli JD.
Neural substrates of fluid reasoning: an fMRI study of neocortical activation during performance of the Raven's Progressive Matrices Test.
Cognit Psychol. 1997 Jun;33(1):43-63.
"We examined brain activation, as measured by functional magnetic resonance imaging, during problem solving in seven young, healthy participants. Participants solved problems selected from the Raven's Progressive Matrices Test, a test known to predict performance on a wide range of reasoning tasks. In three conditions, participants solved problems requiring (1) analytic reasoning; (2) figural or visuospatial reasoning; or (3) simple pattern matching that served as a perceptual-motor control. Right frontal and bilateral parietal regions were activated more by figural than control problems. Bilateral frontal and left parietal, occipital, and temporal regions were activated more by analytic than figural problems. All of these regions were activated more by analytic than match problems. Many of these activations occurred in regions associated with working memory. Figural reasoning activated areas involved in spatial and object working memory. Analytic reasoning activated additional areas involved in verbal working memory and domain-independent associative and executive processes. These results suggest that fluid reasoning is mediated by a composite of working memory systems." [Abstract]

Cabeza R, Dolcos F, Graham R, Nyberg L.
Similarities and differences in the neural correlates of episodic memory retrieval and working memory.
Neuroimage. 2002 Jun;16(2):317-30.
"Functional neuroimaging studies have shown that different cognitive functions activate overlapping brain regions. An activation overlap may occur because a region is involved in operations tapped by different cognitive functions or because the activated area comprises subregions differentially involved in each of the functions. To investigate these issues, we directly compared brain activity during episodic retrieval (ER) and working memory (WM) using event-related functional MRI (fMRI). ER was investigated with a word recognition test, and WM was investigated with a word delayed-response test. Two-phase trials distinguished between retrieval mode and cue-specific aspects of ER, as well as between encoding/maintenance and retrieval aspects of WM. The results revealed a common fronto-parieto-cerebellar network for ER and WM, as well as subregions differentially involved in each function. Specifically, there were two main findings. First, the results differentiated common and specific subregions within the prefrontal cortex: (i) left dorsolateral areas were recruited by both functions, possibly reflecting monitoring operations; (ii) bilateral anterior and ventrolateral areas were more activated during ER than during WM, possibly reflecting retrieval mode and cue-specific ER operations, respectively; and (iii) left posterior/ventral (Broca's area) and bilateral posterior/dorsal areas were more activated during WM than during ER, possibly reflecting phonological and generic WM operations, respectively. Second, hippocampal and parahippocampal regions were activated not only for ER but also for WM. This result suggests that indexing operations mediated by the medial temporal lobes apply to both long-term and short-term memory traces. Overall, our results show that direct cross-function comparisons are critical to understand the role of different brain regions in various cognitive functions." [Abstract] [PDF]

Rypma, Bart, Berger, Jeffrey S., D'Esposito, Mark
The Influence of Working-Memory Demand and Subject Performance on Prefrontal Cortical Activity
J. Cogn. Neurosci. 2002 14: 721-731
"Brain imaging and behavioral studies of working memory (WM) converge to suggest that the ventrolateral prefrontal cortex (PFC) mediates a capacity-limited storage buffer and that the dorsolateral PFC mediates memory organization processes that support supracapacity memory storage. Previous research from our laboratory has shown that the extent to which such memory organization processes are required depends on both task factors (i.e., memory load) and subject factors (i.e., response speed). Task factors exert their effects mainly during WM encoding while subject factors exert their effects mainly during WM retrieval. In this study, we sought to test the generalizability of these phenomena under more difficult memory-demand conditions than have been used previously. During scanning, subjects performed a WM task in which they were required to maintain between 1 and 8 letters over a brief delay. Neural activity was measured during encoding, maintenance, and retrieval task periods using event-related functional magnetic resonance imaging. With increasing memory load, there were reaction time increases and accuracy rate decreases, ventrolateral PFC activation decreases during encoding, and dorsolateral PFC activation increases during maintenance and retrieval. These results suggest that the ventrolateral PFC mediates WM storage and that the dorsolateral PFC mediates strategic memory organization processes that facilitate supracapacity WM storage. Additionally, high-performing subjects showed overall less activation than low-performing subjects, but activation increases with increasing memory load in the lateral PFC during maintenance and retrieval. Low-performing subjects showed overall more activation than high-performing subjects, but minimal activation increases in the dorsolateral PFC with increasing memory load. These results suggest that individual differences in both neural efficiency and cognitive strategy underlie individual differences in the quality of subjects' WM performance." [Abstract]

Silvia A. Bunge, Itamar Kahn, Jonathan D. Wallis, Earl K. Miller, and Anthony D. Wagner
Neural Circuits Subserving the Retrieval and Maintenance of Abstract Rules
J Neurophysiol 90: 3419-3428, 2003. First published 10.1152/jn.00910.2002
"Behavior is often governed by abstract rules or instructions for behavior that can be abstracted from one context and applied to another. Prefrontal cortex (PFC) is thought to be important for representing rules, although the contributions of ventrolateral (VLPFC) and dorsolateral (DLPFC) regions remain under-specified. In the present study, event-related fMRI was used to examine abstract rule representation in humans. Prior to scanning, subjects learned to associate unfamiliar shapes and nonwords with particular rules. During each fMRI trial, presentation of one of these cues was followed by a delay and then by sample and probe stimuli. Match and non-match rules required subjects to indicate whether or not the sample and probe matched; go rules required subjects to make a response that was not contingent on the sample/probe relation. Left VLPFC, parietal cortex, and pre-SMA exhibited sensitivity to rule type during the cue and delay periods. Delay-period activation in these regions, but not DLPFC, was greater when subjects had to maintain response contingencies (match, non-match) relative to when the cue signaled a specific response (go). In contrast, left middle temporal cortex exhibited rule sensitivity during the cue but not delay period. These results support the hypothesis that VLPFC interacts with temporal cortex to retrieve semantic information associated with a cue and with parietal cortex to retrieve and maintain relevant response contingencies across delays. Future investigations of cross-regional interactions will enable full assessment of this account. Collectively, these results demonstrate that multiple, neurally separable processes are recruited during abstract rule representation." [Abstract] [PDF]

Petrides M, Pandya DN.
Comparative cytoarchitectonic analysis of the human and the macaque ventrolateral prefrontal cortex and corticocortical connection patterns in the monkey.
Eur J Neurosci. 2002 Jul;16(2):291-310.
"A comparison of the cytoarchitecture of the human and the macaque monkey ventrolateral prefrontal cortex demonstrated a region in the monkey that exhibits the architectonic characteristic of area 45 in the human brain. This region occupies the dorsal part of the ventrolateral prefrontal convexity just below area 9/46v. Rostroventral to area 45 in the human brain lies a large cortical region labelled as area 47 by Brodmann. The ventrolateral component of this region extending as far as the lateral orbital sulcus has architectonic characteristics similar to those of the ventrolateral prefrontal region labelled by Walker as area 12 in the macaque monkey. We designated this region in both the human and the monkey ventrolateral prefrontal cortex as area 47/12. Thus, area 47/12 designates the specific part of the zone previously labelled as area 47 in the human brain that has the same overall architectonic pattern as that of Walker's area 12 in the macaque monkey brain. The cortical connections of these two areas were examined in the monkey by injecting fluorescent retrograde tracers. Although both area 45 and area 47/12 as defined here had complex multimodal input, they could be differentiated in terms of some of their inputs. Retrograde tracers restricted to area 47/12 resulted in heavy labelling of neurons in the rostral inferotemporal visual association cortex and in temporal limbic areas (i.e. perirhinal and parahippocampal cortex). In contrast, injections of tracers into dorsally adjacent area 45 demonstrated strong labelling in the superior temporal gyrus (i.e. the auditory association cortex) and the multimodal cortex in the upper bank of the superior temporal sulcus." [Abstract]

Wallis JD, Anderson KC, Miller EK.
Single neurons in prefrontal cortex encode abstract rules.
Nature. 2001 Jun 21;411(6840):953-6.
"The ability to abstract principles or rules from direct experience allows behaviour to extend beyond specific circumstances to general situations. For example, we learn the 'rules' for restaurant dining from specific experiences and can then apply them in new restaurants. The use of such rules is thought to depend on the prefrontal cortex (PFC) because its damage often results in difficulty in following rules. Here we explore its neural basis by recording from single neurons in the PFC of monkeys trained to use two abstract rules. They were required to indicate whether two successively presented pictures were the same or different depending on which rule was currently in effect. The monkeys performed this task with new pictures, thus showing that they had learned two general principles that could be applied to stimuli that they had not yet experienced. The most prevalent neuronal activity observed in the PFC reflected the coding of these abstract rules." [Abstract]

Jon M. Fincham, Cameron S. Carter, Vincent van Veen, V. Andrew Stenger, and John R. Anderson
Neural mechanisms of planning: A computational analysis using event-related fMRI
PNAS 99: 3346-3351. 2002.
"To investigate the neural mechanisms of planning, we used a novel adaptation of the Tower of Hanoi (TOH) task and event-related functional MRI. Participants were trained in applying a specific strategy to an isomorph of the five-disk TOH task. After training, participants solved novel problems during event-related functional MRI. A computational cognitive model of the task was used to generate a reference time series representing the expected blood oxygen level-dependent response in brain areas involved in the manipulation and planning of goals. This time series was used as one term within a general linear modeling framework to identify brain areas in which the time course of activity varied as a function of goal-processing events. Two distinct time courses of activation were identified, one in which activation varied parametrically with goal-processing operations, and the other in which activation became pronounced only during goal-processing intensive trials. Regions showing the parametric relationship comprised a frontoparietal system and include right dorsolateral prefrontal cortex [Brodmann's area (BA 9)], bilateral parietal (BA 40/7), and bilateral premotor (BA 6) areas. Regions preferentially engaged only during goal-intensive processing include left inferior frontal gyrus (BA 44). The implications of these results for the current model, as well as for our understanding of the neural mechanisms of planning and functional specialization of the prefrontal cortex, are discussed." [Full Text]

Newman SD, Carpenter PA, Varma S, Just MA.
Frontal and parietal participation in problem solving in the Tower of London: fMRI and computational modeling of planning and high-level perception.
Neuropsychologia. 2003;41(12):1668-82.
"This study triangulates executive planning and visuo-spatial reasoning in the context of the Tower of London (TOL) task by using a variety of methodological approaches. These approaches include functional magnetic resonance imaging (fMRI), functional connectivity analysis, individual difference analysis, and computational modeling. A graded fMRI paradigm compared the brain activation during the solution of problems with varying path lengths: easy (1 and 2 moves), moderate (3 and 4 moves) and difficult (5 and 6 moves). There were three central findings regarding the prefrontal cortex: (1) while both the left and right prefrontal cortices were equally involved during the solution of moderate and difficult problems, the activation on the right was differentially attenuated during the solution of the easy problems; (2) the activation observed in the right prefrontal cortex was highly correlated with individual differences in working memory (measured independently by the reading span task); and (3) different patterns of functional connectivity were observed in the left and right prefrontal cortices. Results obtained from the superior parietal region also revealed left/right differences; only the left superior parietal region revealed an effect of difficulty. These fMRI results converged upon two hypotheses: (1) the right prefrontal area may be more involved in the generation of a plan, whereas the left prefrontal area may be more involved in plan execution; and (2) the right superior parietal region is more involved in attention processes while the left homologue is more of a visuo-spatial workspace. A 4CAPS computational model of the cognitive processes and brain activation in the TOL task integrated these hypothesized mechanisms, and provided a reasonably good fit to the observed behavioral and brain activation data. The multiple research approaches presented here converge on a deepening understanding of the combination of perceptual and conceptual processes in this type of visual problem solving." [Abstract]

Sylvester CY, Wager TD, Lacey SC, Hernandez L, Nichols TE, Smith EE, Jonides J.
Switching attention and resolving interference: fMRI measures of executive functions.
Neuropsychologia. 2003;41(3):357-70.
"Is there a single executive process or are there multiple executive processes that work together towards the same goal in some task? In these experiments, we use counter switching and response inhibition tasks to examine the neural underpinnings of two cognitive processes that have often been identified as potential executive processes: the switching of attention between tasks, and the resolution of interference between competing task responses. Using functional magnetic resonance imaging (fMRI), for both event-related and blocked design tasks, we find evidence for common neural areas across both tasks in bilateral parietal cortex (BA 40), left dorsolateral prefrontal cortex (DLPFC; BA 9), premotor cortex (BA 6) and medial frontal cortex (BA 6/32). However, we also find areas preferentially involved in the switching of attention between mental counts (BA 7, BA 18) and the inhibition of a prepotent motor response (BA 6, BA 10), respectively. These findings provide evidence for the separability of cognitive processes underlying executive control." [Abstract]

Konishi S, Uchida I, Okuaki T, Machida T, Shirouzu I, Miyashita Y.
Neural correlates of recency judgment.
J Neurosci. 2002 Nov 1;22(21):9549-55.
"The prefrontal cortex plays a critical role in recollecting the temporal context of past events. The present study used event-related functional magnetic resonance imaging (fMRI) and explored the neural correlates of temporal-order retrieval during a recency judgment paradigm. In this paradigm, after study of a list of words presented sequentially, subjects were presented with two of the studied words simultaneously and were asked which of the two words was studied more recently. Two types of such retrieval trials with varied (high and low) levels of demand for temporal-order retrieval were intermixed and compared using event-related fMRI. The intraparadigm comparison of high versus low demand trials revealed brain regions with activation that was modulated on the basis of demand for temporal-order retrieval. Multiple lateral prefrontal regions including the middle and inferior lateral prefrontal cortex were prominently activated. Activation was also observed in the anterior prefrontal cortex and the medial temporal cortex, regions well documented to be related to memory retrieval in general. The modulation of brain activity in these regions suggests a detailed pathway that is engaged during recency judgment."
[Full Text]

Hideaki Kawabata, and Semir Zeki
Neural Correlates of Beauty
J Neurophysiol 91: 1699-1705, 2004. 10.1152/jn.00696.2003
"We have used the technique of functional MRI to address the question of whether there are brain areas that are specifically engaged when subjects view paintings that they consider to be beautiful, regardless of the category of painting (that is whether it is a portrait, a landscape, a still life, or an abstract composition). Prior to scanning, each subject viewed a large number of paintings and classified them into beautiful, neutral, or ugly. They then viewed the same paintings in the scanner. The results show that the perception of different categories of paintings are associated with distinct and specialized visual areas of the brain, that the orbito-frontal cortex is differentially engaged during the perception of beautiful and ugly stimuli, regardless of the category of painting, and that the perception of stimuli as beautiful or ugly mobilizes the motor cortex differentially." [Abstract]

Moran JM, Wig GS, Adams RB Jr, Janata P, Kelley WM.
Neural correlates of humor detection and appreciation.
Neuroimage. 2004 Mar;21(3):1055-60.
"Humor is a uniquely human quality whose neural substrates remain enigmatic. The present report combined dynamic, real-life content and event-related functional magnetic resonance imaging (fMRI) to dissociate humor detection ("getting the joke") from humor appreciation (the affective experience of mirth). During scanning, subjects viewed full-length episodes of the television sitcoms Seinfeld or The Simpsons. Brain activity time-locked to humor detection moments revealed increases in left inferior frontal and posterior temporal cortices, whereas brain activity time-locked to moments of humor appreciation revealed increases in bilateral regions of insular cortex and the amygdala. These findings provide evidence that humor depends critically upon extant neural systems important for resolving incongruities (humor detection) and for the expression of affect (humor appreciation)." [Abstract]

Mattay VS, Berman KF, Ostrem JL, Esposito G, Van Horn JD, Bigelow LB, Weinberger DR.
Dextroamphetamine enhances "neural network-specific" physiological signals: a positron-emission tomography rCBF study.
J Neurosci. 1996 Aug 1;16(15):4816-22.
"Previous studies in animals and humans suggest that monoamines enhance behavior-evoked neural activity relative to nonspecific background activity (i.e., increase signal-to-noise ratio). We studied the effects of dextroamphetamine, an indirect monoaminergic agonist, on cognitively evoked neural activity in eight healthy subjects using positron-emission tomography and the O15 water intravenous bolus method to measure regional cerebral blood flow (rCBF). Dextroamphetamine (0.25 mg/kg) or placebo was administered in a double-blind, counterbalanced design 2 hr before the rCBF study in sessions separated by 1-2 weeks. rCBF was measured while subjects performed four different tasks: two abstract reasoning tasks--the Wisconsin Card Sorting Task (WCST), a neuropsychological test linked to a cortical network involving dorsolateral prefrontal cortex and other association cortices, and Ravens Progressive Matrices (RPM), a nonverbal intelligence test linked to posterior cortical systems--and two corresponding sensorimotor control tasks. There were no significant drug or task effects on pCO2 or on global blood flow. However, the effect of dextroamphetamine (i.e., dextroamphetamine vs placebo) on task-dependent rCBF activation (i.e., task - control task) showed double dissociations with respect to task and region in the very brain areas that most distinctly differentiate the tasks. In the superior portion of the left inferior frontal gyrus, dextroamphetamine increased rCBF during WCST but decreased it during RPM (ANOVA F (1,7) = 16.72, p < 0.0046). In right hippocampus, blood flow decreased during WCST but increased during RPM (ANOVA F(1,7) = 18.7, p < 0.0035). These findings illustrate that dextroamphetamine tends to "focus" neural activity, to highlight the neural network that is specific for a particular cognitive task. This capacity of dextroamphetamine to induce cognitively specific signal augmentation may provide a neurobiological explanation for improved cognitive efficiency with dextroamphetamine." [Abstract]

Mazoyer B, Zago L, Mellet E, Bricogne S, Etard O, Houde O, Crivello F, Joliot M, Petit L, Tzourio-Mazoyer N.
Cortical networks for working memory and executive functions sustain the conscious resting state in man.
Brain Res Bull. 2001 Feb;54(3):287-98.
"The cortical anatomy of the conscious resting state (REST) was investigated using a meta-analysis of nine positron emission tomography (PET) activation protocols that dealt with different cognitive tasks but shared REST as a common control state. During REST, subjects were in darkness and silence, and were instructed to relax, refrain from moving, and avoid systematic thoughts. Each protocol contrasted REST to a different cognitive task consisting either of language, mental imagery, mental calculation, reasoning, finger movement, or spatial working memory, using either auditory, visual or no stimulus delivery, and requiring either vocal, motor or no output. A total of 63 subjects and 370 spatially normalized PET scans were entered in the meta-analysis. Conjunction analysis revealed a network of brain areas jointly activated during conscious REST as compared to the nine cognitive tasks, including the bilateral angular gyrus, the left anterior precuneus and posterior cingulate cortex, the left medial frontal and anterior cingulate cortex, the left superior and medial frontal sulcus, and the left inferior frontal cortex. These results suggest that brain activity during conscious REST is sustained by a large scale network of heteromodal associative parietal and frontal cortical areas, that can be further hierarchically organized in an episodic working memory parieto-frontal network, driven in part by emotions, working under the supervision of an executive left prefrontal network." [Abstract]

Johnson-Frey SH.
What's so special about human tool use?
Neuron. 2003 Jul 17;39(2):201-4.
"Evidence suggests homologies in parietofrontal circuits involved in object prehension among humans and monkeys. Likewise, tool use is known to induce functional reorganization of their visuotactile limb representations. Yet, humans are the only species for whom tool use is a defining and universal characteristic. Why? Comparative studies of chimpanzee tool use indicate that critical differences are likely to be found in mechanisms involved in causal reasoning rather than those implementing sensorimotor transformations. Available evidence implicates higher-level perceptual areas in these processes." [Abstract]

Goel V, Dolan RJ.
Reciprocal neural response within lateral and ventral medial prefrontal cortex during hot and cold reasoning.
Neuroimage. 2003 Dec;20(4):2314-21.
"Logic is widely considered the basis of rationality. Logical choices, however, are often influenced by emotional responses, sometimes to our detriment, sometimes to our advantage. To understand the neural basis of emotionally neutral ("cold") and emotionally salient ("hot") reasoning we studied 19 volunteers using event-related fMRI, as they made logical judgments about arguments that varied in emotional saliency. Despite identical logical form and content categories across "hot" and "cold" reasoning conditions, lateral and ventral medial prefrontal cortex showed reciprocal response patterns as a function of emotional saliency of content. "Cold" reasoning trials resulted in enhanced activity in lateral/dorsal lateral prefrontal cortex (L/DLPFC) and suppression of activity in ventral medial prefrontal cortex (VMPFC). By contrast, "hot" reasoning trials resulted in enhanced activation in VMPFC and suppression of activation in L/DLPFC. This reciprocal engagement of L/DLPFC and VMPFC provides evidence for a dynamic neural system for reasoning, the configuration of which is strongly influenced by emotional saliency." [Abstract]

Houde O, Zago L, Crivello F, Moutier S, Pineau A, Mazoyer B, Tzourio-Mazoyer N.
Access to deductive logic depends on a right ventromedial prefrontal area devoted to emotion and feeling: evidence from a training paradigm.
Neuroimage. 2001 Dec;14(6):1486-92.
"Does the human capacity for access to deductive logic depend on emotion and feeling? With positron emission tomography, we compared the brain networks recruited by two groups of subjects who were either able or not able to shift from errors to logical responses in a deductive reasoning task. They were scanned twice while performing the same task, before and after a training session. The error-to-logical shift occurred in a group that underwent logicoemotional training but not in the other group, trained in logic only-a "cold" kind of training. The intergroup comparison pointed out that access to deductive logic involved a right ventromedial prefrontal area known to be devoted to emotion and feeling." [Abstract]

Goel V, Dolan RJ.
Explaining modulation of reasoning by belief.
Cognition. 2003 Feb;87(1):B11-22.
"Although deductive reasoning is a closed system, one's beliefs about the world can influence validity judgements. To understand the associated functional neuroanatomy of this belief-bias we studied 14 volunteers using event-related fMRI, as they performed reasoning tasks under neutral, facilitatory and inhibitory belief conditions. We found evidence for the engagement of a left temporal lobe system during belief-based reasoning and a bilateral parietal lobe system during belief-neutral reasoning. Activation of right lateral prefrontal cortex was evident when subjects inhibited a prepotent response associated with belief-bias and correctly completed a logical task, a finding consistent with its putative role in cognitive monitoring. By contrast, when logical reasoning was overcome by belief-bias, there was engagement of ventral medial prefrontal cortex, a region implicated in affective processing. This latter involvement suggests that belief-bias effects in reasoning may be mediated through an influence of emotional processes on reasoning." [Abstract] [PDF]

Goel V, Buchel C, Frith C, Dolan RJ.
Dissociation of mechanisms underlying syllogistic reasoning.
Neuroimage. 2000 Nov;12(5):504-14.
"A key question for cognitive theories of reasoning is whether logical reasoning is inherently a sentential linguistic process or a process requiring spatial manipulation and search. We addressed this question in an event-related fMRI study of syllogistic reasoning, using sentences with and without semantic content. Our findings indicate involvement of two dissociable networks in deductive reasoning. During content-based reasoning a left hemisphere temporal system was recruited. By contrast, a formally identical reasoning task, which lacked semantic content, activated a parietal system. The two systems share common components in bilateral basal ganglia nuclei, right cerebellum, bilateral fusiform gyri, and left prefrontal cortex. We conclude that syllogistic reasoning is implemented in two distinct systems whose engagement is primarily a function of the presence or absence of semantic content. Furthermore, when a logical argument results in a belief-logic conflict, the nature of the reasoning process is changed by recruitment of the right prefrontal cortex." [Abstract] [PDF]

Jeremy R. Gray, Todd S. Braver, and Marcus E. Raichle
Integration of emotion and cognition in the lateral prefrontal cortex
PNAS 99: 4115-4120. 2002.
"We used functional MRI to test the hypothesis that emotional states can selectively influence cognition-related neural activity in lateral prefrontal cortex (PFC), as evidence for an integration of emotion and cognition. Participants (n = 14) watched short videos intended to induce emotional states (pleasant/approach related, unpleasant/withdrawal related, or neutral). After each video, the participants were scanned while performing a 3-back working memory task having either words or faces as stimuli. Task-related neural activity in bilateral PFC showed a predicted pattern: an Emotion × Stimulus crossover interaction, with no main effects, with activity predicting task performance. This highly specific result indicates that emotion and higher cognition can be truly integrated, i.e., at some point of processing, functional specialization is lost, and emotion and cognition conjointly and equally contribute to the control of thought and behavior. Other regions in lateral PFC showed hemispheric specialization for emotion and for stimuli separately, consistent with a hierarchical and hemisphere-based mechanism of integration." [Full Text]

Phan KL, Taylor SF, Welsh RC, Ho SH, Britton JC, Liberzon I.
Neural correlates of individual ratings of emotional salience: a trial-related fMRI study.
Neuroimage. 2004 Feb;21(2):768-80.
"Accurate appraisal of meaningful environmental signals involves the interpretation of salient information for their intrinsic emotional value and personal relevance. We examined the neural basis for these components of endogenous salience during such appraisals using trial-related functional magnetic resonance imaging (fMRI). Subjects viewed affective pictures and assessed either the emotional intensity or extent of self-relatedness of the content of those pictures. In a parametric factorial design, individualized subjective ratings of these two dimensions were correlated with brain activity. The nucleus accumbens (NAcc) responded to both increasing emotional intensity and self-relatedness. Activity in the amygdala was specifically related to affective judgments and emotional intensity. The volitional act of appraising the extent of personal association specifically engaged the ventral medial prefrontal cortex (MPFC), and additionally recruited dorsal medial frontal regions and insula as the extent of self-relatedness increased. The findings highlight both overlapping and segregated neural representations of intrinsic value and personal relevance during the appraisal of emotional stimuli." [Abstract]

Phan KL, Wager T, Taylor SF, Liberzon I.
Functional neuroanatomy of emotion: a meta-analysis of emotion activation studies in PET and fMRI.
Neuroimage. 2002 Jun;16(2):331-48.
"Neuroimagingstudies with positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) have begun to describe the functional neuroanatomy of emotion. Taken separately, specific studies vary in task dimensions and in type(s) of emotion studied and are limited by statistical power and sensitivity. By examining findings across studies, we sought to determine if common or segregated patterns of activations exist across various emotional tasks. We reviewed 55 PET and fMRI activation studies (yielding 761 individual peaks) which investigated emotion in healthy subjects. Peak activation coordinates were transformed into a standard space and plotted onto canonical 3-D brain renderings. We divided the brain into 20 nonoverlapping regions, and characterized each region by its responsiveness across individual emotions (positive, negative, happiness, fear, anger, sadness, disgust), to different induction methods (visual, auditory, recall/imagery), and in emotional tasks with and without cognitive demand. Our review yielded the following summary observations: (1) The medial prefrontal cortex had a general role in emotional processing; (2) fear specifically engaged the amygdala; (3) sadness was associated with activity in the subcallosal cingulate; (4) emotional induction by visual stimuli activated the occipital cortex and the amygdala; (5) induction by emotional recall/imagery recruited the anterior cingulate and insula; (6) emotional tasks with cognitive demand also involved the anterior cingulate and insula. This review provides a critical comparison of findings across individual studies and suggests that separate brain regions are involved in different aspects of emotion." [Abstract] [PDF]

Zysset S, Huber O, Ferstl E, von Cramon DY.
The anterior frontomedian cortex and evaluative judgment: an fMRI study.
Neuroimage. 2002 Apr;15(4):983-91.
"This study investigated the neuronal basis of evaluative judgment. Judgments can be defined as the assessment of an external or internal stimulus on an internal scale and they are fundamental for decision-making and other cognitive processes. Evaluative judgments (I like George W. Bush: yes/no) are a special type of judgment, in which the internal scale is related to the person's value system (preferences, norms, aesthetic values, etc.). We used functional magnetic resonance imaging to examine brain activation during the performance of evaluative judgments as opposed to episodic and semantic memory retrieval. Evaluative judgment produced significant activation in the anterior frontomedian cortex (BA 10/9), the inferior precuneus (BA 23/31), and the left inferior prefrontal cortex (BA 45/47). The results show a functional dissociation between the activations in the anterior frontomedian cortex and in the inferior precuneus. The latter was mainly activated by episodic retrieval processes, supporting its function as a multimodal association area that integrates the different aspects of retrieved and newly presented information. In contrast, the anterior frontomedian cortex was mainly involved in evaluative judgments, supporting its role in self-referential processes and in the self-initiation of cognitive processes." [Abstract]

Volz KG, Schubotz RI, Von Cramon DY.
Why am I unsure? Internal and external attributions of uncertainty dissociated by fMRI.
Neuroimage. 2004 Mar;21(3):848-57.
"Behavioral evidence suggests that the perceived reason of uncertainty causes different coping strategies to be implemented, particularly frequency ratings with externally attributed uncertainty and memory search with internally attributed uncertainty. We used functional magnetic resonance imaging (fMRI) to investigate whether processes related to these different attributions of uncertainty differ also in their neural substrates. Participants had to predict events that were uncertain due to internal factors, that is, insufficient knowledge. Data were compared with a preceding study in which event prediction was uncertain due to external factors, that is, event probabilities. Parametric analyses revealed the posterior frontomedian cortex, that is, mesial Brodmann Area 8 (BA 8) as the common cortical substrate mediating processes related to uncertainty no matter what the cause of uncertainty. However, processes related to the two differently attributed types of uncertainty differed significantly in relation to the brain network that was coactivated. Only processes related to internally attributed uncertainty elicited activation within the mid-dorsolateral and posterior parietal areas known to underlie working memory (WM) functions. Together, findings from both experiments suggest that there is a common cerebral correlate for uncertain predictions but different correlates for coping strategies of uncertainty. Concluding, BA 8 reflects that we are uncertain, coactivated networks what we do to resolve uncertainty." [Abstract]

von Zerssen GC, Mecklinger A, Opitz B, von Cramon DY.
Conscious recollection and illusory recognition: an event-related fMRI study.
Eur J Neurosci. 2001 Jun;13(11):2148-56.
"In this event-related functional magnetic resonance imaging (fMRI) study we examined the neuronal correlates of the subprocesses underlying recognition memory. In an explicit memory task, participants had to discriminate studied ('old') words from semantically related and unrelated 'new' (unstudied) words. We examined whether the correct rejection of semantically related words which were similar to old words, which had elicited correct responses, was based on conscious recollection of study phase information. In this task, false-positive responses to semantically related new words can be assumed to result from the assessment of the semantic similarity between test words and studied words with minimal recollection. For correct identification of old words and correct rejection of new related words we found common activation in a variety of brain areas that have been shown to be involved in conscious recollection, among them the left middle frontal gyrus, the precuneus, the retrosplenial cortex, the left parahippocampal gyrus and the thalamus. For correct responses to old words, the frontomedian wall, the posterior cingulate cortex and the nucleus accumbens were additionally activated, suggesting an emotional contribution to these judgements. Correct rejections of related new words were associated with additional activation of the right middle frontal gyrus, suggesting higher monitoring demands for these more difficult recognition judgements. False-positive responses to semantically related new words were associated with enhanced activation in the frontomedian wall. The results point to an important role of the prefrontal cortex as well as medial temporal and medial parietal regions of the brain in successful memory retrieval and conscious recollection." [Abstract]

Ferstl EC, von Cramon DY.
What does the frontomedian cortex contribute to language processing: coherence or theory of mind?
Neuroimage. 2002 Nov;17(3):1599-612.
"The frontomedian cortex (FMC) has been shown to be important for coherence processes in language comprehension, i.e., for establishing the pragmatic connection between successively presented sentences. The same brain region has a role during theory-of-mind processes, i.e., during the attribution of other people's actions to their motivations, beliefs, or emotions. In this study, we used event-related functional magnetic resonance imaging at 3 T to disentangle the relative contributions of the FMC to theory-of-mind (ToM) and coherence processes, respectively. The BOLD response of nine participants was recorded while they listened to pragmatically coherent or unrelated sentence pairs. Using a logic instruction for inanimate sentence pairs, ToM processing was discouraged during the first part of the experiment. Using explicit ToM instructions for sentence pairs mentioning human protagonists, ToM processing was induced during the second part. In three of the resulting four conditions a significant increase in the BOLD response was observed in FMC: when ToM instructions were given, both coherent and incoherent trials elicited frontomedian activation, in replication of previous results showing involvement of the FMC during ToM tasks. When logic instructions were given, the coherent trials, but not the incoherent trials, activated the FMC. These results clearly show that the FMC plays a role in coherence processes even in the absence of concomitant ToM processes. The findings support the view of this cortex having a domain-independent functionality related to volitional aspects of the initiation and maintenance of nonautomatic cognitive processes." [Abstract]

Ferstl EC, von Cramon DY.
The role of coherence and cohesion in text comprehension: an event-related fMRI study.
Brain Res Cogn Brain Res. 2001 Jun;11(3):325-40.
"Text processing requires inferences for establishing coherence between successive sentences. In neuropsychological studies and brain imaging studies, these coherence-building processes have been ascribed to the right hemisphere. On the other hand, there is evidence for prefrontal brain damage causing non-aphasic language disorders, in which text level processes are impaired. In this study, we used an event-related, whole-head fMRI methodology to evaluate the contributions of prefrontal areas and the right hemisphere to coherence building. We scanned 12 participants while they read 120 sentence pairs and judged their coherence. Four conditions were used, resulting from crossing coherence and cohesion (i.e. the presence of a lexical connection). A behavioral pretest confirmed that cohesion aided establishing coherence, whereas it hindered the detection of coherence breaks. In the fMRI study, all language conditions yielded activation in left frontolateral and temporolateral regions, when compared to a physical control task. The differences due to coherence of the sentence pairs were most evident in larger activation for coherent as compared to incoherent sentence pairs in the left frontomedian wall, but also in posterior cingulate and precuneal regions. Finally, a left inferior prefrontal area was sensitive to the difficulty of the task, and in particular to the increase in processing costs when cohesion falsely indicated coherence. These results could not provide evidence for a special involvement of the right hemisphere during inferencing. Rather, they suggest that the left frontomedian cortex plays an important role in coherence building." [Abstract]

Elliott R, Rees G, Dolan RJ.
Ventromedial prefrontal cortex mediates guessing.
Neuropsychologia. 1999 Apr;37(4):403-11.
"Guessing is an important component of everyday cognition. The present study examined the neural substrates of guessing using a simple card-playing task in conjunction with functional magnetic resonance imaging (fMRI). Subjects were scanned under four conditions. In two, they were shown images of the back of a playing card and had to guess either the colour or the suit of the card. In the other two they were shown the face of a card and had to report either the colour or the suit. Guessing compared to reporting was associated with significant activations in lateral prefrontal cortex (right more than left), right orbitofrontal cortex, anterior cingulate, bilateral inferior parietal cortex and right thalamus. Increasing the guessing demands by manipulating the number of alternative outcomes was associated with activation of the left lateral and medial orbitofrontal cortex. These data suggest that while simple two choice guessing depends on an extensive neural system including regions of the right lateral prefrontal cortex, activation of orbitofrontal cortex increases as the probabilistic contingencies become more complex. Guessing thus involves not only systems implicated in working memory processes but also depends upon orbitofrontal cortex. This region is not typically activated in working memory tasks and its activation may reflect additional requirements of dealing with uncertainty." [Abstract]

Gomez-Beldarrain, Marian, Harries, Clare, Garcia-Monco, Juan Carlos, Ballus, Emma, Grafman, Jordan
Patients with Right Frontal Lesions are Unable to Assess and Use Advice to Make Predictive Judgments
J. Cogn. Neurosci. 2004 16: 74-89
"Frontal lobe damage impairs decision-making. Most studies have employed gambling and probabilistic tasks, which have an emotional (reward–punishment) component and found that patients with ventromedial sector lesions have exceptional difficulty performing normally on these tasks. We have recently presented an economic decision-making task to patients and normal volunteers that required them to not only forecast an economic outcome but also to weigh advice from four advisors about the possible outcome across 40 trials. We studied 20 patients with right frontal lobe lesions and 9 patients with parietal lobe lesions and compared their performance to 20 matched controls. Frontal lobe lesion patients were inconsistent at using advice and their forecasts were poor. Patients with dorsolateral but not orbito-frontal lesions showed some ability to assess advice. Patients with parietal lobe lesions were good at assessing advice but were slow at doing so; they were consistent but poor at using advice and their use of advice was unrelated to their forecasting. All three patient groups were overconfident in their own performance. In contrast, controls could both use and assess advice, their ability to use advice was mediated by their ability to assess it, and they were not overconfident. Group differences on an overall measure of accuracy on this task were associated with an ability to accurately plan. Differences in ability to assess and forecast were associated with planning and working memory performance. These findings indicate that patients with both right dorsolateral and orbito-frontal lesions may be impaired when required to make complex decisions related to forecasting and judgment. Our findings enlarge the scope of decision-making deficits seen in patients with frontal lobe lesions and indicate additional circumstances in which patients with frontal lobe lesions will have difficulty in deciding." [Full Text]

Sanfey, Alan G., Rilling, James K., Aronson, Jessica A., Nystrom, Leigh E., Cohen, Jonathan D.
The Neural Basis of Economic Decision-Making in the Ultimatum Game
Science 2003 300: 1755-1758
"The nascent field of neuroeconomics seeks to ground economic decisionmaking in the biological substrate of the brain. We used functional magnetic resonance imaging of Ultimatum Game players to investigate neural substrates of cognitive and emotional processes involved in economic decision-making. In this game, two players split a sum of money;one player proposes a division and the other can accept or reject this. We scanned players as they responded to fair and unfair proposals. Unfair offers elicited activity in brain areas related to both emotion (anterior insula) and cognition (dorsolateral prefrontal cortex). Further, significantly heightened activity in anterior insula for rejected unfair offers suggests an important role for emotions in decision-making." [Full Text]

Camerer, Colin F.
PSYCHOLOGY AND ECONOMICS: Enhanced: Strategizing in the Brain
Science 2003 300: 1673-1675 [Full Text]

Shimoyama H, Aihara M, Fukuyama H, Hashikawa K, Aoyagi K, Goldberg E, Nakazawa S.
Context-dependent reasoning in a cognitive bias task Part II. SPECT activation study.
Brain Dev. 2004 Jan;26(1):37-42.
"A cognitive bias task (CBT) delineates two different cognitive selection mechanisms in the prefrontal cortex. To identify functional anatomy of context-dependent reasoning, we used technetium-99mhexamethyl- propyleneamine oxime (99mTc HM-PAO) single photon emission computed tomography (SPECT) and statistical parametric mapping. Twelve right-handed men 20-24 years old were instructed to look at a target card and then select the choice card (among two) that they preferred (modified CBT; mCBT). They also selected a choice card 2 weeks later without prior presentation of a target card (control task). In both tasks, 99mTc HM-PAO was injected intravenously about 15 s after initiation of the mCBT or control task. Brain images were obtained using a gamma camera and reconstructed by a UNIX-based workstation. Statistical analysis compared all activated images to control images. Results associated with P values of less than 0.01 (Z score > 2.36) were depicted on T1-weighted magnetic resonance images. All subjects preferred choices more similar to the target. SPECT activation occurred bilaterally in the dorsolateral prefrontal cortices and middle temporal gyri during performance of the CBT. Additionally, the left inferior prefrontal cortex and left fusiform gyrus showed significant activation compared with the control task. A neural network linking the temporal and prefrontal cortices prominently seen in the left hemisphere participates in context-dependent reasoning. Knowledge of such neural systems is essential for understanding prefrontal lobe function and dysfunction." [Abstract]

Narender Ramnani & Adrian M. Owen
Nature Reviews Neuroscience 5, 184 -194 (2004); doi:10.1038/nrn1343
The anterior prefrontal cortex (aPFC), or Brodmann area 10, is one of the least well understood regions of the human brain. Work with non-human primates has provided almost no indications as to the function of this area. In recent years, investigators have attempted to integrate findings from functional neuroimaging studies in humans to generate models that might describe the contribution that this area makes to cognition. In all cases, however, such explanations are either too tied to a given task to be plausible or too general to be theoretically useful. Here, we use an account that is consistent with the connectional and cellular anatomy of the aPFC to explain the key features of existing models within a common theoretical framework. The results indicate a specific role for this region in integrating the outcomes of two or more separate cognitive operations in the pursuit of a higher behavioural goal. [Abstract] [PDF]

Christoff K, Ream JM, Geddes LP, Gabrieli JD.
Evaluating self-generated information: anterior prefrontal contributions to human cognition.
Behav Neurosci. 2003 Dec;117(6):1161-8.
"The anterior or rostrolateral prefrontal cortex (RLPFC) is frequently recruited during complex cognitive tasks across a wide range of domains, including reasoning, long-term memory retrieval, and working memory. The authors report an event-related functional MRI study, indicating that the RLPFC is specifically involved in the evaluation of internally generated information--or information that cannot be readily perceived from the external environment but has to be inferred or self-generated. The findings are consistent with a hierarchical model of lateral prefrontal organization, with RLPFC contributing only at the highest orders of cognitive transformations. This characterization of RLPFC function may help explain seemingly disparate findings across multiple cognitive domains and could provide a unified account of this region's contribution to human cognition." [Abstract]

Christoff K, Prabhakaran V, Dorfman J, Zhao Z, Kroger JK, Holyoak KJ, Gabrieli JD.
Rostrolateral prefrontal cortex involvement in relational integration during reasoning.
Neuroimage. 2001 Nov;14(5):1136-49.
"Patient and neuroimaging studies indicate that complex reasoning tasks are associated with the prefrontal cortex (PFC). In this study, we tested the hypothesis that the process of relational integration, or considering multiple relations simultaneously, is a component process of complex reasoning that selectively recruits PFC. We used fMRI to examine brain activation during 0-relational, 1-relational, and 2-relational problems adapted from the Raven's Progressive Matrices and hypothesized that PFC would be preferentially recruited by the 2-relational problem type. Event-related responses were modeled by convolving a canonical hemodynamic response function with the response time (RT) associated with each trial. The results across different analyses revealed the same pattern: PFC activation was specific to the comparison between 2- and 1-relational problems and was not observed in the comparison between 1- and 0-relational problems. Furthermore, the process of relational integration was specifically associated with bilateral rostrolateral PFC (RLPFC; lateral area 10) and right dorsolateral PFC (areas 9 and 46). Left RLPFC showed the greatest specificity by remaining preferentially recruited during 2-relational problems even after comparisons were restricted to trials matched for RT and accuracy. The link between RLPFC and the process of relational integration may be due to the associated process of manipulating self-generated information, a process that may characterize RLPFC function." [Abstract] [PDF]

Kroger JK, Sabb FW, Fales CL, Bookheimer SY, Cohen MS, Holyoak KJ.
Recruitment of anterior dorsolateral prefrontal cortex in human reasoning: a parametric study of relational complexity.
Cereb Cortex. 2002 May;12(5):477-85.
"Reasoning and problem solving depend on the ability to represent and integrate complex relationships among stimuli. For example, deciding whether an animal is dangerous requires integrating information about the type of animal, its size, its distance from oneself, and one's proximity to shelter. Relational complexity increases with the number of such interdependent elements that must be simultaneously considered to solve a problem. We used functional magnetic resonance imaging to identify brain regions that respond selectively in processing high levels of relational complexity. Performance on nonverbal reasoning problems in which relational complexity was varied parametrically was compared with performance on control problems in which relational complexity was held constant while difficulty was manipulated by adding distractor forms to the problems. Increasing complexity and adding distractors both led to increased activation in parietal and in dorsolateral prefrontal cortex, with high levels of relational complexity selectively activating anterior left prefrontal cortex. Our data provide evidence that brain regions specific to integrating complex relations among stimuli are distinct from those involved in coping with general task difficulty and with working-memory demands." [Abstract]

Strange, B.A., Henson, R.N.A., Friston, K.J., Dolan, R.J.
Anterior Prefrontal Cortex Mediates Rule Learning in Humans
Cereb. Cortex 2001 11: 1040-1046
"Despite a need for rule learning in everyday life, the brain regions involved in explicit rule induction remain undetermined. Here we use event-related functional magnetic resonance imaging to measure learning-dependent neuronal responses during an explicit categor- ization task. Subjects made category decisions, with feedback, to exemplar letter strings for which the rule governing category membership was periodically changed. Bilateral fronto-polar prefrontal cortices were selectively engaged following rule change. This activation pattern declined with improving task performance reflecting rule acquisition. The vocabulary of letters comprising the exemplars was also periodically changed, independently of rule changes. This exemplar change modulated activation in left anterior hippocampus. Our finding that fronto-polar cortex mediates rule learning supports a functional contribution of this region to generic reasoning and problem-solving behaviours." [Full Text]

Braver TS, Bongiolatti SR.
The role of frontopolar cortex in subgoal processing during working memory.
Neuroimage. 2002 Mar;15(3):523-36.
"Neuroimaging studies have implicated the anterior-most or frontopolar regions of prefrontal cortex (FP-PFC, e.g., Brodmann's Area 10) as playing a central role in higher cognitive functions such as planning, problem solving, reasoning, and episodic memory retrieval. The current functional magnetic resonance imaging (fMRI) study tested the hypothesis that FP-PFC subserves processes related to the monitoring and management of subgoals, while maintaining information in working memory (WM). Subjects were scanned while performing two variants of a simple delayed response WM task. In the control WM condition, subjects monitored for the presence of a specific concrete probe word (LIME) occurring following a specific abstract cue word (FATE). In the subgoal WM condition, subjects monitored for the presence of any concrete probe word immediately following any abstract cue word. Thus, the task required semantic classification of the probe word (the subgoal task), while the cue was simultaneously maintained in WM, so that both pieces of information could be integrated into a target determination. In a second control condition, subjects performed abstract/concrete semantic classification without WM demands. A region within right FP-PFC was identified which showed significant activation during the subgoal WM condition, but no activity in either of the two control conditions. However, this FP-PFC region was not modulated by direct manipulation of active maintenance demands. In contrast, left dorsolateral PFC was affected by active maintenance demands, but the effect did not interact with the presence of a subgoal task. Finally, left ventral PFC regions showed activation in response to semantic classification, but were not affected by WM demands. These results suggest a triple dissociation of function within PFC regions, and further indicate that FP-PFC is selectively engaged by the requirement to monitor and integrate subgoals during WM tasks." [Abstract] [PDF]

Koechlin E, Basso G, Pietrini P, Panzer S, Grafman J.
The role of the anterior prefrontal cortex in human cognition.
Nature. 1999 May 13;399(6732):148-51.
"Complex problem-solving and planning involve the most anterior part of the frontal lobes including the fronto-polar prefrontal cortex (FPPC), which is especially well developed in humans compared with other primates. The specific role of this region in human cognition, however, is poorly understood. Here we show, using functional magnetic resonance imaging, that bilateral regions in the FPPC alone are selectively activated when subjects have to keep in mind a main goal while performing concurrent (sub)goals. Neither keeping in mind a goal over time (working memory) nor successively allocating attentional resources between alternative goals (dual-task performance) could by themselves activate these regions. Our results indicate that the FPPC selectively mediates the human ability to hold in mind goals while exploring and processing secondary goals, a process generally required in planning and reasoning." [Abstract]

Houde O, Zago L, Mellet E, Moutier S, Pineau A, Mazoyer B, Tzourio-Mazoyer N.
Shifting from the perceptual brain to the logical brain: the neural impact of cognitive inhibition training.
J Cogn Neurosci. 2000 Sep;12(5):721-8.
"What happens in the human brain when the mind has to inhibit a perceptual process in order to activate a logical reasoning process? Here, we use functional imaging to show the networks of brain areas involved in a deductive logic task performed twice by the same subjects, first with a perceptual bias and then with a logical response following bias-inhibition training. The main finding is a striking shift in the cortical anatomy of reasoning from the posterior part of the brain (the ventral and dorsal pathways) to a left-prefrontal network including the middle-frontal gyrus, Broca's area, the anterior insula, and the pre-SMA. This result indicates that such brain shifting is an essential element for human access to logical thinking." [Abstract]

Nobre, A. C., Coull, J. T., Maquet, P., Frith, C. D., Vandenberghe, R., Mesulam, M. M.
Orienting Attention to Locations in Perceptual Versus Mental Representations
J. Cogn. Neurosci. 2004 16: 363-373
"Extensive clinical and imaging research has characterized the neural networks mediating the adaptive distribution of spatial attention. In everyday behavior, the distribution of attention is guided not only by extrapersonal targets but also by mental representations of their spatial layout. We used event-related functional magnetic resonance imaging to identify the neural system involved in directing attention to locations in arrays held as mental representations, and to compare it with the system for directing spatial attention to locations in the external world. We found that these two crucial aspects of spatial cognition are subserved by extensively overlapping networks. However, we also found that a region of right parietal cortex selectively participated in orienting attention to the extrapersonal space, whereas several frontal lobe regions selectively participated in orienting attention within on-line mental representations." [Abstract]

Seiki Konishi, Koji Jimura, Tomoki Asari, and Yasushi Miyashita
Transient Activation of Superior Prefrontal Cortex during Inhibition of Cognitive Set
J. Neurosci. 23: 7776-7782. 2003.
"The prefrontal cortex implements a set-shifting function that includes inhibition of a previously acquired cognitive set. The impairment of the inhibitory function results in perseverative behavior that forms one characteristic feature of frontal lobe dysfunction. Previous neuroimaging studies have revealed inhibitory mechanisms in the inferior prefrontal cortex. The present functional magnetic resonance imaging study devised "dual-match" stimuli in a set-shifting paradigm that allowed us to temporally isolate the inhibitory processes recruited during exposure to a previously acquired set. Transient activation time-locked to the isolated inhibition was revealed in the left middle frontal gyrus near the superior frontal sulcus. In a control experiment conducted after subjects had been informed and made aware of the exposure, however, the superior prefrontal activation disappeared, and prominent activation was revealed in a set of brain regions that included the left posterior inferior frontal sulcus. These double dissociation results indicate inhibitory mechanisms in the superior prefrontal cortex, alternative to the inferior prefrontal ones, that are activated depending on the subjects' strategy for inhibition of cognitive set." [Abstract]

Atherton M, Zhuang J, Bart WM, Hu X, He S.
A functional MRI study of high-level cognition. I. The game of chess.
Brain Res Cogn Brain Res. 2003 Mar;16(1):26-31.
"Chess is a game that involves many aspects of high level cognition and requires sophisticated problem solving skills. However, there is little understanding of the neural basis of chess cognition. This study employed functional magnetic resonance imaging (fMRI) to identify cortical areas that are active during the analysis of chess positions compared with a spatial task with matched visual stimuli. Bilateral activation was revealed in the superior frontal lobes, the parietal lobes, and occipital lobes. Some small areas of activation were observed unilaterally in the left hemisphere. The left hemisphere showed more activation than the right. Results are discussed in relation to a similar brain imaging study on the game Go." [Abstract]

Cary R. Savage, Thilo Deckersbach, Stephan Heckers, Anthony D. Wagner, Daniel L. Schacter, Nathaniel M. Alpert, Alan J. Fischman, and Scott L. Rauch
Prefrontal regions supporting spontaneous and directed application of verbal learning strategies: Evidence from PET
Brain 124: 219-231.
"The prefrontal cortex has been implicated in strategic memory processes, including the ability to use semantic organizational strategies to facilitate episodic learning. An important feature of these strategies is the way they are applied in novel or ambiguous situations-failure to initiate effective strategies spontaneously in unstructured settings is a central cognitive deficit in patients with frontal lobe disorders. The current study examined strategic memory with PET and a verbal encoding paradigm that manipulated semantic organization in three encoding conditions: spontaneous, directed and unrelated. During the spontaneous condition, subjects heard 24 words that were related in four categories but presented in mixed order, and they were not informed of this structure beforehand. Any semantic reorganization was, therefore, initiated spontaneously by the subject. In the directed condition, subjects were given a different list of 24 related words and explicitly instructed to notice relationships and mentally group related words together to improve memory. The unrelated list consisted of 24 unrelated words. Behavioural measures included semantic clustering, which assessed active regrouping of words into semantic categories during free recall. In graded PET contrasts (directed > spontaneous > unrelated), two distinct activations were found in left inferior prefrontal cortex (inferior frontal gyrus) and left dorsolateral prefrontal cortex (middle frontal gyrus), corresponding to levels of semantic clustering observed in the behavioural data. Additional covariate analyses in the first spontaneous condition indicated that blood flow in orbitofrontal cortex (OFC) was strongly correlated with semantic clustering scores during immediate free recall. Thus, blood flow in OFC during encoding predicted which subjects would spontaneously initiate effective strategies during free recall. Our findings indicate that OFC performs an important, and previously unappreciated, role in strategic memory by supporting the early mobilization of effective behavioural strategies in novel or ambiguous situations. Once initiated, lateral regions of left prefrontal cortex control verbal semantic organization." [Full Text]

Grossman M, Smith EE, Koenig P, Glosser G, DeVita C, Moore P, McMillan C.
The neural basis for categorization in semantic memory.
Neuroimage. 2002 Nov;17(3):1549-61.
"We asked young adults to categorize written object descriptions into one of two categories, based on a rule or on overall similarity, while we monitored regional brain activity with functional magnetic resonance imaging (fMRI). We found significantly greater recruitment of left dorsolateral prefrontal cortex for rule-based categorization in direct comparison with similarity-based categorization. Recruitment of right ventral frontal cortex and thalamus was uniquely associated with rule-based categorization as well. These observations lend support to the claim that executive functions such as working memory, inhibitory control, and selective attention contribute to rule-based categorization. Right inferior parietal activation was uniquely associated with similarity-based categorization. This region may play an important role in overall feature configuration that is important for this form of categorization. We found other brain regions recruited for both rule-based and similarity-based categorization: Anterior cingulate cortex may support the implementation of executive functions during situations with competing response alternatives; and left inferior parietal cortex may be related to the integration of feature knowledge about objects represented in modality-specific association cortices. We also administered a degraded-similarity condition where the task of categorizing a written object description was made more difficult by perceptually degrading the stimulus materials. The degraded condition and the rule-based condition, but not the similarity-based condition, were associated with caudate activation. The caudate may support resource demands that are not specific for a particular categorization process. These findings associate partially distinct large-scale neural networks with different forms of categorization in semantic memory." [Abstract] [PDF]

Caplan R, Dapretto M.
Making sense during conversation: an fMRI study.
Neuroreport. 2001 Nov 16;12(16):3625-32.
"Although language is thought of as a left hemisphere function, there is increasing evidence that the right hemisphere contributes to language processing by identifying the theme of spoken and written language. Using fMRI, we examined the role played by the right and left hemispheres in making sense of a conversation. When this process involves implicit appraisal of changes in the conversation's topic, the neural network has a right hemisphere bias and includes Broca's and Wernicke's areas, their right hemisphere homologues, right dorsolateral prefrontal cortex, and the cerebellum. When making sense of conversation involves appraisal of the conversation's reasoning, however, the network includes Broca's and Wernicke's areas. Thus, right and left hemisphere systems contribute uniquely to the linguistic skills involved in making sense of a conversation." [Abstract]

Newman SD, Just MA, Carpenter PA.
The synchronization of the human cortical working memory network.
Neuroimage. 2002 Apr;15(4):810-22.
"A verbal reasoning problem at the intersection of verbal working memory, problem-solving, and language comprehension was examined using event-related fMRI to distinguish differences in the differential timing of the response of the various cortical regions that compose the working memory network. Problems were developed such that the process demand as well as the timing of the manipulation of the contents of working memory (i.e., a demanding computation) was varied. Activation was observed in several regions including the dorsolateral prefrontal cortex, the inferior frontal gyrus, and the parietal lobe. Examination of the MR amplitude response revealed that the regions do not all activate simultaneously; instead, their activation time courses reveal differential responses that correspond to their theoretical processing role in the problem-solving task. The coordination of cortical area responses reveals how the various cortical regions synchronize and collaborate in order to accomplish a given cognitive function." [Abstract]

Demonet JF, Thierry G, Cardebat D.
Renewal of the neurophysiology of language: functional neuroimaging.
Physiol Rev. 2005 Jan;85(1):49-95.
Functional neuroimaging methods have reached maturity. It is now possible to start to build the foundations of a physiology of language. The remarkable number of neuroimaging studies performed so far illustrates the potential of this approach, which complements the classical knowledge accumulated on aphasia. Here we attempt to characterize the impact of the functional neuroimaging revolution on our understanding of language. Although today considered as neuroimaging techniques, we refer less to electroencephalography and magnetoencephalography studies than to positron emission tomography and functional magnetic resonance imaging studies, which deal more directly with the question of localization and functional neuroanatomy. This review is structured in three parts. 1) Because of their rapid evolution, we address technical and methodological issues to provide an overview of current procedures and sketch out future perspectives. 2) We review a set of significant results acquired in normal adults (the core of functional imaging studies) to provide an overview of language mechanisms in the "standard" brain. Single-word processing is considered in relation to input modalities (visual and auditory input), output modalities (speech and written output), and the involvement of "central" semantic processes before sentence processing and nonstandard language (illiteracy, multilingualism, and sensory deficits) are addressed. 3) We address the influence of plasticity on physiological functions in relation to its main contexts of appearance, i.e., development and brain lesions, to show how functional imaging can allow fine-grained approaches to adaptation, the fundamental property of the brain. In closing, we consider future developments for language research using functional imaging. [Full Text]

Mason RA, Just MA.
How the brain processes causal inferences in text.
Psychol Sci. 2004 Jan;15(1):1-7.
"Theoretical models of text processing, such as the construction-integration framework, pose fundamental questions about causal inference making that are not easily addressed by behavioral studies. In particular, a common result is that causal relatedness has a different effect on text reading times than on memory for the text: Whereas reading times increase linearly as causal relatedness decreases, memory for the text is best for events that are related by a moderate degree of causal relatedness and is poorer for events with low and high relatedness. Our functional magnetic resonance imaging study of the processing of two-sentence passages that varied in their degree of causal relatedness suggests that the inference process can be analyzed into two components, generation and integration, that are subserved by two large-scale cortical networks (a reasoning system in dorsolateral prefrontal cortex and the right-hemisphere language areas). These two cortical networks, which are distinguishable from the classical left-hemisphere language areas, approximately correspond to the two functional relations observed in the behavioral results." [Abstract]

Drummond SP, Brown GG, Salamat JS.
Brain regions involved in simple and complex grammatical transformations.
Neuroreport. 2003 Jun 11;14(8):1117-22.
"Grammatical transformation is a verbal reasoning task requiring judging the veracity of statements describing the spatial order of letter sets. We studied 18 adults with FMRI while they performed grammatical transformations of varying complexity levels (2-letter, 3-letter, and 4-letter sentences). Brain regions activated by 2-letter sentences included the visuospatial processing regions of the bilateral parietal lobes and the frontal operculum. A linear increase in sentence complexity engaged dorsolateral and ventrolateral prefrontal cortex as well as significantly increased activation within 2LTR areas. These data provide evidence that grammatical transformation reasoning relies primarily on the posterior visuospatial working memory system and need not necessarily engage the prefrontal cortex. Increasing the complexity of grammatical transformation, though, activates prefrontal cortex." [Abstract]

Homae F, Hashimoto R, Nakajima K, Miyashita Y, Sakai KL.
From perception to sentence comprehension: the convergence of auditory and visual information of language in the left inferior frontal cortex.
Neuroimage. 2002 Aug;16(4):883-900.
"We used functional magnetic resonance imaging (fMRI) to characterize cortical activation associated with sentence processing, thereby elucidating where in the brain auditory and visual inputs of words converge during sentence comprehension. Within one scanning session, subjects performed three types of tasks with different linguistic components from perception to sentence comprehension: nonword (N(AV); auditory and visual), phrase (P; either auditory or visual), and sentence (S; either auditory or visual) tasks. In a comparison of the P and N(AV) tasks, the angular and supramarginal gyri showed bilateral activation, whereas the inferior and middle frontal gyri showed left-lateralized activation. A comparison of the S and P tasks, together with a conjunction analysis, revealed a ventral region of the left inferior frontal gyrus (F3t/F3O), which was sentence-processing selective and modality-independent. These results unequivocally demonstrated that the left F3t/F3O is involved in the selection and integration of semantic information that are separable from lexico-semantic processing." [Abstract] [PDF]

Carpenter PA, Just MA, Keller TA, Eddy WF, Thulborn KR.
Time course of fMRI-activation in language and spatial networks during sentence comprehension.
Neuroimage. 1999 Aug;10(2):216-24.
"Functional neuroimaging previously has been considered to provide inadequate temporal resolution to study changes of brain states as a function of cognitive computations; however, we have obtained evidence of differential amounts of brain activity related to high-level cognition (sentence processing) within 1.5 s of stimulus onset. The study used an event-related paradigm with high-speed echoplanar functional magnetic resonance imaging (fMRI) to trace the time course of the brain activation in the temporal and parietal regions as participants comprehended single sentences describing a spatial configuration. Within the first set of images, on average 1 s from when the participant begins to read a sentence, there was significant activation in a key cortical area involved in language comprehension (the left posterior temporal gyrus) and visuospatial processing (the left and right parietal regions). In all three areas, the amount of activation during sentence comprehension was higher for negative sentences than for their affirmative counterparts, which are linguistically less complex. The effect of negation indicates that the activation in these areas is modulated by the difficulty of the linguistic processing. These results suggest a relatively rapid coactivation in both linguistic and spatial cortical regions to support the integration of information from multiple processing streams." [Abstract]

Kohler, Evelyne, Keysers, Christian, Umilta, M. Alessandra, Fogassi, Leonardo, Gallese, Vittorio, Rizzolatti, Giacomo
Hearing Sounds, Understanding Actions: Action Representation in Mirror Neurons
Science 2002 297: 846-848
"Many object-related actions can be recognized by their sound. We found neurons in monkey premotor cortex that discharge when the animal performs a specific action and when it hears the related sound. Most of the neurons also discharge when the monkey observes the same action. These audiovisual mirror neurons code actions independently of whether these actions are performed, heard, or seen. This discovery in the monkey homolog of Broca's area might shed light on the origin of language: audiovisual mirror neurons code abstract contents-the meaning of actions-and have the auditory access typical of human language to these contents." [Full Text]

Hamzei F, Rijntjes M, Dettmers C, Glauche V, Weiller C, Buchel C.
The human action recognition system and its relationship to Broca's area: an fMRI study.
Neuroimage. 2003 Jul;19(3):637-44.
"Primate studies have identified populations of neurons that are capable of action recognition. These "mirror neurons" show spiking activity both when the monkey executes or observes a grasping movement. These neurons are located in the ventral premotor cortex, possibly the homologue of "Broca's area" in human. This led to the speculation that action recognition and language production share a common system [Trends Neurosci. 21 (1998), 188]. To test this hypothesis, we combined an action recognition with a language production (VERB) and a grasping movement task (MOVE) by using functional magnetic resonance imaging. Action recognition-related activation was observed in the left inferior frontal gyrus and on the border between the inferior frontal gyrus and precentral gyrus (defined as IFG/PG), the ventral occipitotemporal junction, the superior and inferior parietal cortex, and in the intraparietal sulcus in the left hemisphere. An overlap of activations due to the language production, movement execution, and action recognition was found in the parietal cortex, the left inferior frontal gyrus, and the IFG-PG border (IFG/PG). The activation peaks of action recognition and verb generation were always different in single subjects, but no consistent spatial relationship was detected, in accord with the hypothesis that action recognition and language production share a common functional architecture." [Abstract]

Miall RC.
Connecting mirror neurons and forward models.
Neuroreport. 2003 Dec 2;14(17):2135-7.
"SUMMARY: Two recent developments in motor neuroscience are promising the extension of theoretical concepts from motor control towards cognitive processes, including human social interactions and understanding the intentions of others. The first of these is the discovery of what are now called mirror neurons, which code for both observed and executed actions. The second is the concept of internal models, and in particular recent proposals that forward and inverse models operate in paired modules. These two ideas will be briefly introduced, and a recent suggestion linking between the two processes of mirroring and modelling will be described which may underlie our abilities for imitating actions, for cooperation between two actors, and possibly for communication via gesture and language." [Abstract] [PDF]

Corballis MC.
From mouth to hand: gesture, speech, and the evolution of right-handedness.
Behav Brain Sci. 2003 Apr;26(2):199-208; discussion 208-60.
"The strong predominance of right-handedness appears to be a uniquely human characteristic, whereas the left-cerebral dominance for vocalization occurs in many species, including frogs, birds, and mammals. Right-handedness may have arisen because of an association between manual gestures and vocalization in the evolution of language. I argue that language evolved from manual gestures, gradually incorporating vocal elements. The transition may be traced through changes in the function of Broca's area. Its homologue in monkeys has nothing to do with vocal control, but contains the so-called "mirror neurons," the code for both the production of manual reaching movements and the perception of the same movements performed by others. This system is bilateral in monkeys, but predominantly left-hemispheric in humans, and in humans is involved with vocalization as well as manual actions. There is evidence that Broca's area is enlarged on the left side in Homo habilis, suggesting that a link between gesture and vocalization may go back at least two million years, although other evidence suggests that speech may not have become fully autonomous until Homo sapiens appeared some 170,000 years ago, or perhaps even later. The removal of manual gesture as a necessary component of language may explain the rapid advance of technology, allowing late migrations of Homo sapiens from Africa to replace all other hominids in other parts of the world, including the Neanderthals in Europe and Homo erectus in Asia. Nevertheless, the long association of vocalization with manual gesture left us a legacy of right-handedness." [Abstract]

Leslie KR, Johnson-Frey SH, Grafton ST.
Functional imaging of face and hand imitation: towards a motor theory of empathy.
Neuroimage. 2004 Feb;21(2):601-7.
"Empathy requires the ability to map the feelings of others onto our own nervous system. Until recently, there was no plausible mechanism to explain how such a mapping might occur. The discovery of mirror neurons, however, suggests that the nervous system is capable of mapping the observed actions of others onto the premotor cortex of the self, at least for reaching and grasping movements. Is there a mirroring system for emotive actions, such as facial expression? Subjects (N = 15; all right-handed; eight men, seven women) watched movies of facial expressions (smile or frown) and hand movements (move index or middle finger) while brain activity was imaged using functional magnetic resonance imaging (fMRI). Subjects watched the movies under three different conditions: passive viewing, active imitation, and an active motor control. Subjects also performed a verb generation task to functionally identify language-processing areas. We found evidence for a common cortical imitation circuit for both face and hand imitation, consisting of Broca's area, bilateral dorsal and ventral premotor areas, right superior temporal gyrus (STG), supplementary motor area, posterior temporo-occipital cortex, and cerebellar areas. For faces, passive viewing led to significant activation in the right ventral premotor area, whereas imitation produced bilateral activation. This result is consistent with evidence for right hemisphere (RH) dominance for emotional processing, and suggests that there may be a right hemisphere mirroring system that could provide a neural substrate for empathy." [Abstract]

Tai YF, Scherfler C, Brooks DJ, Sawamoto N, Castiello U.
The human premotor cortex is 'mirror' only for biological actions.
Curr Biol. 2004 Jan 20;14(2):117-20.
"Previous work has shown that both human adults and children attend to grasping actions performed by another person but not necessarily to those made by a mechanical device. According to recent neurophysiological data, the monkey premotor cortex contains "mirror" neurons that discharge both when the monkey performs specific manual grasping actions and when it observes another individual performing the same or similar actions. However, when a human model uses tools to perform grasping actions, the mirror neurons are not activated. A similar "mirror" system has been described in humans, but whether or not it is also tuned specifically to biological actions has never been tested. Here we show that when subjects observed manual grasping actions performed by a human model a significant neural response was elicited in the left premotor cortex. This activation was not evident for the observation of grasping actions performed by a robot model commanded by an experimenter. This result indicates for the first time that in humans the mirror system is biologically tuned. This system appears to be the neural substrate for biological preference during action coding." [Abstract]

Mason MF, Banfield JF, Macrae CN.
Thinking about actions: the neural substrates of person knowledge.
Cereb Cortex. 2004 Feb;14(2):209-14.
"Despite an extensive literature on the neural substrates of semantic knowledge, how person-related information is represented in the brain has yet to be elucidated. Accordingly, in the present study we used functional magnetic resonance imaging (fMRI) to investigate the neural correlates of person knowledge. Focusing on the neural substrates of action knowledge, participants reported whether or not a common set of behaviors could be performed by people or dogs. While dogs and people are capable of performing many of the same actions (e.g. run, sit, bite), we surmised that the representation of this knowledge would be associated with distinct patterns of neural activity. Specifically, person judgments were expected to activate cortical areas associated with theory of mind (ToM) reasoning. The results supported this prediction. Whereas action-related judgments about dogs were associated with activity in various regions, including the occipital and parahippocampal gyri; identical judgments about people yielded activity in areas of prefrontal cortex, notably the right middle and medial frontal gyri. These findings suggest that person knowledge may be functionally dissociable from comparable information about other animals, with action-related judgments about people recruiting neural activity that is indicative of ToM reasoning." [Abstract]

Grezes J, Frith CD, Passingham RE.
Inferring false beliefs from the actions of oneself and others: an fMRI study.
Neuroimage. 2004 Feb;21(2):744-50.
"The ability to make judgments about mental states is critical to social interactions. Simulation theory suggests that the observer covertly mimics the activity of the observed person, leading to shared states of mind between the observer and the person observed. We tested this hypothesis by investigating the neural networks activated while subjects watched videos of themselves and of others lifting a box, and judged the beliefs of the actors about the weight of the box. A parietal premotor circuit was recruited during action perception, and the activity started earlier when making judgments about one's own actions as opposed to those of others. This earlier activity in action-related structures can be explained by simulation theory on the basis that when one observes one's own actions, there is a closer match between the simulated and perceived action than there is when one observes the actions of others. When the observers judged the actions to reflect a false belief, there was activation in the superior temporal sulcus, orbitofrontal, paracingulate cortex and cerebellum. We suggest that this reflects a mismatch between the perceived action and the predicted action's outcomes derived from simulation." [Abstract]

Saxe R, Kanwisher N.
People thinking about thinking people. The role of the temporo-parietal junction in "theory of mind".
Neuroimage. 2003 Aug;19(4):1835-42.
"Humans powerfully and flexibly interpret the behaviour of other people based on an understanding of their minds: that is, we use a "theory of mind." In this study we distinguish theory of mind, which represents another person's mental states, from a representation of the simple presence of another person per se. The studies reported here establish for the first time that a region in the human temporo-parietal junction (here called the TPJ-M) is involved specifically in reasoning about the contents of another person's mind. First, the TPJ-M was doubly dissociated from the nearby extrastriate body area (EBA; Downing et al., 2001). Second, the TPJ-M does not respond to false representations in non-social control stories. Third, the BOLD response in the TPJ-M bilaterally was higher when subjects read stories about a character's mental states, compared with stories that described people in physical detail, which did not differ from stories about nonhuman objects. Thus, the role of the TPJ-M in understanding other people appears to be specific to reasoning about the content of mental states." [Abstract]

Donald T. Stuss, Gordon G. Gallup, Jr, and Michael P. Alexander
The frontal lobes are necessary for `theory of mind'
Brain 124: 279-286. 2001.
"Patients with limited focal frontal and nonfrontal lesions were tested for visual perspective taking and detecting deception. Frontal lobe lesions impaired the ability to infer mental states in others, with dissociation of performance within the frontal lobes. Lesions throughout the frontal lobe, with some suggestion of a more important role for the right frontal lobe, were associated with impaired visual perspective taking. Medial frontal lesions, particularly right ventral, impaired detection of deception. The former may require cognitive processes of the lateral and superior medial frontal regions, the latter affective connections of the ventral medial frontal with amygdala and other limbic regions." [Full Text]

Stone VE, Cosmides L, Tooby J, Kroll N, Knight RT.
Selective impairment of reasoning about social exchange in a patient with bilateral limbic system damage.
Proc Natl Acad Sci U S A. 2002 Aug 20;99(17):11531-6. Epub 2002 Aug 12.
"Social exchange is a pervasive feature of human social life. Models in evolutionary biology predict that for social exchange to evolve in a species, individuals must be able to detect cheaters (nonreciprocators). Previous research suggests that humans have a cognitive mechanism specialized for detecting cheaters. Here we provide neurological evidence indicating that social exchange reasoning can be selectively impaired while reasoning about other domains is left intact. The patient, R.M., had extensive bilateral limbic system damage, affecting orbitofrontal cortex, temporal pole, and amygdala. We compared his performance on two types of reasoning problem that were closely matched in form and equally difficult for control subjects: social contract rules (of the form, "If you take the benefit, then you must satisfy the requirement") and precaution rules (of the form, "If you engage in hazardous activity X, then you must take precaution Y"). R.M. performed significantly worse in social contract reasoning than in precaution reasoning, when compared both with normal controls and with other brain-damaged subjects. This dissociation in reasoning performance provides evidence that reasoning about social exchange is a specialized and separable component of human social intelligence, and is consistent with other research indicating that the brain processes information about the social world differently from other types of information." [Full Text]

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Recent Reasoning Neuroimaging Research

1) Shkurko AV
Is social categorization based on relational ingroup/outgroup opposition? A meta-analysis.
Soc Cogn Affect Neurosci. 2012 Jul 30;
Social categorization is known to be an important part of social cognition. The categorizations we use, despite their multitude, frequently take the form of the general ingroup/outgroup distinction. A meta-analysis of 33 fMRI studies, reporting selective activations to various social groups, was used to identify common neural structures responsible for relational representation of social structure. Activation Likelihood Estimation (ALE) analysis revealed areas in bilateral amygdala, cingulate gyrus, fusiform gyrus, right TPJ and right insula as implementing various aspects of social categorization. Activation of amygdala can be associated with modulation of behavioral response to subjectively significant stimuli. A more ventral part of ACC can be associated with self-referential reasoning about ingroup members while a more dorsal part of ACC is involved in the regulation of emotions toward outgroup members. Right insula can be engaged in the modulation of outgroup avoidance behavior. FG appears to be directly involved in social categorization process via top-down modulation of social perception. Yet it is difficult to associate any of the revealed clusters with the relational ingroup/outgroup structure. [PubMed Citation] [Order full text from Infotrieve]

2) Willeumier K, Taylor DV, Amen DG
Elevated body mass in National Football League players linked to cognitive impairment and decreased prefrontal cortex and temporal pole activity.
Transl Psychiatry. 2012 Feb 21;2:e68.
Obesity is a risk factor for neurodegenerative disease and has been shown to adversely affect cognitive function. Professional athletes who participate in sports, which expose them to repetitive concussions, may be at heightened risk for cognitive impairment. Here, we investigated the effects of body mass as measured by waist-to-height ratio (WHtR) on regional cerebral blood flow using single-photon emission computed tomography imaging in 38 healthy weight (WHtR mean 49.34±2.8; age 58±9.6) and 38 overweight (WHtR mean 58.7±4.7; age 58±13.3) retired National Football League football players. After matching for age and position, we used a two sample t-test to determine the differences in blood flow in healthy versus overweight subjects. Statistical parametric mapping revealed a higher WHtR ratio is associated with decreased blood flow in Brodmann areas 8, 9 and 10, brain regions involved in attention, reasoning and executive function (P<0.05, family-wise error) along with deficits in the temporal pole. Moreover, overweight athletes had significant decrease in attention (P=0.01326), general cognitive proficiency (P=0.012; Microcog: Assessment of Cognitive Functioning) and memory (P=0.005; Mild Cognitive Impairment Screen). The association between elevated WHtR percentage and decreased blood flow in the prefrontal cortex and temporal pole may be correlated with the decreased performance on tests of attention and memory. These findings suggest that a weight management program may be critical to the health of athletes who have been exposed to mild brain trauma during their careers. [PubMed Citation] [Order full text from Infotrieve]

3) Hodges JR
Alzheimer's Disease and the Frontotemporal Dementias: Contributions to Clinico-Pathological Studies, Diagnosis, and Cognitive Neuroscience.
J Alzheimers Dis. 2012 Jul 5;
This review focuses on six key papers published in the mid 2000 s based on work conducted in Cambridge. The first two relate to clinico-pathological studies which established that Alzheimer's disease (AD) is a relatively common cause of focal cortical syndromes, notably progressive aphasia (largely nonfluent), progressive apraxia, and posterior cortical atrophy with complex visual symptoms. Building on these findings, criteria for the progressive aphasias have been developed which define the variant associated with AD (progressive logopenic aphasia). Memory in the dementias has been a major area of interest and one paper discussed here explored the neural basis for episodic and semantic memory failure in AD and semantic dementia. Despite very different memory profiles, the two disorders both cause severe hippocampal hypometabolism and atrophy but differ in the degree of involvement of other memory related structures. This work drew attention to the role of pathology in non-hippocampal structures early in AD. The next two articles deal with the behavioral variant frontotemporal dementia (bvFTD) which we have shown is associated with breakdown in theory of mind, social reasoning, empathy, and emotion processing and contributed to work on the neural basis of social cognition. We also identified a subgroup of bvFTD who fail to progress over many years, termed phenocopy cases, who are differentiated by their lack of atrophy on MRI. The final paper described the application of the Addenbrooke's Cognitive Examination-Revised, which has proven a useful brief assessment tool for the early detection of a range of neurodegenerative disorders including AD and FTD. It also appears to be helpful in predicting those with mild cognitive impairment who will progress to frank dementia. [PubMed Citation] [Order full text from Infotrieve]

4) Garbelli R, Milesi G, Medici V, Villani F, Didato G, Deleo F, D'Incerti L, Morbin M, Mazzoleni G, Giovagnoli AR, Parente A, Zucca I, Mastropietro A, Spreafico R
Blurring in patients with temporal lobe epilepsy: clinical, high-field imaging and ultrastructural study.
Brain. 2012 Aug;135(Pt 8):2337-49.
Magnetic resonance imaging-positive temporal lobe atrophy with temporo-polar grey/white matter abnormalities (usually called 'blurring') has been frequently reported in patients with temporal lobe epilepsy associated with hippocampal sclerosis. The poor distinction of grey and white matter has been attributed to various causes, including developmental cortical abnormalities, gliosis, myelin alterations, a non-specific increase in temporal lobe water content and metabolic/perfusion alterations. However, there is still no consensus regarding the genesis of these abnormalities and no histopathological proof for a structural nature of magnetic resonance imaging changes. The aim of this study was to investigate the pathological substrate of temporo-polar blurring using different methodological approaches and evaluate the possible clinical significance of the abnormalities. The study involved 32 consecutive patients with medically intractable temporal lobe epilepsy and hippocampal sclerosis who underwent surgery after a comprehensive electroclinical and imaging evaluation. They were divided into two groups on the basis of the presence/absence of temporo-polar blurring. Surgical specimens were examined neuropathologically, and selected samples from both groups underwent high-field 7?T magnetic resonance imaging and ultrastructural studies. At the clinical level, the two groups were significantly different in terms of age at epilepsy onset (earlier in the patients with blurring) and epilepsy duration (longer in the patients with blurring). Blurring was also associated with lower neuropsychological test scores, with a significant relationship to abstract reasoning. On 7?T magnetic resonance image examination, the borders between the grey and white matter were clear in all of the samples, but only those with blurring showed a dishomogeneous signal in the white matter, with patchy areas of hyperintensity mainly in the depth of the white matter. Sections from the patients with blurring that were processed for myelin staining revealed dishomogeneous staining of the white matter, which was confirmed by analyses of the corresponding semi-thin sections. Ultrastructural examinations revealed the presence of axonal degeneration and a significant reduction in the number of axons in the patients with blurring; there were no vascular alterations in either group. These data obtained using different methodological approaches provide robust evidence that temporo-polar blurring is caused by the degeneration of fibre bundles and suggest slowly evolving chronic degeneration with the redistribution of the remaining fibres. The article also discusses the correlations between the morphological findings and clinical data. [PubMed Citation] [Order full text from Infotrieve]

5) Luo J, Liu X, Stupple EJ, Zhang E, Xiao X, Jia L, Yang Q, Li H, Zhang Q
Cognitive control in belief-laden reasoning during conclusion processing: An ERP study.
Int J Psychol. 2012 Jun 21;
Belief bias is the tendency to accept conclusions that are compatible with existing beliefs more frequently than those that contradict beliefs. It is one of the most replicated behavioral findings in the reasoning literature. Recently, neuroimaging studies using functional magnetic resonance imaging (fMRI) and event-related potentials (ERPs) have provided a new perspective and have demonstrated neural correlates of belief bias that have been viewed as supportive of dual-process theories of belief bias. However, fMRI studies have tended to focus on conclusion processing, while ERPs studies have been concerned with the processing of premises. In the present research, the electrophysiological correlates of cognitive control were studied among 12 subjects using high-density ERPs. The analysis was focused on the conclusion presentation phase and was limited to normatively sanctioned responses to valid-believable and valid-unbelievable problems. Results showed that when participants gave normatively sanctioned responses to problems where belief and logic conflicted, a more positive ERP deflection was elicited than for normatively sanctioned responses to nonconflict problems. This was observed from -400 to -200?ms prior to the correct response being given. The positive component is argued to be analogous to the late positive component (LPC) involved in cognitive control processes. This is consistent with the inhibition of empirically anomalous information when conclusions are unbelievable. These data are important in elucidating the neural correlates of belief bias by providing evidence for electrophysiological correlates of conflict resolution during conclusion processing. Moreover, they are supportive of dual-process theories of belief bias that propose conflict detection and resolution processes as central to the explanation of belief bias. [PubMed Citation] [Order full text from Infotrieve]

6) Morgan B, Terburg D, Thornton HB, Stein DJ, van Honk J
Paradoxical facilitation of working memory after basolateral amygdala damage.
PLoS One. 2012;7(6):e38116.
Working memory is a vital cognitive capacity without which meaningful thinking and logical reasoning would be impossible. Working memory is integrally dependent upon prefrontal cortex and it has been suggested that voluntary control of working memory, enabling sustained emotion inhibition, was the crucial step in the evolution of modern humans. Consistent with this, recent fMRI studies suggest that working memory performance depends upon the capacity of prefrontal cortex to suppress bottom-up amygdala signals during emotional arousal. However fMRI is not well-suited to definitively resolve questions of causality. Moreover, the amygdala is neither structurally or functionally homogenous and fMRI studies do not resolve which amygdala sub-regions interfere with working memory. Lesion studies on the other hand can contribute unique causal evidence on aspects of brain-behaviour phenomena fMRI cannot "see". To address these questions we investigated working memory performance in three adult female subjects with bilateral basolateral amygdala calcification consequent to Urbach-Wiethe Disease and ten healthy controls. Amygdala lesion extent and functionality was determined by structural and functional MRI methods. Working memory performance was assessed using the Wechsler Adult Intelligence Scale-III digit span forward task. State and trait anxiety measures to control for possible emotional differences between patient and control groups were administered. Structural MRI showed bilateral selective basolateral amygdala damage in the three Urbach-Wiethe Disease subjects and fMRI confirmed intact functionality in the remaining amygdala sub-regions. The three Urbach-Wiethe Disease subjects showed significant working memory facilitation relative to controls. Control measures showed no group anxiety differences. Results are provisionally interpreted in terms of a 'cooperation through competition' networks model that may account for the observed paradoxical functional facilitation effect. [PubMed Citation] [Order full text from Infotrieve]

7) Orban GA, Rizzolatti G
An area specifically devoted to tool use in human left inferior parietal lobule.
Behav Brain Sci. 2012 Aug;35(4):234.
A comparative fMRI study by Peeters et al. (2009) provided evidence that a specific sector of left inferior parietal lobule is devoted to tool use in humans, but not in monkeys. We propose that this area represents the neural substrate of the human capacity to understand tool use by using causal reasoning. [PubMed Citation] [Order full text from Infotrieve]

8) Wende KC, Straube B, Stratmann M, Sommer J, Kircher T, Nagels A
Neural correlates of continuous causal word generation.
Neuroimage. 2012 Sep;62(3):1399-407.
Causality provides a natural structure for organizing our experience and language. Causal reasoning during speech production is a distinct aspect of verbal communication, whose related brain processes are yet unknown. The aim of the current study was to investigate the neural mechanisms underlying the continuous generation of cause-and-effect coherences during overt word production. During fMRI data acquisition participants performed three verbal fluency tasks on identical cue words: A novel causal verbal fluency task (CVF), requiring the production of multiple reasons to a given cue word (e.g. reasons for heat are fire, sun etc.), a semantic (free association, FA, e.g. associations with heat are sweat, shower etc.) and a phonological control task (phonological verbal fluency, PVF, e.g. rhymes with heat are meat, wheat etc.). We found that, in contrast to PVF, both CVF and FA activated a left lateralized network encompassing inferior frontal, inferior parietal and angular regions, with further bilateral activation in middle and inferior as well as superior temporal gyri and the cerebellum. For CVF contrasted against FA, we found greater bold responses only in the left middle frontal cortex. Large overlaps in the neural activations during free association and causal verbal fluency indicate that the access to causal relationships between verbal concepts is at least partly based on the semantic neural network. The selective activation in the left middle frontal cortex for causal verbal fluency suggests that distinct neural processes related to cause-and-effect-relations are associated with the recruitment of middle frontal brain areas. [PubMed Citation] [Order full text from Infotrieve]

9) Schilling C, Kühn S, Paus T, Romanowski A, Banaschewski T, Barbot A, Barker GJ, Brühl R, Büchel C, Conrod PJ, Dalley JW, Flor H, Ittermann B, Ivanov N, Mann K, Martinot JL, Nees F, Rietschel M, Robbins TW, Smolka MN, Ströhle A, Kathmann N, Garavan H, Heinz A, Schumann G, Gallinat J
Cortical thickness of superior frontal cortex predicts impulsiveness and perceptual reasoning in adolescence.
Mol Psychiatry. 2012 Jun 5;
Impulsiveness is a pivotal personality trait representing a core domain in all major personality inventories. Recently, impulsiveness has been identified as an important modulator of cognitive processing, particularly in tasks that require the processing of large amounts of information. Although brain imaging studies have implicated the prefrontal cortex to be a common underlying representation of impulsiveness and related cognitive functioning, to date a fine-grain and detailed morphometric analysis has not been carried out. On the basis of ahigh-resolution magnetic resonance scans acquired in 1620 healthy adolescents (IMAGEN), the individual cortical thickness (CT) was estimated. Correlations between Cloninger's impulsiveness and CT were studied in an entire cortex analysis. The cluster identified was tested for associations with performance in perceptual reasoning tasks of the Wechsler Intelligence Scale for Children (WISC IV). We observed a significant inverse correlation between trait impulsiveness and CT of the left superior frontal cortex (SFC; Monte Carlo Simulation P<0.01). CT within this cluster correlated with perceptual reasoning scores (Bonferroni corrected) of the WISC IV. On the basis of a large sample of adolescents, we identified an extended area in the SFC as a correlate of impulsiveness, which appears to be in line with the trait character of this prominent personality facet. The association of SFC thickness with perceptual reasoning argues for a common neurobiological basis of personality and specific cognitive domains comprising attention, spatial reasoning and response selection. The results may facilitate the understanding of the role of impulsiveness in several psychiatric disorders associated with prefrontal dysfunctions and cognitive deficits.Molecular Psychiatry advance online publication, 5 June 2012; doi:10.1038/mp.2012.56. [PubMed Citation] [Order full text from Infotrieve]

10) Semrud-Clikeman M, Fine JG, Bledsoe J, Zhu DC
Gender Differences in Brain Activation on a Mental Rotation Task.
Int J Neurosci. 2012 Jun 21;
ABSTRACT Few neuroimaging studies have explored gender differences on mental rotation tasks. Most studies have utilized samples with both genders, samples mainly consisting of men, or samples with six or fewer females. Graduate students in science fields or liberal arts programs (20 males, 20 females) completed a mental rotation task during functional magnetic resonance imaging (fMRI). When a pair of cube figures was shown, the participant made a keypad response based on whether the pair is the same/similar or different. Regardless of gender, the bilateral middle frontal gyrus, bilateral intraparietal sulcus (IPS), and the left precuneus were activated when a subject tried to solve the mental rotation task. Increased activation in the right inferior frontal gyrus/middle frontal gyrus, the left precuneus/posterior cingulate cortex/cuneus region, and the left middle occipital gyrus was found for men as compared to women. Better accuracy and shorter response times were correlated with an increased activation in the bilateral intraparietal sulcus. No significant brain activity differences related to mental rotation were found between academic majors. These findings suggest that networks involved in visual attention appear to be more strongly activated in the mental rotation tasks in men as compared to women. It also suggests that men use a more automatic process when analyzing complex visual reasoning tasks while women use a more top-down process. [PubMed Citation] [Order full text from Infotrieve]

11) Shokri-Kojori E, Motes MA, Rypma B, Krawczyk DC
The network architecture of cortical processing in visuo-spatial reasoning.
Sci Rep. 2012;2:411.
Reasoning processes have been closely associated with prefrontal cortex (PFC), but specifically emerge from interactions among networks of brain regions. Yet it remains a challenge to integrate these brain-wide interactions in identifying the flow of processing emerging from sensory brain regions to abstract processing regions, particularly within PFC. Functional magnetic resonance imaging data were collected while participants performed a visuo-spatial reasoning task. We found increasing involvement of occipital and parietal regions together with caudal-rostral recruitment of PFC as stimulus dimensions increased. Brain-wide connectivity analysis revealed that interactions between primary visual and parietal regions predominantly influenced activity in frontal lobes. Caudal-to-rostral influences were found within left-PFC. Right-PFC showed evidence of rostral-to-caudal connectivity in addition to relatively independent influences from occipito-parietal cortices. In the context of hierarchical views of PFC organization, our results suggest that a caudal-to-rostral flow of processing may emerge within PFC in reasoning tasks with minimal top-down deductive requirements. [PubMed Citation] [Order full text from Infotrieve]

12) Tamm L, Juranek J
Fluid reasoning deficits in children with ADHD: Evidence from fMRI.
Brain Res. 2012 Jul 17;1465:48-56.
Attention-Deficit/Hyperactivity Disorder (ADHD) is associated with deficits in fluid reasoning, which may be related to self-regulation of cognition and behavior, and requires intact attention, working memory, and inhibition skills. No functional magnetic resonance imaging (fMRI) studies have directly examined fluid reasoning in ADHD which is surprising given that studies demonstrate a consistent network of brain regions involved in fluid reasoning that are also implicated in the pathogenesis of ADHD. Twenty-two right-handed, non-medicated children (12 ADHD, 10 controls) ages 8-12years completed a fluid reasoning task during which fMRI data were collected. The primary comparison of interest was activation during the fluid reasoning compared to the control condition. Behavioral data showed that children with ADHD tended to be less accurate with faster reaction times in the fluid reasoning condition compared to controls, and were significantly less accurate in the control condition. Controls activated more than participants with ADHD in the right intraparietal sulcus and the left lateral cerebellum in the fluid reasoning condition. Results showed hypoactivation in ADHD in regions critical for fluid reasoning. These results add to the literature suggesting a role for parietal and cerebellar regions in cognition and ADHD. [PubMed Citation] [Order full text from Infotrieve]

13) Schneider K, Pauly KD, Gossen A, Mevissen L, Michel TM, Gur RC, Schneider F, Habel U
Neural Correlates of Moral Reasoning in Autism Spectrum Disorder.
Soc Cogn Affect Neurosci. 2012 May 7;
In our study, we tried to clarify whether patients with autism spectrum disorder (ASD) reveal different moral decision patterns as compared to healthy subjects and whether common social interaction difficulties in ASD are reflected in altered brain activation during different aspects of moral reasoning.28 patients with high-functioning ASD and 28 healthy subjects matched for gender, age, and education took part in an event-related functional magnetic resonance imaging study. Participants were confronted with textual dilemma situations followed by proposed solutions to which they could agree or disagree.On a neural level, moral decision making was associated with activation in anterior medial prefrontal regions, the temporo-parietal junction (TPJ), and the precuneus for both groups. However, while patients and healthy controls did not exhibit significant behavioral differences, ASD patients showed decreased activation in limbic regions, particularly the amygdala, as well as increased activation in the anterior and the posterior cingulate gyrus during moral reasoning.Alterations of brain activation in patients might thus indicate specific impairments in empathy. However, activation increases in brain regions associated with the "default mode network" and self-referential cognition also provide evidence for an altered way of patients' cerebral processing with regard to decision making based on social information. [PubMed Citation] [Order full text from Infotrieve]

14) Kennedy KM, Rodrigue KM, Devous MD, Hebrank AC, Bischof GN, Park DC
Effects of beta-amyloid accumulation on neural function during encoding across the adult lifespan.
Neuroimage. 2012 Aug 1;62(1):1-8.
Limited functional imaging evidence suggests that increased beta-amyloid deposition is associated with alterations in brain function, even in healthy older adults. However, the majority of these findings report on resting-state activity or functional connectivity in adults over age 60. Much less is known about the impact of beta-amyloid on neural activations during cognitive task performance, or the impact of amyloid in young and middle-aged adults. The current study measured beta-amyloid burden from PET imaging using (18)Florbetapir, in a large continuous age sample of highly-screened, healthy adults (N=137; aged 30-89years). The same participants also underwent fMRI scanning, performing a memory encoding task. Using both beta-amyloid burden and age as continuous predictors of encoding activity, we report a dose-response relationship of beta-amyloid load to neural function, beyond the effects of age. Specifically, individuals with greater amyloid burden evidence less neural activation in bilateral dorsolateral prefrontal cortex, a region important for memory encoding, as well as reduced neural modulation in areas associated with default network activity: bilateral superior/medial frontal and lateral temporal cortex. Importantly, this reduction of both activation and suppression as a function of amyloid load was found across the lifespan, even in young- and middle-aged individuals. Moreover, this frontal and temporal amyloid-reduced activation/suppression was associated with poorer processing speed, verbal fluency, and fluid reasoning in a subgroup of individuals with elevated amyloid, suggesting that it is detrimental, rather than compensatory in nature. [PubMed Citation] [Order full text from Infotrieve]

15) Gregory S, Ffytche D, Simmons A, Kumari V, Howard M, Hodgins S, Blackwood N
The Antisocial Brain: Psychopathy Matters: A Structural MRI Investigation of Antisocial Male Violent Offenders.
Arch Gen Psychiatry. 2012 May 7;
CONTEXT: The population of men who display persistent antisocial and violent behavior is heterogeneous. Callous-unemotional traits in childhood and psychopathic traits in adulthood characterize a distinct subgroup. OBJECTIVE: To identify structural gray matter (GM) differences between persistent violent offenders who meet criteria for antisocial personality disorder and the syndrome of psychopathy (ASPD+P) and those meeting criteria only for ASPD (ASPD-P). DESIGN: Cross-sectional case-control structural magnetic resonance imaging study. SETTING: Inner-city probation services and neuroimaging research unit in London, England. PARTICIPANTS: Sixty-six men, including 17 violent offenders with ASPD+P, 27 violent offenders with ASPD-P, and 22 healthy nonoffenders participated in the study. Forensic clinicians assessed participants using the Structured Clinical Interview for DSM-IV and the Psychopathy Checklist-Revised. MAIN OUTCOME MEASURES: Gray matter volumes as assessed by structural magnetic resonance imaging and volumetric voxel-based morphometry analyses. RESULTS: Offenders with ASPD+P displayed significantly reduced GM volumes bilaterally in the anterior rostral prefrontal cortex (Brodmann area 10) and temporal poles (Brodmann area 20/38) relative to offenders with ASPD-P and nonoffenders. These reductions were not attributable to substance use disorders. Offenders with ASPD-P exhibited GM volumes similar to the nonoffenders. CONCLUSIONS: Reduced GM volume within areas implicated in empathic processing, moral reasoning, and processing of prosocial emotions such as guilt and embarrassment may contribute to the profound abnormalities of social behavior observed in psychopathy. Evidence of robust structural brain differences between persistently violent men with and without psychopathy adds to the evidence that psychopathy represents a distinct phenotype. This knowledge may facilitate research into the etiology of persistent violent behavior. [PubMed Citation] [Order full text from Infotrieve]

16) Sherman EM, Brooks BL, Fay-McClymont TB, MacAllister WS
Detecting epilepsy-related cognitive problems in clinically referred children with epilepsy: is the WISC-IV a useful tool?
Epilepsia. 2012 Jun;53(6):1060-6.
[PubMed Citation] [Order full text from Infotrieve]

17) Prasad V, Rho J, Cifu A
The Diagnosis and Treatment of Pulmonary Embolism: A Metaphor for Medicine in the Evidence-Based Medicine Era.
Arch Intern Med. 2012 Apr 2;
BACKGROUND: The history of pulmonary embolism (PE) provides a fascinating portrait of a well-established diagnosis and standard of care treatment moving into the age of evidence-based medicine. METHODS: We examined the history of PE and the practice of treating PE with anticoagulation. RESULTS: Pulmonary embolism is a diagnostic category whose definition and treatment have both changed in the past century. Initially, PE was recognizable only when massive, with the signs and symptoms of right heart failure. Anticoagulants were established as the cornerstone of PE management with a single randomized controlled trial of 35 patients in 1960 and based on commonsense pathophysiologic reasoning. Since then, the diagnostic category of PE has been broadened, and the advent of computed tomography pulmonary angiography has yielded nearly a doubling of the incidence of the disease, without a concordant decrease in mortality. Although anticoagulation remains the cornerstone of management, open questions remain: what end points are altered by anticoagulation? What is the number needed to treat? CONCLUSIONS: Trials of newer anticoagulants and longer durations of anticoagulation have not yielded real improvements over heparin, inviting doubts regarding its efficacy. Thus, PE is the quintessential diagnosis of medicine not because it represents our greatest success, but because it captures all the complexity of medicine in the evidence-based era. It may serve as a metaphor for many other conditions in medicine, including coronary artery disease. New trials in the field continue to test trivialities, whereas fundamental questions are unanswered. [PubMed Citation] [Order full text from Infotrieve]

18) Reniers RL, Corcoran R, Völlm BA, Mashru A, Howard R, Liddle PF
Moral decision-making, ToM, empathy and the default mode network.
Biol Psychol. 2012 Jul;90(3):202-10.
Automatic intuitions and deliberate reasoning, sourcing internal representations of our personal norms and values, contribute to our beliefs of what is right and wrong. We used fMRI to directly compare moral (M) and non-moral (NM) decision-making processes using scenarios requiring conscious deliberation, whereby the main character declared an intention to take a course of action. Furthermore, we examined the relationship between BOLD signal, associated with M>NM decision-making, and moral judgment competence, psychopathy, and empathy. We observed greater activity in various parts of Theory of Mind, empathy and default mode networks during M>NM decision-making. There was a trend for high scores on primary psychopathy to correlate with decreased M>NM BOLD activation in an area extending from dorsolateral prefrontal cortex to medial prefrontal cortex. We suggest that moral decision-making entails a greater degree of internally directed processing, such as self-referential mental processing and the representation of intentions and feelings, than non-moral decision-making. [PubMed Citation] [Order full text from Infotrieve]

19) Eschle D
[Numbness in the hands].
Praxis (Bern 1994). 2012 Mar 28;101(7):477-81.
My hands are numb is a common complaint in primary care. Generally, carpal tunnel syndrome can be suspected. This case report explains typical aspects of clinical reasoning used by neurologists to confirm the diagnosis, and also provides some details of «red flags» based on history and examination. Additionally, a short introduction to electrodiagnostic procederes is included and illustrated with diagrams. [PubMed Citation] [Order full text from Infotrieve]

20) Macdonald S
Strategies for reducing microemboli during carotid artery stenting.
J Cardiovasc Surg (Torino). 2012 Feb;53(1 Suppl 1):23-6.
Carotid stenting in standard risk patients has recently received supportive recommendations from the American Heart Association, in a guideline document endorsed by 14 societies with diverse but vested interest in carotid intervention. The procedural hazard i.e. the composite endpoint: all-stroke/death/myocardial infarction (MI) for carotid stenting and endarterectomy are equivalent, as is survival free of ipsilateral stroke for the two interventional strategies. However, the microembolic burden generated by endarterectomy and stenting is discrepant and although the fate and clinical relevance of diffusion-weighted magnetic resonance imaging new white lesions and of microembolic signals on transcranial Doppler remain disputed, empathic reasoning would suggest that technical and/or procedural modifications should be explored and employed during carotid stenting in order to try addressing microemboli. This article seeks to define those procedural steps likely to be associated with microemboli during carotid stenting and thus provide avoidance manoeuvres and/or possible solutions. [PubMed Citation] [Order full text from Infotrieve]