Spectral decomposition of resting state electroencephalogram reveals unique theta/alpha activity in schizophrenia.

Resting state electroencephalographic (EEG) activity in schizophrenia (SZ) is frequently characterised by increased power at slow frequencies and/or a reduction of peak alpha frequency. Here we investigated the nature of these effects. As most studies to date have been limited by reliance on a priori frequency bands which impose an assumed structure on the data, we performed a data-driven analysis of resting EEG recorded in SZ patients and healthy controls (HC). The sample consisted of 39 chronic SZ and 36 matched HC. The EEG was recorded with a dense electrode array. Power spectral densities were decomposed via Varimax-rotated principal component analysis (PCA) over all participants and for each group separately. Spectral PCA was repeated at the cortical level on cortical current source density computed from standardised low resolution brain electromagnetic tomography. There was a trend for power in the theta/alpha range to be increased in SZ compared to HC, and peak alpha frequency was significantly reduced in SZ. PCA revealed that this frequency shift was because of the presence of a spectral component in the theta/alpha range (6-9 Hz) that was unique to SZ. The source distribution of the SZ > HC theta/alpha effect involved mainly prefrontal and parahippocampal areas. Abnormal low frequency resting EEG activity in SZ was accounted for by a unique theta/alpha oscillation. Other reports have described a similar phenomenon suggesting that the neural circuits oscillating in this range are relevant to SZ pathophysiology.

Exploring cultural contributions to the neuropsychology of social cognition: the advanced clinical solutions.

INTRODUCTION: Culture and social cognition are deeply intertwined, yet how this rich intersectionality is expressed neuropsychologically remains an important question. METHOD: In a convenience sample of 128 young adults (mean age = 24.9 years) recruited from a majority-minority urban university, we examined performance-based neuropsychological measures of social cognition, the Advanced Clinical Solutions-Social Perception (ACS-SP), in relation to both cultural orientation, as assessed by the Individualism-Collectivism Scale (ICS) and spoken English language, as assessed by the oral word pronunciation measure of the Wide Range Achievement Test-4 (WRAT4). RESULTS: Results indicated higher WRAT4 scores correlated with better performance across all ACS-SP measures of social cognition. Controlling for these associations in spoken English, partial correlations linked lower scores across both prosody interpretation and affect naming ACS-SP tasks with a propensity to view social relationships vertically, irrespective of individualistic or collectivistic orientations. Hierarchical regression results showed that cultural orientation and English-language familiarity each specifically and uniquely contributed to ACS-SP performance for matching prosody with facial expressions. CONCLUSIONS: These findings underscore the importance of incorporating and prioritizing both language and cultural factors in neuropsychological studies of social cognition. They may be viewed as offering strong support for expanding the boundaries of the construct of social cognition beyond its current theoretical framework of one that privileges Western, educated, industralized, rich and democratic (WEIRD) values, customs, and epistemologies.

College student mental health: Psychiatric risk and psychological wellbeing.

OBJECTIVE: To examine both psychiatric risk and psychological wellbeing in a college student sample drawn from a majority-minority university. PARTICIPANTS: 100 participants (42% White; 70 females), mean age, 21.22 years. METHODS: Univariate and multivariate analyses examined the relationship of psychiatric risk (Brief Symptom Inventory; BSI) and psychological wellbeing (Mental Health Continuum-Short Form; MHC-SF) with student stress, cognition, Adverse Childhood Experiences (ACEs) and a new Positive Childhood Experiences (PCEs) scale. RESULTS: Risk correlated with increased student stress, higher ACEs and lower PCEs, whereas wellbeing correlated with lower student stress, better neuropsychological functioning, lower ACE and increased PCEs. PCEs predicted enhanced MHC-SF wellbeing and reduced BSI risk, accounting for 22.4% and 13.7% of variance in these measures, respectively. ACEs predicted elevated BSI risk and diminished MHC-SF wellbeing accounting for 8.6% and 5.9% of variance in these measures, respectively. CONCLUSION: College student mental health may benefit from practices aim specifically to enhance wellbeing, stress-resistance, and cognition.

Towards a Heuristic Neuropsychological Model of Adjudicative Competency.

This study sought to delineate the neuropsychological processes that undergird the psycho-legal concept of competency to stand trial (CST). Accordingly, we retrospectively examined the relationship between clinical judgments of competence or incompetence of defendants committed to a maximum-security psychiatric facility and neuropsychological measures of cognitive and social intelligence and declarative memory. Results indicated that both groups (competent and incompetent) showed similar levels of depressed cognitive intelligence with Wechsler full-scale IQ levels falling in the upper end of the borderline range. Compared with defendants clinically judged as incompetent, defendants recommended as competent scored significantly higher on measures of social intelligence and episodic memory, with the most pronounced advantage occurring on tests of verbal memory that place heavy demands on encoding, consolidation, and retrieval of aurally presented narrative material. Cognitive capacities in areas of social intelligence and episodic memory may play critical roles in developing a heuristic neuropsychological model of CST. The evaluation of these domains offers implications for the assessment, restoration, and understanding of CST.

Loosening of Associations in Chronic Schizophrenia: Intersectionality of Verbal Learning, Negative Symptoms, and Brain Structure.

In 1908, Bleuler proposed a unitary theory of schizophrenia, hypothesizing a "loosening of associations" as the central mechanism underlying disturbances in thinking, motivation, and affective expression. Here, we test Bleuler's model in an archival sample of 79 healthy controls and 76 patients with chronic schizophrenia who had completed neuropsychological tests, including a measure of learning of novel word pairs, which was specifically selected to probe the structure and formation of new verbal associations. The patients also had positive and negative symptoms ratings, including measures of flat affect, anhedonia, and thought disorder. A subset of patients and controls (n = 39) had available prior archival 3-T magnetic resonance imaging (MRI) measures of prefrontal cortex (PFC) gray matter volumes. In relation to controls, patients showed evidence of a selective impairment in associative learning, independent of their overall reduced neuropsychological functioning. This neuropsychological impairment, in turn, correlated significantly with overall levels of negative but not positive symptoms, with the data showing an especially strong contribution of flattened emotional expression to verbal associate learning deficits in this patient sample. Moreover, the archival MRI data were consistent with prior research pointing to an important role of the PFC in supporting verbal associate learning and memory in patients and controls. Taken together, the current results provided evidence of a selective impairment in schizophrenia on a PFC-supported verbal associate learning and memory task, which was accompanied by negative symptoms in general, and flattened emotional expression, in particular.

Brain structural abnormalities of the associative striatum in adolescents and young adults at genetic high-risk of schizophrenia: Implications for illness endophenotypes.

OBJECTIVE: Dysfunction in cortico-striatal circuitry represents a core component of the pathophysiology in schizophrenia (SZ) but its potential as a candidate endophenotype of the illness is often confounded by neuroleptic medication. METHODS: Accordingly, 26 adolescent and young adult participants at genetic high-risk for schizophrenia, but who were asymptomatic and neuroleptic naïve, and 28 age-matched controls underwent 1.5T structural magnetic resonance imaging of the striatum, manually parcellated into limbic (LST), associative (AST), and sensorimotor (SMST) functional subregions. RESULTS: In relation to their age peers, participants at genetic high-risk for schizophrenia showed overall lower striatal gray matter volume with their most pronounced loss, bilaterally in the AST, but not the LST or SMST. Neuropsychological testing revealed reduced executive functioning for genetically at-risk participants, although the groups did not differ significantly in overall intelligence or oral reading. For controls but not for at-genetic high-risk participants, stronger executive functioning correlated with increased bilateral AST volume. CONCLUSIONS: Reduced bilateral AST volume in genetic high-risk adolescents and young adults, accompanied by heritable loss of higher cognitive brain-behavior relationships, might serve as a useful endophenotype of SZ.

Psychiatric risk and resilience: Plasticity genes and positive mental health.

OBJECTIVE: The at-risk mental state (ARMS) for psychosis has long played a key role in diathesis-stress models of schizophrenia. More recent studies, however, have called for extending the boundaries of the ARMS construct beyond attenuated psychosis in nonhelp-seeking samples to include not only other vulnerability indicators but also protective factors related to genotype, mental health, personality, and cognition. METHOD: Accordingly, we assessed in a sample of 100 college students, the ARMS construct with the Brief Prodromal Questionnaire (PQ-B) for psychosis, in conjunction with measures of positive mental health, childhood adversity, psychiatric symptoms, personality traits, social cognition, and genetic variables derived from assays of the serotonin transporter (5-HTTLPR) and the brain-derived neurotrophic factor (BDNF). RESULTS: Higher PQ-B scores correlated positively with vulnerability indicators of childhood adversity and heightened levels of a wide variety of psychiatric symptoms but correlated negatively with protective factors of better overall mental health, social cognition as well as with a distinct NEO profile marked by reduced neuroticism and elevated agreeableness and conscientiousness. Multivariate analyses indicated that a composite ARMS measure comprised of PQ-B scores plus anxiety and depression symptoms revealed significant genotype differences, with lowest risk and highest resilience for allelic carriers of 5-HTTLPR-short and BDNF Met polymorphisms. CONCLUSIONS: Results provided support for extending the ARMS construct, pointing to important contributions of personality, social cognition, and genes that support neural plasticity in mitigating vulnerability and enhancing resilience and well-being.

In search of positive mental health: Personality profiles and genetic polymorphisms.

Individuals vary greatly in their mental health and these differences may play a critical role in stress resistance, risk reduction and illness recovery. Here we ask how these differences may be related to normal variation in personality and genotype. One hundred healthy college students completed measures of mental health (Mental Health Continuum-Short Form [MHC-SF]), personality (NEO Five Factor Inventory) and adverse childhood experiences. Participants also provided saliva samples, genotyped for both the serotonin transporter (5-HTTLPR) and the brain-derived neurotrophic factor (BDNF), each assayed for naturally occurring polymorphisms, 5-HTTLPR (short/long) and BDNF (valine/methionine). Mental health correlated strongly with the NEO triad of conscientiousness-extraversion-neuroticism, with largest contributions to MHC-SF scores for conscientiousness, followed by extraversion and then neuroticism. The personality trait interaction of extraversion × conscientiousness uniquely accounted for approximately 44.22% 44.62% of the variance in MHC-SF scores. Polygenic comparisons showed a significant gene × gene interaction, with highest mental health for 5-HTTLPR-S, Met carriers. Together these results provided support for distinct yet interacting roles of personality and genetics in the phenotypical expression of mental health.

Color Stroop and negative priming in schizophrenia: an fMRI study.

Disturbances in selective attention represent a core characteristic of schizophrenia, whose neural underpinnings have yet to be fully elucidated. Consequently, we recorded brain activation using functional magnetic resonance imaging (fMRI) while 15 patients with schizophrenia and 15 age-matched controls performed a well-established measure of selective attention-the color Stroop negative priming task. We focused on two aspects of performance: overriding pre-potent responses (Stroop effect) and inhibition of prior negatively primed trials (negative priming effect). Behaviorally, controls demonstrated both significant Stroop and negative priming effects, while schizophrenic subjects only showed the Stroop effect. For the Stroop effect, fMRI indicated significantly greater activation in frontal regions-medial frontal gyrus/anterior cingulate gyrus and middle frontal gyrus for controls-but greater activation in medial parietal regions (posterior cingulate gyrus/precuneus) for patients. Negative priming elicited significant activation in right dorsolateral prefrontal cortex for both groups, but also in left dorsolateral prefrontal cortex for patients. These different patterns of fMRI activation may reflect faulty interaction in schizophrenia within networks of brain regions that are vital to selective attention.

A diffusion tensor imaging study of the anterior limb of the internal capsule in schizophrenia.

Frontal-subcortical cognitive and limbic feedback loops modulate higher cognitive functioning. The final step in these feedback loops is the thalamo-cortical projection through the anterior limb of the internal capsule (AL-IC). Using diffusion tensor imaging (DTI), we evaluated abnormalities in the AL-IC fiber tract in schizophrenia. Participants comprised 16 chronic schizophrenia patients and 19 male, normal controls, who were group matched for handedness, age, and parental socioeconomic status, and underwent DTI on a 1.5 Tesla GE system. We measured the diffusion indices, fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD), and manually segmented, based on FA maps, AL-IC volume, normalized for intracranial contents (ICC). The results showed a significant reduction in the ICC-corrected volume of the AL-IC in schizophrenia, but did not show diffusion measure group differences in the AL-IC in FA, MD, RD or AD. In addition, in the schizophrenia patients, AL-IC FA correlated positively with performance on measures of spatial and verbal declarative/episodic memory, and right AL-IC ICC-corrected volume correlated positively with more perseverative responses on the Wisconsin Card Sort Test (WCST). We found a reduction in AL-IC ICC-corrected volume in schizophrenia, without FA, MD, RD or AD group differences, implicating the presence of a structural abnormality in schizophrenia in this subcortical white matter region which contains important cognitive, and limbic feedback pathways that modulate prefrontal cortical function. Despite not demonstrating a group difference in FA, we found that AL-IC FA was a good predictor of spatial and verbal declarative/episodic memory performance in schizophrenia.

IQ subtypes in schizophrenia: distinct symptom and neuropsychological profiles.

Intellectual decline, a key component of cognitive impairment in schizophrenia, varies considerably across individuals. To examine such cognitive heterogeneity, we applied cluster analysis of IQ and oral reading scores in 73 patients with schizophrenia. The following 3 empirically-derived subtypes emerged: intellectually compromised (42%) with similarly subaverage IQ (M = 79.90) and oral reading (M = 84.03); intellectually deteriorated (29%) with subaverage IQ (M = 86.81) but average oral reading (M = 107.71); and intellectually preserved (29%) with average IQ (M = 108.38) and oral reading (M = 104.43). Compromised and deteriorated clusters showed impairments in both executive function and memory, whereas the preserved cluster showed only reduced executive functioning. The 3 clusters also differed in symptom patterns; with intellectually compromised and intellectually deteriorated both rated with higher negative than positive symptoms, in contrast to the opposite pattern of intellectually preserved. Cluster symptom and neuropsychological profiles may help to validate empirically-derived IQ subtypes in schizophrenia.

Distinct contribution of working memory and social comprehension failures in neuropsychological impairment in schizophrenia.

Neuropsychological impairment represents a core characteristic of schizophrenia, but its underlying components have yet to be clearly established. Using a comprehensive battery of standardized measures of intelligence, declarative episodic memory, and executive function, we hypothesized that the variance in neuropsychological performance in schizophrenia may reflect at least 2 distinct sources related to failures of (a) the central executive division of working memory and (b) social comprehension. In comparison to age-matched controls, patients with schizophrenia showed not only overall reduced scores on Wechsler intelligence and memory scales and Wisconsin Card Sorting Test (WCST) of executive function, but they also demonstrated different patterns of performance for each of these tests. Hierarchical regression revealed executive attentional control, measured by Trails B performance speed, and social comprehension, measured by Wechsler IQ Comprehension and Picture Arrangement subtests, each accounted for a unique and specific proportion of variance in test scores for the patient group, even when controlling for general intelligence. Failures in social comprehension and executive attentional control may account for distinct sources of variance in the neuropsychological impairment of schizophrenia.

Orbitofrontal Sulcogyral Pattern as a Transdiagnostic Trait Marker of Early Neurodevelopment in the Social Brain.

Objective. To systematically assess previous findings on the orbitofrontal sulcogyral pattern in psychiatric disorders and to address the utility of this pattern as a transdiagnostic trait marker of early neurodevelopment in the social brain. Methods. An online literature search was conducted using the PubMed database from inception to August 2019. Studies included in this review were based on the Chiavaras's original classification method of this H-shaped sulcus (type I, II, and III), intermediate orbital sulcus (IOS), and posterior orbital sulcus (POS). Results. Twenty-six studies were included in the review. Sixteen studies (62%) focused on schizophrenia spectrum (Sz) disorders, and the remaining studies focused on autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), history of extremely preterm and extremely low birth weight, bipolar disorder (BD), panic disorder, obsessive-compulsive disorder, cannabis users, and pathological gambling. In Sz, compared with healthy controls, the orbitofrontal sulcogyral pattern was decreased in type I, increased in type II and III, and there were fewer numbers of IOS and POS reported, although specificity in sex and hemispheric dominance was not consistent. BD and neurodevelopmental disorders in ASD and ADHD showed a similar pattern of alteration to that observed in the Sz. Conclusions. The present review of the orbitofrontal sulcogyral pattern indicated that type I expression might reflect a neurodevelopmental protective marker, and type II and III expressions, as well as fewer numbers of IOS and POS, might reflect neurodevelopmental risk markers. These trait markers may be transdiagnostic among socially disabling diseases.

Faulty Executive Attention and Memory Interactions in Schizophrenia: Prefrontal Gray Matter Volume and Neuropsychological Impairment.

We hypothesized that neuropsychological disturbance in schizophrenia (SZ) may reflect faulty interactions of executive attention and episodic memory, emanating, in part, from reduced prefrontal cortex (PFC) gray matter volume. Participants with SZ (n = 84) and age-matched (n = 77) controls completed both the Wisconsin Card Sorting Test (WCST) and the Wechsler Memory Scale-Third Edition (WMS-III), used, respectively, as measures of executive attention and episodic memory. A subset of SZ (n = 27) and control (n = 17) groups also had available 3-T magnetic resonance imaging (MRI) studies of the PFC. For SZ, but not control groups, neuropsychological results indicated that executive attention interacted significantly with episodic memory, with failures of executive attention, as reflected by increased WCST perseverative errors, directly linked to poor performance on the WMS-III measure of delayed visual recall of action scenes. MRI results indicated reduced left PFC gray matter volume for SZ group, which in turn correlated significantly with their deficits in visual memory but not in executive attention. Results showed that 61% of the variance in neuropsychological performance in the SZ group was attributed to gray matter volume of left inferior prefrontal gyrus gray matter volume. PFC-mediated failure of executive attention-episodic memory interactions may represent an important mechanism in neuropsychological disturbance in SZ.

Auditory Cortex Volume and Gamma Oscillation Abnormalities in Schizophrenia.

We investigated whether the gray matter volume of primary auditory cortex (Heschl's gyrus [HG]) was associated with abnormal patterns of auditory γ activity in schizophrenia, namely impaired γ synchronization in the 40-Hz auditory steady-state response (ASSR) and increased spontaneous broadband γ power. (The γ data were previously reported in Hirano et al, JAMA Psychiatry, 2015;72:813-821). Participants were 24 healthy controls (HC) and 23 individuals with chronic schizophrenia (SZ). The ASSR was obtained from the electroencephalogram to click train stimulation at 20, 30, and 40 Hz rates. Dipole source localization of the ASSR was used to provide a spatial filter of auditory cortex activity, from which ASSR evoked power and phase locking factor (PLF), and induced γ power were computed. HG gray matter volume was derived from structural magnetic resonance imaging at 3 T with manually traced regions of interest. As expected, HG gray matter volume was reduced in SZ compared with HC. In SZ, left hemisphere ASSR PLF and induced γ power during the 40-Hz stimulation condition were positively and negatively correlated with left HG gray matter volume, respectively. These results provide evidence that cortical gray matter structure, possibly resulting from reduced synaptic connectivity at the microcircuit level, is related to impaired γ synchronization and increased spontaneous γ activity in schizophrenia.

Real-time fMRI feedback impacts brain activation, results in auditory hallucinations reduction: Part 1: Superior temporal gyrus -Preliminary evidence.

Auditory hallucinations (AH) are one of the core symptoms of schizophrenia (SZ) and constitute a significant source of suffering and disability. One third of SZ patients experience pharmacology-resistant AH, so an alternative/complementary treatment strategy is needed to alleviate this debilitating condition. In this study, real-time functional Magnetic Resonance Imaging neurofeedback (rt-fMRI NFB), a non-invasive technique, was used to teach 10 SZ patients with pharmacology-resistant AH to modulate their brain activity in the superior temporal gyrus (STG), a key area in the neurophysiology of AH. A functional task was designed in order to provide patients with a specific strategy to help them modify their brain activity in the desired direction. Specifically, they received neurofeedback from their own STG and were trained to upregulate it while listening to their own voice recording and downregulate it while ignoring a stranger's voice recording. This guided performance neurofeedback training resulted in a) a significant reduction in STG activation while ignoring a stranger's voice, and b) reductions in AH scores after the neurofeedback session. A single, 21-minute session of rt-fMRI NFB was enough to produce these effects, suggesting that this approach may be an efficient and clinically viable alternative for the treatment of pharmacology-resistant AH.

Miswiring of Frontostriatal Projections in Schizophrenia.

We investigated brain wiring in chronic schizophrenia and healthy controls in frontostriatal circuits using diffusion magnetic resonance imaging tractography in a novel way. We extracted diffusion streamlines in 27 chronic schizophrenia and 26 healthy controls connecting 4 frontal subregions to the striatum. We labeled the projection zone striatal surface voxels into 2 subtypes: dominant-input from a single cortical subregion, and, functionally integrative, with mixed-input from diverse cortical subregions. We showed: 1) a group difference for total striatal surface voxel number (P = .045) driven by fewer mixed-input voxels in the left (P  = .007), but not right, hemisphere; 2) a group by hemisphere interaction for the ratio quotient between voxel subtypes (P  = .04) with a left (P  = .006), but not right, hemisphere increase in schizophrenia, also reflecting fewer mixed-input voxels; and 3) fewer mixed-input voxel counts in schizophrenia (P  = .045) driven by differences in left hemisphere limbic (P  = .007) and associative (P  = .01), but not sensorimotor, striatum. These results demonstrate a less integrative pattern of frontostriatal structural connectivity in chronic schizophrenia. A diminished integrative pattern yields a less complex input pattern to the striatum from the cortex with less circuit integration at the level of the striatum. Further, as brain wiring occurs during early development, aberrant brain wiring could serve as a developmental biomarker for schizophrenia.

Real-time fMRI neurofeedback reduces auditory hallucinations and modulates resting state connectivity of involved brain regions: Part 2: Default mode network -preliminary evidence.

Auditory hallucinations (AHs) are one of the most distressing symptoms of schizophrenia (SZ) and are often resistant to medication. Imaging studies of individuals with SZ show hyperactivation of the default mode network (DMN) and the superior temporal gyrus (STG). Studies in SZ show DMN hyperconnectivity and reduced anticorrelation between DMN and the central executive network (CEN). DMN hyperconnectivity has been associated with positive symptoms such as AHs while reduced DMN anticorrelations with cognitive impairment. Using real-time fMRI neurofeedback (rt-fMRI-NFB) we trained SZ patients to modulate DMN and CEN networks. Meditation is effective in reducing AHs in SZ and to modulate brain network integration and increase DMN anticorrelations. Consequently, patients were provided with meditation strategies to enhance their abilities to modulate DMN/CEN. Results show a reduction of DMN hyperconnectivity and increase in DMNCEN anticorrelation. Furthermore, the change in individual DMN connectivity significantly correlated with reductions in AHs. This is the first time that meditation enhanced through rt-fMRI-NFB is used to reduce AHs in SZ. Moreover, it provides the first empirical evidence for a direct causal relation between meditation enhanced rt-fMRI-NFB modulation of DMNCEN activity and post-intervention modulation of resting state networks ensuing in reductions in frequency and severity of AHs.

Left auditory cortex gamma synchronization and auditory hallucination symptoms in schizophrenia.

BACKGROUND: Oscillatory electroencephalogram (EEG) abnormalities may reflect neural circuit dysfunction in neuropsychiatric disorders. Previously we have found positive correlations between the phase synchronization of beta and gamma oscillations and hallucination symptoms in schizophrenia patients. These findings suggest that the propensity for hallucinations is associated with an increased tendency for neural circuits in sensory cortex to enter states of oscillatory synchrony. Here we tested this hypothesis by examining whether the 40 Hz auditory steady-state response (ASSR) generated in the left primary auditory cortex is positively correlated with auditory hallucination symptoms in schizophrenia. We also examined whether the 40 Hz ASSR deficit in schizophrenia was associated with cross-frequency interactions. Sixteen healthy control subjects (HC) and 18 chronic schizophrenia patients (SZ) listened to 40 Hz binaural click trains. The EEG was recorded from 60 electrodes and average-referenced offline. A 5-dipole model was fit from the HC grand average ASSR, with 2 pairs of superior temporal dipoles and a deep midline dipole. Time-frequency decomposition was performed on the scalp EEG and source data. RESULTS: Phase locking factor (PLF) and evoked power were reduced in SZ at fronto-central electrodes, replicating prior findings. PLF was reduced in SZ for non-homologous right and left hemisphere sources. Left hemisphere source PLF in SZ was positively correlated with auditory hallucination symptoms, and was modulated by delta phase. Furthermore, the correlations between source evoked power and PLF found in HC was reduced in SZ for the LH sources. CONCLUSION: These findings suggest that differential neural circuit abnormalities may be present in the left and right auditory cortices in schizophrenia. In addition, they provide further support for the hypothesis that hallucinations are related to cortical hyperexcitability, which is manifested by an increased propensity for high-frequency synchronization in modality-specific cortical areas.

Orbitofrontal volume deficit in schizophrenia and thought disorder.

Orbitofrontal Cortex (OFC) structural abnormality in schizophrenia has not been well characterized, probably due to marked anatomical variability and lack of consistent definitions. We previously reported OFC sulcogyral pattern alteration and its associations with social disturbance in schizophrenia, but OFC volume associations with psychopathology and cognition have not been investigated. We compared chronically treated schizophrenia patients with healthy control (HC) subjects, using a novel, reliable parcellation of OFC subregions and their association with cognition, especially the Iowa Gambling Task (IGT), and with schizophrenic psychopathology including thought disorder. Twenty-four patients with schizophrenia and 25 age-matched HC subjects underwent MRI. OFC Regions of Interest (ROI) were manually delineated according to anatomical boundaries: Gyrus Rectus (GR); Middle Orbital Gyrus (MiOG); and Lateral Orbital Gyrus (LOG). The OFC sulcogyral pattern was also classified. Additionally, MiOG probability maps were created and compared between groups in a voxel-wise manner. Both groups underwent cognitive evaluations using the IGT, Wisconsin Card Sorting Test, and Trail Making Test (TMT). An 11% bilaterally smaller MiOG volume was observed in schizophrenia, compared with HC (F(1,47) = 17.4, P = 0.0001). GR and LOG did not differ, although GR showed a rightward asymmetry in both groups (F(1,47) = 19.2, P < 0.0001). The smaller MiOG volume was independent of the OFC sulcogyral pattern, which differed in schizophrenia and HC (chi2 = 12.49, P = 0.002). A comparison of MiOG probability maps suggested that the anterior heteromodal region was more affected in the schizophrenia group than the posterior paralimbic region. In the schizophrenia group, a smaller left MiOG was strongly associated with worse 'positive formal thought disorder' (r = -0.638, P = 0.001), and a smaller right MiOG with a longer duration of the illness (r = -0.618, P = 0.002). While schizophrenics showed poorer performance than HC in the IGT, performance was not correlated with OFC volume. However, within the HC group, the larger the right hemisphere MiOG volume, the better the performance in the IGT (r = 0.541, P = 0.005), and the larger the left hemisphere volume, the faster the switching attention performance for the TMT, Trails B (r = -0.608, P = 0.003). The present study, applying a new anatomical parcellation method, demonstrated a subregion-specific OFC grey matter volume deficit in patients with schizophrenia, which was independent of OFC sulcogyral pattern. This volume deficit was associated with a longer duration of illness and greater formal thought disorder. In HC the finding of a quantitative association between OFC volume and IGT performance constitutes, to our knowledge, the first report of this association.