the thalamus in bipolar disorder


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(Updated 1/12/04)

Juckel G, Hegerl U, Mavrogiorgou P, Gallinat J, Mager T, Tigges P, Dresel S, Schroter A, Stotz G, Meller I, Greil W, Moller HJ.
Clinical and biological findings in a case with 48-hour bipolar ultrarapid cycling before and during valproate treatment.
J Clin Psychiatry 2000 Aug;61(8):585-93
"BACKGROUND: The rare cases of patients with 48-hour ultrarapid cycling allow close investigation of mood cycles in affective disorders, because rhythmic changes in psychopathologic state and biological parameters happen very precisely. METHOD: A 67-year-old white man who had experienced bipolar 48-hour ultrarapid cycling (DSM-IV 296.80) for several years was studied without any medication and then again studied 4 weeks later during treatment with valproate (1800 mg/day). RESULTS: Objective and self ratings revealed pronounced manic states 1 day and depressed states the following day, which were found to be accompanied by rhythmic fluctuations in behavior and electroencephalographic parameters, blood cortisol and growth hormone levels (both elevated on depressive days), and urinary metanephrine (dopamine metabolite) and norepinephrine levels (both elevated on manic days). Using single photon emission computed tomography, regional blood flow in the left thalamus was lower than in the right thalamus on the manic day, while symmetric perfusion of the thalamus was found on the depressive day. Under valproate treatment, the patient remitted completely, and significant rhythmic changes in most of the biological parameters were no longer detectable. CONCLUSION: The biological findings in this patient with bipolar 48-hour ultrarapid cycling, which correspond to those in other types of affective disorders, suggest that disturbances in the diencephalon-pituitary axis may be especially correlated to pathologic changes of mood." [Abstract]

Benke T, Kurzthaler I, Schmidauer Ch, Moncayo R, Donnemiller E.
Mania caused by a diencephalic lesion.
Neuropsychologia 2002;40(3):245-52
"We describe the case of a young male patient, SN, who suffered a MR-documented ischaemic lesion of both dorsomedial thalami and presented with a transient maniform syndrome. SN's neuropsychological, structural and functional imaging findings are compared with similar reported cases and are discussed in the framework of fronto-subcortical circuits and their proposed behavioural disorders. SN's mania was characterized by restlessness, mood elevation, a tendency for pleasurable activities, inflated self-esteem and loss of disease awareness. Other symptoms were sexual disinhibition, tactlessness, abnormal discourse, and reduced need for food and sleep. His neuropsychological assessment revealed an anterograde amnesia, and an impairment of frontal-executive functions. A SPECT-study showed diaschisis-related areas of hypoperfusion in both prefrontal regions which were interpreted as equivalents of SN's frontal-dysexecutive syndrome. In addition, there was a perfusion deficit in the right orbitofrontal cortex, which was taken as the imaging correlate of SN's secondary mania and personality disorder. These findings suggest that SN's mania and his other symptoms result from the twofold disruption of fronto-subcortical connections, namely of the right orbitofrontal loop which is concerned with mood regulation and socially appropriate behaviour, and of the dorsolateral prefrontal loop which mediates executive cognitive functions." [Abstract]

Bogousslavsky J, Ferrazzini M, Regli F, Assal G, Tanabe H, Delaloye-Bischof A.
Manic delirium and frontal-like syndrome with paramedian infarction of the right thalamus.
J Neurol Neurosurg Psychiatry 1988 Jan;51(1):116-9
"A disinhibition syndrome affecting speech (with logorrhoea, delirium, jokes, laughs, inappropriate comments, extraordinary confabulations), was the main manifestation of a right-sided thalamic infarct involving the dorsomedian nucleus, intralaminar nuclei and medial part of the ventral lateral nucleus. Resolution of conflicting tasks was severely impaired, suggesting frontal lobe dysfunction. These abnormalities correlated with the finding on SPECT of a marked hypoperfusion in the overlying hemisphere predominating in the frontal region. We suggest that this behavioural syndrome was produced by disconnecting the dorsomedian nucleus from the frontal lobe and limbic system." [Abstract]

Cummings JL, Mendez MF.
Secondary mania with focal cerebrovascular lesions.
Am J Psychiatry 1984 Sep;141(9):1084-7
"The authors describe two patients with secondary mania associated with right thalamic infarctions. Both patients exhibited hemisensory loss, denial of illness, and amnesia for the manic episode. One improved with lithium therapy and the other recovered without specific pharmacologic intervention. A review of reported cases reveals that most focal lesions associated with secondary mania involve the diencephalic region and that the majority of lateralized lesions are on the right side." [Abstract]

Kromkamp M, Uylings HB, Smidt MP, Hellemons AJ, Burbach JP, Kahn RS.
Decreased thalamic expression of the homeobox gene DLX1 in psychosis.
Arch Gen Psychiatry. 2003 Sep;60(9):869-74.
"CONTEXT: A shared vulnerability to develop psychosis can be related to abnormalities in thalamic circuits in schizophrenia and bipolar disorder and could be a genetic link between these disorders. Homeobox genes involved in development and differentiation of the brain could play an important role in these disorders. OBJECTIVE: To determine whether patients with schizophrenia and bipolar disorder have different thalamic expression patterns of 2 homeobox genes, DLX1 and SHOX2 (alias OG12X or SHOT) compared with psychiatric and nonpsychiatric control subjects. DESIGN: Postmortem sections containing the thalamic mediodorsal nucleus were subjected to in situ hybridization with mouse Dlx1 and human SHOX2 RNA probes. The number of both DLX1- and SHOX2-positive neurons relative to Nissl-stained neurons was estimated in systematic randomly sampled volume probes.Patients Fifteen patients with schizophrenia, 15 with bipolar disorder with or without history of psychosis, 15 with major depressive disorder, and 15 nonpsychiatric controls from the Stanley Foundation Brain Bank. MAIN OUTCOME MEASURE: Relative numbers of DLX1- and SHOX2-positive neurons in patients with schizophrenia and bipolar disorder with history of psychosis compared with psychiatric and nonpsychiatric controls. RESULTS: Patients with a history of psychosis showed significantly decreased relative numbers of DLX1-positive neurons compared with patients without history of psychosis and nonpsychiatric controls (P =.02), whereas no differences could be found in relative numbers of SHOX2-positive neurons (P>.15). Results were obtained blind to diagnosis, symptoms, or any other variable except hemisphere. CONCLUSION: Decreased thalamic expression of DLX1 in schizophrenia and bipolar disorder with psychosis suggests shared genetic deficits in expression of this homeobox gene." [Abstract]

Manuel A. Castro-Alamancos, and Maria E. Calcagnotto
High-Pass Filtering of Corticothalamic Activity by Neuromodulators Released in the Thalamus During Arousal: In Vitro and In Vivo
J Neurophysiol 85: 1489-1497, 2001.
"The thalamus is the principal relay station of sensory information to the neocortex. In return, the neocortex sends a massive feedback projection back to the thalamus. The thalamus also receives neuromodulatory inputs from the brain stem reticular formation, which is vigorously activated during arousal. We investigated the effects of two neuromodulators, acetylcholine and norepinephrine, on corticothalamic responses in vitro and in vivo. Results from rodent slices in vitro showed that acetylcholine and norepinephrine depress the efficacy of corticothalamic synapses while enhancing their frequency-dependent facilitation. This produces a stronger depression of low-frequency responses than of high-frequency responses. The effects of acetylcholine and norepinephrine were mimicked by muscarinic and alpha(2)-adrenergic receptor agonists and blocked by muscarinic and alpha-adrenergic antagonists, respectively. Stimulation of the brain stem reticular formation in vivo also strongly depressed corticothalamic responses. The suppression was very strong for low-frequency responses, which do not produce synaptic facilitation, but absent for high-frequency corticothalamic responses. As in vitro, application of muscarinic and alpha-adrenergic antagonists into the thalamus in vivo abolished the suppression of corticothalamic responses induced by stimulating the reticular formation. In conclusion, cholinergic and noradrenergic activation during arousal high-pass filters corticothalamic activity. Thus, during arousal only high-frequency inputs from the neocortex are allowed to reach the thalamus. Neuromodulators acting on corticothalamic synapses gate the flow of cortical activity to the thalamus as dictated by behavioral state." [Full Text]

Castro-Alamancos, Manuel A.
Role of Thalamocortical Sensory Suppression during Arousal: Focusing Sensory Inputs in Neocortex
J. Neurosci. 2002 22: 9651-9655
"The thalamus serves as a gate that regulates the flow of sensory inputs to the neocortex, and this gate is controlled by neuromodulators from the brainstem reticular formation that are released during arousal. We found recently that sensory-evoked responses are suppressed in the neocortex during arousal. This sensory suppression results from the activity-dependent depression of the thalamocortical connection caused by increased tonic firing of thalamocortical cells during arousal. In the present study, the functional consequences of thalamocortical suppression during arousal were investigated using the vibrissae system of rodents. The results show that thalamocortical suppression is associated with a strong reduction in the spread of sensory inputs through the cortex, thus reducing the size of sensory representations. In addition, when the responses of single cells to principal and adjacent whiskers are compared, the response to the adjacent whiskers was found to be strongly suppressed, much more so than that of principal whiskers. Consequently, the receptive fields of cortical neurons become more focused to the principal whisker. The results indicate that thalamocortical suppression during arousal serves to focus sensory inputs to their appropriate representations in neocortex, which may be computationally helpful for the spatial processing of sensory information."

Guillery RW.
Anatomical evidence concerning the role of the thalamus in corticocortical communication: a brief review.
J Anat 1995 Dec;187 ( Pt 3):583-92
"Two distinct types of thalamic nucleus are proposed on the basis of the afferent fibres that they receive from ascending pathways and from the cerebral cortex. 'First order nuclei' receive primary afferent fibres, definable on the basis of their origin and their intrathalamic synaptic relationships, from ascending pathways. These nuclei receive corticothalamic afferents from pyramidal cells in cortical layer 6, which also send branches to the thalamic reticular nucleus and appear to have a modulatory function. 'Higher order nuclei' receive most or all of their 'primary afferents' from pyramidal cells in cortical layer 5. These resemble the ascending primary afferents in the first order nuclei in terms of fine structure, synaptic relationships and in lacking a branch to the thalamic reticular nucleus. The higher order nuclei also receive modulatory afferents from layer 6. It is proposed that the higher-order nuclei are largely concerned with transmitting information about the output of one cortical area to another cortical area, and that they are likely to play a key role in corticocortical communication and higher cortical functions." [Abstract]

Blumberg HP, Martin A, Kaufman J, Leung HC, Skudlarski P, Lacadie C, Fulbright RK, Gore JC, Charney DS, Krystal JH, Peterson BS.
Frontostriatal abnormalities in adolescents with bipolar disorder: preliminary observations from functional MRI.
Am J Psychiatry. 2003 Jul;160(7):1345-7.
"OBJECTIVE: This study investigated whether the functional abnormalities in prefrontal systems observed in adult bipolar disorder are manifested in adolescents with this illness. METHOD: Ten adolescents with bipolar disorder and 10 healthy comparison subjects participated in a color-naming Stroop task during event-related functional magnetic resonance imaging. RESULTS: Signal increases in the left putamen and thalamus were significantly greater in the bipolar disorder group than in the healthy group. Age correlated positively with signal increases in the bilateral rostroventral prefrontal cortex and the striatum in the healthy group but not in the bipolar disorder group. In the bipolar disorder subjects, depressive symptoms correlated positively with signal increases in the ventral striatum. CONCLUSIONS: These findings suggest the presence of dysfunction in the subcortical portions of the frontostriatal circuits in adolescents with bipolar disorder. The absence of the prefrontal abnormalities that were observed previously in adults and the absence of the age-related increases in prefrontal activity observed in normal comparison subjects suggest that a developmental disturbance in prefrontal function may emerge in bipolar disorder over the course of adolescence." [Abstract]

Dasari M, Friedman L, Jesberger J, Stuve TA, Findling RL, Swales TP, Schulz SC.
A magnetic resonance imaging study of thalamic area in adolescent patients with either schizophrenia or bipolar disorder as compared to healthy controls.
Psychiatry Res 1999 Oct 11;91(3):155-62
"The purpose of this study was to compare thalamic size in adolescent patients with either schizophrenia or bipolar disorder and healthy controls. T2-weighted axial magnetic resonance images were used to manually define the area of the thalamus for 20 schizophrenia patients, 15 bipolar patients and 16 normal control subjects, all of whom were adolescents. Two orthogonal planned contrasts were tested: Contrast 1, patients with schizophrenia vs. patients with bipolar disorder; and Contrast 2, both patient groups taken as a single group compared to controls. Contrast 1 was not statistically significant for right or left thalamic area. Contrast 2 was statistically significant and indicated reductions in thalamic area in the patients as compared to controls. The same pattern of results emerged after adjustment for total brain volume. Our results indicate that thalamic abnormalities reported in adult schizophrenic and bipolar patients are also observed in adolescent patients. Our findings also add to the evidence implicating the thalamus in the pathophysiology of schizophrenia and bipolar disorder." [Abstract]

Caetano SC, Sassi R, Brambilla P, Harenski K, Nicoletti M, Mallinger AG, Frank E, Kupfer DJ, Keshavan MS, Soares JC.
MRI study of thalamic volumes in bipolar and unipolar patients and healthy individuals.
Psychiatry Res 2001 Dec 30;108(3):161-8
"The thalamus is a key structure in brain anatomic circuits potentially involved in the pathophysiology of mood disorders. Available findings from studies that examined this brain region in mood disorder patients have been conflicting. To examine the hypothesis of anatomical abnormalities in the thalamus in patients with mood disorders, we conducted a magnetic resonance imaging (MRI) study in 25 bipolar patients (mean age+/-S.D.=34.4+/-9.8 years), 17 unipolar patients (mean age+/-S.D.=42.8+/-9.2 years), and 39 healthy control subjects (mean age+/-S.D.=36.6+/-9.7 years). Thalamic volumes Gray Matter were measured blindly with a semi-automated technique. Multivariate analysis of variance, with age and gender as covariates, revealed no significant differences in left or right thalamic volumes among bipolar patients, unipolar patients and healthy individuals. There were no significant effects of gender, age at illness onset, episode type, number of episodes, length of illness, or family history of mood disorders on thalamic measurements. Although functional abnormalities in the thalamus are likely to be implicated in the pathophysiology of mood disorders, no abnormalities in thalamic size appear present in bipolar or unipolar individuals." [Abstract]

Starkstein SE, Fedoroff P, Berthier ML, Robinson RG.
Manic-depressive and pure manic states after brain lesions.
Biol Psychiatry 1991 Jan 15;29(2):149-58
"Although mania is a rare complication of brain lesions, recent reports have emphasized the importance of lesion location and genetic predisposition in these patients. In the present study we compared patients who developed a bipolar affective disorder (i.e., mania and depression) after a brain lesion with patients who only developed mania. Although no significant between-group differences were found on demographic variables, the manic-depressed group showed significantly more impairments on the Mini Mental State Exam than the mania only group. All the bipolar patients had subcortical lesions (mainly right head of the caudate and right thalamus), while patients with unipolar mania had significantly higher frequency of cortical involvement (mainly right orbitofrontal and basotemporal cortices). It is suggested that subcortical and cortical right hemisphere lesions may produce different neurochemical and/or remote metabolic brain changes that may underlie the production of either a bipolar disease or a unipolar mania." [Abstract]

Zubieta JK, Huguelet P, Ohl LE, Koeppe RA, Kilbourn MR, Carr JM, Giordani BJ, Frey KA.
High vesicular monoamine transporter binding in asymptomatic bipolar I disorder: sex differences and cognitive correlates.
Am J Psychiatry 2000 Oct;157(10):1619-28
"OBJECTIVE: It has been hypothesized that anomalies in monoaminergic function underlie some of the manifestations of bipolar disorder. In this study the authors examined the possibility that trait-related abnormalities in the concentration of monoaminergic synaptic terminals may be present in patients with asymptomatic bipolar disorder type I. METHOD: The concentration of a stable presynaptic marker, the vesicular monoamine transporter protein (VMAT2), was quantified with (+)[(11)C]dihydrotetrabenazine (DTBZ) and positron emission tomography. Sixteen asymptomatic patients with bipolar I disorder who had a prior history of mania with psychosis (nine men and seven women) and individually matched healthy subjects were studied. Correlational analyses were conducted to examine the relationship between regional VMAT2 binding, cognitive function, and clinical variables. RESULTS: VMAT2 binding in the thalamus and ventral brainstem of the bipolar patients was higher than that in the comparison subjects. VMAT2 concentrations in these regions correlated with performance on measures of frontal, executive function. In addition, sex differences in VMAT2 binding were detected in the thalamus of the bipolar patients; the male patients had higher binding than the women. No sex differences in binding were observed in the healthy comparison group. CONCLUSIONS: These initial results suggest that higher than normal VMAT2 expression and, by extension, concentration of monoaminergic synaptic terminals, may represent a trait-related abnormality in patients with bipolar I disorder and that male and female patients show different patterns. Also, VMAT2 concentrations may be associated with some of the cognitive deficits encountered in euthymic bipolar disorder." [Abstract]

Deicken RF, Eliaz Y, Feiwell R, Schuff N.
Increased thalamic N-acetylaspartate in male patients with familial bipolar I disorder.
Psychiatry Res 2001 Feb 28;106(1):35-45
"N-Acetylaspartate (NAA) in the anterior and mediodorsal thalamic regions was measured using proton magnetic resonance spectroscopic imaging (1H-MRSI) in 15 euthymic male patients with familial bipolar I disorder and compared to values in 15 male control subjects to determine if there was evidence for altered neuronal/axonal integrity. MRI tissue segmentation methods were also utilized to obtain tissue-contribution estimates for each MRSI voxel. Relative to the comparison group, the patients with bipolar I disorder demonstrated significantly higher NAA and creatine in both the right and left thalamus. NAA was also significantly higher in the left thalamus compared to the right in both bipolar I patients and controls. There were no group or lateralized differences in the percentages of different tissue types within the MRSI voxels, suggesting that the thalamic NAA and creatine alterations were not an artifact of variations in tissue type percentages in the MRSI voxels. There was also no significant association between NAA or creatine and illness duration. The findings of increased thalamic NAA bilaterally may represent neuronal hypertrophy or hyperplasia, reduced glial cell density, or abnormal synaptic and dendritic pruning. Increased thalamic creatine bilaterally may represent altered cellular energy metabolism and is consistent with prior studies demonstrating changes in thalamic metabolism in mood disorders." [Abstract]

Kulisevsky J, Berthier ML, Gironell A, Pascual-Sedano B, Molet J, Pares P.
Mania following deep brain stimulation for Parkinson's disease.
Neurology. 2002 Nov 12;59(9):1421-4.
"Three patients with PD developed manic behavior after bilateral implantation of electrodes for deep-brain stimulation (DBS). Common to all three patients were manic symptoms unremitting after levodopa reduction or stimulation "off," lower electrodes positioning caudal to the subthalamic nucleus area, postoperative DBS with the lower contacts (0) of the quadripolar electrodes, and resolution of the manic episodes coinciding with stimulation through higher contacts." [Abstract]

Romito LM, Raja M, Daniele A, Contarino MF, Bentivoglio AR, Barbier A, Scerrati M, Albanese A.
Transient mania with hypersexuality after surgery for high frequency stimulation of the subthalamic nucleus in Parkinson's disease.
Mov Disord. 2002 Nov;17(6):1371-4.
"Among 30 Parkinson's disease patients who received high frequency stimulation of the subthalamic nucleus, 5 developed remarkable disorders of mood or sexual behavior after the implant. We describe 2 men who developed mania and hypersexuality a few days after the implant that lasted for some months and then gradually disappeared spontaneously." [Abstract]

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Recent Thalamus in Bipolar Disorder Research

1) Chang WC, Lee CM, Shyu BC
Temporal and spatial dynamics of thalamus-evoked activity in the anterior cingulate cortex.
Neuroscience. 2012 Jul 16;
In the present study, multielectrode array (MEA) recording was used to illustrate the spatial-temporal progression of anterior cingulate cortex (ACC) activity following stimulation of the thalamus in a thalamocingulate pathway-preserved slice. The MEA was placed under the slice that contained the ACC, and 60 channels of extracellular local field potentials evoked by bipolar electrical stimulation within the thalamus were analyzed. Several distinct thalamic-evoked responses were identified. The early negative component (N1; amplitude, -35.7 ± 5.9 ?V) emerged in layer VI near the cingulum 8.4 ± 0.5 ms after stimulation. N1 progressed upward to layers V and II/III in a lateral-to-medial direction. Subsequently, a positive component (P; amplitude, 27.0 ± 3.2 ?V) appeared 12.0 ± 0.6 ms after stimulation in layer VI. At 26.8 ± 1.1 ms, a second negative component (N2; amplitude, -20.9 ± 2.7 ?V) became apparent in layers II/III and V, followed by a more ventrolateral component (N3; amplitude, -18.9 ± 2.9 ?V) at 42.8 ± 2.6 ms. These two late components spread downward to layer VI in a medial-to-lateral direction. The trajectory paths of the evoked components were consistently represented with varied medial thalamic stimulation intensities and sites. Both AMPA/kainate and N-methyl-D-aspartate-type glutamate receptors involved in monosynaptic and polysynaptic transmission participated in this thalamocortical pathway. Morphine mainly diminished the two negative synaptic components, and this suppressive effect was reversed by naloxone. The present study confirmed that functional thalamocingulate activity was preserved in the brain-slice preparation. The thalamus-evoked responses were activated and progressed along a deep surface-deep trajectory loop across the ACC layers. Glutamatergic neurotransmitters were crucially involved in information processing. Opioid interneurons may play a modulatory role in regulating the signal flows in the cingulate cortex. [PubMed Citation] [Order full text from Infotrieve]

2) Kristensen LV, Sandager-Nielsen K, Hansen HH
K(v) 7 (KCNQ) channel openers normalize central 2-deoxyglucose uptake in a mouse model of mania and increase prefrontal cortical and hippocampal serine-9 phosphorylation levels of GSK3β.
J Neurochem. 2012 May;121(3):373-82.
Several metabolic neuroimaging studies have indicated that bipolar patients with mania exhibit alterations in metabolic activity, suggesting that perturbations in corticolimbic function contribute to the functional deficits associated with the disease. Because pharmacological stimulation of K(v)7 channel function has shown anti-manic like efficacy in the D-amphetamine and chlordiazepoxide (AMPH+CDP) induced hyperactivity mouse model of mania, we addressed whether this effect of K(v)7 channels could be associated with changes in cerebral [¹?C]2-deoxyglucose (2-DG) uptake, a surrogate marker of brain metabolic activity. Acute administration of the Kv7 channel modulators, retigabine (pan K(v)7.2-K(v)7.5 channel opener) and ICA-27243 (K(v)7.2/K(v)7.3 channel-preferring opener) reduced 2-DG uptake in several mouse forebrain structures with a brain regional signature similar to the mood stabilizers, lithium and valproate. Combined administration of AMPH+CDP enhanced 2-DG uptake in the striatum, cortex and thalamus, and both retigabine and ICA-27243 fully prevented this stimulatory effect of AMPH+CDP. In addition, both K(v)7 channel openers dose-dependently increased phospho-serine-9 levels of GSK3? in the prefrontal cortex and hippocampus, a common molecular mechanism shared by anti-manic drugs. In combination, these data emphasize the potential of K(v)7 channel openers in the treatment of bipolar disorder, and suggest that heteromeric K(v)7.2/K(v)7.3 channels may present a novel anti-manic therapeutic target. [PubMed Citation] [Order full text from Infotrieve]

3) Chen HC, Chuang CC, Tzaan WC, Hsu PW
Application of neuroendoscopy in the treatment of obstructive hydrocephalus secondary to hypertensive intraventricular hemorrhage.
Neurol India. 2011 Nov-Dec;59(6):861-6.
[PubMed Citation] [Order full text from Infotrieve]

4) McCormick LM, Buchanan JR, Onwuameze OE, Pierson RK, Paradiso S
Beyond alcoholism: Wernicke-Korsakoff syndrome in patients with psychiatric disorders.
Cogn Behav Neurol. 2011 Dec;24(4):209-16.
[PubMed Citation] [Order full text from Infotrieve]

5) Chen Z, Cui L, Li M, Jiang L, Deng W, Ma X, Wang Q, Huang C, Wang Y, Collier DA, Gong Q, Li T
Voxel based morphometric and diffusion tensor imaging analysis in male bipolar patients with first-episode mania.
Prog Neuropsychopharmacol Biol Psychiatry. 2012 Mar 30;36(2):231-8.
[PubMed Citation] [Order full text from Infotrieve]

6) Watson DR, Anderson JM, Bai F, Barrett SL, McGinnity TM, Mulholland CC, Rushe TM, Cooper SJ
A voxel based morphometry study investigating brain structural changes in first episode psychosis.
Behav Brain Res. 2012 Feb 1;227(1):91-9.
Schizophrenia (SCZ) and bipolar disorder (BP) are associated with neuropathological brain changes, which are believed to disrupt connectivity between brain processes and may have common properties. Patients at first psychotic episode are unique, as one can assess brain alterations at illness inception, when many confounders are reduced or absent. SCZ (N=25) and BP (N=24) patients were recruited in a regional first episode psychosis MRI study. VBM methods were used to study gray matter (GM) and white matter (WM) differences between patient groups and case by case matched controls. For both groups, deficits identified are more discrete than those typically reported in later stages of illness. SCZ patients showed some evidence of GM loss in cortical areas but most notable were in limbic structures such as hippocampus, thalamus and striatum and cerebellum. Consistent with disturbed neural connectivity WM alterations were also observed in limbic structures, the corpus callosum and many subgyral and sublobar regions in the parietal, temporal and frontal lobes. BP patients displayed less evidence of volume changes overall, compared to normal healthy participants, but those changes observed were primarily in WM areas which overlapped with regions identified in SCZ, including thalamus and cerebellum and subgyral and sublobar sites. At first episode of psychosis there is evidence of a neuroanatomical overlap between SCZ and BP with respect to brain structural changes, consistent with disturbed neural connectivity. There are also important differences however in that SCZ displays more extensive structural alteration. [PubMed Citation] [Order full text from Infotrieve]

7) Karchemskiy A, Garrett A, Howe M, Adleman N, Simeonova DI, Alegria D, Reiss A, Chang K
Amygdalar, hippocampal, and thalamic volumes in youth at high risk for development of bipolar disorder.
Psychiatry Res. 2011 Dec 30;194(3):319-25.
Children of parents with bipolar disorder (BD), especially those with attention deficit hyperactivity disorder (ADHD) and symptoms of depression or mania, are at significantly high risk for developing BD. As we have previously shown amygdalar reductions in pediatric BD, the current study examined amygdalar volumes in offspring of parents (BD offspring) who have not yet developed a full manic episode. Youth participating in the study included 22 BD offspring and 22 healthy controls of comparable age, gender, handedness, and IQ. Subjects had no history of a manic episode, but met criteria for ADHD and moderate mood symptoms. MRI was performed on a 3T GE scanner, using a 3D volumetric spoiled gradient echo series. Amygdalae were manually traced using BrainImage Java software on positionally normalized brain stacks. Bipolar offspring had similar amygdalar volumes compared to the control group. Exploratory analyses yielded no differences in hippocampal or thalamic volumes. Bipolar offspring do not show decreased amygdalar volume, possibly because these abnormalities occur after more prolonged illness rather than as a preexisting risk factor. Longitudinal studies are needed to determine whether amygdalar volumes change during and after the development of BD. [PubMed Citation] [Order full text from Infotrieve]

8) Kao C, Forbes JA, Stayman A, Sun DA, Carron R, Benabid AL, Konrad P
High-frequency cortical stimulation augments recovery of thalamocortical oscillations from hypoxia in rat brain slices.
Neuromodulation. 2011 Mar-Apr;14(2):104-10; discussion 110.
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9) Polanía R, Paulus W, Nitsche MA
Modulating cortico-striatal and thalamo-cortical functional connectivity with transcranial direct current stimulation.
Hum Brain Mapp. 2011 Sep 16;
Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that has been shown to alter cortical excitability and activity via application of weak direct currents. Beyond intracortical effects, functional imaging as well as behavioral studies are suggesting additional tDCS-driven alterations of subcortical areas, however, direct evidence for such effects is scarce. We aimed to investigate the impact of tDCS on cortico-subcortical functional networks by seed functional connectivity analysis of different striatal and thalamic regions to prove tDCS-induced alterations of the cortico-striato-thalamic circuit. fMRI resting state data sets were acquired immediately before and after 10 min of bipolar tDCS during rest, with the anode/cathode placed over the left primary motor cortex (M1) and the cathode/anode over the contralateral frontopolar cortex. To control for possible placebo effects, an additional sham stimulation session was carried out. Functional coupling between the left thalamus and the ipsilateral primary motor cortex (M1) significantly increased following anodal stimulation over M1. Additionally, functional connectivity between the left caudate nucleus and parietal association cortices was significantly strengthened. In contrast, cathodal tDCS over M1 decreased functional coupling between left M1 and contralateral putamen. In summary, in this study, we show for the first time that tDCS modulates functional connectivity of cortico-striatal and thalamo-cortical circuits. Here we highlight that anodal tDCS over M1 is capable of modulating elements of the cortico-striato-thalamo-cortical functional motor circuit. Hum Brain Mapp, 2011. © 2011 Wiley-Liss, Inc. [PubMed Citation] [Order full text from Infotrieve]

10) Lencer R, Keedy SK, Reilly JL, McDonough BE, Harris MS, Sprenger A, Sweeney JA
Altered transfer of visual motion information to parietal association cortex in untreated first-episode psychosis: implications for pursuit eye tracking.
Psychiatry Res. 2011 Oct 31;194(1):30-8.
Visual motion processing and its use for pursuit eye movement control represent a valuable model for studying the use of sensory input for action planning. In psychotic disorders, alterations of visual motion perception have been suggested to cause pursuit eye tracking deficits. We evaluated this system in functional neuroimaging studies of untreated first-episode schizophrenia (N=24), psychotic bipolar disorder patients (N=13) and healthy controls (N=20). During a passive visual motion processing task, both patient groups showed reduced activation in the posterior parietal projection fields of motion-sensitive extrastriate area V5, but not in V5 itself. This suggests reduced bottom-up transfer of visual motion information from extrastriate cortex to perceptual systems in parietal association cortex. During active pursuit, activation was enhanced in anterior intraparietal sulcus and insula in both patient groups, and in dorsolateral prefrontal cortex and dorsomedial thalamus in schizophrenia patients. This may result from increased demands on sensorimotor systems for pursuit control due to the limited availability of perceptual motion information about target speed and tracking error. Visual motion information transfer deficits to higher-level association cortex may contribute to well-established pursuit tracking abnormalities, and perhaps to a wider array of alterations in perception and action planning in psychotic disorders. [PubMed Citation] [Order full text from Infotrieve]

11) Foland-Ross LC, Bookheimer SY, Lieberman MD, Sugar CA, Townsend JD, Fischer J, Torrisi S, Penfold C, Madsen SK, Thompson PM, Altshuler LL
Normal amygdala activation but deficient ventrolateral prefrontal activation in adults with bipolar disorder during euthymia.
Neuroimage. 2012 Jan 2;59(1):738-44.
Functional neuroimaging studies have implicated the involvement of the amygdala and ventrolateral prefrontal cortex (vlPFC) in the pathophysiology of bipolar disorder. Hyperactivity in the amygdala and hypoactivity in the vlPFC have been reported in manic bipolar patients scanned during the performance of an affective faces task. Whether this pattern of dysfunction persists during euthymia is unclear. Using functional magnetic resonance imaging (fMRI), 24 euthymic bipolar and 26 demographically matched healthy control subjects were scanned while performing an affective task paradigm involving the matching and labeling of emotional facial expressions. Neuroimaging results showed that, while amygdala activation did not differ significantly between groups, euthymic patients showed a significant decrease in activation of the right vlPFC (BA47) compared to healthy controls during emotion labeling. Additionally, significant decreases in activation of the right insula, putamen, thalamus and lingual gyrus were observed in euthymic bipolar relative to healthy control subjects during the emotion labeling condition. These data, taken in context with prior studies of bipolar mania using the same emotion recognition task, could suggest that amygdala dysfunction may be a state-related abnormality in bipolar disorder, whereas vlPFC dysfunction may represent a trait-related abnormality of the illness. Characterizing these patterns of activation is likely to help in understanding the neural changes related to the different mood states in bipolar disorder, as well as changes that represent more sustained abnormalities. Future studies that assess mood-state related changes in brain activation in longitudinal bipolar samples would be of interest. [PubMed Citation] [Order full text from Infotrieve]

12) Delvecchio G, Fossati P, Boyer P, Brambilla P, Falkai P, Gruber O, Hietala J, Lawrie SM, Martinot JL, McIntosh AM, Meisenzahl E, Frangou S
Common and distinct neural correlates of emotional processing in Bipolar Disorder and Major Depressive Disorder: a voxel-based meta-analysis of functional magnetic resonance imaging studies.
Eur Neuropsychopharmacol. 2012 Feb;22(2):100-13.
Neuroimaging studies have consistently shown functional brain abnormalities in patients with Bipolar Disorder (BD) and Major Depressive Disorder (MDD). However, the extent to which these two disorders are associated with similar or distinct neural changes remains unclear. We conducted a systematic review of functional magnetic resonance imaging studies comparing BD and MDD patients to healthy participants using facial affect processing paradigms. Relevant spatial coordinates from twenty original studies were subjected to quantitative Activation Likelihood Estimation meta-analyses based on 168 BD and 189 MDD patients and 344 healthy controls. We identified common and distinct patterns of neural engagement for BD and MDD within the facial affect processing network. Both disorders were associated with increased engagement of limbic regions. Diagnosis-specific differences were observed in cortical, thalamic and striatal regions. Decreased ventrolateral prefrontal cortical engagement was associated with BD while relative hypoactivation of the sensorimotor cortices was seen in MDD. Increased responsiveness in the thalamus and basal ganglia were associated with BD. These findings were modulated by stimulus valence. These data suggest that whereas limbic overactivation is reported consistently in patients with mood disorders, future research should consider the relevance of a wider network of regions in formulating conceptual models of BD and MDD. [PubMed Citation] [Order full text from Infotrieve]

13) Marburger T, Prayson R
Angiocentric glioma: a clinicopathologic review of 5 tumors with identification of associated cortical dysplasia.
Arch Pathol Lab Med. 2011 Aug;135(8):1037-41.
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14) Kempton MJ, Salvador Z, Munafò MR, Geddes JR, Simmons A, Frangou S, Williams SC
Structural neuroimaging studies in major depressive disorder. Meta-analysis and comparison with bipolar disorder.
Arch Gen Psychiatry. 2011 Jul;68(7):675-90.
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15) Zhang L, Li CT, Su TP, Hu XZ, Lanius RA, Webster MJ, Chung MY, Chen YS, Bai YM, Barker JL, Barrett JE, Li XX, Li H, Benedek DM, Ursano R
P11 expression and PET in bipolar disorders.
J Psychiatr Res. 2011 Nov;45(11):1426-31.
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16) Richieri R, Boyer L, Farisse J, Colavolpe C, Mundler O, Lancon C, Guedj E
Predictive value of brain perfusion SPECT for rTMS response in pharmacoresistant depression.
Eur J Nucl Med Mol Imaging. 2011 Sep;38(9):1715-22.
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17) Sui J, Pearlson G, Caprihan A, Adali T, Kiehl KA, Liu J, Yamamoto J, Calhoun VD
Discriminating schizophrenia and bipolar disorder by fusing fMRI and DTI in a multimodal CCA+ joint ICA model.
Neuroimage. 2011 Aug 1;57(3):839-55.
Diverse structural and functional brain alterations have been identified in both schizophrenia and bipolar disorder, but with variable replicability, significant overlap and often in limited number of subjects. In this paper, we aimed to clarify differences between bipolar disorder and schizophrenia by combining fMRI (collected during an auditory oddball task) and diffusion tensor imaging (DTI) data. We proposed a fusion method, "multimodal CCA+ joint ICA", which increases flexibility in statistical assumptions beyond existing approaches and can achieve higher estimation accuracy. The data collected from 164 participants (62 healthy controls, 54 schizophrenia and 48 bipolar) were extracted into "features" (contrast maps for fMRI and fractional anisotropy (FA) for DTI) and analyzed in multiple facets to investigate the group differences for each pair-wised groups and each modality. Specifically, both patient groups shared significant dysfunction in dorsolateral prefrontal cortex and thalamus, as well as reduced white matter (WM) integrity in anterior thalamic radiation and uncinate fasciculus. Schizophrenia and bipolar subjects were separated by functional differences in medial frontal and visual cortex, as well as WM tracts associated with occipital and frontal lobes. Both patients and controls showed similar spatial distributions in motor and parietal regions, but exhibited significant variations in temporal lobe. Furthermore, there were different group trends for age effects on loading parameters in motor cortex and multiple WM regions, suggesting that brain dysfunction and WM disruptions occurred in identified regions for both disorders. Most importantly, we can visualize an underlying function-structure network by evaluating the joint components with strong links between DTI and fMRI. Our findings suggest that although the two patient groups showed several distinct brain patterns from each other and healthy controls, they also shared common abnormalities in prefrontal thalamic WM integrity and in frontal brain mechanisms. [PubMed Citation] [Order full text from Infotrieve]

18) Marchand WR, Lee JN, Garn C, Thatcher J, Gale P, Kreitschitz S, Johnson S, Wood N
Striatal and cortical midline activation and connectivity associated with suicidal ideation and depression in bipolar II disorder.
J Affect Disord. 2011 Oct;133(3):638-45.
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19) Fleck DE, Kotwal R, Eliassen JC, Lamy M, Delbello MP, Adler CM, Durling M, Cerullo MA, Strakowski SM
Preliminary evidence for increased frontosubcortical activation on a motor impulsivity task in mixed episode bipolar disorder.
J Affect Disord. 2011 Sep;133(1-2):333-9.
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20) Li Q, Li H, Roughton K, Wang X, Kroemer G, Blomgren K, Zhu C
Lithium reduces apoptosis and autophagy after neonatal hypoxia-ischemia.
Cell Death Dis. 2010;1:e56.
Lithium is used in the treatment of bipolar mood disorder. Reportedly, lithium can be neuroprotective in models of adult brain ischemia. The purpose of this study was to evaluate the effects of lithium in a model of neonatal hypoxic-ischemic brain injury. Nine-day-old male rats were subjected to unilateral hypoxia-ischemia (HI) and 2?mmol/kg lithium chloride was injected i.p. immediately after the insult. Additional lithium injections, 1?mmol/kg, were administered at 24-h intervals. Pups were killed 6, 24 or 72?h after HI. Lithium reduced the infarct volume from 24.7±2.9 to 13.8±3.3?mm(3) (44.1%) and total tissue loss (degeneration + lack of growth) from 67.4±4.4 to 38.4±5.9?mm(3) (43.1%) compared with vehicle at 72?h after HI. Injury was reduced in the cortex, hippocampus, thalamus and striatum. Lithium reduced the ischemia-induced dephosphorylation of glycogen synthase kinase-3? and extracellular signal-regulated kinase, the activation of calpain and caspase-3, the mitochondrial release of cytochrome c and apoptosis-inducing factor, as well as autophagy. We conclude that lithium could mitigate the brain injury after HI by inhibiting neuronal apoptosis. The lithium doses used were in the same range as those used in bipolar patients, suggesting that lithium might be safely used for the avoidance of neonatal brain injury. [PubMed Citation] [Order full text from Infotrieve]