Unbalanced fronto-pallidal neurocircuit underlying set shifting in obsessive-compulsive disorder.

Maladaptive habitual behaviours of obsessive-compulsive disorder are characterized by cognitive inflexibility, which hypothetically arises from dysfunctions of a certain cortico-basal ganglia-thalamo-cortical circuit including the ventrolateral prefrontal region. Inside this neurocircuit, an imbalance between distinct striatal projections to basal ganglia output nuclei, either directly or indirectly via the external globus pallidus, is suggested to be relevant for impaired arbitration between facilitation and inhibition of cortically initiated activity. However, current evidence of individually altered cortico-striatal or thalamo-cortical connectivities is insufficient to understand how cortical dysconnections are linked to the imbalanced basal ganglia system in patients. In this study, we aimed to identify aberrant ventrolateral prefronto-basal ganglia-thalamic subnetworks representing direct-indirect imbalance and its association with cognitive inflexibility in patients. To increase network detection sensitivity, we constructed a cortico-basal ganglia-thalamo-cortical network model incorporating striatal, pallidal and thalamic subregions defined by unsupervised clustering in 105 medication-free patients with obsessive-compulsive disorder (age = 25.05 ± 6.55 years, male/female = 70/35) and 99 healthy controls (age = 23.93 ± 5.80 years, male/female = 64/35). By using the network-based statistic method, we analysed group differences in subnetworks formed by suprathreshold dysconnectivities. Using linear regression models, we tested subnetwork dysconnectivity effects on symptom severity and set-shifting performance assessed by well-validated clinical and cognitive tests. Compared with the healthy controls, patients were slower to track the Part B sequence of the Trail Making Test when the effects of psychomotor and visuospatial functions were adjusted (t = 3.89, P < 0.001) and made more extradimensional shift errors (t = 4.09, P < 0.001). In addition to reduced fronto-striatal and striato-external pallidal connectivities and hypoconnected striato-thalamic subnetwork [P = 0.001, family-wise error rate (FWER) corrected], patients had hyperconnected fronto-external pallidal (P = 0.012, FWER corrected) and intra-thalamic (P = 0.015, FWER corrected) subnetworks compared with the healthy controls. Among the patients, the fronto-pallidal subnetwork alteration, especially ventrolateral prefronto-external globus pallidal hyperconnectivity, was associated with relatively fewer extradimensional shifting errors (ß = -0.30, P = 0.001). Our findings suggest that the hyperconnected fronto-external pallidal subnetwork may have an opposite effect to the imbalance caused by the reduced indirect pathway (fronto-striato-external pallidal) connectivities in patients. This ventrolateral prefrontal hyperconnectivity may help the external globus pallidus disinhibit basal ganglia output nuclei, which results in behavioural inhibition, so as to compensate for the impaired set shifting. We suggest the ventrolateral prefrontal and external globus pallidus as neuromodulatory targets for inflexible habitual behaviours in obsessive-compulsive disorder.

Neural signatures of individual variability in context-dependent perception of ambiguous facial expression.

How do we incorporate contextual information to infer others' emotional state? Here we employed a naturalistic context-dependent facial expression estimation task where participants estimated pleasantness levels of others' ambiguous expression faces when sniffing different contextual cues (e.g., urine, fish, water, and rose). Based on their pleasantness rating data, we placed participants on a context-dependency continuum and mapped the individual variability in the context-dependency onto the neural representation using a representational similarity analysis. We found that the individual variability in the context-dependency of facial expression estimation correlated with the activity level of the pregenual anterior cingulate cortex (pgACC) and the amygdala and was also decoded by the neural representation of the ventral anterior insula (vAI). A dynamic causal modeling revealed that those with higher context-dependency exhibited a greater degree of the modulation from vAI to the pgACC. These findings provide novel insights into the neural circuitry associated with the individual variability in context-dependent facial expression estimation and the first empirical evidence for individual variability in the predictive accounts of affective states.

Distinct neural networks associated with obsession and delusion: a connectome-wide association study.

BACKGROUND: Obsession and delusion are theoretically distinct from each other in terms of reality testing. Despite such phenomenological distinction, no extant studies have examined the identification of common and distinct neural correlates of obsession and delusion by employing biologically grounded methods. Here, we investigated dimensional effects of obsession and delusion spanning across the traditional diagnostic boundaries reflected upon the resting-state functional connectivity (RSFC) using connectome-wide association studies (CWAS). METHODS: Our study sample comprised of 96 patients with obsessive-compulsive disorder, 75 patients with schizophrenia, and 65 healthy controls. A connectome-wide analysis was conducted to examine the relationship between obsession and delusion severity and RFSC using multivariate distance-based matrix regression. RESULTS: Obsession was associated with the supplementary motor area, precentral gyrus, and superior parietal lobule, while delusion was associated with the precuneus. Follow-up seed-based RSFC and modularity analyses revealed that obsession was related to aberrant inter-network connectivity strength. Additional inter-network analyses demonstrated the association between obsession severity and inter-network connectivity between the frontoparietal control network and the dorsal attention network. CONCLUSIONS: Our CWAS study based on the Research Domain Criteria (RDoC) provides novel evidence for the circuit-level functional dysconnectivity associated with obsession and delusion severity across diagnostic boundaries. Further refinement and accumulation of biomarkers from studies embedded within the RDoC framework would provide useful information in treating individuals who have some obsession or delusion symptoms but cannot be identified by the category of clinical symptoms alone.

Are Bigger Brains Smarter? Evidence From a Large-Scale Preregistered Study.

A positive relationship between brain volume and intelligence has been suspected since the 19th century, and empirical studies seem to support this hypothesis. However, this claim is controversial because of concerns about publication bias and the lack of systematic control for critical confounding factors (e.g., height, population structure). We conducted a preregistered study of the relationship between brain volume and cognitive performance using a new sample of adults from the United Kingdom that is about 70% larger than the combined samples of all previous investigations on this subject ( N = 13,608). Our analyses systematically controlled for sex, age, height, socioeconomic status, and population structure, and our analyses were free of publication bias. We found a robust association between total brain volume and fluid intelligence ( r = .19), which is consistent with previous findings in the literature after controlling for measurement quality of intelligence in our data. We also found a positive relationship between total brain volume and educational attainment ( r = .12). These relationships were mainly driven by gray matter (rather than white matter or fluid volume), and effect sizes were similar for both sexes and across age groups.

Frontostriatal functional connectivity and striatal dopamine synthesis capacity in schizophrenia in terms of antipsychotic responsiveness: an [18F]DOPA PET and fMRI study.

BACKGROUND: Given that only a subgroup of patients with schizophrenia responds to first-line antipsychotic drugs, a key clinical question is what underlies treatment response. Observations that prefrontal activity correlates with striatal dopaminergic function, have led to the hypothesis that disrupted frontostriatal functional connectivity (FC) could be associated with altered dopaminergic function. Thus, the aim of this study was to investigate the relationship between frontostriatal FC and striatal dopamine synthesis capacity in patients with schizophrenia who had responded to first-line antipsychotic drug compared with those who had failed but responded to clozapine. METHODS: Twenty-four symptomatically stable patients with schizophrenia were recruited from Seoul National University Hospital, 12 of which responded to first-line antipsychotic drugs (first-line AP group) and 12 under clozapine (clozapine group), along with 12 matched healthy controls. All participants underwent resting-state functional magnetic resonance imaging and [18F]DOPA PET scans. RESULTS: No significant difference was found in the total PANSS score between the patient groups. Voxel-based analysis showed a significant correlation between frontal FC to the associative striatum and the influx rate constant of [18F]DOPA in the corresponding region in the first-line AP group. Region-of-interest analysis confirmed the result (control group: R2 = 0.019, p = 0.665; first-line AP group: R2 = 0.675, p < 0.001; clozapine group: R2 = 0.324, p = 0.054) and the correlation coefficients were significantly different between the groups. CONCLUSIONS: The relationship between striatal dopamine synthesis capacity and frontostriatal FC is different between responders to first-line treatment and clozapine treatment in schizophrenia, indicating that a different pathophysiology could underlie schizophrenia in patients who respond to first-line treatments relative to those who do not.

Altered functional network architecture in orbitofronto-striato-thalamic circuit of unmedicated patients with obsessive-compulsive disorder.

Dysfunction of corticostriatal loops has been proposed to underlie certain cognitive and behavioral problems associated with various neuropsychiatric disorders, such as obsessive-compulsive disorder (OCD) characterized by repetitive, unwanted thoughts, and behaviors. Although functional abnormalities in the loops involving the orbitofronto-striato-thalamic (OFST) circuitry in patients with OCD have been reported, our understanding of a link between disruptions in the architecture of the intrinsic functional network of the OFST circuit and their symptoms remain incomplete. Using resting-state functional MRI in conjunction with unsupervised clustering and multilevel functional connectivity (FC) techniques, FC of the OFST network and its topological organization in 61 OCD patients versus 61 matched controls were characterized. Patients exhibited disruptions in small-world properties of the OFST circuit, which indicates an imbalance between functional integration and segregation. Patients also showed decreased FC between the central orbitofrontal cortex and dorsomedial striatum but increased FC between the medial thalamus and striatal areas. Using one of the largest samples of unmedicated OCD patients to date, our findings provide evidence supporting the OFST dysconnection hypothesis in OCD as a basic pathophysiological mechanism underlying the disorder, showing the disruption of FC between specific cortical, striatal, and thalamic clusters and aberrant topological patterns of the OFST circuit. Hum Brain Mapp 38:109-119, 2017. © 2016 Wiley Periodicals, Inc.

Cortical thickness in obsessive-compulsive disorder: multisite mega-analysis of 780 brain scans from six centres.

BACKGROUND: There is accumulating evidence for the role of fronto-striatal and associated circuits in obsessive-compulsive disorder (OCD) but limited and conflicting data on alterations in cortical thickness. AIMS: To investigate alterations in cortical thickness and subcortical volume in OCD. METHOD: In total, 412 patients with OCD and 368 healthy adults underwent magnetic resonance imaging scans. Between-group analysis of covariance of cortical thickness and subcortical volumes was performed and regression analyses undertaken. RESULTS: Significantly decreased cortical thickness was found in the OCD group compared with controls in the superior and inferior frontal, precentral, posterior cingulate, middle temporal, inferior parietal and precuneus gyri. There was also a group × age interaction in the parietal cortex, with increased thinning with age in the OCD group relative to controls. CONCLUSIONS: Our findings are partially consistent with earlier work, suggesting that group differences in grey matter volume and cortical thickness could relate to the same underlying pathology of OCD. They partially support a frontostriatal model of OCD, but also suggest that limbic, temporal and parietal regions play a role in the pathophysiology of the disorder. The group × age interaction effects may be the result of altered neuroplasticity.

Moral competence and brain connectivity: A resting-state fMRI study.

Moral competence (MC) refers to the ability to apply certain moral orientations in a consistent and differentiated manner when judging moral issues. People greatly differ in terms of MC, however, little is known about how these differences are implemented in the brain. To investigate this question, we used functional magnetic resonance imaging and examined resting-state functional connectivity (RSFC) in n=31 individuals with MC scores in the highest 15% of the population and n=33 individuals with MC scores in the lowest 15%, selected from a large sample of 730 Master of Business Administration (MBA) students. Compared to individuals with lower MC, individuals with higher MC showed greater amygdala-ventromedial prefrontal connectivity, which may reflect better ability to cope with emotional conflicts elicited by moral dilemmas. Moreover, individuals with higher MC showed less inter-network connectivity between the amygdalar and fronto-parietal networks, suggesting a more independent operation of these networks. Our findings provide novel insights into how individual differences in moral judgment are associated with RSFC in brain circuits related to emotion processing and cognitive control.

Structural covariance of neostriatal and limbic regions in patients with obsessive-compulsive disorder.

BACKGROUND: Frontostriatal and frontoamygdalar connectivity alterations in patients with obsessive-compulsive disorder (OCD) have been typically described in functional neuroimaging studies. However, structural covariance, or volumetric correlations across distant brain regions, also provides network-level information. Altered structural covariance has been described in patients with different psychiatric disorders, including OCD, but to our knowledge, alterations within frontostriatal and frontoamygdalar circuits have not been explored. METHODS: We performed a mega-analysis pooling structural MRI scans from the Obsessive-compulsive Brain Imaging Consortium and assessed whole-brain voxel-wise structural covariance of 4 striatal regions (dorsal and ventral caudate nucleus, and dorsal-caudal and ventral-rostral putamen) and 2 amygdalar nuclei (basolateral and centromedial-superficial). Images were preprocessed with the standard pipeline of voxel-based morphometry studies using Statistical Parametric Mapping software. RESULTS: Our analyses involved 329 patients with OCD and 316 healthy controls. Patients showed increased structural covariance between the left ventral-rostral putamen and the left inferior frontal gyrus/frontal operculum region. This finding had a significant interaction with age; the association held only in the subgroup of older participants. Patients with OCD also showed increased structural covariance between the right centromedial-superficial amygdala and the ventromedial prefrontal cortex. LIMITATIONS: This was a cross-sectional study. Because this is a multisite data set analysis, participant recruitment and image acquisition were performed in different centres. Most patients were taking medication, and treatment protocols differed across centres. CONCLUSION: Our results provide evidence for structural network-level alterations in patients with OCD involving 2 frontosubcortical circuits of relevance for the disorder and indicate that structural covariance contributes to fully characterizing brain alterations in patients with psychiatric disorders.

Power spectral aspects of the default mode network in schizophrenia: an MEG study.

BACKGROUND: Symptoms of schizophrenia are related to deficits in self-monitoring function, which may be a consequence of irregularity in aspects of the default mode network (DMN). Schizophrenia can also be characterized by a functional abnormality of the brain activity that is reflected in the resting state. Oscillatory analysis provides an important understanding of resting brain activity. However, conventional methods using electroencephalography are restricted because of low spatial resolution, despite their excellent temporal resolution.The aim of this study was to investigate resting brain oscillation and the default mode network based on a source space in various frequency bands such as theta, alpha, beta, and gamma using magnetoencephalography. In addition, we investigated whether these resting and DMN activities could distinguish schizophrenia patients from normal controls. To do this, the power spectral density of each frequency band at rest was imaged and compared on a spatially normalized brain template in 20 patients and 20 controls. RESULTS: The spatial distribution of DMN activity in the alpha band was similar to that found in previous fMRI studies. The posterior cingulate cortex (PCC) and lateral inferior parietal cortex were activated at rest, while the medial prefrontal cortex (MPFC) was deactivated at rest rather than during the task. Although the MPFC and PCC regions exhibited contrasting activation patterns, these two regions were significantly coherent at rest. The DMN and resting activities of the PCC were increased in schizophrenia patients, predominantly in the theta and alpha bands. CONCLUSIONS: By using MEG to identify the DMN regions, predominantly in the alpha band, we found that both resting and DMN activities were augmented in the posterior cingulate in schizophrenia patients. Furthermore, schizophrenia patients exhibited decreased coherence between the PCC and MPFC in the gamma band at rest.

Functional brain network properties correlate with individual risk tolerance in young adults.

Background: Individuals differ substantially in their degree of acceptance of risks, referred to as risk tolerance, and these differences are associated with real-life outcomes such as risky health-related behaviors. While previous studies have identified brain regions that are functionally associated with individual risk tolerance, little is known about the relationship between individual risk tolerance and whole-brain functional organization. Methods: This study investigated whether the topological properties of individual functional brain networks in healthy young adults (n = 67) are associated with individual risk tolerance using resting-state fMRI data in conjunction with a graph theoretical analysis approach. Results: The analysis revealed that individual risk tolerance was positively associated with global topological properties, including the normalized clustering coefficient and small-worldness, which represent the degree of information segregation and the balance between information segregation and integration in a network, respectively. Additionally, individuals with higher risk tolerance exhibited greater centrality in the ventromedial prefrontal cortex (vmPFC), which is associated with the subjective value of the available options. Conclusion: These results extend our understanding of how individual differences in risk tolerance, especially in young adults, are associated with functional brain organization, particularly regarding the balance between segregation and integration in functional networks, and highlight the important role of the connections between the vmPFC and the rest of the brain in the functional networks in relation to risk tolerance.

White matter-based brain network topological properties associated with individual impulsivity.

Delay discounting (DD), a parameter derived from the intertemporal choice task, is a representative behavioral indicator of choice impulsivity. Previous research reported not only an association between DD and impulsive control disorders and negative health outcomes but also the neural correlates of DD. However, to date, there are few studies investigating the structural brain network topologies associated with individual differences in DD and whether self-reported measures (BIS-11) of impulsivity associated with DD share the same or distinct neural mechanisms is still unclear. To address these issues, here, we combined graph theoretical analysis with diffusion tensor imaging to investigate the associations between DD and the topological properties of the structural connectivity network and BIS-11 scores. Results revealed that people with a steep DD (greater impatience) had decreased small-worldness (a shift toward weaker small-worldnization) and increased degree centrality in the medial superior prefrontal cortex, associated with subjective value in the task. Though DD was associated with the BIS-11 motor impulsiveness subscale, this subscale was linked to topological properties different from DD; that is, high motor impulsiveness was associated with decreased local efficiency (less segregation) and decreased degree centrality in the precentral gyrus, involved in motor control. These findings provide insights into the systemic brain characteristics underlying individual differences in impulsivity and potential neural markers which could predict susceptibility to impulsive behaviors.

Different topological patterns in structural covariance networks between high and low delay discounters.

Introduction: People prefer immediate over future rewards because they discount the latter's value (a phenomenon termed "delay discounting," used as an index of impulsivity). However, little is known about how the preferences are implemented in brain in terms of the coordinated pattern of large-scale structural brain networks. Methods: To examine this question, we classified high discounting group (HDG) and low discounting group (LDG) in young adults by assessing their propensity for intertemporal choice. We compared global and regional topological properties in gray matter volume-based structural covariance networks between two groups using graph theoretical analysis. Results: HDG had less clustering coefficient and characteristic path length over the wide sparsity range than LDG, indicating low network segregation and high integration. In addition, the degree of small-worldness was more significant in HDG. Locally, HDG showed less betweenness centrality (BC) in the parahippocampal gyrus and amygdala than LDG. Discussion: These findings suggest the involvement of structural covariance network topology on impulsive choice, measured by delay discounting, and extend our understanding of how impulsive choice is associated with brain morphological features.

Hippocampal atrophy is associated with hearing loss in cognitively normal adults.

Objectives: A growing body of evidence suggests that age-related hearing loss (HL) is associated with morphological changes of the cerebral cortex, but the results have been drawn from a small amount of data in most studies. The aim of this study is to investigate the correlation between HL and gray matter volume (GMV) in a large number of subjects, strictly controlling for an extensive set of possible biases. Methods: Medical records of 576 subjects who underwent pure tone audiometry, brain magnetic resonance imaging (MRI), and the Korean Mini-Mental State Exam (K-MMSE) were reviewed. Among them, subjects with normal cognitive function and free of central nervous system disorders or coronary artery disease were included. Outliers were excluded after a sample homogeneity check. In the end, 405 subjects were enrolled. Pure tone hearing thresholds were determined at 0.5, 1, 2, and 4 kHz in the better ear. Enrolled subjects were divided into 3 groups according to pure tone average: normal hearing (NH), mild HL (MHL), and moderate-to-severe HL (MSHL) groups. Using voxel-based morphometry, we evaluated GMV changes that may be associated with HL. Sex, age, total intracranial volume, type of MRI scanner, education level, K-MMSE score, smoking status, and presence of hypertension, diabetes mellitus and dyslipidemia were used as covariates. Results: A statistically significant negative correlation between the hearing thresholds and GMV of the hippocampus was elucidated. Additionally, in group comparisons, the left hippocampal GMV of the MSHL group was significantly smaller than that of the NH and MHL groups. Conclusion: Based on the negative correlation between hearing thresholds and hippocampal GMV in cognitively normal old adults, the current study indicates that peripheral deafferentation could be a potential contributing factor to hippocampal atrophy.

Reduced fronto-callosal fiber integrity in unmedicated OCD patients: a diffusion tractography study.

It is widely accepted that abnormalities in the frontal area of the brain underpin the pathophysiology of obsessive-compulsive disorder (OCD). Fundamental to this investigation is the delineation of frontal white matter tracts including dorsal and ventral frontal projections of interhemispheric connections. While previous investigations of OCD have examined the dorsal and ventral frontal regions, the corresponding callosal connections have not been investigated, despite their importance. We recruited twenty patients with OCD (15 drug-naïve and 5 currently unmedicated) and demographically similar healthy controls, and conducted fiber tractography and post hoc quantitative analysis using diffusion tensor imaging. We extracted fractional anisotropy (FA) of the fronto-callosal fibers along the entire length of the tract. Function-specific [by the Brodmann area region-of-interest (ROI) approach] and region-specific (by the length-parameterization approach) tracts were defined. In addition, we devised a new index of dorsal-ventral imbalance (DVII) of fiber integrity. Significant FA decreases were observed in orbitofrontal and dorsolateral prefrontal projections of the corpus callosum (P < 0.05, false discovery rate-corrected) with higher function/region sensitivity than voxel-based or ROI-based approaches. Importantly, OCD patients also exhibited significantly higher ventral-greater-than-dorsal asymmetry of FA values than normal controls (P < 0.05, FDR-corrected). This study is the first to investigate fiber integrity in the dorsal/ventral frontal parts of the callosal tractography in unmedicated OCD patients. Using a more quantitative method in terms of functional and regional specificity than previous studies, we report abnormalities in interhemispheric connectivity of both dorsal and ventral networks in the pathophysiology of OCD.

Sex differences in the behavioral inhibition system and ventromedial prefrontal cortex connectivity.

The reinforcement sensitivity theory proposes brain-behavioral systems that underlie individual differences in sensitivity to punishment and reward. Such trait sensitivity is assessed using the behavioral inhibition/activation system (BIS/BAS) scales. Recent studies have reported sex-linked neuroanatomical correlates of the BIS/BAS, especially in the regions belonging to the valuation and salience networks that are associated with the representation of subjective value (SV), whereas less effort has been focused on investigating the neurofunctional aspects associated with sex differences in the BIS/BAS. We tested whether functional connectivity (FC) of the regions associated with the representation of SV mediates the relationship between sex and BIS sensitivity in healthy young adults by using resting-state functional magnetic resonance imaging data and self-reported BIS/BAS measures. Compared with males, females had heightened BIS sensitivity and increased FC between the ventromedial prefrontal cortex (vmPFC) seed and posterior parietal areas; this FC mediated the impact of sex on BIS sensitivity. Given that the observed vmPFC FC maps are considered part of the default-mode network, which is involved in ruminative processes, and that the BIS is associated with rumination and negative affect, our results may have implications for psychiatric disorders such as depression and anxiety, both of which have high incidence in females.

The Relationship Between Frontostriatal Connectivity and Striatal Dopamine Function in Schizophrenia: An 18F-DOPA PET and Diffusion Tensor Imaging Study in Treatment Responsive and Resistant Patients.

OBJECTIVE: Striatal dopamine dysfunction caused by cortical abnormalities is a leading hypothesis of schizophrenia. Although prefrontal cortical pathology is negatively correlated with striatal dopamine synthesis, the relationship between structural frontostriatal connectivity and striatal dopamine synthesis has not been proved in patients with schizophrenia with different treatment response. We therefore investigated the relationship between frontostriatal connectivity and striatal dopamine synthesis in treatment-responsive schizophrenia (non-TRS) and compared them to treatment-resistant schizophrenia (TRS) and healthy controls (HC). METHODS: Twenty-four patients with schizophrenia and twelve HC underwent [18F] DOPA PET scans to measure dopamine synthesis capacity (the influx rate constant Kicer) and diffusion 3T MRI to measure structural connectivity (fractional anisotropy, FA). Connectivity was assessed in 2 major frontostriatal tracts. Associations between Kicer and FA in each group were evaluated using Spearman's rho correlation coefficients. RESULTS: Non-TRS showed a negative correlation (r=-0.629, p=0.028) between connectivity of dorsolateral prefrontal cortex-associative striatum (DLPFC-AST) and dopamine synthesis capacity of associative striatum but this was not evident in TRS (r=-0.07, p=0.829) and HC (r=-0.277, p=0.384). CONCLUSION: Our findings are consistent with the hypothesis of dysregulation of the striatal dopaminergic system being related to prefrontal cortex pathology localized to connectivity of DLPFC-AST in non-TRS, and also extend the hypothesis to suggest that different mechanisms underlie the pathophysiology of non-TRS and TRS.

Midsagittal structural differences and sexual dimorphism of the corpus callosum in obsessive-compulsive disorder.

Neurobiological abnormalities in various brain regions, including the orbitofrontal cortex, basal ganglia, and thalamus, have been found in patients with obsessive-compulsive disorder (OCD), and impairment in white matter connectivity in these regions has recently been suggested. To investigate structural connectivity in OCD, we used the midsagittal area and thickness to assess the morphology of the corpus callosum (CC), the largest connecting fiber tract in the human brain. Midsagittal magnetic resonance images of the CC were acquired from 69 adult patients with OCD and 69 matched normal controls. We calculated and compared the total area and the areas of five subregions of the CC as well as the distances between 200 equidistant points on the top and bottom of lines on the surface of the CC in the two groups. The absolute total area of the CC was significantly larger in OCD patients than in controls when brain size, age, gender, and IQ were controlled. Significant enlargements in CC1, CC2, and CC5 were seen in OCD patients before correction for multiple comparisons. The thickness of the caudal part of the splenium was greater in OCD patients than in controls. The analysis according to gender showed that only male OCD patients differed from male controls with respect to the area of the CC. These findings reflect structural abnormalities in the CC, and especially in the splenium, in adult patients with OCD. Abnormal interhemispheric connectivity, including the parietotemporal and occipital areas, may affect the pathophysiology of OCD. Sexual dimorphism in the CC of OCD patients should be considered.

Altered brain activation in ventral frontal-striatal regions following a 16-week pharmacotherapy in unmedicated obsessive-compulsive disorder.

Recent studies have reported that cognitive inflexibility associated with impairments in a frontal-striatal circuit and parietal region is a core cognitive deficit of obsessive-compulsive disorder (OCD). However, few studies have examined progressive changes in these regions following clinical improvement in obsessive-compulsive symptoms. To determine if treatment changes the aberrant activation pattern associated with task switching in OCD, we examined the activation patterns in brain areas after treatment. The study was conducted on 10 unmedicated OCD patients and 20 matched controls using event-related functional magnetic resonance imaging. Treatment improved the clinical symptoms measured by the Yale-Brown Obsessive Compulsive Scale and behavioral flexibility indicated by the switching cost. At baseline, OCD showed significantly less activation in the dorsal and ventral frontal-striatal circuit and parietal regions under the task-switch minus task-repeat condition compared with controls. After treatment, the neural responses in the ventral frontal-striatal circuit in OCD were partially normalized, whereas the activation deficit in dorsal frontoparietal regions that mediate shifting attention or behavioral flexibility persisted. It is suggested that altered brain activation in ventral frontal-striatal regions in OCD patients is associated with their cognitive flexibility and changes in these regions may underlie the pathophysiology of OCD.

Brain Activation of Patients With Obsessive-Compulsive Disorder During a Mental Rotation Task: A Functional MRI Study.

Functional neuroimaging studies have implicated alterations in frontostriatal and frontoparietal circuits in obsessive-compulsive disorder (OCD) during various tasks. To date, however, brain activation for visuospatial function in conjunction with symptoms in OCD has not been comprehensively evaluated. To elucidate the relationship between neural activity, cognitive function, and obsessive-compulsive symptoms, we investigated regional brain activation during the performance of a visuospatial task in patients with OCD using functional magnetic resonance imaging (fMRI). Seventeen medication-free patients with OCD and 21 age-, sex-, and IQ-matched healthy controls participated in this study. Functional magnetic resonance imaging data were obtained while the subjects performed a mental rotation (MR) task. Brain activation during the task was compared between the two groups using a two-sample t-test. Voxel-wise whole-brain multiple regression analyses were also performed to examine the relationship between obsessive-compulsive symptom severity and neural activity during the task. The two groups did not differ in MR task performance. Both groups also showed similar task-related activation patterns in frontoparietal regions with no significant differences. Activation in the right dorsolateral prefrontal cortex in patients with OCD during the MR task was positively associated with their total Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores. This study identified the specific brain areas associated with the interaction between symptom severity and visuospatial cognitive function during an MR task in medication-free patients with OCD. These findings may serve as potential neuromodulation targets for OCD treatment.