Hyperactive Error Responses and Altered Connectivity in Ventromedial and Frontoinsular Cortices in Obsessive-Compulsive Disorder

Background: Obsessive-compulsive disorder (OCD) is characterized by alterations in brain connectivity, particularly within the default mode network (DMN) and the salience network (SN). Investigating these connectivity differences can provide a deeper understanding of the neural mechanisms underlying OCD. Methods: This cross-sectional study involved 58 patients diagnosed with OCD and 38 healthy control subjects, totaling 96 participants. Resting-state functional MRI (fMRI) data were acquired and analyzed using the CONN toolbox to examine functional connectivity within intrinsic resting-state networks. Graph theory metrics were applied to evaluate node connections and the overall network topology. Clinical symptoms were assessed using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), and their correlations with connectivity patterns and graph-theory parameters were analyzed. Results: The OCD patients and healthy controls were matched in terms of age, gender, marital status, socioeconomic status, and handedness. However, OCD patients had significantly worse general health, quality of life, and higher levels of depression and anxiety. Network analyses revealed altered whole-brain connectivity in OCD patients, particularly within the DMN and the frontoparietal network. The most significant between-group connectivity differences were observed between the posterior parietal cortex (PPC) and the precuneus. Disruptions in the DMN, specifically altered connectivity between the medial prefrontal cortex and posterior cingulate cortex, and changes in the SN involving the anterior insula and anterior cingulate cortex, were significantly correlated with the severity of OCD symptoms. Conclusions: The findings suggest that OCD is associated with distinct alterations in DMN connectivity, which may play a critical role in the disorder's pathophysiology. These disruptions offer potential targets for therapeutic intervention. Further research is needed to explore these connectivity changes in larger cohorts and at various stages of OCD to better understand their clinical significance.

Objective To investigate the regulatory effect of cognitive behavioral therapy (CBT) on the functional connectivity of cognitive control network in untreated obsessive-compulsive disorder (OCD) patients, so as to provide evidence for understanding the neurobiological mechanism of CBT. Methods A total of 45 OCD patients and 45 matched normal controls were recruited at the outpatient clinic in Beijing Anding Hospital. Four therapists provided 14 times of CBT treatment for OCD patients. All subjects underwent clinical symptom assessment and magnetic resonance imaging at baseline and at the end of 12 weeks. The clinical symptoms were assessed by the psychiatrists using Y-BOCS, HAMD17 and HAMA. The clinical symptoms of OCD patients before and after CBT treatment were compared. The GRETNA software package was used to preprocess the resting-state fMRI data. The whole brain function network was constructed with the template of Power 264 functional brain area as the network node. The function connection intensity outside the cognitive control network was calculated, and the function connection of 2 groups of brain networks at two timepoints were compared by repeated measurement of variance analysis. Results A total of 41 patients completed CBT. The scores of obsessive-compulsive symptoms, anxiety symptoms and depressive symptoms decreased at the end of 12th week, of which 32 patients were improved (Y-BOCS reduction ≥35%). Single factor repeated analysis of variance and post hoc tests were performed between patients with improvement and normal controls. At baseline, the functional connection between the cingulo-opercular network and the salience network of OCD patients was lower than that of the normal control (0.172±0.060 vs. 0.215±0.076, t=1.731, P=0.040), it increased after treatment (0.186±0.171 vs. 0.172±0.060, t=2.480, P=0.010). At baseline, the functional connection of cingulo-opercular network and subcortical network in OCD patients was lower than that of normal control (0.119±0.081 vs. 0.129±0.070, t=1.640, P=0.040), and it increased after treatment (0.130±0.161 vs. 0.119±0.081, t=2.421, P=0.020). At baseline, the functional connection between the frontal-parietal network and subcortical network was lower than that of normal controls (-0.004±0.039 vs. 0.021±0.054, t=2.280, P=0.020), and it increased after treatment (0.020±0.042 vs.-0.004±0.039, t=-2.300 P=0.020). Conclusions CBT could effectively improve obsessive-compulsive symptoms accompanying with improvement of the external functional connectivity of cognitive control network in OCD patients. Key words: Obsessive-compulsive disorder; Cognitive therapy; Cognitive control network; Functional connectivity

Reversal Learning as a Neuropsychological Indicator for the Neuropathology of Obsessive Compulsive Disorder? A Behavioral Study

Altered connectivity within and between the default mode, central executive, and salience networks in obsessive-compulsive disorder

FRONTIERS COMMENTARY article Front. Psychiatry, 04 May 2016 Volume 7 - 2016 | https://doi.org/10.3389/fpsyt.2016.00078

Background: Neuroimaging studies show that obsessive–compulsive disorder (OCD) is characterized by an alteration of the cortico–striato–thalamo–cortical (CSTC) system in terms of an imbalance of activity between the direct and the indirect loop of the CSTC. As resting-state functional connectivity (FC) studies investigated only specific parts of the CSTC in patients with OCD up to now, the present study aimed at exploring FC in the CSTC as a whole.Methods: We investigated potential alterations in resting-state FC within the CSTC system in 44 OCD patients and 40 healthy controls by taking into consideration all relevant nodes of the direct and indirect CSTC loop.Results: Compared to healthy controls, OCD patients showed an increased FC between the left subthalamic nucleus (STN) and the left external globus pallidus (GPe), as well as an increased FC between the left GPe and the left internal globus pallidus (GPi).Conclusion: These findings may contribute to a better understanding of the OCD pathophysiology by providing further information on the connectivity alterations within specific regions of the CSTC system. In particular, increased FC between the STN and the left GPe may play a major role in OCD pathology. This assumption is consistent with the fact that these regions are also the main target sites of therapeutic deep brain stimulation in OCD.

Background: Previous studies have indicated the resting-state default mode network (DMN) related connectivity serving as predictor of sustained attention performance in healthy people. Interestingly, sustained attention deficits as well as DMN-involved functional connectivity (FC) alterations are common in both patients with schizophrenia (SCZ) and with obsessive-compulsive disorder (OCD). Thus, the present study was designed to investigate whether the DMN related resting-state connectivity alterations in these two psychiatric disorders were neural correlates of their sustained attention impairments.Methods: The study included 17 SCZ patients, 35 OCD patients and 36 healthy controls (HCs). Sustained attention to response task was adopted to assess the sustained attention. Resting-state scan was administrated and seed-based whole-brain FC analyses were performed with seeds located in classical DMN regions including bilateral medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC).Results: Both SCZ and OCD patients had poorer sustained attention than HCs. Sustained attention deficits in OCD was negatively correlated with their impaired FC of right mPFC-left superior frontal gyrus (SFG) within DMN, and that in SCZ was significantly correlated with their altered FC of left mPFC-bilateral anterior cingulate cortex (ACC) which indicated interaction between DMN and salience network. In addition, the FC between left mPFC and right parietal lobe indicating the interaction between DMN and frontal-parietal network was correlated with sustained attention in both SCZ and OCD.Conclusion: These findings suggest the importance of DMN-involved connectivity, both within and between networks in underlying sustained attention deficits in OCD and SCZ. Results further support the potential of resting-state FC in complementing information for cognitive deficits in psychiatric disorders.

Obsessive-compulsive disorder (OCD) is a chronic psychiatric illness with complex clinical manifestations. Cognitive dysfunction may underlie OC symptoms. The frontoparietal network (FPN) is a key region involved in cognitive control. However, the findings of impaired FPN regions have been inconsistent. We employed meta-analysis to identify the fMRI-specific abnormalities of the FPN in OCD. PubMed, Web of Science, Scopus, and EBSCOhost were searched to screen resting-state functional magnetic resonance imaging (rs-fMRI) studies exploring dysfunction in the FPN of OCD patients using three indicators: the amplitude of low-frequency fluctuation/fractional amplitude of low-frequency fluctuation (ALFF/fALFF), regional homogeneity (ReHo) and functional connectivity (FC). We compared all patients with OCD and control group in a primary analysis, and divided the studies by medication in secondary meta-analyses with the activation likelihood estimation (ALE) algorithm. A total of 31 eligible studies with 1359 OCD patients (756 men) and 1360 healthy controls (733 men) were included in the primary meta-analysis. We concluded specific changes in brain regions of FPN, mainly in the left dorsolateral prefrontal cortex (DLPFC, BA9), left inferior frontal gyrus (IFG, BA47), left superior temporal gyrus (STG, BA38), right posterior cingulate cortex (PCC, BA29), right inferior parietal lobule (IPL, BA40) and bilateral caudate. Additionally, altered connectivity within- and between-FPN were observed in the bilateral DLPFC, right cingulate gyrus and right thalamus. The secondary analyses showed improved convergence relative to the primary analysis. OCD patients showed dysfunction FPN, including impaired local important nodal brain regions and hypoconnectivity within the FPN (mainly in the bilateral DLPFC), during the resting state. Moreover, FPN appears to interact with the salience network (SN) and default mode network (DMN) through pivotal brain regions. Consistent with the hypothesis of fronto-striatal circuit dysfunction, especially in the dorsal cognitive circuit, these findings provide strong evidence for integrating two pathophysiological models of OCD.

Obsessive compulsive disorder (OCD) is a serious mental disease highly associated with the dysfunctional dynamics of brain networks. The default mode network (DMN) is an essential brain network responding to various cognitive functions, which has been reported the abnormality in OCD patients. However, the underlying evolutions of temporal-spatial neurodynamics in fast-changing DMN activity of OCD remains largely unclear. In the present work, we tried to address this issue by tracking the neurodynamic structure of electrophysiological DMN activity in OCD patients during the resting state. To achieve this purpose, we reconstructed the DMN source activity from the scalp EEG signal with the exact low-resolution brain electromagnetic tomography (LORETA) algorithm, and applied coactive micropattern (CAMP) analysis developed by our previous studies to characterize DMN dynamics. We observed three CAMPs with distinct spatial structures in DMN dynamics for the normal subjects, while there were four different CAMPs in OCD patients. More interestingly, the temporal features of CAMPs which displayed similar spatial structures in two groups were also significantly altered in OCD patients compared with those in normal subjects, implying an abnormal DMN dynamic structure for OCD. Moreover, stronger DMN source connectivity in different CAMP networks emerged in OCD patients, where the posterior cingulate cortex and frontal cortex might be two hub regions with more increased connectivity. Overall, our results showed pathological alterations in the dynamic configuration of the DMN in OCD patients and revealed the neural brain network mechanism for OCD. All these findings could deepen our understanding of the neural pathology of OCD and might provide potential electrophysiological markers for diagnosing OCD patients clinically.

Despite emotion regulation being altered in patients with obsessive-compulsive disorder (OCD), no studies have investigated its relation to multimodal amygdala connectivity. We compared corticolimbic functional and structural connectivity between OCD patients and healthy controls (HCs), and correlated this with the dispositional use of emotion regulation strategies and with OCD severity. OCD patients (n=73) and HCs (n=42) were assessed for suppression and reappraisal strategies using the Emotion Regulation Questionnaire (ERQ) and for OCD severity using the Yale-Brown Obsessive-Compulsive Scale. Resting-state functional magnetic resonance imaging (rs-fMRI) connectivity maps were generated using subject-specific left amygdala (LA) and right amygdala (RA) masks. We identified between-group differences in amygdala whole-brain connectivity, and evaluated the moderating effect of ERQ strategies. Significant regions and amygdala seeds were used as targets in probabilistic tractography analysis. Patients scored higher in suppression and lower in reappraisal. We observed higher rs-fMRI RA-right postcentral gyrus (PCG) connectivity in HC, and in patients this was correlated with symptom severity. Reappraisal scores were associated with higher negative LA-left insula connectivity in HC, and suppression scores were negatively associated with LA-precuneus and angular gyri connectivity in OCD. Structurally, patients showed higher mean diffusivity in tracts connecting the amygdala with the other targets. RA-PCG connectivity is diminished in patients, while disrupted emotion regulation is related to altered amygdala connectivity with the insula and posterior brain regions. Our results are the first showing, from a multimodal perspective, the association between amygdala connectivity and specific emotional processing domains, emphasizing the importance of amygdala connectivity in OCD pathophysiology.

Altered resting-state amygdala-cerebellar functional connectivity is associated with intolerance of uncertainty in patients with obsessive-compulsive disorder: A longitudinal study.

Abnormal functional network of the thalamic subregions in adult patients with obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD) is an anxiety disorder with significant morbidity whose pathophysiology is not fully understood. Neuroimaging studies have characterized OCD in terms of elevated striatal and prefrontal reactivity to emotion provocation. This neural model may be informed by investigation of functional connectivity in OCD, identifying alterations in how sensory information is integrated into frontostriatal regions. The current study employed functional magnetic resonance imaging (fMRI) to compare neural activity and connectivity in 31 OCD patients (12 washing and 19 checking subtypes) and 17 healthy volunteers in an emotion provocation paradigm using visual stimuli. OCD status was associated with hyper-activation of the posterior cingulate (PCg) in response to emotion provocation. Additionally, OCD patients demonstrated elevated PCg functional connectivity with the visual cortices and frontostriatal regions. Exploratory analyses suggested that stimulus-provoked activity and connectivity was elevated for checking subtypes in motor cortices, and elevated in washing subtypes in the anterior insula and orbitofrontal cortex. The PCg's role in moderating connectivity between the visual cortex and frontolimbic regions is muted in OCD, consistent with the PCg's suggested role in regulating attention towards emotional stimuli. Exploratory analyses suggest distinct PCg connectivity profiles in OCD subtypes, with checking linked to motor activation, but washing linked to a network supporting emotional salience. The study was not powered to fully investigate the effects of medication, patients often endorsed secondary symptom subtypes that muddied washing/checking distinctions, and the emotion provocation paradigm was of limited intensity compared to life stressors.

The aim of this study is to determine whether the levels of zonulin and occludin, tight junctions (TJ) proteins in the intestinal epithelium, will differ between obsessive compulsive disorder (OCD) patients and healthy controls. We also intended to investigate whether these would vary in OCD patients with and without major depressive disorder (MDD) comorbidity and in comparison with healthy controls. Sixty patients diagnosed with OCD and 30 healthy controls were included in the study. The cases were administered the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the Hamilton Depression Rating Scale (HDRS). The patients were divided into two subgroups based on their HDRS scores and presence of MDD comorbidity. Zonulin and occludin levels were measured using the ELISA method. The research was carried out between April 2021 and October 2021. Zonulin and occludin levels were significantly higher in the OCD patient group than in the control group (p<0.001). The levels of both were also significantly higher in the OCD patients with MDD comorbidity (OCD+MDD) compared to those without MDD (OCD-MDD) (p<0.001). Zonulin and occludin levels also rose significantly as disease severity increased in the OCD patient group (respectively; p<0.001, p=0.001). The levels of both increased in line with the severity of depression based on HDRS scores in the OCD+MDD group (p<0.001). A positive correlation was determined between the duration of OCD and zonulin and occludin levels. Evaluation of the entire OCD group revealed a moderate positive correlation between Y-BOCS and HDRS scores and zonulin and occludin. Zonulin and occludin levels in this research were significantly higher in the patients with OCD than in the healthy controls. That elevation was positively correlated with disease duration and severity, and the increase was significantly more pronounced in OCD with MDD comorbidity. These findings point to a possible disorder in the intestinal barrier and blood-brain barrier in OCD patients.

Chronic tics and Tourette syndrome in patients with obsessive–compulsive disorder