Increased cortico-subcortical functional connectivity in schizophrenia

It has been widely reported that structural and functional connectivities are disturbed in cortical networks in schizophrenia (SZ). However, much less is known about the structural and functional connectivities between cortical and subcortical regions in SZ. Here, diffusion tensor imaging (DTI) data was used to identify consistent cortico-subcortical structural connection patterns across SZ patients and controls, and thus 13 common cortical Regions of Interest (ROIs) were determined. DTI and resting state fMRI (R-fMRI) datasets were used to assess the structural and functional connectivities between the 13 cortical ROIs and 12 subcortical regions in 8 SZ patients and 10 normal controls. It was found that there are significantly increased functional connectivities for 7 cortico-subcortical connections between the 13 cortical ROIs and 12 subcortical regions. Among most of these connections, the functional connectivity strength was doubled in SZ in comparison to controls. The cortical ROIs with functional hyper-connectivities to subcortical regions are localized in frontal and parietal lobes. However, no significant difference in the structural connectivity between these cortical and subcortical regions was found between SZ and controls. Additional analysis results showed 4 significantly increased and 2 significantly decreased cortico-cortical connections. Our study results suggest the functional hyper-connectivity between cortical and subcortical regions, adding further evidence to literature findings that SZ is a disorder of connectivity between components of large-scale brain networks. The result of either increased or decreased functional connectivities among cortical ROIs exhibits the complex pattern of disturbance of brain networks in SZ.     

Disturbed Functional Connectivity of Cortical Activation during Semantic Discrimination in Patients with Schizophrenia and Subjects at Genetic High-risk

Schizophrenia has a strong genetic component that is relevant to the understanding of the pathophysiology of the syndrome. Thus, recent investigations have shifted from studies of diagnosed patients with schizophrenia to examining their unaffected relatives. Previous studies found that during language processing, relatives thought to be at genetic high-risk for the disorder exhibit aberrant functional activation in regions of language processing, specifically in the left inferior frontal gyrus (Broca’s area). However, functional connectivity among the regions involved in language pathways is not well understood. In this study, we examined the functional connectivity between a seed located in Broca’s area and the remainder of the brain during a visual lexical decision task, in 20 schizophrenia patients, 21 subjects at genetic high risk for the disorder and 21 healthy controls. Both the high-risk subjects and patients showed significantly reduced activation correlations between seed and regions related to visual language processing. Compared to the high-risk subjects, the schizophrenia patients showed even fewer regions that were correlated with the seed regions. These results suggest that there is aberrant functional connectivity within cortical language circuitry in high-risk subjects and patients with schizophrenia. Broca’s area, which is one of the important regions for language processing in healthy controls, had a significantly reduced role in the high-risk subjects and patients with schizophrenia. Our findings are consistent with the existence of an underlying biological disturbance that begins in genetically at risk individuals and progresses to a greater extent in those who eventually develop schizophrenia.     

DTNBP1 is associated with imaging phenotypes in schizophrenia

Dystrobrevin binding protein 1 (DTNBP1) has been identified as putative schizophrenia susceptibility gene, but it remains unknown whether polymorphisms relate to altered cerebral structure. We examined relationships between a previously implicated DTNBP1 risk variant [P1578] and global and segmented brain tissue volumes and regional cortical thickness in schizophrenia (n = 62; 24 risk carriers) and healthy subjects (n = 42; 11 risk carriers), across ethnic groups and within Caucasians. Schizophrenia patients showed similar brain volumes, but significantly reduced brain‐size adjusted gray matter and CSF volumes and cortical thinning in a widespread neocortical distribution compared to controls. DTNBP1 risk was found associated with reduced brain volume, but not with tissue sub‐compartments. Cortical thickness, which was weakly associated with brain size, showed regional variations in association with genetic risk, although effects were dominated by highly significant genotype by diagnosis interactions over broad areas of cortex. Risk status was found associated with regional cortical thinning in patients, particularly in temporal networks, but with thickness increases in controls. DTNBP1 effects for brain volume and cortical thickness appear driven by different neurobiological processes. Smaller brain volumes observed in risk carriers may relate to previously reported DTNBP1/cognitive function relationships irrespective of diagnosis. Regional cortical thinning in patient, but not in control risk carriers, may suggest that DTNBP1 interacts with other schizophrenia‐related risk factors to affect laminar thickness. Alternatively, DTNBP1 may influence neural processes for which individuals with thicker cortex are less vulnerable. Although DTNBP1 relates to cortical thinning in schizophrenia, morphological changes in the disorder are influenced by additional genetic and/or environmental factors. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.     

Focal and global brain measurements in siblings of patients with schizophrenia

Background: It remains unclear whether structural brain abnormalities in schizophrenia are caused by genetic and/or disease-related factors. Structural brain abnormalities have been found in nonpsychotic first-degree relatives of patients with schizophrenia, but results are inconclusive. This large magnetic resonance imaging study examined brain structures in patients with schizophrenia, their nonpsychotic siblings, and healthy control subjects using global and focal brain measurements. Methods: From 155 patients with schizophrenia, their 186 nonpsychotic siblings, and 122 healthy controls (including 25 sibling pairs), whole-brain scans were obtained. Segmentations of total brain, gray matter (GM), and white matter of the cerebrum, lateral and third ventricle, and cerebellum volumes were obtained. For each subject, measures of cortical thickness and GM density maps were estimated. Group differences in volumes, cortical thickness, and GM density were analyzed using Structural Equation Modeling, hence controlling for familial dependency of the data. Results: Patients with schizophrenia, but not their nonpsychotic siblings, showed volumetric differences, cortical thinning, and reduced GM density as compared with control subjects. Conclusions: This study did not reveal structural brain abnormalities in nonpsychotic siblings of patients with schizophrenia compared with healthy control subjects using multiple imaging methods. Therefore, the structural brain abnormalities observed in patients with schizophrenia are for the largest part explained by disease-related factors.     

fMRI study of language activation in schizophrenia, schizoaffective disorder and in individuals genetically at high risk

BACKGROUND: Structural and functional abnormalities have been found in language-related brain regions in patients with schizophrenia. We previously reported findings pointing to differences in word processing between people with schizophrenia and individuals who are at high-risk for schizophrenia using a voxel-based (whole brain) fMRI approach. We now extend this finding to specifically examine functional activity in three language related cortical regions using a larger cohort of individuals. METHOD: A visual lexical discrimination task was performed by 36 controls, 21 subjects at high genetic-risk for schizophrenia, and 20 patients with schizophrenia during blood oxygenation level dependent (BOLD) fMRI scanning. Activation in bilateral inferior frontal gyri (Brodmann's area 44-45), bilateral inferior parietal lobe (Brodmann's area 39-40), and bilateral superior temporal gyri (Brodmann's area 22) was investigated. For all subjects, two-tailed Pearson correlations were calculated between the computed laterality index and a series of cognitive test scores determining language functioning. RESULTS: Regional activation in Brodmann's area 44-45 was left lateralized in normal controls, while high-risk subjects and patients with schizophrenia or schizoaffective disorder showed more bilateral activation. No significant differences among the three diagnostic groups in the other two regions of interest (Brodmann's area 22 or areas 39-40) were found. Furthermore, the apparent reasons for loss of leftward language lateralization differed between groups. In high-risk subjects, the loss of lateralization was based on reduced left hemisphere activation, while in the patient group, it was due to increased right side activation. Language ability related cognitive scores were positively correlations with the laterality indices obtained from Brodmann's areas 44-45 in the high-risk group, and with the laterality indices from Brodmann's areas 22 and 44-45 in the patient group. CONCLUSIONS: This study reinforces previous language related imaging studies in high-risk subjects and patients with schizophrenia suggesting that reduced functional lateralization in language related frontal cortex may be a vulnerability marker for schizophrenia. Future studies will determine whether it is predictive of who develops illness.     

Regionally localized thinning of the cerebral cortex in schizophrenia

BACKGROUND: Schizophrenia is characterized by small reductions in cortical gray matter volume, particularly in the temporal and prefrontal cortices. The question of whether cortical thickness is reduced in schizophrenia has not been addressed using magnetic resonance imaging (MRI) techniques. Our objectives were to test the hypothesis that cortical thinning in patients with schizophrenia (relative to control subjects) is greater in temporal and prefrontal regions of interest (ROIs) than in control ROIs (superior parietal, calcarine, postcentral, central, and precentral cortices), and to obtain an unbiased estimate of the distribution of cortical thinning in patients (relative to controls) by constructing mean and statistical cortical thickness difference maps. METHODS: Participants included 33 right-handed outpatients receiving medication and meeting DSM-IV criteria for schizophrenia and 32 healthy volunteers, matched on age and parental socioeconomic status. After high-resolution MRI scans, models of the gray-white and pial surfaces were generated for each individual's cortex, and the distance between these 2 surfaces was used to compute cortical thickness. A surface-based averaging technique that aligned the main cortical folds across individuals allowed between-group comparisons of thickness within ROIs, and at multiple, uniformly sampled loci across the cortical ribbon. RESULTS: Relative to controls, patients showed greater cortical thinning in temporal-prefrontal ROIs than in control ROIs, as revealed by a significant (P<.009) interaction between group and region type. Cortical thickness difference maps revealed significant (at P<.05, corrected) thinning within the orbitofrontal cortices bilaterally; the inferior frontal, inferior temporal, and occipitotemporal cortices on the left; and within the medial temporal and medial frontal cortices on the right. Superior parietal and primary somatosensory and motor cortices were relatively spared, even at subthreshold significance levels. CONCLUSIONS: Patients with chronic schizophrenia showed widespread cortical thinning that particularly affected the prefrontal and temporal cortices. This thinning might reflect underlying neuropathological abnormalities in cortical structure.     

Global Association Between Cortical Thinning and White Matter Integrity Reduction in Schizophrenia

Previous neuroimaging studies have revealed that both gray matter (GM) and white matter (WM) are altered in several morphological aspects in schizophrenia patients. Although several studies reported associations between GM and WM alterations in restricted regions, the existence of a global association between GM and WM pathologies is unknown. Considering the wide distribution of GM morphological changes and the profound genetic background of WM abnormalities, it would be natural to postulate a global association between pathologies of GM and WM in schizophrenia. In this investigation, we studied 35 schizophrenia patients and 35 healthy control subjects using T1-weighted magnetic resonance imaging and diffusion tensor imaging (DTI) and investigated the association between GM thickness and WM fractional anisotropy (FA) as a proxy of pathology in each tissue. To investigate cortical thickness, surface-based analysis was used. The mean cortical thickness for the whole brain was computed for each hemisphere, and group comparisons were performed. For DTI data, mean FA for the whole brain was calculated, and group comparisons were performed. Subsequently, the correlation between mean cortical thickness and mean FA was investigated. Results showed that the mean cortical thickness was significantly thinner, and the mean FA was significantly lower in schizophrenia patients. Only in the patient group the mean cortical thickness and mean FA showed significant positive correlations in both hemispheres. This correlation remained significant even after controlling for demographic and clinical variables. Thus, our results indicate that the GM and WM pathologies of schizophrenia are intertwined at the global level.Key words: schizophrenia, white matter integrity, diffusion tensor imaging, cortical thickness, surface-based approach     

Reduced left angular gyrus volume in first-episode schizophrenia

OBJECTIVE: Research suggests that the normal left-greater-than-right angular gyrus volume asymmetry is reversed in chronic schizophrenia. The authors examined whether angular gyrus volume and asymmetry were abnormal in patients with first-episode schizophrenia. METHOD: Magnetic resonance imaging scans were obtained from 14 inpatients at their first hospitalization for psychosis and 14 normal comparison subjects. Manual editing was undertaken to delineate postcentral, supramarginal, and angular gyri gray matter volumes. RESULTS: Group comparisons revealed that the left angular gyrus gray matter volume in patients was 14.8% less than that of the normal subjects. None of the other regions measured showed significant group volume or asymmetry differences. CONCLUSIONS: Patients with new-onset schizophrenia showed smaller left angular gyrus volumes than normal subjects, consistent with other studies showing parietal lobe volume abnormalities in schizophrenia. Angular gyrus pathology in first-episode patients suggests that the angular gyrus may be a neuroanatomical substrate for the expression of schizophrenia.     

Brain cortical thickness and surface area correlates of neurocognitive performance in patients with schizophrenia, bipolar disorder, and healthy adults

Relationships between cortical brain structure and neurocognitive functioning have been reported in schizophrenia, but findings are inconclusive, and only a few studies in bipolar disorder have addressed this issue. This is the first study to directly compare relationships between cortical thickness and surface area with neurocognitive functioning in patients with schizophrenia (n = 117) and bipolar disorder (n = 121) and healthy controls (n = 192). MRI scans were obtained, and regional cortical thickness and surface area measurements were analyzed for relationships with test scores from 6 neurocognitive domains. In the combined sample, cortical thickness in the right rostral anterior cingulate was inversely related to working memory, and cortical surface area in four frontal and temporal regions were positively related to neurocognitive functioning. A positive relationship between left transverse temporal thickness and processing speed was specific to schizophrenia. A negative relationship between right temporal pole thickness and working memory was specific to bipolar disorder. In conclusion, significant cortical structure/function relationships were found in a large sample of healthy controls and patients with schizophrenia or bipolar disorder. The differences that were found between schizophrenia and bipolar may indicate differential relationship patterns in the two disorders, which may be of relevance for understanding the underlying pathophysiology.     

Voxel-based morphometry versus region of interest: a comparison of two methods for analyzing gray matter differences in schizophrenia

Many previous studies exploring cortical gray matter (GM) differences in schizophrenia have used "region of interest" (ROI) measurements to manually delineate GM volumes. Recently, some investigators have instead employed voxel-based morphometry (VBM), an automated whole-brain magnetic resonance image measurement technique. The purpose of the current study was to compare the above methods in calculating GM distributions in schizophrenia patients relative to matched controls. Using ROIs, Buchanan et al. (Buchanan, R.W., Francis, A., Arango, C., Miller, K., Lefkowitz, D.M., McMahon, R.P., Barta, P.E. and Pearlson, G.D., 2004. Morphometric assessment of the heteromodal association cortex in schizophrenia. Am J Psychiatry. 161 (2), 322-331.) found decreased dorsolateral prefrontal GM volume and altered symmetry of inferior parietal GM in schizophrenia patients. We hypothesized that VBM analyses of the same data would complement the ROI findings. As predicted, VBM analyses replicated results of less left inferior and right superior frontal cortical GM in schizophrenia. Additionally, VBM uncovered a significantly lower concentration of GM in the middle and superior temporal gyri, sought but not detected using ROIs, but did not replicate the parietal changes. The principal explanation for these differences may be the methodological differences between voxel-averaged, landmark-based ROI analyses and the single, voxel-by-voxel whole brain VBM measurements. Although VBM is rapid and fully automated, it is not a replacement for manual ROI-based analyses. Both methods provide different types of information and should thus be used in tandem.     

Medial temporal lobe in childhood-onset schizophrenia.

The majority of anatomic and neuroimaging studies in adult-onset schizophrenia demonstrate decreased volumes of the medial temporal lobe when compared with findings in normal individuals. The goal of this study was to investigate the hypothesis that subjects with childhood-onset schizophrenia would show decreased volumes of the medial temporal lobe when compared to normal children. Thirteen children meeting DSM-III-R criteria for schizophrenia (mean age 14.2+/-3.8 years) and 20 normal children (mean age 12.0+/-2.8 years) were investigated. MRI scans were performed on a 1.5-T GE Signa MR scanner using a coronal plane SPGR at 1.4-mm slice thickness. Volumes were assessed by manually tracing bilateral hippocampus, amygdala and temporal lobes. After adjustment for age and total brain volume, the amygdala was significantly larger in the schizophrenics than in the control subjects, and this volume increase was more pronounced on the left side. Hippocampus volumes did not differ significantly across groups. There was a nearly significant left-greater-than-right asymmetry of the amygdala in the schizophrenic group but not in the normal group. A nearly significant right-greater-than-left asymmetry was found in the anterior hippocampus for both schizophrenic and control groups. These findings are consistent with previous reports of at least initial sparing of temporal lobe regions in childhood-onset schizophrenia.     

Cortical Thickness Reduction in Individuals at Ultra-High-Risk for Psychosis

Although schizophrenia is characterized by gray matter (GM) abnormalities, particularly in the prefrontal and temporal cortices, it is unclear whether cerebral cortical GM is abnormal in individuals at ultra-high-risk (UHR) for psychosis. We addressed this issue by studying cortical thickness in this group with magnetic resonance imaging (MRI). We measured cortical thickness of 29 individuals with no family history of psychosis at UHR, 31 patients with schizophrenia, and 29 healthy matched control subjects using automated surface-based analysis of structural MRI data. Hemispheric mean and regional cortical thickness were significantly different according to the stage of the disease. Significant cortical differences across these 3 groups were found in the distributed area of cerebral cortices. UHR group showed significant cortical thinning in the prefrontal cortex, anterior cingulate cortex, inferior parietal cortex, parahippocampal cortex, and superior temporal gyrus compared with healthy control subjects. Significant cortical thinning in schizophrenia group relative to UHR group was found in all the regions described above in addition with posterior cingulate cortex, insular cortex, and precentral cortex. These changes were more pronounced in the schizophrenia group compared with the control subjects. These findings suggest that UHR is associated with cortical thinning in regions that correspond to the structural abnormalities found in schizophrenia. These structural abnormalities might reflect functional decline at the prodromal stage of schizophrenia, and there may be progressive thinning of GM cortex over time.     

Asymmetry of prefrontal cortical convolution complexity in males with attention-deficit/hyperactivity disorder using fractal information dimension

Background and purpose: Prefrontal cortex, known to be a crucial region for the function of attention, is generally thought to be largely associated with the pathogenesis of attention-deficit hyperactivity disorder (ADHD). Most previous structural imaging studies of ADHD reported abnormality of grey matter volume in prefrontal region. However, volume measure is affected by the size of the interrogated brain, which may cause the inconsistence of the volume based findings. The purpose of the current paper is to use a scale-free measure, fractal information dimension (FID), to assess the prefrontal cortical convolution complexity and asymmetry in ADHD patients. Methods: MRI scans from 12 boys with ADHD and 11 controls were carefully processed. Prefrontal cortex was outlined manually. FIDs of bilateral prefrontal cortical surface were examined in each case. Group differences of the bilateral prefrontal cortical convolution complexities and the asymmetry pattern were statistically tested. Results: We found a left-greater-than-right prefrontal cortical convolution complexity pattern in both groups. However, compared with healthy controls, the left prefrontal cortical convolution complexities of ADHD patients were significantly reduced, resulting in significant reduction of the normal left-greater-than-right cortical convolution complexity asymmetry pattern. Conclusion: This study confirms and extends the existing anatomical knowledge about the brains of people with ADHD. The cortical convolution analysis method may also be applied to quantitatively assess changes in other neuropsychiatric syndromes as well.     

Voxel-based morphometry of grey matter densities in subjects at high risk of schizophrenia

The grey matter (GM) segments from T1 structural magnetic resonance (MR) images of the brain in subjects at high risk of schizophrenia (n=146) were compared with normal control subjects (n=36) and first episode schizophrenic subjects (n=34) using automated voxel-based morphometry (VBM). The subjects were recruited for the Edinburgh High Risk Study (EHRS) and regional brain volumes had previously been measured using a semi-automated volumetric region of interest (ROI) method of analysis. For the current report, the images were processed using a study specific template and statistically analysed using the SPM99 program. The small volume correction tool in SPM was also used to restrict the analyses to specific voxels. Reductions in the probability of grey matter (GM) density were seen bilaterally in the anterior cingulate, and as a trend in the left parahippocampal gyrus for the high-risk vs. control subjects. In contrast, first episode schizophrenia subjects had less GM than high-risk subjects in several frontal and temporal regions. These results are compatible with the findings of our previous volumetric ROI analysis.     

Differences and similarities in insular and temporal pole MRI gray matter volume abnormalities in first-episode schizophrenia and affective psychosis

CONTEXT: Whether psychoses associated with schizophrenia and affective disorder represent manifestations of different disorders or the same disorder is an important but unresolved question in psychiatry. Results of previous volumetric magnetic resonance imaging investigations indicate that gray matter volume reductions in neocortical regions may be specific to schizophrenia. OBJECTIVE: To simultaneously evaluate multiple olfactocentric paralimbic regions, which play crucial roles in human emotion and motivation, in first-episode patients with schizophrenia and affective psychosis. DESIGN: A cross-sectional study using high-spatial resolution magnetic resonance imaging in patients with schizophrenia and affective psychosis at their first hospitalization. SETTING: Inpatient units at a private psychiatric hospital. PARTICIPANTS: Fifty-three first-episode patients, 27 with schizophrenia and 26 with affective (mainly manic) psychosis, and 29 control subjects. MAIN OUTCOME MEASURES: Using high-spatial resolution magnetic resonance imaging, the gray matter volumes of 2 olfactocentric paralimbic regions of interest, the insular cortex and the temporal pole, were evaluated. RESULTS: A bilateral volume reduction in insular cortex gray matter was specific to first-episode patients with schizophrenia. In contrast, both first-episode psychosis groups showed a volume reduction in left temporal pole gray matter and an absence of normal left-greater-than-right asymmetry. Region of interest correlations showed that only patients with schizophrenia lacked a positive correlation between left temporal pole and left anterior amygdala-hippocampal complex gray matter volumes, whereas both psychosis groups were similar in lacking normal positive correlations between left temporal pole and left anterior superior temporal gyrus gray matter volumes. CONCLUSIONS: These partially different and partially similar patterns of structural abnormalities in olfactocentric paralimbic regions and their associated abnormalities in other temporolimbic regions may be important factors in the differential and common manifestations of the 2 psychoses.     

Associations of cortical thickness and cognition in patients with schizophrenia and healthy controls

Previous studies have found varying relationships between cognitive functioning and brain volumes in patients with schizophrenia. However, cortical thickness may more closely reflect cytoarchitectural characteristics than gray matter density or volume estimates. Here, we aimed to compare associations between regional variation in cortical thickness and executive functions, memory, as well as verbal and spatial processing in patients with schizophrenia and healthy controls (HCs). We obtained magnetic resonance imaging and neuropsychological data for 131 patients and 138 matched controls. Automated cortical pattern matching methods allowed testing for associations with cortical thickness estimated as the shortest distance between the gray/white matter border and the pial surface at thousands of points across the entire cortical surface. Two independent measures of working memory showed robust associations with cortical thickness in lateral prefrontal cortex in HCs, whereas patients exhibited associations between working memory and cortical thickness in the right middle and superior temporal lobe. This study provides additional evidence for a disrupted structure-function relationship in schizophrenia. In line with the prefrontal inefficiency hypothesis, schizophrenia patients may engage a larger compensatory network of brain regions other than frontal cortex to recall and manipulate verbal material in working memory.     

Cerebral cortical thickness and a history of obstetric complications in schizophrenia

Introduction

Magnetic resonance imaging (MRI) studies have demonstrated that patients with schizophrenia have thinner brain cortices compared with healthy control subjects. Neurodevelopment is vulnerable to obstetric complications (OCs) such as hypoxia and birth trauma, factors that are also related to increased risk of developing schizophrenia. With the hypothesis that OCs might explain the thinner cortices found in schizophrenia, we studied patients with schizophrenia and healthy controls subjects for association between number and severity of OCs and variation in cortical thickness.

Methods

MRI scans of 54 adults with schizophrenia or schizoaffective disorder and 54 healthy controls were acquired at Karolinska Institutet, Stockholm, Sweden. Measures of brain cortical thickness were obtained using automated computer processing (FreeSurfer). OCs were assessed from obstetric records and scored blindly according to the McNeil–Sjöström scale. At numerous cortical locations, putative effects of OCs on cortical thickness variation were tested for each trimester, for labour, for composite OC scores, severe OC scores, and hypoxia scores among patients and controls separately.

Results

Number and severity of OCs varied among both patient and control subjects but were not associated with cortical thickness in either of the groups. Patients demonstrated thinner brain cortices but there were no significant differences in number and severity of OC scores across groups.

Conclusion

In the present study, number and severity of obstetric complications were not associated with brain cortical thickness, in patients with schizophrenia or in healthy control subjects. The thinner brain cortices found in patients with schizophrenia were not explained by a history of OCs.     

Abnormalities of the corpus callosum in non-psychotic high-risk offspring of schizophrenia patients

Alterations in the structure of the corpus callosum (CC) have been observed in schizophrenia. Offspring of schizophrenia parents have 10-15 times higher risk for developing schizophrenia. We examined CC volume in offspring at genetic high-risk (HR) subjects. Since the sub-regions of the CC are topographically mapped to cortical brain regions, we hypothesized that HR subjects may show a decrement in total volume and differential volume decreases in sub-regions of the CC. The offspring of schizophrenia parents (HR; n = 70; 36 males) and healthy volunteers with no family or personal history of psychotic disorders (healthy controls (HC); n = 73; 37 males) matched for age, gender and education were selected for the study. Magnetic resonance images were collected using a GE 1.5 T scanner and processed using FreeSurfer image analysis software. The CC was divided into five neuroanatomically based partitions. The volume of total CC and the five sub-regions were measured blind to clinical information. With covariation for intracranial volume, HR subjects had significantly reduced total CC, more prominently observed in the anterior splenium. An age-related increase in CC volume was found in the anterior and posterior splenium of healthy controls but not in HR subjects. The volume reduction was greater in male than female HR subjects. The volume reduction in the CC may reflect a reduction in axonal fibers crossing the hemispheres and/or myelination between the left and right temporo-parietal cortices. The absence of an age-related volume increase suggests an abnormal developmental trajectory that may underlie susceptibility to schizophrenia.     

Alterations in functional activation in euthymic bipolar disorder and schizophrenia during a working memory task

Dysfunctions in prefrontal cortical networks are thought to underlie working memory (WM) impairments consistently observed in both subjects with bipolar disorder and schizophrenia. It remains unclear, however, whether patterns of WM‐related hemodynamic responses are similar in bipolar and schizophrenia subjects compared to controls. We used fMRI to investigate differences in blood oxygen level dependent activation during a WM task in 21 patients with euthymic bipolar I, 20 patients with schizophrenia, and 38 healthy controls. Subjects were presented with four stimuli (abstract designs) followed by a fifth stimulus and required to recall whether the last stimulus was among the four presented previously. Task‐related brain activity was compared within and across groups. All groups activated prefrontal cortex (PFC), primary and supplementary motor cortex, and visual cortex during the WM task. There were no significant differences in PFC activation between controls and euthymic bipolar subjects, but controls exhibited significantly increased activation (cluster‐corrected P < 0.05) compared to patients with schizophrenia in prefrontal regions including dorsolateral prefrontal cortex (DLPFC). Although the bipolar group exhibited intermediate percent signal change in a functionally defined DLPFC region of interest with respect to the schizophrenia and control groups, effects remained significant only between patients with schizophrenia and controls. Schizophrenia and bipolar disorder may share some behavioral, diagnostic, and genetic features. Differences in the patterns of WM‐related brain activity across groups, however, suggest some diagnostic specificity. Both patient groups showed some regional task‐related hypoactivation compared to controls across the brain. Within DLPFC specifically, patients with schizophrenia exhibited more severe WM‐related dysfunction than bipolar subjects. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.     

Alterations of whole-brain cortical area and thickness in mild cognitive impairment and Alzheimer's disease

Gray matter volume and density of several brain regions, determined by magnetic resonance imaging (MRI), are decreased in Alzheimer's disease (AD). Animal studies have indicated that changes in cortical area size is relevant to thinking and behavior, but alterations of cortical area and thickness in the brains of individuals with AD or its likely precursor, mild cognitive impairment (MCI), have not been reported. In this study, 25 MCI subjects, 30 AD subjects, and 30 age-matched normal controls were recruited for brain MRI scans and Functional Activities Questionnaire (FAQ) assessments. Based on the model using FreeSurfer software, two brain lobes were divided into various regions according to the Desikan-Killiany atlas and the cortical area and thickness of every region was compared and analyzed. We found a significant increase in cortical area of several regions in the frontal and temporal cortices, which correlated negatively with MMSE scores, and a significant decrease in cortical area of several regions in the parietal cortex and the cingulate gyrus in AD subjects. Increased cortical area was also seen in some regions of the frontal and temporal cortices in MCI subjects, whereas the cortical thickness of the same regions was decreased. Our observations suggest characteristic differences of the cortical area and thickness in MCI, AD, and normal control subjects, and these changes may help diagnose both MCI and AD.