Search

Obsessive-compulsive disorder (OCD) is a debilitating psychiatric condition that is difficult to treat due to our limited understanding of its pathophysiology. Functional connectivity in brain networks, as evaluated through neuroimaging studies, plays a pivotal role in understanding OCD. While both electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) have been extensively employed in OCD research, few have fully synthesized their findings. To bridge this gap, we reviewed 166 studies (10 EEG, 156 fMRI) published up to December 2023. In EEG studies, OCD exhibited lower connectivity in delta and alpha bands, with inconsistent findings in other frequency bands. Resting-state fMRI studies reported conflicting connectivity patterns within the default mode network (DMN) and sensorimotor cortico-striato-thalamo-cortical (CSTC) circuitry. Many studies observed decreased resting-state connectivity between the DMN and salience network (SN), implicating the 'triple network model' in OCD. Task-related hyperconnectivity within the DMN-SN and hypoconnectivity between the SN and frontoparietal network suggest OCD-related cognitive inflexibility, potentially due to triple network dysfunction. In conclusion, our review highlights diverse connectivity differences in OCD, revealing complex brain network interplay that contributes to symptom manifestation. However, the presence of conflicting findings underscores the necessity for targeted research to achieve a comprehensive understanding of the pathophysiology of OCD., (© The Author(s) 2024. Published by Oxford University Press.)

Despite a theory that an imbalance in goal-directed versus habitual systems serve as building blocks of compulsions, research has yet to delineate how this occurs during arbitration between the two systems in obsessive-compulsive disorder. Inspired by a brain model in which the inferior frontal cortex selectively gates the putamen to guide goal-directed or habitual actions, this study aimed to examine whether disruptions in the arbitration process via the fronto-striatal circuit would underlie imbalanced decision-making and compulsions in patients. Thirty patients with obsessive-compulsive disorder [mean (standard deviation) age = 26.93 (6.23) years, 12 females (40%)] and 30 healthy controls [mean (standard deviation) age = 24.97 (4.72) years, 17 females (57%)] underwent functional MRI scans while performing the two-step Markov decision task, which was designed to dissociate goal-directed behaviour from habitual behaviour. We employed a neurocomputational model to account for an uncertainty-based arbitration process, in which a prefrontal arbitrator (i.e. inferior frontal gyrus) allocates behavioural control to a more reliable strategy by selectively gating the putamen. We analysed group differences in the neural estimates of uncertainty of each strategy. We also compared the psychophysiological interaction effects of system preference (goal-directed versus habitual) on fronto-striatal coupling between groups. We examined the correlation between compulsivity score and the neural activity and connectivity involved in the arbitration process. The computational model captured the subjects' preferences between the strategies. Compared with healthy controls, patients had a stronger preference for the habitual system (t = -2.88, P = 0.006), which was attributed to a more uncertain goal-directed system (t = 2.72, P = 0.009). Before the allocation of controls, patients exhibited hypoactivity in the inferior frontal gyrus compared with healthy controls when this region tracked the inverse of uncertainty (i.e. reliability) of goal-directed behaviour (P = 0.001, family-wise error rate corrected). When reorienting behaviours to reach specific goals, patients exhibited weaker right ipsilateral ventrolateral prefronto-putamen coupling than healthy controls (P = 0.001, family-wise error rate corrected). This hypoconnectivity was correlated with more severe compulsivity (r = -0.57, P = 0.002). Our findings suggest that the attenuated top-down control of the putamen by the prefrontal arbitrator underlies compulsivity in obsessive-compulsive disorder. Enhancing fronto-striatal connectivity may be a potential neurotherapeutic approach for compulsivity and adaptive decision-making., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

The insula plays a significant role in the neural mechanisms of obsessive-compulsive disorder. Previous studies have identified functional and structural abnormalities in insula in obsessive-compulsive disorder patients. The predictive coding model in the context of interoception can explain the psychological and neuropathological manifestations observed in obsessive-compulsive disorder. The model is based on the degree of laminar differentiation of cerebral cortex. The interindividual differences in a local measure of brain structure often covary with interindividual differences in other brain regions. We investigated the anatomical network involving the insula in a drug-naïve obsessive-compulsive disorder sample. We recruited 58 obsessive-compulsive disorder patients and 84 matched health controls. The cortical thickness covariance maps between groups were compared at each vertex. We also evaluated the modulation of Yale-Brown Obsessive-Compulsive Scale scores and obsessive-compulsive disorder duration on thickness covariance. Our findings indicated that the thickness covariance seeded from granular and dysgranular insula are different compared with controls. The duration and severity of obsessive-compulsive disorder can modulate the thickness covariance of granular and dysgranular insula with posterior cingulate cortex and rostral anterior cingulate cortex. Our results revealed aberrant insular structural characteristics and cortical thickness covariance in obsessive-compulsive disorder patients, contributing to a better understanding of the involvement of insula in the pathological mechanisms underlying obsessive-compulsive disorder., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Gyrification patterns reflect early neurodevelopment and could be highly heritable. While some discrepant results have been reported, the most consistent finding was that patients with obsessive-compulsive disorder showed altered gyrification patterns in the orbitofrontal cortex. Nevertheless, no study has investigated the alterations in gyrification in unaffected first-degree relatives of patients with obsessive-compulsive disorder. We measured local gyrification by the FreeSurfer software in 23 unaffected first-degree relatives of patients with obsessive-compulsive disorder and 52 healthy control participants. We explored differences in the local gyrification index using vertex-wise whole-brain analysis and a region of interest-based approach in the medial and lateral orbitofrontal cortex. There was no significant difference in the local gyrification index between the 2 groups in the vertex-wise whole-brain analysis. Region of interest analyses showed that, compared with healthy controls, first-degree relatives showed significantly reduced local gyrification index in the left medial and lateral orbitofrontal cortex. A negative correlation was observed between the reduced local gyrification index in lateral orbitofrontal cortex and the subclinical anxiety scores of first-degree relatives. Our results showed that first-degree relatives of patients with obsessive-compulsive disorder had an altered local gyrification index in the orbitofrontal cortex. Especially, reduced local gyrification index in lateral orbitofrontal cortex associated with subclinical anxiety symptom could be a potential neurodevelopmental marker for the illness onset., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Obsessive-compulsive disorder (OCD) is a spectrum disorder with high interindividual heterogeneity. We propose a comprehensible framework integrating normative model and non-negative matrix factorization (NMF) to quantitatively estimate the neuroanatomical heterogeneity of OCD from a dimensional perspective. T1-weighted magnetic resonance images of 98 first-episode untreated patients with OCD and matched healthy controls (HCs, n = 130) were acquired. We derived individualized differences in gray matter morphometry using normative model and parsed them into latent disease factors using NMF. Four robust disease factors were identified. Each patient expressed multiple factors and exhibited a unique factor composition. Factor compositions of patients were significantly correlated with severity of symptom, age of onset, illness duration, and exhibited sex differences, capturing sources of clinical heterogeneity. In addition, the group-level morphological differences obtained with two-sample t test could be quantitatively derived from the identified disease factors, reconciling the group-level and subject-level findings in neuroimaging studies. Finally, we uncovered two distinct subtypes with opposite morphological differences compared with HCs from factor compositions. Our findings suggest that morphological differences of individuals with OCD are the unique combination of distinct neuroanatomical patterns. The proposed framework quantitatively estimating neuroanatomical heterogeneity paves the way for precision medicine in OCD., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Previous studies have suggested that specific fronto-striatal circuits are associated with impaired motor response inhibition in patients with obsessive-compulsive disorder (OCD) and their relatives. However, no study has investigated the underlying resting-state network associated with motor response inhibition in the unaffected first-degree relatives of patients with OCD. We measured motor response inhibition using stop-signal task, and obtained resting-state fMRI in 23 first-degree relatives and 52 healthy control participants. We explored the group differences in the functional network from seed regions-of-interest (ROIs) associated with motor response inhibition abilities. We used the inferior frontal gyrus (IFG) and pre-supplementary motor area (pre-SMA) as seed-ROIs. A significant group difference was observed in functional connectivity between the pre-SMA and inferior parietal lobule. In the relative group, reduced functional connectivity between these areas was associated with a longer stop-signal reaction time. Additionally, relatives showed significantly greater functional connectivity between the IFG and SMA, precentral, and postcentral areas. Our results could provide new insights into the resting-state neural activity of the pre-SMA underlying impaired motor response inhibition of unaffected first-degree relatives. In addition, our results suggested that relatives have an altered connectivity of the sensorimotor region, similar to that of patients with OCD shown in previous literature., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The diagnosis of obsessive-compulsive disorder (OCD) has been linked with changes in frontostriatal resting-state connectivity. However, replication of prior findings is lacking, and the mechanistic understanding of these effects is incomplete. To confirm and advance knowledge on changes in frontostriatal functional connectivity in OCD, participants with OCD and matched healthy controls underwent resting-state functional, structural and diffusion neuroimaging. Functional connectivity changes in frontostriatal systems were here replicated in individuals with OCD (n = 52) compared with controls (n = 45). OCD participants showed greater functional connectivity (t = 4.3, PFWE = 0.01) between the nucleus accumbens (NAcc) and the orbitofrontal cortex (OFC) but lower functional connectivity between the dorsal putamen and lateral prefrontal cortex (t = 3.8, PFWE = 0.04) relative to controls. Computational modelling suggests that NAcc-OFC connectivity changes reflect an increased influence of NAcc over OFC activity and reduced OFC influence over NAcc activity (posterior probability, Pp > 0.66). Conversely, dorsal putamen showed reduced modulation over lateral prefrontal cortex activity (Pp > 0.90). These functional deregulations emerged on top of a generally intact anatomical substrate. We provide out-of-sample replication of opposite changes in ventro-anterior and dorso-posterior frontostriatal connectivity in OCD and advance the understanding of the neural underpinnings of these functional perturbations. These findings inform the development of targeted therapies normalizing frontostriatal dynamics in OCD., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The dysfunctional patterns of microstates dynamics in obsessive-compulsive disorder (OCD) remain uncertain. Using high-density electrical neuroimaging (EEG) at rest, we explored microstates deterioration in OCD and whether abnormal microstates patterns are associated with a dysregulation of the resting-state networks interplay. We used EEG microstates analyses, TESS method for sources reconstruction, and General Linear Models to test for the effect of disease severity on neural responses. OCD patients exhibited an increased contribution and decreased duration of microstates C and D, respectively. Activity was decreased in the Salience Network (SN), associated with microstate C, but increased in the Default Mode Network (DMN) and Executive Control Network (ECN), respectively, associated with microstates E and D. The hyperactivity of the right angular gyrus in the ECN correlated with the symptoms severity. The imbalance between microstates C and D invalidates the hypothesis that this electrophysiological pattern is specific to psychosis. Demonstrating that the SN-ECN dysregulation manifests as abnormalities in microstates C and D, we confirm that the SN deterioration in OCD is accompanied by a failure of the DMN to deactivate and aberrant compensatory activation mechanisms in the ECN. These abnormalities explain typical OCD clinical features but also detachment from reality, shared with psychosis., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The high heterogeneity of obsessive-compulsive disorder (OCD) denies attempts of traditional case-control studies to derive neuroimaging biomarkers indicative of precision diagnosis and treatment., Methods: To handle the heterogeneity, we uncovered subject-level altered structural covariance by adopting individualized differential structural covariance network (IDSCN) analysis. The IDSCN measures how structural covariance edges in a patient deviated from those in matched healthy controls (HCs) yielding subject-level differential edges. One hundred patients with OCD and 106 HCs were recruited and whose T1-weighted anatomical images were acquired. We obtained individualized differential edges and then clustered patients into subtypes based on these edges., Results: Patients presented tremendously low overlapped altered edges while frequently shared altered edges within subcortical-cerebellum network. Two robust neuroanatomical subtypes were identified. Subtype 1 presented distributed altered edges while subtype 2 presented decreased edges between default mode network and motor network compared with HCs. Altered edges in subtype 1 predicted the total Yale-Brown Obsessive Compulsive Scale score while that in subtype 2 could not., Conclusions: We depict individualized structural covariance aberrance and identify that altered connections within subcortical-cerebellum network are shared by most patients with OCD. These 2 subtypes provide new insights into taxonomy and facilitate potential clues to precision diagnosis and treatment of OCD., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Compulsion is one of core symptoms of obsessive-compulsive disorder (OCD). Although many studies have investigated the neural mechanism of compulsion, no study has used brain-based measures to predict compulsion. Here, we used connectome-based predictive modeling (CPM) to identify networks that could predict the levels of compulsion based on whole-brain functional connectivity in 57 OCD patients. We then applied a computational lesion version of CPM to examine the importance of specific brain areas. We also compared the predictive network strength in OCD with unaffected first-degree relatives (UFDR) of patients and healthy controls. CPM successfully predicted individual level of compulsion and identified networks positively (primarily subcortical areas of the striatum and limbic regions of the hippocampus) and negatively (primarily frontoparietal regions) correlated with compulsion. The prediction power of the negative model significantly decreased when simulating lesions to the prefrontal cortex and cerebellum, supporting the importance of these regions for compulsion prediction. We found a similar pattern of network strength in the negative predictive network for OCD patients and their UFDR, demonstrating the potential of CPM to identify vulnerability markers for psychopathology., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Patients with obsessive-compulsive disorder (OCD) exhibit abnormality in their subjective perception of internal sensation, a process known as interoceptive sensibility (IS), as well as altered functioning of the insula, a key neural structure for interoception. We investigated the multivariate structure of IS in 77 OCD patients and 53 controls and examined associations of IS with resting-state functional connectivity (FC) of the insula within the OCD group. For each group, principal component analysis was performed on 8 subscales of the Multidimensional Assessment of Interoceptive Awareness assessing putatively "adaptive" and "maladaptive" aspects of IS. Associations between IS components and insula FC in the OCD group were evaluated using seed regions placed in each of 3 subdivisions of the insula (posterior, anterior dorsal, and anterior ventral). Behaviorally, controls showed a 2-component solution broadly categorized into "adaptive" and "maladaptive" IS, while OCD patients exhibited a 3-component solution. The general tendency to notice or be aware of sensation loaded onto an "adaptive" IS component in controls but loaded onto both "adaptive" and "maladaptive" IS components in OCD. Within OCD, insula FC was differentially associated with distinct aspects of IS, identifying network connections that could serve as future targets for the modulation of IS in OCD., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

An imbalance between the goal-directed and habitual learning systems has been proposed to underlie compulsivity in obsessive-compulsive disorder (OCD). In addition, the overall balance between these systems may be influenced by stress hormones. We examined the multimodal networks underlying these dual learning systems. Both functional and structural measures indicated reduced connectivity within the goal-directed subnetwork (FC: P = 0.042; SC-FN: P = 0.014) and reduced connectivity between the goal-directed and habitual subnetworks (FC: P = 0.014; SC-FA: P = 0.052), but no differences within the habitual subnetwork in patients with OCD compared with controls. Path modeling indicated that anatomical connectivity in the goal-directed subnetwork influenced compulsive symptoms (R2 = 0.41), whereas functional connectivity within the habit subnetwork and between goal-directed and habitual subnetworks influenced obsessive symptoms (R2 = 0.63). In addition, the relationship between anatomical connectivity in the goal-directed subnetwork and compulsion was moderated by the stress hormone ACTH (adrenocorticotropic hormone), such that at low levels of ACTH greater connectivity resulted in lower compulsion, but at high levels of ACTH this relationship was reversed. These results provide new insights into the neural correlates of the imbalance between dual learning systems, and their relationship with symptom dimensions in patients with OCD. It may further support the reconceptualization of OCD as "compulsive-obsessive disorder," with a greater focus on the transdiagnostic dimension of compulsivity., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Social communication differences are seen in autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and obsessive-compulsive disorder (OCD), but the brain mechanisms contributing to these differences remain largely unknown. To address this gap, we used a data-driven and diagnosis-agnostic approach to discover brain correlates of social communication differences in ASD, ADHD, and OCD, and subgroups of individuals who share similar patterns of brain-behavior associations. A machine learning pipeline (regression clustering) was used to discover the pattern of association between structural brain measures (volume, surface area, and cortical thickness) and social communication abilities. Participants (n = 416) included children with a diagnosis of ASD (n = 192, age = 12.0[5.6], 19% female), ADHD (n = 109, age = 11.1[4.1], 18% female), or OCD (n = 50, age = 12.3[4.2], 42% female), and typically developing controls (n = 65, age = 11.6[7.1], 48% female). The analyses revealed (1) associations with social communication abilities in distributed cortical and subcortical networks implicated in social behaviors, language, attention, memory, and executive functions, and (2) three data-driven, diagnosis-agnostic subgroups based on the patterns of association in the above networks. Our results suggest that different brain networks may contribute to social communication differences in subgroups that are not diagnosis-specific., (© The Author(s) 2021. Published by Oxford University Press.)

A phenomenon in schizophrenia patients that deserves attention is the high comorbidity rate with obsessive-compulsive disorder (OCD). Little is known about the neurobiological basis of schizo-obsessive comorbidity (SOC). We aimed to investigate whether specific changes in white matter exist in patients with SOC and the relationship between such abnormalities and clinical parameters. Twenty-eight patients with SOC, 28 schizophrenia patients, 30 OCD patients, and 30 demographically matched healthy controls were recruited. Using Tract-based Spatial Statistics and Probabilistic Tractography, we examined the pattern of white matter abnormalities in these participants. We also used ANOVA and Support Vector Classification of various white matter indices and structural connection probability to further examine white matter changes among the 4 groups. We found that patients with SOC had decreased fractional anisotropy (FA) and increased radial diffusivity in the right sagittal stratum and the left crescent of the fornix/stria terminalis compared with healthy controls. We also found changed connection probability in the Default Mode Network, the Subcortical Network, the Attention Network, the Task Control Network, the Visual Network, the Somatosensory Network, and the cerebellum in the SOC group compared with the other 3 groups. The classification results further revealed that FA features could differentiate the SOC group from the other 3 groups with an accuracy of .78. These findings highlight the specific white matter abnormalities found in patients with SOC., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Clinical and neuroimaging data support the idea that schizo-obsessive comorbidity (SOC), similar to obsessive-compulsive disorder (OCD) and schizophrenia (SCZ), may be a distinct brain disorder. In this study, we examined the strength of resting-state functional connectivity (rsFC) between 19 subregions of the default mode network (DMN) and whole brain voxels in 22 patients with SOC features, 20 patients with SCZ alone, 22 patients with OCD, and 22 healthy controls (HC). The main results demonstrated that patients with SOC exhibited the highest rsFC strength within subregions of the DMN and the lowest rsFC strength between the DMN and subregions of the salience network (SN) compared with the other 3 groups. In addition, compared with HCs, all 3 patient groups exhibited increased rsFC between subregions of the DMN and the executive control network (ECN). The SOC and SCZ group both exhibited increased rsFC between subregions of the DMN and the middle temporal gyrus, but the OCD group exhibited decreased rsFC between them. These findings highlight a specific alteration in functional connectivity in the DMN in patients with SOC, and provide new insights into the dysfunctional brain organization of different mental disorders.

Compulsions are repetitive, stereotyped thoughts and behaviors designed to reduce harm. Growing evidence suggests that the neurocognitive mechanisms mediating behavioral inhibition (motor inhibition, cognitive inflexibility) reversal learning and habit formation (shift from goal-directed to habitual responding) contribute toward compulsive activity in a broad range of disorders. In obsessive compulsive disorder, distributed network perturbation appears focused around the prefrontal cortex, caudate, putamen, and associated neuro-circuitry. Obsessive compulsive disorder-related attentional set-shifting deficits correlated with reduced resting state functional connectivity between the dorsal caudate and the ventrolateral prefrontal cortex on neuroimaging. In contrast, experimental provocation of obsessive compulsive disorder symptoms reduced neural activation in brain regions implicated in goal-directed behavioral control (ventromedial prefrontal cortex, caudate) with concordant increased activation in regions implicated in habit learning (presupplementary motor area, putamen). The ventromedial prefrontal cortex plays a multifaceted role, integrating affective evaluative processes, flexible behavior, and fear learning. Findings from a neuroimaging study of Pavlovian fear reversal, in which obsessive compulsive disorder patients failed to flexibly update fear responses despite normal initial fear conditioning, suggest there is an absence of ventromedial prefrontal cortex safety signaling in obsessive compulsive disorder, which potentially undermines explicit contingency knowledge and may help to explain the link between cognitive inflexibility, fear, and anxiety processing in compulsive disorders such as obsessive compulsive disorder., (© The Author 2017. Published by Oxford University Press on behalf of CINP.)

Autism spectrum disorder (ASD) and obsessive-compulsive disorder (OCD) often share phenotypes of repetitive behaviors, possibly underpinned by abnormal decision-making. To compare neural correlates underlying decision-making between these disorders, brain activation of boys with ASD (N = 24), OCD (N = 20) and typically developing controls (N = 20) during gambling was compared, and computational modeling compared performance. Patients were unimpaired on number of risky decisions, but modeling showed that both patient groups had lower choice consistency and relied less on reinforcement learning compared to controls. ASD individuals had disorder-specific choice perseverance abnormalities compared to OCD individuals. Neurofunctionally, ASD and OCD boys shared dorsolateral/inferior frontal underactivation compared to controls during decision-making. During outcome anticipation, patients shared underactivation compared to controls in lateral inferior/orbitofrontal cortex and ventral striatum. During reward receipt, ASD boys had disorder-specific enhanced activation in inferior frontal/insular regions relative to OCD boys and controls. Results showed that ASD and OCD individuals shared decision-making strategies that differed from controls to achieve comparable performance to controls. Patients showed shared abnormalities in lateral-(orbito)fronto-striatal reward circuitry, but ASD boys had disorder-specific lateral inferior frontal/insular overactivation, suggesting that shared and disorder-specific mechanisms underpin decision-making in these disorders. Findings provide evidence for shared neurobiological substrates that could serve as possible future biomarkers., (© The Author 2017. Published by Oxford University Press.)

Why do we make hasty decisions for short-term gain? Rapid decision-making with limited accumulation of evidence and delay discounting are forms of decisional impulsivity. The subthalamic nucleus is implicated in inhibitory function but its role in decisional impulsivity is less well-understood. Here we assess decisional impulsivity in subjects with obsessive compulsive disorder who have undergone deep brain stimulation of the limbic and associative subthalamic nucleus. We show that stimulation of the subthalamic nucleus is causally implicated in increasing decisional impulsivity with less accumulation of evidence during probabilistic uncertainty and in enhancing delay discounting. Subthalamic stimulation shifts evidence accumulation in subjects with obsessive-compulsive disorder towards a functional less cautious style closer to that of healthy controls emphasizing its adaptive nature. Thus, subjects with obsessive compulsive disorder on subthalamic stimulation may be less likely to check for evidence (e.g. checking that the stove is on) with no difference in subjective confidence (or doubt). In a separate study, we replicate in humans (154 healthy controls) using resting state functional connectivity, tracing studies conducted in non-human primates dissociating limbic, associative and motor frontal hyper-direct connectivity with anterior and posterior subregions of the subthalamic nucleus. We show lateralization of functional connectivity of bilateral ventral striatum to right anterior ventromedial subthalamic nucleus consistent with previous observations of lateralization of emotionally evoked activity to right ventral subthalamic nucleus. We use a multi-echo sequence with independent components analysis, which has been shown to have enhanced signal-to-noise ratio, thus optimizing visualization of small subcortical structures. These findings in healthy controls converge with the effective contacts in obsessive compulsive disorder patients localized within the anterior and ventral subthalamic nucleus. We further show that evidence accumulation is associated with anterior associative-limbic subthalamic nucleus and right dorsolateral prefrontal functional connectivity in healthy controls, a region implicated in decision-making under uncertainty. Together, our findings highlight specificity of the anterior associative-limbic subthalamic nucleus in decisional impulsivity. Given increasing interest in the potential for subthalamic stimulation in psychiatric disorders and the neuropsychiatric symptoms of Parkinson's disease, these findings have clinical implications for behavioural symptoms and cognitive effects as a function of localization of subthalamic stimulation., (© The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Obsessive-compulsive disorder (OCD) is a disabling, mostly chronic, psychiatric condition with significant social and economic impairments and is a major public health issue. However, numerous patients are resistant to currently available pharmacological and psychological interventions. Given that recent animal studies and magnetic resonance spectroscopy research points to glutamate dysfunction in OCD, we investigated the metabotropic glutamate receptor 5 (mGluR5) in patients with OCD and healthy controls. We determined mGluR5 distribution volume ratio (DVR) in the brain of ten patients with OCD and ten healthy controls by using [11C]ABP688 positron-emission tomography. As a clinical measure of OCD severity, the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was employed. We found no significant global difference in mGluR5 DVR between patients with OCD and healthy controls. We did, however, observe significant positive correlations between the Y-BOCS obsession sub-score and mGluR5 DVR in the cortico-striatal-thalamo-cortical brain circuit, including regions of the amygdala, anterior cingulate cortex, and medial orbitofrontal cortex (Spearman's ρ's⩾ = 0.68, p < 0.05). These results suggest that obsessions in particular might have an underlying glutamatergic pathology related to mGluR5. The research indicates that the development of metabotropic glutamate agents would be useful as a new treatment for OCD.

Several neuroimaging studies of patients with OCD have pointed to basal ganglia and the frontal cortical regions being relevant for an understanding of the pathophysiology and therapy of OCD. In a search for the neural substrate underlying the therapeutic action of paroxetine in the therapy of OCD we measured regional glucose metabolism in a PET study of 20 OCD patients before and after at least 3 months of treatment. We used 18-fluoro-deoxyglucose PET-scanning to measure regional cerebral glucose metabolic rate (rCMRglc) in 20 non-depressed patients fulfilling DSM-IV criteria for OCD. Patients were studied before and after 12-20 wk of treatment with the serotonin re-uptake inhibitor paroxetine. Clinical assessment rating with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) was performed before the first and after the second study. The PET data was analysed regionally using statistical parametric mapping (SPM-96). A clinical improvement was indicated by a mean decrease of 55% in the Y-BOCS score. There was no difference in global cerebral metabolism before and after treatment whereas a post-treatment reduction in normalized rCMRglc was found in the right caudate nucleus. This finding also showed a significant positive correlation with symptom severity. Our results support hypotheses regarding a malfunction of the cortico-striato-thalamic system in the pathophysiology of OCD and particularly point to the caudate nucleus playing an important role for the therapeutic action of paroxetine in the treatment of OCD.