Functional connectivity in obsessive-compulsive disorder and its subtypes.

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

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

Background: A large amount of resting-state functional magnetic resonance imaging (rs-fMRI) studies have revealed abnormalities of regional homogeneity (ReHo, an index of localized intraregional connectivity) in the obsessive-compulsive disorder (OCD) in the past few decades, However, the findings of these ReHo studies have remained inconsistent. Hence, we performed a meta-analysis to investigate the concurrence across ReHo studies for clarifying the most consistent localized connectivity underpinning this disorder.Methods: A systematic review of online databases was conducted for whole-brain rs-fMRI studies comparing ReHo between OCD patients and healthy control subjects (HCS). Anisotropic effect size version of the seed-based d mapping, a voxel-wise meta-analytic approach, was adopted to explore regions of abnormal ReHo alterations in OCD patients relative to HCS. Additionally, meta-regression analyses were conducted to explore the potential effects of clinical features on the reported ReHo abnormalities.Results: Ten datasets comprising 359 OCD patients and 361 HCS were included. Compared with HCS, patients with OCD showed higher ReHo in the bilateral inferior frontal gyri and orbitofrontal cortex (OFC). Meanwhile, lower ReHo was identified in the supplementary motor area (SMA) and bilateral cerebellum in OCD patients. Meta-regression analysis demonstrated that the ReHo in the OFC was negatively correlated with illness duration in OCD patients.Conclusions: Our meta-analysis gave a quantitative overview of ReHo findings in OCD and demonstrated that the most consistent localized connectivity abnormalities in individuals with OCD are in the prefrontal cortex. Meanwhile, our findings provided evidence that the hypo-activation of SMA and cerebellum might be associated with the pathophysiology of OCD.

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.

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.

Unprecedented 4D spatiotemporal infant regional cerebral blood flow framework and region-specific physiology–function coupling across infancy were elucidated, highlighting strong physiology–function coupling specifically at the default-mode network to meet extraneuronal metabolic demand for network emergence.

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

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.

Cognitive theories of obsessive-compulsive disorder (OCD) stress the importance of dysfunctional beliefs in the development and maintenance of the disorder. However, a neurobiological understanding of these cognitive models, including thought-action fusion (TAF), is surprisingly lacking. Thus, this functional magnetic resonance imaging study aimed to investigate whether altered functional connectivity (FC) is associated with the TAF paradigm in OCD patients. Forty-one OCD patients and 47 healthy controls (HCs) participated in a functional magnetic resonance imaging study using a TAF task, in which they were asked to read the name of a close or a neutral person in association with positive and negative statements. The conventional TAF condition (negative statements/close person) induced significant FC between the regions of interest (ROIs) identified using multivoxel pattern analysis and the visual association areas, default mode network subregions, affective processing, and several subcortical regions in both groups. Notably, sparser FC was observed in OCD patients. Further analysis confined to the cortico-striato-thalamo-cortical (CSTC) and affective networks demonstrated that OCD patients exhibited reduced ROI FC with affective regions and greater ROI FC with CSTC components in the TAF condition compared to HCs. Within the OCD patients, middle cingulate cortex-insula FC was correlated with TAF and responsibility scores. Our TAF paradigm revealed altered context-dependent engagement of the CSTC and affective networks in OCD patients. These findings suggest that the neurobiology of cognitive models corresponds to current neuroanatomical models of OCD. Further, they elucidate the underlying neurobiological mechanisms of OCD at the circuit-based level.

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.

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.

Evidence suggests that obsessive compulsive disorder (OCD) is associated with an overactive error control system. A key role in error detection and control has been ascribed to the fronto-cingulate system. However, the exact functional interplay between the single components of this network in OCD is largely unknown. Therefore, the present study combined a univariate data analysis and effective connectivity analysis using dynamic causal modeling (DCM) to examine error control in 21 patients with OCD and 21 matched healthy controls. All subjects performed an adapted version of the Stroop color-word task while undergoing fMRI scans. Enhanced activation in the fronto-cingulate system could be detected in OCD patients during the incongruent task condition. Additionally, task-related modulation of effective connectivity from the dorsal ACC to left DLPFC was significantly stronger in OCD patients. These findings are consistent with an overactive error control system in OCD subserving suppression of prepotent responses during decision-making.

Neurobiological models of obsessive-compulsive disorder (OCD) emphasize disturbances in the function and connectivity of brain corticostriatal networks, or "loops." Although neuroimaging studies of patients have supported this network model of OCD, very few have applied measurements that are sensitive to brain connectivity features. Using resting-state functional magnetic resonance imaging, we tested the hypothesis that OCD is associated with disturbances in the functional connectivity of primarily ventral corticostriatal regions, measured from coherent spontaneous fluctuations in the blood oxygenation level-dependent (BOLD) signal. Case-control cross-sectional study. Hospital referral OCD unit and magnetic resonance imaging facility. A total of 21 patients with OCD (10 men, 11 women) and 21 healthy control subjects matched for age, sex, and estimated intelligence. Voxelwise statistical parametric maps testing the strength of functional connectivity of 4 striatal seed regions of interest (dorsal caudate nucleus, ventral caudate/nucleus accumbens, dorsal putamen, and ventral putamen) with remaining brain areas. For both groups, there was a clear distinction in the pattern of cortical connectivity of dorsal and ventral striatal regions, consistent with the notion of segregated motor, associative, and limbic corticostriatal networks. Between groups, patients with OCD had significantly increased functional connectivity along a ventral corticostriatal axis, implicating the orbitofrontal cortex and surrounding areas. The specific strength of connectivity between the ventral caudate/nucleus accumbens and the anterior orbitofrontal cortex predicted patients' overall symptom severity (r(2) = 0.57; P < .001). Additionally, patients with OCD showed evidence of reduced functional connectivity of the dorsal striatum and lateral prefrontal cortex, and of the ventral striatum with the region of the midbrain ventral tegmental area. This study directly supports the hypothesis that OCD is associated with functional alterations of brain corticostriatal networks. Specifically, our findings emphasize abnormal and heightened functional connectivity of ventrolimbic corticostriatal regions in patients with OCD.

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Altered resting-state functional connectivity in patients with obsessive–compulsive disorder: A magnetoencephalography study