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Obsessive-compulsive disorder (OCD) is a prevalent and often severely disabling illness with onset generally in childhood or adolescence. Although white matter deficits have been implicated in the neurobiology of OCD, few studies have been conducted in pediatric patients when the brain is still developing and have examined their functional correlat...
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Context 1
... with OCD exhibited significantly higher FA compared to matched healthy volunteers in four white matter tracts: the left dorsal cingulum bundle (p ¼ 0.005; k E ¼ 638), the splenium of the corpus callosum (p ¼ 0.007; k E ¼ 567), the right corticospinal tract (p ¼ 0.008; k E ¼ 552), and the left inferior fronto-occipital fasciculus (p ¼ 0.043; k E ¼ 286) (see Figures 1-4 and Table 2). No regions of significantly lower FA in the patients compared to healthy volunteers were identified at this threshold. ...
Citations
... Correlation analysis suggested that the abnormal EC of Hb-hippocampus was negatively related to the obsessive-compulsive symptom in OCD, which indicated patients with severe OCD symptoms may exhibit a compensatory neural activity in EC of Hb-hippocampus. Previous neuroimaging studies have identified compensatory neural activity in OCD, finding that the compensatory processes may result in normal or only subtly perturbed performance despite the substantial abnormalities in underlying capacities (Gruner & Pittenger, 2017;Gruner et al., 2012;Henseler et al., 2008;Ullman & Pullman, 2015). The potential effect of medications on the EC of Hb-hippocampus in patients with OCD was also excluded in this study. ...
Background
Previous studies have suggested that the habenula (Hb) may be involved in the mechanism of obsessive-compulsive disorder (OCD). However, the specific role of Hb in OCD remains unclear. This study aimed to explore the structural and functional abnormalities of Hb in OCD and their relationship with the clinical symptoms.
Methods
Eighty patients with OCD and 85 healthy controls (HCs) were recruited as the primary dataset. The grey matter volume, resting-state functional connectivity (FC), and effective connectivity (EC) of the Hb were calculated and compared between OCD group and HCs. An independent replication dataset was used to verify the stability and robustness of the results.
Results
Patients with OCD exhibited smaller Hb volume and increased FC of right Hb-left hippocampus than HCs. Dynamic causal model revealed an increased EC from left hippocampus to right Hb and a less inhibitory causal influence from the right Hb to left hippocampus in the OCD group compared to HCs. Similar results were found in the replication dataset.
Conclusions
This study suggested that abnormal structure of Hb and hippocampus-Hb connectivity may contribute to the pathological basis of OCD.
... Notably, these brain regions, as well as their connective tracts, are strongly overlapped with regions that have demonstrated alterations in preterm birth. Altered white matter connectivity between prefrontal and subcortical regions has been shown to be implicated in executive function processes such as IC [29,40,58]. For example, Noble et al. [58] found that white matter FA in the cingulum bundle (CB) and SLF mediated the relationship between years of education and performance on an IC task. ...
Preterm birth (PTB) is associated with increased risk for unfavorable outcomes such as deficits in attentional control and related brain structure alterations. Crucially, PTB is more likely to occur within the context of poverty. The current study examined associations between PTB and inhibitory control (IC) implicated brain regions/tracts and task performance, as well as the moderating role of early life poverty on the relation between PTB and IC-implicated regions/tracts/task performance. 2,899 children from the ABCD study were sampled for this study. Mixed effects models examined the relation between PTB and subsequent IC performance as well as prefrontal gray matter volume, white matter fractional anisotropy (FA), and mean diffusivity (MD). Household income was examined as a moderator. PTB was significantly associated with less improvement in IC task performance over time and decreased FA in left uncinate fasciculus (UF) and cingulum bundle (CB). Early life poverty moderated the relation between PTB and both CB FA and UF MD.
... Most studies demonstrated MD, AD, and RD values were increased in paediatric OCD patients compared to healthy controls. However, there was a report of lower RD in paediatric OCD patients compared to healthy controls in four WM areas: the left dorsal cingulum bundle, the splenium, the right corticospinal tract, and the left inferior fronto-occipital fasciculus (Gruner et al., 2012). There was a trend of FA reduction in paediatric OCD patients compared to healthy controls. ...
... There was a trend of FA reduction in paediatric OCD patients compared to healthy controls. However, two studies revealed higher FA in paediatric OCD patients than in HC in the left inferior longitudinal fasciculus, bilateral superior longitudinal fasciculus, right and left inferior fronto-occipital fasciculus, bilateral corticospinal tract, corpus callosum, splenium and genu, bilateral forceps major, bilateral forceps minor, left dorsal cingulum bundle and right uncinate fasciculus (Gruner et al., 2012;Zarei et al., 2011). Two studies did not show any WM tract alterations in paediatric OCD (Pagliaccio et al., 2020;Piras et al., 2021a, b, c). ...
... Six studies showed that FA measures in the corpus callosum were significantly different in paediatric OCD compared to HCs. Two studies demonstrated that paediatric OCD patients had higher FA values in splenium and genu of the corpus callosum (Gruner et al., 2012;Zarei et al., 2011). FA tends to increase in the early puberty (Brouwer et al., 2012). ...
Microstructural alterations in white matter are evident in obsessive-compulsive disorder (OCD) both in adult and paediatric populations. Paediatric patients go through the process of maturation and thus may undergo different pathophysiology than adult OCD. Findings from studies in paediatric obsessive-compulsive disorder have been inconsistent, possibly due to their small sample size or heterogeneous populations. The aim of this review is to provide a comprehensive overview of white matter structures in paediatric obsessive-compulsive disorder and their correlation with clinical features. Based on PRISMA guidelines, we performed a systematic search on diffusion tensor imaging studies that reported fractional anisotropy, mean diffusivity, radial diffusivity, or axial diffusivity alterations between paediatric patients with obsessive-compulsive disorder and healthy controls using voxel-based analysis, or tract-based spatial statistics. We identified fifteen relevant studies. Most studies reported changes predominantly in the corpus callosum, cingulum, arcuate fasciculus, uncinate fasciculus, inferior longitudinal fasciculus, superior longitudinal fasciculus, inferior fronto-occipital fasciculus, corticospinal tract, forceps minor and major, and the cerebellum in paediatric obsessive-compulsive disorder. These alterations included increased and decreased fractional anisotropy and radial diffusivity, and increased mean and axial diffusivity in different white matter tracts. These changes were associated with obsessive-compulsive disorder symptoms. Moreover, specific genetic polymorphisms were linked with cerebellar white matter changes in paediatric obsessive-compulsive disorder. White matter changes are widespread in paediatric OCD patients. These changes are often associated with symptoms however there are controversies in the direction of changes in some tracts.
... dMRI tractography has become an indispensable tool for studies on various brain disorders including, but not limited to, multiple sclerosis (MS) ( Fleischer et al., 2019;Sbardella et al., 2013 ), amnestic mild cognitive impairment (aMCI) ( Bai et al., 2009;Zhao et al., 2017a ), Alzheimer's disease ( Jack and Holtzman, 2013;Lo et al., 2010;Mito et al., 2018;Toga and Thompson, 2013 ), stroke ( Mukherjee, 2005 ), schizophrenia ( Collin et al., 2016;Goldsmith et al., 2018;Voineskos, 2014 ), depression ( De Witte andMueller, 2017;Korgaonkar et al., 2014 ), obsessive-compulsive disorder (OCD) ( Cao et al., 2021;Chiu et al., 2011;Gan et al., 2017;Gruner et al., 2012;Koch et al., 2014;Widge et al., 2021 ), attention-deficit hyperactivity disorder (ADHD) ( Cao et al., 2014;2013;Damatac et al., 2020;Hong et al., 2014 ) and autism ( Ikuta et al., 2014;Langen et al., 2012;Thomas et al., 2011;Zhang et al., 2018a ). In this section, we are condensing the explanation using two exemplar disorders, multiple sclerosis and schizophrenia , as the methods utilized in the study of such are representative of the work done across a breadth of disorders. ...
Diffusion magnetic resonance imaging (dMRI) tractography is an advanced imaging technique that enables in vivo reconstruction of the brain’s white matter connections at macro scale. It provides an important tool for quantitative mapping of the brain’s structural connectivity using measures of connectivity or tissue microstructure. Over the last two decades, the study of brain connectivity using dMRI tractography has played a prominent role in the neuroimaging research landscape. In this paper, we provide a high-level overview of how tractography is used to enable quantitative analysis of the brain’s structural connectivity in health and disease. We focus on two types of quantitative analyses of tractography, including: 1) tract-specific analysis that refers to research that is typically hypothesis-driven and studies particular anatomical fiber tracts, and 2) connectome-based analysis that refers to research that is more data-driven and generally studies the structural connectivity of the entire brain. We first provide a review of methodology involved in three main processing steps that are common across most approaches for quantitative analysis of tractography, including methods for tractography correction, segmentation and quantification. For each step, we aim to describe methodological choices, their popularity, and potential pros and cons. We then review studies that have used quantitative tractography approaches to study the brain’s white matter, focusing on applications in neurodevelopment, aging, neurological disorders, mental disorders, and neurosurgery. We conclude that, while there have been considerable advancements in methodological technologies and breadth of applications, there nevertheless remains no consensus about the “best” methodology in quantitative analysis of tractography, and researchers should remain cautious when interpreting results in research and clinical applications.
... Finally, decreased FA in 29 additional brain regions, identified by less than 3 papers per region, were found (see Supplementary Table 1) (Benedetti et al., 2013;Gan et al., 2017;Garibotto et al., 2010;Gonçalves et al., 2015;Hawco et al., 2017;He et al., 2017;Lázaro et al., 2014;Li et al., 2014b;Lochner et al., 2012;van de Vondervoort et al., 2019;Zhong et al., 2019) and increased FA in 12 (Agam et al., 2014;Fitzgerald et al., 2014;Gruner et al., 2012;Hartmann et al., 2016;Lochner et al., 2012;van de Vondervoort et al., 2019;Zhong et al., 2019). ...
Neuropsychiatric disorders including generalized anxiety disorder (GAD), obsessive-compulsive disorder (OCD), major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ) have been considered distinct categories of diseases despite their overlapping characteristics and symptomatology. We aimed to provide an in-depth review elucidating the role of glutamate/Glx and white matter (WM) abnormalities in these disorders from a transdiagnostic perspective. The PubMed online database was searched for studies published between 2010 and 2021. After careful screening, 401 studies were included. The findings point to decreased levels of glutamate in the Anterior Cingulate Cortex in both SZ and BD, whereas Glx is elevated in the Hippocampus in SZ and MDD. With regard to WM abnormalities, the Corpus Callosum and superior Longitudinal Fascicle were the most consistently identified brain regions showing decreased fractional anisotropy (FA) across all the reviewed disorders, except GAD. Additionally, the Uncinate Fasciculus displayed decreased FA in all disorders, except OCD. Decreased FA was also found in the inferior Longitudinal Fasciculus, inferior Fronto-Occipital Fasciculus, Thalamic Radiation, and Corona Radiata in SZ, BD, and MDD. Decreased FA in the Fornix and Corticospinal Tract were found in BD and SZ patients. The Cingulum and Anterior Limb of Internal Capsule exhibited decreased FA in MDD and SZ patients. The results suggest a gradual increase in severity from GAD to SZ defined by the number of brain regions with WM abnormality which may be partially caused by abnormal glutamate levels. WM damage could thus be considered a potential marker of some of the main neuropsychiatric disorders.
... 17,[41][42][43] Slowness may arise from either meticulousness or intrusive thoughts of patients with OCD. 44 One other study to date, to our knowledge, has reported adverse effects of SSRIs on WCST performance in pediatric patients with OCD, 45 whereas other studies have reported either null or positive effects of medication. 46,47 An explanation for our findings is that the group receiving medications may have had a more severe form of the disorder that necessitated treatment with psychotropic medication. ...
Importance
Adults with obsessive-compulsive disorder (OCD) display perseverative behavior in stable environments but exhibit vacillating choice when payoffs are uncertain. These findings may be associated with intolerance of uncertainty and compulsive behaviors; however, little is known about the mechanisms underlying learning and decision-making in youths with OCD because research into this population has been limited.
Objective
To investigate cognitive mechanisms associated with decision-making in youths with OCD by using executive functioning tasks and computational modeling.
Design, Setting, and Participants
In this cross-sectional study, 50 youths with OCD (patients) and 53 healthy participants (controls) completed a probabilistic reversal learning (PRL) task between January 2014 and March 2020. A separate sample of 27 patients and 46 controls completed the Wisconsin Card Sorting Task (WCST) between January 2018 and November 2020. The study took place at the University of Cambridge in the UK.
Main Outcomes and Measures
Decision-making mechanisms were studied by fitting hierarchical bayesian reinforcement learning models to the 2 data sets and comparing model parameters between participant groups. Model parameters included reward and punishment learning rates (feedback sensitivity), reinforcement sensitivity and decision consistency (exploitation), and stickiness (perseveration). Associations of receipt of serotonergic medication with performance were assessed.
Results
In total, 50 patients (29 female patients [58%]; median age, 16.6 years [IQR, 15.3-18.0 years]) and 53 controls (30 female participants [57%]; median age, 16.4 years [IQR, 14.8-18.0 years]) completed the PRL task. A total of 27 patients (18 female patients [67%]; median age, 16.1 years [IQR, 15.2-17.2 years]) and 46 controls (28 female participants [61%]; median age, 17.2 [IQR, 16.3-17.6 years]) completed the WCST. During the reversal phase of the PRL task, patients made fewer correct responses (mean [SD] proportion: 0.83 [0.16] for controls and 0.61 [0.31] for patients; 95% CI, −1.31 to −0.64) and switched choices more often following false-negative feedback (mean [SD] proportion: 0.09 [0.16] for controls vs 0.27 [0.34] for patients; 95% CI, 0.60-1.26) and true-positive feedback (mean [SD] proportion: 0.93 [0.17] for controls vs 0.73 [0.34] for patients; 95% CI, −2.17 to −1.31). Computational modeling revealed that patients displayed enhanced reward learning rates (mean difference [MD], 0.21; 95% highest density interval [HDI], 0.04-0.38) but decreased punishment learning rates (MD, −0.29; 95% HDI, −0.39 to −0.18), reinforcement sensitivity (MD, −4.91; 95% HDI, −9.38 to −1.12), and stickiness (MD, −0.35; 95% HDI, −0.57 to −0.11) compared with controls. There were no group differences on standard WCST measures and computational model parameters. However, patients who received serotonergic medication showed slower response times (mean [SD], 1420.49 [279.71] milliseconds for controls, 1471.42 [212.81] milliseconds for patients who were unmedicated, and 1738.25 [349.23] milliseconds for patients who were medicated) (control vs medicated MD, −320.26 [95% CI, −547.00 to −88.68]) and increased unique errors (mean [SD] proportion: 0.001 [0.004] for controls, 0.002 [0.004] for patients who were unmedicated, and 0.008 [0.01] for patients who were medicated) (control vs medicated MD, −0.007 [95% CI, −3.14 to −0.36]) on the WCST.
Conclusions and Relevance
The results of this cross-sectional study indicated that youths with OCD showed atypical probabilistic reversal learning but were generally unimpaired on the deterministic WCST, although unexpected results were observed for patients receiving serotonergic medication. These findings have implications for reframing the understanding of early-onset OCD as a disorder in which decision-making is associated with uncertainty in the environment, a potential target for therapeutic treatment. These results provide continuity with findings in adults with OCD.
... contrast to noise ratio, diffusion data quality, diffusion measures, motion artifacts, multicenter data der (ADHD) (Ameis et al., 2016;van Ewijk, Heslenfeld, Zwiers, Buitelaar, & Oosterlaan, 2012;Wu et al., 2017), dyslexia (Vandermosten, Boets, Wouters, & Ghesquiere, 2012;Wang et al., 2017;Yeatman, Dougherty, Ben-Shachar, & Wandell, 2012), autism spectrum disorder (ASD; Andrews et al., 2019;Ismail et al., 2016;Travers et al., 2012), and obsessive-compulsive disorder (OCD; Gruner et al., 2012;Jayarajan et al., 2012;Silk, Chen, Seal, & Vance, 2013, among others). While such studies have been helpful in elucidating differences in microstructural properties in these populations, there has been no systematic evaluation of how variable signal to noise ratio (SNR) and/or the presence of artifact relates to any of the dependent variables of interest, despite the fact that reports consistently note more motion and artifacts among children, especially those with neurodevelopmental disorders (Afacan et al., 2016;Dosenbach et al., 2017;Greene et al., 2018). ...
Diffusion magnetic resonance imaging (dMRI) datasets are susceptible to several confounding factors related to data quality, which is especially true in studies involving young children. With the recent trend of large-scale multicenter studies, it is more critical to be aware of the varied impacts of data quality on measures of interest. Here, we investigated data quality and its effect on different diffusion measures using a multicenter dataset. dMRI data were obtained from 691 participants (5–17 years of age) from six different centers. Six data quality metrics—contrast to noise ratio, outlier slices, and motion (absolute, relative, translation, and rotational)—and four diffusion measures—fractional anisotropy, mean diffusivity, tract density, and length—were computed for each of 36 major fiber tracts for all participants. The results indicated that four out of six data quality metrics (all except absolute and translation motion) differed significantly between centers. Associations between these data quality metrics and the diffusion measures differed significantly across the tracts and centers. Moreover, these effects remained significant after applying recently proposed harmonization algorithms that purport to remove unwanted between-site variation in diffusion data. These results demonstrate the widespread impact of dMRI data quality on diffusion measures. These tracts and measures have been routinely associated with individual differences as well as group-wide differences between neurotypical populations and individuals with neurological or developmental disorders. Accordingly, for analyses of individual differences or group effects (particularly in multisite dataset), we encourage the inclusion of data quality metrics in dMRI analysis.
... This theory has been attractive because it makes some intuitive sense-i.e., compulsions are often colloquially considered as an inability to restrain oneself from performing particular actions. A variety of tasks have been used to formally test this idea, including Go/NoGo (Snyder et al., 2015), Stop Signal Reaction Time (SSRT) [60,102,103], and Stroop [104][105][106][107]. Though a meta-analysis has not demonstrated impairments on the Go/NoGo task (Snyder et al., 2015), OCD patients demonstrate moderate performance deficits on the Stroop task, with the strongest impact on interference scores and time on incongruent Stroop [108]. ...
... A variety of tasks have been used to formally test this idea, including Go/NoGo (Snyder et al., 2015), Stop Signal Reaction Time (SSRT) [60,102,103], and Stroop [104][105][106][107]. Though a meta-analysis has not demonstrated impairments on the Go/NoGo task (Snyder et al., 2015), OCD patients demonstrate moderate performance deficits on the Stroop task, with the strongest impact on interference scores and time on incongruent Stroop [108]. One study provides evidence that Stroop abnormalities in children and adolescents with OCD are correlated with decreased functional anisotropy in the cingulum bundle [105], but further work is needed to examine the role of PFC regions in mediating these phenotypic changes in OCD. Impairments in inhibition on the SSRT have been specifically associated with abnormalities in the PFC, including alterations in gray matter volume (decreased in OFC and inferior frontal; increased in anterior cingulate [109]). ...
... In addition, fMRI demonstrated functional differences in PFC during SSRT performance, including increased activity in preSMA during successful inhibition trials in OCD patients compared to controls, and decreased activity in the inferior frontal cortex [110], a region that has been consistently linked to response inhibition on this task [111]. However, note that though there is evidence that response inhibition is impaired in OCD and may even serve as an endophenotype (i.e., impairments are also observed in first-degree relatives [60]), a comprehensive meta-analysis has suggested a more complex picture [49], consistent with the fact that there is also significant evidence of normal performance on many of these tasks in OCD (Stop signal- [109,112]; Go/No-go (Snyder et al., 2015); Stroop [104][105][106][107]. Although abnormal interference in the Stroop task was associated with a medium effect size across 23 studies, only a small effect size was seen for commission errors across 15 studies of multiple response inhibition tasks (Go/No-Go; continuous performance task; SSRT), with the upper limit of the confidence intervals approaching zero. ...
Obsessive Compulsive Disorder (OCD) is a highly prevalent and severe neuropsychiatric disorder, with an incidence of 1.5–3% worldwide. However, despite the clear public health burden of OCD and relatively well-defined symptom criteria, effective treatments are still limited, spotlighting the need for investigation of the neural substrates of the disorder. Human neuroimaging studies have consistently highlighted abnormal activity patterns in prefrontal cortex (PFC) regions and connected circuits in OCD during both symptom provocation and performance of neurocognitive tasks. Because of recent technical advances, these findings can now be leveraged to develop novel targeted interventions. Here we will highlight current theories regarding the role of the prefrontal cortex in the generation of OCD symptoms, discuss ways in which this knowledge can be used to improve treatments for this often disabling illness, and lay out challenges in the field for future study.
... A review of the individual studies in youth with OCD reveal underperformance on tests of set-shifting in four studies (Andrés et al., 2007;Gottwald et al., 2018;Gruner et al., 2012;Isık Taner et al., 2011;Shin et al., 2008) but comparable performance to non-psychiatric controls in four studies (Beers et al., 1999;Kodaira et al., 2012;Negreiros et al., 2020;Ornstein et al., 2010;Wilton et al., 2020). In the domain of response inhibition, seven studies report no difference from controls (Andrés et al., 2007;Chang et al., 2007;Huyser et al., 2011;Negreiros et al., 2020;Ornstein et al., 2010;Wilton et al., 2020;Woolley et al., 2008), one study reported better performance (Beers et al., 1999) and another underperformance (Woolley et al., 2008) relative to non-psychiatric controls. ...
There is a paucity of literature on neuropsychological functions in youth with obsessive-compulsive disorder (OCD). Most studies have small sample sizes and have yielded inconsistent results. A recent meta-analysis failed to identify any significant impairments. We studied neuropsychological functions (attention, verbal fluency, working memory, set-shifting, response inhibition, planning and visuospatial abilities) in a large sample of youth with OCD (n = 97) in comparison with controls who did not have OCD (n = 50). After controlling for the confounding effects (age, sex, severity of depression and anxiety, presence of comorbid attention-deficit hyperactivity disorder, any tic disorder, number of comorbidities, and non-verbal intelligence measured by the standard progressive matrices), the youth with OCD significantly underperformed with large effect sizes compared to controls, only on the test of ‘behavioral reversal’, measured by the Object Alternation Test (trials to reach criterion p < 0.001, Cohen's d = 1.49; perseverative errors p < 0.001, Cohen's d = 1.31). Patients also underperformed on a task of planning, but it was statistically insignificant. Certain comorbid disorders, antipsychotic use and age of onset did not influence neuropsychological performance significantly. Our study demonstrates that youth with OCD may have impaired ‘set-shifting’ in the form of ‘behavioral reversal’ and possibly planning, findings broadly consistent with the literature in adults and with the fronto-striatal model of OCD. It is possible that youth may accumulate more neuropsychological impairments over a period, as the illness continues into adulthood.
... There is evidence that the human brain's protracted myelination 46,47 underpins myelin vulnerability along a continuum from early to late stages of development and disease 48 . Thus, it has been suggested that pediatric OCD could be a neurodevelopmental disorder with potentially differing patterns of myelination occurring throughout life 49 . Indeed, evidence in healthy subjects indicates that the psychiatric trait of compulsivity is linked to reduced myelin growth that emerges only during adolescence (being present only to a minor extent in childhood) as a result of aberrant developmental processes 23 . ...
Microstructural alterations in cortico-subcortical connections are thought to be present in obsessive–compulsive disorder (OCD). However, prior studies have yielded inconsistent findings, perhaps because small sample sizes provided insufficient power to detect subtle abnormalities. Here we investigated microstructural white matter alterations and their relation to clinical features in the largest dataset of adult and pediatric OCD to date. We analyzed diffusion tensor imaging metrics from 700 adult patients and 645 adult controls, as well as 174 pediatric patients and 144 pediatric controls across 19 sites participating in the ENIGMA OCD Working Group, in a cross-sectional case-control magnetic resonance study. We extracted measures of fractional anisotropy (FA) as main outcome, and mean diffusivity, radial diffusivity, and axial diffusivity as secondary outcomes for 25 white matter regions. We meta-analyzed patient-control group differences (Cohen’s d) across sites, after adjusting for age and sex, and investigated associations with clinical characteristics. Adult OCD patients showed significant FA reduction in the sagittal stratum (d = −0.21, z = −3.21, p = 0.001) and posterior thalamic radiation (d = −0.26, z = −4.57, p < 0.0001). In the sagittal stratum, lower FA was associated with a younger age of onset (z = 2.71, p = 0.006), longer duration of illness (z = −2.086, p = 0.036), and a higher percentage of medicated patients in the cohorts studied (z = −1.98, p = 0.047). No significant association with symptom severity was found. Pediatric OCD patients did not show any detectable microstructural abnormalities compared to controls. Our findings of microstructural alterations in projection and association fibers to posterior brain regions in OCD are consistent with models emphasizing deficits in connectivity as an important feature of this disorder.
