Gray matter volume in schizophrenia and bipolar disorder with psychotic features

There is growing evidence that schizophrenia (SZ) and bipolar disorder (BD) overlap significantly in risk factors, neurobiological features, clinical presentations, and outcomes. SZ is characterized by well documented gray matter (GM) abnormalities in multiple frontal, temporal and subcortical structures. Recent voxel-based morphometry (VBM) studies and meta-analyses in BD also report GM reductions in overlapping, albeit less widespread, brain regions. Psychosis, a hallmark of SZ, is also experienced by a significant proportion of BD patients and there is evidence that psychotic BD may be characterized by specific clinical and pathophysiological features. However, there are few studies comparing GM between SZ and psychotic BD. In this study we compared GM volumes in a sample of 58 SZ patients, 28 BD patients experiencing psychotic symptoms and 43 healthy controls using whole-brain voxel-based morphometry. SZ patients had GM reductions in multiple frontal and temporal regions compared to healthy controls and in the subgenual cortex compared to psychotic BD patients. GM volume was increased in the right posterior cerebellum in SZ patients compared to controls. However, psychotic BD patients did not show significant GM deficits compared to healthy controls or SZ patients. We conclude that GM abnormality as measured by VBM analysis is less pronounced in psychotic BD compared to SZ. This may be due to disease-specific factors or medications used more commonly in BD.     

Voxel-based morphometric analysis on the volume of gray matter in bipolar I disorder

A number of previous studies have found that bipolar disorder is associated with abnormalities of brain structure. In this study we used optimized voxel-based morphometry (VBM) to compare gray matter volume between patients with bipolar I disorder and healthy controls. Twenty-four bipolar I patients (15 males and nine females) and 36 healthy controls (21 males and 15 females), who were well matched for age and gender, were scanned using structural magnetic resonance imaging. Gray matter volume was assessed and compared using optimized VBM, and the correlation between duration of illness/number of episodes and regional volumes was analyzed. There was no difference in whole-brain gray matter volume between the two groups. Optimized vVBM showed that subjects with bipolar I disorder had smaller volumes in the left inferior parietal lobule, right superior temporal gyrus, right middle frontal gyrus and left caudate. Only the volume of the right middle frontal gyrus was correlated with duration of illness and number of episodes in patients. These results suggest widespread gray matter defects in bipolar I disorder, which may play an important role in onset of the illness.     

A voxel-based morphometry study of frontal gray matter correlates of impulsivity

Impulsivity is a personality trait exhibited by healthy individuals, but excessive impulsivity is associated with some mental disorders. Lesion and functional neuroimaging studies indicate that the ventromedial prefrontal region (VMPFC), including the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC) and medial prefrontal cortex, and the amygdala may modulate impulsivity and aggression. However, no morphometric study has examined the association between VMPFC and impulsivity. We hypothesized that healthy subjects with high impulsivity would have smaller volumes in these brain regions compared with those with low impulsivity. Sixty-two healthy subjects were studied (age 35.4 +/- 12.1 years) using a 1.5-T MRI system. The Barratt impulsiveness scale (BIS) was used to assess impulsivity. Images were processed using an optimized voxel-based morphometry (VBM) protocol. We calculated the correlations between BIS scale scores and the gray matter (GM) and white matter (WM) volumes of VMPFC and amygdala. GM volumes of the left and right OFC were inversely correlated with the BIS total score (P = 0.04 and 0.02, respectively). Left ACC GM volumes had a tendency to be inversely correlated with the BIS total score (P = 0.05). Right OFC GM volumes were inversely correlated with BIS nonplanning impulsivity, and left OFC GM volumes were inversely correlated with motor impulsivity. There were no significant WM volume correlations with impulsivity. The results of this morphometry study indicate that small OFC volume relate to high impulsivity and extend the prior finding that the VMPFC is involved in the circuit modulating impulsivity.     

Optimized voxel-based morphometry of gray matter volume in first-episode, antipsychotic-naive schizophrenia

This study examined gray matter (GM) volume abnormalities in first-episode, antipsychotic-na?ve Indian schizophrenia patients. Magnetic resonance images of 18 schizophrenia patients and 18 matched healthy comparison subjects were analyzed by optimized voxel-based morphometry. Schizophrenia patients had significantly smaller global GM and greater global CSF volumes and smaller regional GM volume in superior frontal, inferior frontal, cingulate, post-central, superior temporal and parahippocampal gyri, inferior parietal lobule, insula, caudate nuclei, thalamus and cerebellum. Findings suggest limbic, heteromodal cortical, striatal, thalamic and cerebellar abnormalities in schizophrenia.     

Structural changes in the gray matter of unmedicated patients with obsessive-compulsive disorder: a voxel-based morphometric study

The aim of the current study was to use whole brain voxel-based morphometry（VBM）to assess the gray matter（GM）changes in unmedicated patients with obsessive-compulsive disorder（OCD）compared with normal controls.We compared the GM volumes in28 patients with 22 matched healthy controls using a1.5T MRI.Three-dimensional T1-weighted magnetic resonance images were obtained from all participants.VBM was performed to detect GM volume differences between the two groups.We detected increased regional GM volumes in the bilateral middle temporal gyri,bilateral middle occipital gyri,bilateral globus pallidus,right inferior parietal gyrus,left superior parietal gyrus,right parahippocampus,right supramarginal gyrus,right medial superior frontal gyrus,and left inferior frontal opercular cortex in the OCD patients relative to controls（P〈0.001,uncorrected,cluster size〉100 voxels）.No decreased GM volume was found in the OCD group compared with normal controls.Our findings suggest that structural changes in the GM are not limited to fronto-striato-thalamic circuits in the pathogenesis of OCD.Temporo-parietal cortex may also play an important role.     

The co-existence of geriatric depression and amnestic mild cognitive impairment detrimentally affect gray matter volumes: Voxel-based morphometry study

While late-life depression (LLD) and amnestic mild cognitive impairment (aMCI), alone and in combination, is associated with an increased risk of incident Alzheimer's disease (AD), the neurobiological mechanisms of this link are unclear. We examined the main and interactive effects of LLD and aMCI on the gray matter (GM) volumes in 72 physically healthy participants aged 60 and older. Participants were separated into normal controls, cognitively normal depressed, non-depressed aMCI, and depressed aMCI groups. Optimized voxel-based morphometry estimated GM volumes. The main and interactive effects of LLD and aMCI, and of depressive symptoms and episodic memory deficits on the GM volumes were analyzed. While decreased GM volumes in the mood regulating circuitry structures were associated with depression, GM atrophy in regions essential for various cognitive performance were related to aMCI. LLD-aMCI interactions were associated with widespread subcortical and cortical GM volume loss of brain structures implicated in AD. The interactions between episodic memory deficits and depressive symptom severity are associated with volume loss in right inferior frontal gyrus/anterior insula and left medial frontal gyrus clusters. Our findings suggest that the co-existence of these clinical phenotypes is a potential marker for higher risk of AD.     

Anterior cingulate volumes associated with trait impulsivity in individuals with bipolar disorder

Objective:  Impulsivity is associated with the clinical outcome and likelihood of risky behaviors among bipolar disorder (BD) patients. Our previous study showed an inverse relationship between impulsivity and orbitofrontal cortex (OFC) volume in healthy subjects. We hypothesized that BD patients would show an inverse relationship between impulsivity and volumes of the OFC, anterior cingulate cortex (ACC), medial prefrontal cortex, and amygdala, which have been implicated in the pathophysiology of BD.
Methods:  Sixty-three BD patients were studied (mean ± SD age = 38.2 ± 11.5 years; 79% female). The Barratt Impulsiveness Scale (BIS), version 11A, was used to assess trait impulsivity. Images were processed using SPM2 and an optimized voxel-based morphometry protocol. We examined the correlations between BIS scores and the gray matter (GM) and white matter (WM) volumes of the prespecified regions.
Results:  Left rostral ACC GM volume was inversely correlated with the BIS total score ( t  =   3.95, p_corrected = 0.003) and the BIS motor score ( t  =   5.22, p_corrected < 0.001). In contrast to our hypothesis, OFC volumes were not significantly associated with impulsivity in BD. No WM volume of any structure was significantly correlated with impulsivity. No statistical association between any clinical variable and the rostral ACC GM volumes reached significance.
Conclusions:  Based on our previous findings and the current results, impulsivity may have a different neural representation in BD and healthy subjects, and the ACC may be involved in the pathophysiology of abnormal impulsivity regulation in BD patients.     

Regional gray matter changes in bipolar disorder: a voxel-based morphometric study

OBJECTIVE: To investigate structural abnormalities in bipolar disorder (BD) using optimized voxel-based morphometry (VBM) in closely matched patients and controls, and to examine the relationship of clinical features with regional gray matter (GM) volumes. METHODS: Twenty-four patients (six male) aged 19-59 years (mean=38.21 years, SD=11.04 years) with DSM-IV bipolar I disorder were compared with 25 control subjects, matched on age, sex, and years of education. VBM analyses were conducted on high-resolution T1-weighted brain magnetic resonance imaging to detect regional GM volume differences between groups, ensuring statistical correlation for age, sex and total intracranial volumes. Within the patient groups, regional GM changes were also investigated. RESULTS: Compared to controls, BD patients had increased GM volume in left parahippocampal gyrus and decreased GM volume in left middle temporal gyrus. Family history, psychotic symptoms and lithium status were associated with regional GM abnormalities in BD patients. CONCLUSIONS: This study presents evidence of gray matter volume abnormalities in adults with bipolar I disorder. Regional variation in relation to clinical factors suggests a neurobiological basis for clinical heterogeneity and posits the possibility of trait deficits.     

Action observation training modifies brain gray matter structure in healthy adult individuals

Action observation training (AOT) is thought to facilitate motor system function. We applied voxelwise methods to assess the regional modifications of brain gray matter (GM) volumes and white matter (WM) architecture in healthy subjects following AOT and their correlations with improvements at motor and cognitive functional scales. Forty-two righ-handed healthy subjects were randomized into an experimental (AOT-G, n = 20) and a control (C-G, n = 22) group. The training lasted 2 weeks and consisted of 10 sessions of 45 min each during which subjects watched videos of daily-life actions (AOT-G) or landscapes (C-G), alternated by the execution with the right hand of actions presented in the AOT-G videos. At baseline and follow up, motor and cognitive functional measures as well as brain structural MRI scans were obtained. Tensor-based morphometry and tract-based spatial statistics were used to map longitudinal modifications of GM and WM structures and their correlation with functional scales. After training, both groups improved at cognitive tests, whereas the AOT-G also improved hand motor performance. Following training, no modifications of WM diffusion tensor MRI indexes were detected. After training, compared to C-G, AOT-G had increased volume of the left superior frontal gyrus and decreased volume of the right lingual gyrus. Compared to AOT-G, C-G showed increased volume of the right middle frontal gyrus and left inferior temporal gyrus. In AOT-G, GM volume changes correlated with improvements at cognitive tests. Ten-day AOT in healthy individuals modifies GM structure, promoting structural brain plasticity and functional competence.     

Regional gray matter volume deficits in adolescents with first-episode psychosis

ObjectiveThe current study combined baseline voxel-based morphometry and 1-year clinical follow-up assessments to examine whether and where regional gray matter (GM) volumes differed between a control group and diagnostic subgroups of early-onset first-episode psychosis (FEP).MethodMagnetic resonance imaging brain scans were obtained from 70 patients with early-onset FEP, and 51 non-FEP controls. Early-onset FEP was defined as age younger than 18 years and a duration of positive symptoms of less than 6 months. The age range of the sample was 7 to 18 years. After a 1-year follow-up, patients were stratified into three subgroups: schizophrenia (n = 25), bipolar I disorder (n = 20), and other psychoses (n = 25). Regional GM volumes of each patient subgroup were compared with those of the control group.ResultsA follow-up diagnosis of schizophrenia was associated with GM volume deficits in the left medial and left middle frontal gyrus; bipolar I disorder was related to a GM volume deficit in the left medial frontal gyrus; and not having a follow-up diagnosis of schizophrenia or bipolar disorder was associated with smaller bilateral GM volumes in the insula and right middle occipital gyrus.ConclusionsLeft medial frontal GM volume deficits were common in the groups with schizophrenia and bipolar I disorder, which may point to shared underlying pathological findings.     

Structural brain MRI abnormalities in pediatric patients with migraine

Morphometric MRI studies in adult patients with migraine have consistently demonstrated atrophy of several gray matter (GM) regions involved in pain processing. We explored the regional distribution of GM and white matter (WM) abnormalities in pediatric patients with episodic migraine and their correlations with disease clinical manifestations. Using a 3.0 T scanner, brain T2-weighted and 3D T1-weighted scans were acquired from 12 pediatric migraine patients and 15 age-matched healthy controls. GM and WM volumetric abnormalities were estimated using voxel-based morphometry (p < 0.05, family-wise error corrected). Compared to controls, pediatric migraine patients experienced a significant GM atrophy of several regions of the frontal and temporal lobes which are part of the pain-processing network. They also had an increased volume of the right putamen. The left fusiform gyrus had an increased volume in patients with aura compared to patients without aura and controls, whereas it was significantly atrophied in patients without aura when compared to the other two groups. No abnormalities of WM volume were detected. In migraine patients, regional GM atrophy was not correlated with disease duration and attack frequency, whereas a negative correlation was found between increased volume of the putamen and disease duration (r = ?0.95, p < 0.05). These results show that GM morphometric abnormalities do occur in pediatric patients with migraine. The presence of such abnormalities early in the disease course, and the absence of correlation with patient clinical characteristics suggest that they may represent a phenotypic biomarker of this condition.     

Temporal lobe changes in early,untreated Parkinson's disease

The purpose of this study was to determine if focal cortical abnormalities may occur in early Parkinson's disease (PD). We studied 26 untreated patients with early PD and 14 healthy control subjects, with cognitive screening and magnetic resonance imaging (MRI). Voxel‐based morphometry was used to assess for the presence of localized cortical grey matter (GM) and/or subcortical white matter (WM) changes. Patient and control groups showed no differences in age or gender distribution. Females had a greater GM% than males (P = 0.001). Comparison of patients and controls revealed no difference in local GM volumes. In PD, however, there was decreased WM volume in the anterior right fusiform gyrus and superior temporal gyrus. There were no correlations between the California Verbal Learning Test long delay free recall, Judgment of Line Orientation, Trail Making A or B and either the GM or WM localized volumes. These results suggest that right anterior temporal lobe changes occur in untreated patients with PD. The earliest changes may occur in subcortical white matter rather than temporal cortex. © 2009 Movement Disorder Society     

Voxel-based morphometry study of brain volumetry and diffusivity in amyotrophic lateral sclerosis patients with mild disability

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive and simultaneous degeneration of upper and lower motor neurons. The pathological process associated to ALS, albeit more pronounced in the motor/premotor cortices and along the corticospinal tracts (CST), does not spare extra-motor brain gray (GM) and white (WM) matter structures. However, it remains unclear whether such extra-motor cerebral abnormalities occur with mildly disabling disease, and how irreversible tissue loss and intrinsic tissue damage are interrelated. To this end, we used an optimized version of voxel-based morphometry (VBM) analysis to investigate the patterns of regional GM density changes and to quantify GM and WM diffusivity alterations of the entire brain from mildly disabled patients with ALS. A high-resolution T1-weighted 3D magnetization-prepared rapid acquisition gradient echo and a pulsed gradient spin-echo single shot echo-planar sequence of the brain were acquired from 25 mildly disabled patients with ALS and 18 matched healthy controls. An analysis of covariance was used to compare volumetry and diffusivity measurements between patients and controls. Compared with controls, ALS patients had significant clusters of locally reduced GM density (P < 0.001) in the right premotor cortex, left inferior frontal gyrus (IFG), and superior temporal gyrus (STG), bilaterally. In ALS patients contrasted to controls, we also found significant clusters of locally increased MD (P < 0.001) in the splenium of the corpus callosum and in the WM adjacent to the IFG, STG, and middle temporal gyrus (MTG) of the right hemisphere, and in the WM adjacent to the MTG and lingual gyrus in the left hemisphere. Compared with controls, ALS patients also had significant clusters of locally decreased FA values (P < 0.001) in the CST in the midbrain and corpus callosum, bilaterally. This study supports the notion that ALS is a multisystem disorder and suggests that extra-motor involvement may be an early feature of the disease.     

Voxel-based morphometric study of brain volume changes in patients with Alzheimer’s disease assessed according to the Clinical Dementia Rating score

We evaluated the volume reduction of gray matter (GM) and white matter (WM) in patients with an Alzheimer’s disease (AD) assessment based on the Clinical Dementia Rating (CDR) score. Patients with AD (n = 61), with no subcortical WM ischemia, and healthy control patients (n = 33) underwent T1-weighted spoiled gradient echo sequences, which were analyzed using voxel-based morphometry. Global GM volume reduction was observed in patients with a CDR score of 1 or a CDR score of 2, and WM volume reduction was observed in patients with a CDR score of 2. Regional GM volume reduction was found in the right inferior frontal gyrus, bilateral dorso-lateral and medial temporal lobes; WM volume reduction was found in the bilateral temporal subcortex (family-wise error, p < 0.01). A CDR score of 0.5 was associated with volume reduction in the left olfactory gyrus. The peak z-score and spatial extent of volume reduction increased with increasing CDR score and were higher on the left side. GM volume reduction increased with increasing CDR scores and suggests a possible pathomechanism of AD.     

Neuroanatomical correlates of depression and apathy in Parkinson's disease: magnetic resonance imaging studies

Depression and apathy are among the most common neuropsychiatric disturbances in Parkinson's disease (PD), and among the most important factors associated with a poor quality of life. However, their neural bases remain unclear. The results of the magnetic resonance imaging (MRI) studies on depression in PD differ dramatically. Some of them proposed a role of morphologic changes in the mediodorsal thalamus. In contrast to previous voxel-based morphometry (VBM) data, our study did not confirm a decrease in gray matter (GM) density in any brain region of depressed PD patients. Instead, a more severe white matter (WM) loss in the right frontal lobe was found, including the anterior cingulate bundle and the inferior orbitofrontal (OF) region. We suggested that the negative correlation between the severity of depression and WM density in the right OF region reinforces the hypothesis of depression in PD as a "disconnection syndrome". Only one MRI study using VBM found that high apathy scores correlated with low GM density values in the right (posterior) cingulate gyrus and the bilateral inferior frontal gyrus, in line with the findings in Alzheimer's disease and elderly adults with major depression.     

Evidence of white matter changes on diffusion tensor imaging in frontotemporal dementia

BACKGROUND: Two major clinical variants of frontotemporal dementia (FTD) have been described: frontal variant (fvFTD) and temporal variant (tvFTD). OBJECTIVE: To analyze white matter (WM) and gray matter (GM) tissue organization in patients with fvFTD and tvFTD by means of diffusion tensor imaging and voxel-based morphometry, and the correlations with neuropsychological and behavioral variables. DESIGN AND SETTING: Frontotemporal dementia clinic-based cohort and structural magnetic resonance imaging acquisition for voxel-based morphometry and diffusion tensor imaging measurements. Abnormalities were detected by a comparison with healthy control subjects. These variables were also correlated with clinical scores. Patients Thirty-six patients (28 with fvFTD and 8 with tvFTD) in early disease stage and 23 healthy controls who underwent standardized clinical and neuropsychological evaluation and magnetic resonance imaging. INTERVENTIONS: Diffusion tensor imaging and voxel-based morphometry. MAIN OUTCOME MEASURES: Neuroimaging analyses resulted in localized GM atrophy and reductions of white matter densities; the latter correlated with behavioral scores. RESULTS: Voxel-based morphometry analysis showed separate patterns of GM atrophy in the 2 groups. Diffusion tensor imaging showed different WM reduction patterns in patients with fvFTD and tvFTD. The fvFTD group showed a selective WM reduction in the superior longitudinal fasciculus, interconnecting the frontal and occipital and the temporal and parietal regions. Conversely, patients with tvFTD were characterized by WM reductions in the inferior longitudinal fasciculus, which affected the connections between anterior temporal and frontal regions. The WM reductions in fvFTD paralleled both behavioral disturbances measured by Frontal Behavioral Inventory and neuropsychological deficits affecting frontal functions. CONCLUSIONS: The fvFTD and tvFTD variants are associated not only with selective local GM reductions but also with significant WM damage in early disease phase. The different WM patterns contribute to the different clinical syndromes in FTD and could be responsible for the further progression of atrophy in the later disease stages.     

MRI brain volume abnormalities in young, nonpsychotic relatives of schizophrenia probands are associated with subsequent prodromal symptoms

Schizophrenia is characterized by subtle but well-replicated total and regional (frontal and temporal) brain tissue volume deficits. Studies of individuals at-risk for developing schizophrenia suggest that the onset of brain volume decrement may closely pre-date overt manifestations of schizophrenia, making brain volume abnormalities potential predictors for early identification. In an ongoing longitudinal morphometric MRI study of young, nonpsychotic first- or second-degree relatives of schizophrenia probands, we compared brain volumes in 46 relatives who are still within age range for developing schizophrenia against comparison groups of 46 schizophrenia patients and 46 healthy volunteers without family history of schizophrenia. Relatives had similar brain volume abnormalities as schizophrenia patients albeit less severe. Relatives had significantly larger whole brain, frontal, temporal and parietal gray matter (GM) volumes than patients. Relatives also had significantly smaller frontal GM volumes than healthy volunteers. Both relatives and patients had significantly larger whole brain WM (specifically parietal WM) volumes compared to healthy volunteers. Abnormally greater WM volumes in relatives and patients are suggestive of genetically-mediated dysmaturation of the age-expected myelination during adolescence through mid adulthood. On prodromal symptoms assessed in relatives one year after MRI brain scans, initial GM deficits as well as larger WM volumes correlated significantly with greater severity of subsequent prodromal symptoms. Together with previous genetic high-risk studies of adolescent or young adult relatives, these findings indicate that premorbid MRI brain abnormalities may be of predictive value for the early identification of schizophrenia.     

Putaminal gray matter volume decrease in panic disorder: an optimized voxel-based morphometry study

Our study aimed to identify gray matter volume differences between panic disorder patients and healthy volunteers using optimized voxel-based morphometry. Gray matter volume was compared between 18 panic subjects and 18 healthy volunteers. Panic disorder severity scale (PDSS) and Zung self-rating anxiety scale (Z-SAS) were administered. Gray matter volumes of bilateral putamen were decreased in panic subjects relative to healthy comparison subjects (corrected P < 0.05). Decreased gray matter volume was also observed in the right precuneus, right inferior temporal gyrus, right inferior frontal gyrus, left superior temporal gyrus, and left superior frontal gyrus at a less conservative level of significance. PDSS score negatively correlated with gray matter volume in the left putamen, right putamen, right inferior frontal gyrus, and left superior frontal gyrus in panic subjects. The duration of illness negatively correlated with left putaminal gray matter volume. There was also a negative correlation between gray matter volume in right putamen and Z-SAS score in panic subjects. The current study reports a putaminal gray matter volume decrease in panic subjects, which may be related to the clinical severity of panic disorder.     

Different gray matter patterns in chronic schizophrenia and chronic bipolar disorder patients identified using voxel-based morphometry

Gray matter (GM) volume deficits have been described in patients with schizophrenia (Sz) and bipolar disorder (BD), but to date, few studies have directly compared GM volumes between these syndromes with methods allowing for whole-brain comparisons. We have used structural magnetic resonance imaging (MRI) and voxel-based morphometry (VBM) to compare GM volumes between 38 Sz and 19 BD chronic patients. We also included 24 healthy controls. The results revealed a widespread cortical (dorsolateral and medial prefrontal and precentral) and cerebellar deficit as well as GM deficits in putamen and thalamus in Sz when compared to BD patients. Besides, a subcortical GM deficit was shown by Sz and BD groups when compared to the healthy controls, although a putaminal reduction was only evident in the Sz patients. In this comparison, the BD patients showed a limited cortical and subcortical GM deficit. These results support a partly different pattern of GM deficits associated to chronic Sz and chronic BD, with some degree of overlapping.     

Frontal lobe gray matter density decreases in bipolar I disorder.

BACKGROUND: This study was conducted to explore differences in gray and white matter density between bipolar and healthy comparison groups using voxel-based morphometry (VBM). METHODS: Brain magnetic resonance imaging was performed for 39 subjects with bipolar I disorder and 43 comparison subjects. Images were registered into a proportional stereotaxic space and segmented into gray matter, white mater, and cerebrospinal fluid. Statistical parametric mapping was used to calculate differences in gray and white matter density between groups. RESULTS: Bipolar subjects had decreased gray matter density in left anterior cingulate gyrus (Brodmann's area [BA] 32, 7.3% decrease), an adjacent left medial frontal gyrus (BA 10, 6.9% decrease), right inferior frontal gyrus (BA 47, 9.2% decrease), and right precentral gyrus (BA 44, 6.2% decrease), relative to comparison subjects. CONCLUSIONS: The observation of a gray matter density decrease in the left anterior cingulate, which processes emotions, in bipolar subjects is consistent with prior reports that used region-of-interest analytic methods. Decreased gray matter density in the right inferior frontal gyrus, which processes nonverbal and intrinsic functions, supports nondominant hemisphere dysfunction as a component of bipolar disorder.