Unmedicated Obsessive-compulsive Disorder Research Articles

Reduced resting-state functional connectivity of default mode network subsystems in patients with obsessive-compulsive disorder

ObjectivesNeuroimaging studies have reported extensive resting-state functional connectivity (rsFC) abnormalities in the default mode network (DMN) in patients with obsessive-compulsive disorder (OCD), but findings are inconsistent. DMN can be divided into three subsystems: core, dorsal medial prefrontal cortex (dMPFC), and medial temporal lobe (MTL). This study aimed to explore abnormalities in rsFC strength within and between DMN subsystems in OCD patients, and their relationship with clinical symptoms. MethodsThis study recruited 39 OCD patients and 45 healthy controls (HCs). OCD symptoms were assessed using the Yale-Brown Obsessive-Compulsive Scale (YBOCS). The seed-to-seed method was used to construct rsFC matrix. The rsFC strength within and between the three DMN subsystems were calculated. ResultsCompared to the HC group, the OCD group exhibited reduced rsFC strength within core subsystem (F = 7.799, p = 0.007, Bonferroni corrected p = 0.042). Further, this reduction was also observed in the unmedicated OCD group (n = 19), but not in the medicated OCD group (n = 18). In addition, rsFC strength within core subsystem was negatively correlated with the obsession subscale of YBOCS in the OCD group (r = −0.512, p = 0.004, Bonferroni corrected p = 0.008). Further, this correlation was also significant in the unmedicated OCD group, but not in the medicated OCD group. ConclusionsOur findings suggest that reduced rsFC strength within core subsystem is a feature of OCD patients and may serve as a potential biomarker of obsession severity. Moreover, pharmacological treatments may affect rsFC strength in DMN.

Habit Learning in OCD: Preliminary Data from a Spanish Sample

IntroductionInstrumental learning involves goal-directed and habitual systems. The Slips-of-Action Task (SOAT) is extensively used to measure habit tendencies and the likelihood of making erroneous responses for devalued outcomes. The SOAT provides a Devaluation Sensitivity Index (DSI), a measure of the balance between relative goal-directed and habitual learning. Individuals with Obsessive-Compulsive Disorder (OCD) often engage in repetitive actions, suggesting a potential deficit in goal-directed control and an increased reliance on habitual learning. Previous literature has shown that medicated OCD adults performed worse on the SOAT task than healthy controls.ObjectivesTo compare habit learning performance in an unmedicated sample:-Goal 1: Between OCD and Healthy Controls (HC)-Goal 2: Across four groups: adult OCD, adult HC, children OCD, and children HC MethodsParticipants: Eighty-three participants (44 OCD patients and 38 healthy controls) completed the study with usable task data. The 44 OCD patients comprised 17 adults (mean age: 26.76 years, SD: 8.61 years) and 27 children/adolescents (mean age: 12.84 years, SD: 2.59 years). The 38 healthy controls included 17 adults (mean age: 30 years, SD: 7.49 years) and 21 children/adolescents (mean age: 14.1 years, SD: 2.19 years). All participants were unmedicated. Measures: Participants completed an adapted version of the “Fabulous Fruit Game”, which included an instrumental training phase to learn Stimulus-Response-Outcomes (S-R-O) associations and a SOAT to assess the strength of learned S-R-O associations. DSI was calculated by subtracting the percentage of responses made toward devalued outcomes from the percentage of responses made toward still valuable outcomes. Behavioral Analyses: Student’s t-test comparing individuals with OCD to HC and a ONEWAY ANOVA to examine group differences across multiple categories.ResultsGoal 1: DSI comparison between individuals with OCD and HC revealed a significant difference, with HC demonstrating superior performance (t (60.9) = 2.60, p = .012, Cohen’s d = .546). Goal 2: The overall DSI comparison across adult OCD, adult HC, children OCD, and children HC showed a non-significant difference (F(3) = 3.407, p = 0.22). However, post hoc analysis revealed significant differences between Adult HC and Youth OCD (I-J Scheffe = 28.82, p = .033), indicating superior performance in adult HC.ConclusionsThis study highlights altered Habit Learning in unmedicated OCD individuals, supported by significant DSI differences compared to HC. Age-related distinctions were observed, emphasizing the need for age-sensitive interventions in understanding and addressing habit-related challenges in OCD.Disclosure of InterestNone Declared

Externally orienting cues improve cognitive control in OCD

Background and objectivesAn executive overload model of obsessive-compulsive disorder (OCD) posits that broad difficulties with executive functioning in OCD result from an overload on the executive system by obsessive thoughts. It implies that, if individuals with OCD “snap out” of their obsessive thoughts, their performance on neurocognitive tasks will improve. MethodsWe test this prediction using the revised Attention Network Test, ANT-R, and distinct subsamples of data from unmedicated OCD and healthy controls (HC). ANT-R includes Simon and Flanker tasks; in both, incongruent trials take longer to resolve (‘conflict costs’). On some trials, a warning cue helps participants to respond faster (‘alerting benefits’). In OCD (N = 34) and HC (N = 46), matched on age, IQ, and sex, we tested (1) the effect of OCD on alerting benefits, and (2) the effect of OCD on warning cue related reductions in conflict costs. In a distinct subsample of OCD (N = 32) and HC (N = 51), we assessed whether alerting benefits and cue-related reductions in conflict costs are associated differently with different OCD symptoms. ResultsA warning cue can help individuals with OCD more than HC to improve performance on Simon and Flanker tasks. This effect is positively associated with severity of contamination symptoms. LimitationsThis study did not directly assess how distracted participants are by obsessive thoughts. It relied on the ANT-R subtraction measures. Symptom severity was assessed using self-report measures. ConclusionsDifficulties in resolving conflict during decision-making in OCD can be modulated by a warning cue presented immediately before an attentional task.

White matter diffusion estimates in obsessive-compulsive disorder across 1653 individuals: machine learning findings from the ENIGMA OCD Working Group

White matter pathways, typically studied with diffusion tensor imaging (DTI), have been implicated in the neurobiology of obsessive-compulsive disorder (OCD). However, due to limited sample sizes and the predominance of single-site studies, the generalizability of OCD classification based on diffusion white matter estimates remains unclear. Here, we tested classification accuracy using the largest OCD DTI dataset to date, involving 1336 adult participants (690 OCD patients and 646 healthy controls) and 317 pediatric participants (175 OCD patients and 142 healthy controls) from 18 international sites within the ENIGMA OCD Working Group. We used an automatic machine learning pipeline (with feature engineering and selection, and model optimization) and examined the cross-site generalizability of the OCD classification models using leave-one-site-out cross-validation. Our models showed low-to-moderate accuracy in classifying (1) “OCD vs. healthy controls” (Adults, receiver operator characteristic-area under the curve = 57.19 ± 3.47 in the replication set; Children, 59.8 ± 7.39), (2) “unmedicated OCD vs. healthy controls” (Adults, 62.67 ± 3.84; Children, 48.51 ± 10.14), and (3) “medicated OCD vs. unmedicated OCD” (Adults, 76.72 ± 3.97; Children, 72.45 ± 8.87). There was significant site variability in model performance (cross-validated ROC AUC ranges 51.6–79.1 in adults; 35.9–63.2 in children). Machine learning interpretation showed that diffusivity measures of the corpus callosum, internal capsule, and posterior thalamic radiation contributed to the classification of OCD from HC. The classification performance appeared greater than the model trained on grey matter morphometry in the prior ENIGMA OCD study (our study includes subsamples from the morphometry study). Taken together, this study points to the meaningful multivariate patterns of white matter features relevant to the neurobiology of OCD, but with low-to-moderate classification accuracy. The OCD classification performance may be constrained by site variability and medication effects on the white matter integrity, indicating room for improvement for future research.

Personality traits as predictors for treatment response to sertraline among unmedicated obsessive-compulsive Disorder: A 12-weeks retrospective longitudinal study

The effectiveness of selective serotonin reuptake inhibitors (SSRIs) as a primary treatment for obsessive-compulsive disorder (OCD) remains uncertain. Even after undergoing standard SSRIs treatment, 40%–60% of individuals with OCD persistently endure symptoms. Recent studies proposed that personality traits may influence the diversity of OCD treatment results. Thus, in this retrospective study, we evaluated the Eysenck Personality Questionnaire (EPQ) scores of 51 untreated patients with OCD and 35 healthy controls. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was employed to assess OCD symptom severity at weeks 0, 2, 4, 8, and 12 of sertraline treatment. The primary outcome focused on the reduction rate of Y-BOCS scores (response: ≥25%; marked response: ≥50%). Our findings revealed that individuals with OCD demonstrated a significantly higher neuroticism score compared to healthy controls. Correlation analyses exposed a positive link between psychoticism and the duration of the disease. Moreover, family history strongly correlated with both obsessive thoughts and the total Y-BOCS score. Subsequent univariate Cox proportional analyses indicated that both low neuroticism and high extraversion traits could forecast the response to sertraline. Furthermore, only a high extraversion trait was linked to a marked response. Our results support the idea that personality traits may contribute to OCD vulnerability and predict sertraline treatment outcomes.

Hyperconnecitivity between dorsal attention and frontoparietal networks predicts treatment response in obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD) presented with repetitive obsessions and/or compulsions were associated with disrupted resting-state functional connectivity (rs-FC). To investigate the pharmacological treatment effect on rs-FC changes in OCD patients we conducted the seed-to-voxel FC analyses using dorsal attention network (DAN), default mode network (DMN), salience network (SN) and frontoparietal network (FPN) and basal ganglia seeds. Twenty-two healthy subjects and twenty-four unmedicated OCD patients underwent resting-state functional magnetic resonance imaging. Patients were rescanned after 12 weeks of escitalopram treatment. We found increased FC both within the DAN and between the DAN and the FPN which was ameliorated after medication and correlated significantly with the clinical improvement in obsession scores. We also observed an anticorrelation between the left caudate and the supplementary motor area in unmedicated OCD patients which also normalized with treatment. Results further showed treatment related normalization of orbitofrontal cortex hyperconnectivity with DMN and hypoconnectivity with DAN whereas aberrant FC between the SN and visual areas appears to be a medication effect. We suggest that DAN to FPN hyperconnectivity which is positively correlated with clinical improvement in obsession scores at pre-treatment stage in present study has a potential for being a neuroimaging marker to predict the treatment response in OCD.

Associations of medication with subcortical morphology across the lifespan in OCD: Results from the international ENIGMA Consortium

BackgroundWidely used psychotropic medications for obsessive-compulsive disorder (OCD) may change the volumes of subcortical brain structures, and differently in children vs. adults. We measured subcortical volumes cross-sectionally in patients finely stratified for age taking various common classes of OCD drugs. MethodsThe ENIGMA-OCD consortium sample (1081 medicated/1159 unmedicated OCD patients and 2057 healthy controls aged 6–65) was divided into six successive 6–10-year age-groups. Individual structural MRIs were parcellated automatically using FreeSurfer into 8 regions-of-interest (ROIs). ROI volumes were compared between unmedicated and medicated patients and controls, and between patients taking serotonin reuptake inhibitors (SRIs), tricyclics (TCs), antipsychotics (APs), or benzodiazepines (BZs) and unmedicated patients. ResultsCompared to unmedicated patients, volumes of accumbens, caudate, and/or putamen were lower in children aged 6–13 and adults aged 50–65 with OCD taking SRIs (Cohen's d = −0.24 to −0.74). Volumes of putamen, pallidum (d = 0.18–0.40), and ventricles (d = 0.31–0.66) were greater in patients aged 20–29 receiving APs. Hippocampal volumes were smaller in patients aged 20 and older taking TCs and/or BZs (d = −0.27 to −1.31). ConclusionsResults suggest that TCs and BZs could potentially aggravate hippocampal atrophy of normal aging in older adults with OCD, whereas SRIs may reduce striatal volumes in young children and older adults. Similar to patients with psychotic disorders, OCD patients aged 20–29 may experience subcortical nuclear and ventricular hypertrophy in relation to APs. Although cross-sectional, present results suggest that commonly prescribed agents exert macroscopic effects on subcortical nuclei of unknown relation to therapeutic response.

Abnormal white-matter rich-club organization in obsessive-compulsive disorder.

Rich‐club organization is key to efficient global neuronal signaling and integration of information. Alterations interfere with higher‐order cognitive processes, and are common to several psychiatric and neurological conditions. A few studies examining the structural connectome in obsessive–compulsive disorder (OCD) suggest lower efficiency of information transfer across the brain. However, it remains unclear whether this is due to alterations in rich‐club organization. In the current study, the structural connectome of 28 unmedicated OCD patients, 8 of their unaffected siblings and 28 healthy controls was reconstructed by means of diffusion‐weighted imaging and probabilistic tractography. Topological and weighted measures of rich‐club organization and connectivity were computed, alongside global and nodal measures of network integration and segregation. The relationship between clinical scores and network properties was explored. Compared to healthy controls, OCD patients displayed significantly lower topological and weighted rich‐club organization, allocating a smaller fraction of all connection weights to the rich‐club core. Global clustering coefficient, local efficiency, and clustering of nonrich club nodes were significantly higher in OCD patients. Significant three‐group differences emerged, with siblings displaying highest and lowest values in different measures. No significant correlation with any clinical score was found. Our results suggest weaker structural connectivity between rich‐club nodes in OCD patients, possibly resulting in lower network integration in favor of higher network segregation. We highlight the need of looking at network‐based alterations in brain organization and function when investigating the neurobiological basis of this disorder, and stimulate further research into potential familial protective factors against the development of OCD.

Aberrant cortico-striatal white matter connectivity and associated subregional microstructure of the striatum in obsessive-compulsive disorder.

The striatum and its cortical circuits play central roles in the pathophysiology of obsessive-compulsive disorder (OCD). The striatum is subdivided by cortical connections and functions; however, the anatomical aberrations in different cortico-striatal connections and coexisting microstructural anomalies in striatal subregions of OCD patients are poorly understood. Thus, we aimed to elucidate the aberrations in cortico-striatal white matter (WM) connectivity and the associated subregional microstructure of the striatum in patients with OCD. From diffusion tensor/kurtosis imaging of 107 unmedicated OCD patients and 110 matched healthy controls (HCs), we calculated the cortico-striatal WM connectivity and segmented the striatum using probabilistic tractography. For the segmented striatal subregions, we measured average diffusion kurtosis values, which represent microstructural complexity. Connectivity and mean kurtosis values in each cortical target and associated striatal subregions were compared between groups. We identified significantly reduced orbitofrontal WM connectivity with its associated striatal subregion in patients with OCD compared to that in HCs. However, OCD patients exhibited significantly increased caudal-motor and parietal connectivity with the associated striatal subregions. The mean kurtosis values of the striatal subregions connected to the caudal-motor and parietal cortex were significantly decreased in OCD patients. Our results highlighted contrasting patterns of striatal WM connections with the orbitofrontal and caudal-motor/parietal cortices, thus supporting the cortico-striatal circuitry imbalance model of OCD. We suggest that aberrations in WM connections and the microstructure of their downstream regions in the caudal-motor-/parietal-striatal circuits may underlie OCD pathophysiology and further provide potential neuromodulation targets for the treatment of OCD.

Reduced T cell immunity in unmedicated, comorbidity-free obsessive-compulsive disorder: An immunophenotyping study

BackgroundImmune system aberrations have been postulated to play a role in the pathophysiology of Obsessive-compulsive disorder (OCD). This study was aimed to examine the profile of immune cell subsets in peripheral blood of un-medicated OCD patients. MethodThirteen drug-naïve/free OCD patients and twenty-six age & sex matched healthy controls were recruited. Immunophenotyping was carried out by staining the whole blood specimens with fluorescent monoclonal antibodies against the cell surface markers such as CD45, CD3, CD16, CD56, CD8, CD4, CD28, CD25 and CD127, followed by data acquisition on BD FACSVerse™ flow cytometer. The proportions of CD4 and CD8 T cells; T regulatory (Tregs), Natural Killer (NK) cells and NK-T cells were compared between patients with OCD and healthy control subjects. ResultsSignificantly reduced percentage of T regulatory (Treg) cells was observed in individuals with OCD compared to healthy control subjects [1.0 ± 0.7 vs. 1.9 ± 1.4; p = 0.03, r = 0.33]. ConclusionTreg cells play a crucial role in regulating the immune response, especially by suppressing the functional activities of T cells. In this study, decreased population of Treg cells essentially indicates a dysregulated T cell and/or T cell mediated immune activation in drug-naïve OCD patients. This preliminary observation might form the basis of further studies examining the immuno-inflammatory/autoimmune origin of OCD.

Network-based functional connectivity predicts response to exposure therapy in unmedicated adults with obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is associated with alterations in cortico-striato-thalamo-cortical brain networks, but some resting-state functional magnetic resonance imaging studies report more diffuse alterations in brain connectivity. Few studies have assessed functional connectivity within or between networks across the whole brain in unmedicated OCD patients or how patterns of connectivity predict response to exposure and ritual prevention (EX/RP) therapy, a first-line treatment for OCD. Herein, multiband resting-state functional MRI scans were collected from unmedicated, adult patients with OCD (n = 41) and healthy participants (n = 36); OCD patients were then offered twice weekly EX/RP (17 sessions). A whole-brain-network-based statistic approach was used to identify group differences in resting-state connectivity. We detected altered pre-treatment functional connectivity between task-positive regions in the temporal gyri (middle and superior) and regions of the cingulo-opercular and default networks in individuals with OCD. Signal extraction was performed using a reconstruction independent components analysis and isolated two independent subcomponents (IC1 and IC2) within this altered connectivity. In the OCD group, linear mixed-effects models tested whether IC1 or IC2 values predicted the slope of change in Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores across EX/RP treatment. Lower (more different from controls) IC2 score significantly predicted greater symptom reduction with EX/RP (Bonferroni-corrected p = 0.002). Collectively, these findings suggest that an altered balance between task-positive and task-negative regions centered around temporal gyri may contribute to difficulty controlling intrusive thoughts or urges to perform ritualistic behaviors.

Disrupted functional connectivity of precuneus subregions in obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD) is a chronic and disablingpsychiatric disorder with high lifetime prevalence, yet the underlying pathogenesis remains not fully understood. Increasing neuroimaging evidence has shown that the disrupted activity of brain functional hubs might contribute to the pathophysiology of OCD. Precuneus is an important brain hub which showed structural and functional abnormalities in OCD patients. However, the functional heterogeneity of the precuneus subregion has not been considered and its relation to OCD symptomatology remains to be elucidated. In this paper, a total of 73 unmedicated OCD patients and 79 matched healthy subjects were recruited and the heterogeneous functional connectivities (FCs) of the precuneus subregions were investigated using resting-state functional magnetic resonance imaging. The FC-based subdivision of the precuneus was performed using the K-means clustering algorithm, which led to a tripartite functional parcellation of precuneus. For each subregion, the distinct connectivity pattern with the whole brain was shown, using both voxel-wise and module-wise analysis, respectively. Decreased FC between dorsal posterior precuneus and vermis (corrected p<0.01) was shown in the patient group, which was negatively correlated with patient compulsions score (ρ = − 0.393, p = 0.001), indicating its contribution to the compulsive behavior inhibition of OCD. Our work might provide new insights into the understanding of precuneus subregion function and the importance of dorsal precuneus-cerebellum functional connectivity in OCD pathophysiology.

Disrupted pathways from the frontal-parietal cortices to basal nuclei and the cerebellum are a feature of the obsessive-compulsive disorder spectrum and can be used to aid in early differential diagnosis

A marker for distinguishing patients with obsessive-compulsive disorder (OCD) spectrum has not yet been identified. Whole-brain resting-state effective and functional connectivity (rsEC and rsFC, respectively) networks were constructed for 50 unmedicated OCD (U-OCD) patients, 45 OCD patients in clinical remission (COCD), 47 treatment-resistant OCD (T-OCD) patients, 42 chronic schizophrenia patients who exhibit OCD symptoms (SCHOCD), and 50 healthy controls (HCs). Multivariate pattern analysis (MVPA) was performed to investigate the accuracy of using connectivity alterations to distinguished among the aforementioned groups. Compared to HCs, rsEC connections were significantly disrupted in the U-OCD (n = 15), COCD (n = 8), and T-OCD (n = 19) groups. Additionally, 21 rsEC connections were significantly disrupted in the T-OCD group compared to the SCHOCD group. The disrupted rsEC networks were associated mainly with the frontal-parietal cortex, basal ganglia, limbic regions, and the cerebellum. Classification accuracies for distinguishing OCD patients from HCs and SCHOCD patients ranged from 66.6% to 98.0%. In conclusion, disrupted communication from the frontal-parietal cortices to subcortical basal nuclei and the cerebellum may represent a functional pathological feature of the OCD spectrum. MVPA based on both abnormal rsEC and rsFC patterns may aid in early differential diagnosis of OCD.

Disrupted pathways from frontal-parietal cortex to basal ganglia and cerebellum in patients with unmedicated obsessive compulsive disorder as observed by whole-brain resting-state effective connectivity analysis – a small sample pilot study

To date, a systematic characterization of abnormalities in resting-state effective connectivity (rsEC) in obsessive-compulsive disorder (OCD) is lacking. The present study aimed to systematically characterize whole-brain rsEC in OCD patients as compared to healthy controls. Using resting-state fMRI data of 50 unmedicated patients with OCD and 50 healthy participants, we constructed whole-brain rsEC networks using Granger causality analysis followed by univariate and multivariate comparisons between patients and controls. Similar analyses were performed for resting-state functional connectivity (rsFC) networks to examine how rsFC and rsEC differentially capture abnormal brain connectivity in OCD. Univariate comparisons identified 10 rsEC networks that were significantly disrupted in patients, and which were mainly associated with frontal-parietal cortex, basal ganglia, and cerebellum. Conversely, abnormal rsFC networks were widely distributed throughout the whole brain. Multivariate pattern analysis revealed a classification accuracy as high as 80.5% for distinguishing patients from controls using combined whole-brain rsEC and rsFC. The results of the present study suggest disrupted communication of information from frontal-parietal cortex to basal ganglia and cerebellum in OCD patients. Using combined whole-brain rsEC and rsFC, multivariate pattern analysis revealed a classification accuracy as high as 80.5% for distinguishing patients from controls. The alterations observed in OCD patients could aid in identifying treatment mechanisms for OCD.

The effects of cognitive behavioral therapy on the whole brain structural connectome in unmedicated patients with obsessive-compulsive disorder

Cognitive behavioral therapy (CBT) is considered a first-line treatment for patients with obsessive-compulsive disorder (OCD), and it possesses advantages over pharmacological treatments in stronger tolerance to distress, lower rates of drop out and relapse, and no physical “side-effects”. Previous studies have reported CBT-related alterations in focal brain regions and connections. However, the effects of CBT on whole-brain structural networks have not yet been elucidated. Here, we collected diffusion MRI data from 34 unmedicated OCD patients before and after 12 weeks of CBT. Fifty healthy controls (HCs) were also scanned twice at matched intervals. We constructed individual brain white matter connectome and performed a graph-theoretical network analysis to investigate the effects of CBT on whole-brain structural topology. We observed significant group-by-time interactions on the global network clustering coefficient and the nodal clustering of the left lingual gyrus, the left middle temporal gyrus, the left precuneus, and the left fusiform gyrus of 26 CBT responders in OCD patients. Further analysis revealed that these CBT responders showed prominently higher global and nodal clustering compared to HCs at baseline and reduced to normal levels after CBT. Such significant changes in the nodal clustering of the left lingual gyrus were also found in 8 CBT non-responders. The pre-to-post decreases in nodal clustering of the left lingual gyrus and the left fusiform gyrus positively correlated with the improvements in obsessive-compulsive symptoms in the CBT-responding patients. These findings indicated that the network segregation of the whole-brain white matter network in OCD patients was abnormally higher and might recover to normal after CBT, which provides mechanistic insights into the CBT response in OCD and potential imaging biomarkers for clinical practice.

Evidence for trial-by-trial dynamic adjustment of task control in unmedicated adults with OCD

According to the conflict monitoring theory, executive control requires two separable processes: conflict-monitoring and conflict-resolution. Deficits in executive control have been observed in adults with obsessive-compulsive disorder (OCD). However, it is not yet clear whether these deficits can be attributed to deficits in conflict-monitoring, in conflict-resolution, or in both. We examined this question by administrating the Simon task to 67 unmedicated adults with OCD and 67 matched controls. The interference effect (incongruent minus congruent) was used to measure conflict-resolution. Trial-by-trial dynamic adaptation (i.e., the Gratton effect), which is indicated by smaller interference effect after conflict-laden trials compared to after non-conflict-laden trials, was used to measure conflict-monitoring. A similar interference effect was found in both the OCD and HC groups with no significant between group differences. Following incongruent trials, the interference effect became smaller for the control group as expected, but was completely eliminated for the OCD group. These data add to the accumulating evidence indicating that conflict-resolution is not globally deficient in unmedicated OCD patients and provide direct evidence that conflict-monitoring is heightened in OCD patients. Our results challenge the assumption of cognitive inflexibility in OCD and highlight the importance of studying unmedicated subjects when investigating executive control.

Static and dynamic network properties of the repetitive transcranial magnetic stimulation target predict changes in emotion regulation in obsessive-compulsive disorder

BackgroundRepetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique to treat psychiatric disorders, such as obsessive-compulsive disorder (OCD). However, the rTMS response varies across subjects. Objective/hypothesisWe hypothesize that baseline network properties of the rTMS target may help understand this variation and predict response. MethodsExcitatory rTMS to the dorsolateral prefrontal cortex (dlPFC) was applied in 19 unmedicated OCD patients, while inhibitory dlPFC-rTMS was applied in 17 healthy controls. The vertex was used as an active control target (19 patients, 18 controls). The rTMS response was operationalized as the individual change in state distress rating during an emotion regulation task. At baseline, subjects underwent resting-state functional MRI. The brain network was constructed by calculating wavelet coherence between regional activity of regions in the Brainnetome atlas. Local and integrative static connectivity and the dynamic network role of the target were calculated. Baseline target region network features were non-parametrically correlated to rTMS response. ResultsIn the dlPFC-stimulated patients, greater local connectivity (Kendall’s Tau = −0.415, p = 0.013) and less promiscuous role of the target (Kendall’s Tau = 0.389, p = 0.025) at baseline were related to greater distress reduction after excitatory rTMS. There were no significant associations in healthy subjects nor in the active control stimulated patients. ConclusionsPre-treatment network topological indices predict rTMS-induced emotional response changes in OCD, such that greater baseline resting-state local connectivity and less temporal integration of the target region imply greater stimulation effects. These results may lead the way towards personalized neuromodulation in OCD.

Abnormal Regional Homogeneity in Patients With Obsessive-Compulsive Disorder and Their Unaffected Siblings: A Resting-State fMRI Study.

Objective: Previous studies suggest that abnormal brain structure and function may be neuroimaging endophenotypes of obsessive-compulsive disorder (OCD). Comparing the intrinsic brain activity of OCD patients and their unaffected siblings will help to further understand the susceptibility to, and pathological mechanisms of, OCD. We used a case–control study design aiming to establish whether the abnormal regional homogeneity (ReHo) found in OCD patients also exists in their unaffected siblings. Method: Fifteen unmedicated OCD patients, 15 of their unaffected siblings, and 30 healthy controls (HCs) received resting-state functional magnetic resonance imaging (r-s fMRI) scanning and clinical evaluation. We used the ReHo method to analyze the inter-regional synchronized activity of all participants. One-way analysis of covariance with post hoc tests was used to compare the ReHo maps across groups. A Pearson correlation analysis was conducted to assess the correlations between clinical characteristics and abnormal ReHo in OCD patients. Results: Relative to HCs, OCD patients and their unaffected siblings showed overlapping higher ReHo values in the right dorsolateral prefrontal cortex (DLPFC). Patients with OCD showed increased ReHo in left middle frontal gyrus (MFG) relative to both their unaffected siblings and HCs. In addition to the right DLPFC and left MFG, OCD patients, compared with HCs, also showed abnormal ReHo in other regions, including higher ReHo in the right superior parietal cortex and lower ReHo in the left inferior parietal cortex, right parahippocampal region, left thalamus, and right inferior temporal cortex. Compared with HCs, the unaffected siblings of patients with OCD had significantly higher ReHo in the right inferior parietal cortex, right MFG, and right supplementary motor area. There was no association between clinical symptoms and abnormal ReHo values in OCD patients. Conclusions: This study found overlapping higher ReHo values in the right DLPFC of OCD patients and their unaffected siblings. Our results suggest that the higher ReHo in the right DLPFC may be a potential neuroimaging endophenotype, which may reflect an increased genetic risk of OCD.

Brain neurochemistry in unmedicated obsessive-compulsive disorder patients and effects of 12-week escitalopram treatment: 1 H-magnetic resonance spectroscopy study.

The purpose of this study was to examine treatment-related neurochemical changes in 28 unmedicated obsessive-compulsive disorder (OCD) patients using 1 H-magnetic resonance spectroscopy (1 H-MRS). We included subjects diagnosed with OCD (n = 28), each with a total duration of illness of less than 5 years, as a study group and age- and sex-matched healthy controls (n = 26). The inclusion criteria for the OCD group were right-handed individuals aged 18 years or older who had not been on any specific treatment for OCD for the last at least 8 weeks and who had no other psychiatric comorbidity. A pre-post and case-control design was employed in which OCD patients underwent 1 H-MRS at baseline and 12 weeks after treatment with escitalopram (n = 21). Clinical assessment was carried out using a semi-structured pro forma Yale-Brown Obsessive Compulsive Scale and the World Health Organization Disability Assessment Scale 2.0 before and after treatment. Volume-localized 1 H-MRS was carried out with a 3-Tesla Philips MR scanner. Our data suggested higher levels of myoinositol (mI), total choline (tCho), and glutamate+glutamine (Glx) in the medial thalamus at pre-assessment in OCD subjects as compared to healthy controls and a significant reduction in tCho and Glx after treatment in OCD subjects. The mI levels in the caudate nucleus and Glx levels in the anterior cingulate cortex were significantly correlated with disease severity on the Yale-Brown Obsessive Compulsive Scale. Our study supports the hypothesis of a hyper-glutaminergic state (as suggested by increased Glx levels) and neurodegeneration (as suggested by increased tCho and mI in the thalamus) in cortico-striato-thalamocortical circuitry in OCD patients as suggested by previous studies using MRS as well as other functional imaging studies.

The right thalamic glutamate level correlates with functional connectivity with right dorsal anterior cingulate cortex/middle occipital gyrus in unmedicated obsessive-compulsive disorder: A combined fMRI and 1H-MRS study.

The imbalance in neurotransmitter and neuronal metabolite concentration within cortico-striato-thalamo-cortical (CSTC) circuit contributes to obsessive-compulsive disorder's (OCD) onset. Previous studies showed that glutamate mediated upregulation of resting-state activity in healthy people. However, there have been few studies investigating the correlational features between functional and neurochemical alterations in OCD. We utilize a combined resting-state functional magnetic resonance imaging (rs-fMRI) and proton magnetic resonance spectroscopy (1H-MRS) approach to investigate the altered functional connectivity (FC) in association with glutamatergic dysfunction in OCD pathophysiology. Three regions of interest are investigated, i.e., medial prefrontal cortex and bilateral thalamus, for seed-based whole-brain FC analysis as well as MRS data acquisition. There are 23 unmedicated adult OCD patients and 23 healthy controls recruited for brain FC analysis. Among them, 12 OCD and 8 controls are performed MRS data acquisition. Besides abnormal FC within CSTC circuit, we also find altered FCs in large-scale networks outside CSTC circuit, including occipital area and limbic and motor systems. The decreased FC between right thalamus and right middle occipital gyrus (MOG) is correlated with glutamatergic signal within right thalamus in OCD patients. Moreover, the FC between right thalamus and right dorsal anterior cingulate cortex (dACC) is associated with glutamate level in right thalamus, specifically in patient's group. Finally, the FC between right thalamus and right MOG is correlated with patient's Yale-Brown Obsessive Compulsive Scale (YBOCS) compulsion and total scores, while the right thalamic glutamatergic signal is associated with YBOCS-compulsion score. Our findings showed that the coupled intrinsic functional-biochemical alterations existed both within CSTC circuit and from CSTC to occipital lobe in OCD pathophysiology.