Topological Properties of Functional Brain Connectivity in Obsessive-Compulsive Disorder

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

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.

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.

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.

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

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.

Objective: Obsessive-compulsive disorder (OCD) may affect the quality of life (QOL), family relations, professional performance, and relationships of the individual in many other areas. The evidence has emphasized the relevance of examining QOL as a critical outcome in mental health studies. This study aimed to examine possible effects of clinical and demographic features including insight and suicidality on the QOL in patients with OCD. Method: The sample of this study consists of 80 patients diagnosed with OCD according to DSM-IV and 80 healthy volunteers. A sociodemographic and clinical data form and the World Health Organization Quality of Life brief form-Turkish version (WHOQOOL-BREF-TR) were administered to the participants. In addition, the patient group was assessed with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the Hamilton Depression Rating Scale (HAM-D). Insight was evaluated by using the insight item of Y-BOCS and the Overvalued Ideas Scale (OVIS). Results: The average scores for the physical health, psychological health, and social relationship domains of WHOQOOL-BREF-TR were lower in the patient group; however, there was no significant difference in the environmental health domain between the two groups. Negative correlations were found between the severity of the disease, age at illness onset and QOL subdomains. Besides, a history of suicide attempt had a statistically significant effect on all subscales of quality of life. Insight had no significant effect on any QOL subscale. Conclusion: This study shows that the quality of life is affected in OCD and this is partly related to the severity of the disease and suicidality but not to insight. Considering the effects of quality of life in both the treatment and follow-up of this patient group, the importance of identifying the factors affecting the quality of life will be better understood in OCD patients. Further large-scale longitudinal studies are needed to clarify this issue.

Neuroimaging studies have confirmed that acupuncture can promote static functional reorganization in poststroke patients with motor dysfunction. But its effect on dynamic brain networks remains unclear. This study is aimed at investigating how acupuncture affected the brain's dynamic functional network connectivity (dFNC) after ischemic stroke. We conducted a single-center, randomised controlled neuroimaging study in ischemic stroke patients. A total of 53 patients were randomly divided into the true acupoint treatment group (TATG) and the sham acupoint treatment group (SATG) at a ratio of 2 : 1. Clinical assessments and magnetic resonance imaging (MRI) scans were performed on subjects before and after treatment. We used dFNC analysis to estimate distinct dynamic connectivity states. Then, the temporal properties and strength of functional connectivity (FC) matrix were compared within and between the two groups. The correlation analysis between dynamic characteristics and clinical scales was also calculated. All functional network connectivity (FNC) matrices were clustered into 3 connectivity states. After treatment, the TATG group showed a reduced mean dwell time and found attenuated FC between the sensorimotor network (SMN) and the frontoparietal network (FPN) in state 3, which was a sparsely connected state. The FC between the dorsal attention network (DAN) and the default mode network (DMN) was higher after treatment in the TATG group in state 1, which was a relative segregated state. The SATG group preferred to increase the mean dwell time and FC within FPN in state 2, which displayed a local tightly connected state. In addition, we found that the FC value increased between DAN and right frontoparietal network (RFPN) in state 1 in the TATG group after treatment compared to the SATG group. Correlation analyses before treatment showed that the Fugl-Meyer Assessment (FMA) lower score was negatively correlated with the mean dwell time in state 3. FMA score showed positive correlation with FC in RFPN-SMN in state 3. FMA-lower score was positively correlated with FC in DAN-DMN and DAN-RFPN in state 1. Acupuncture has the potential to modulate abnormal temporal properties and promote the balance of separation and integration of brain function. True acupoint stimulation may have a more positive effect on regulating the brain's dynamic function. Clinical Trial Registration. This trial is registered with Chinese Clinical Trials Registry (ChiCTR1800016263).

Alterations in resting-state local functional connectivity in obsessive-compulsive disorder

The effects of childhood trauma and adult stress on obsessive-compulsive symptoms: the role of inflammation markers and thalamic functional connectivity.

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.

Abnormal functional connectivity of the putamen in obsessive-compulsive disorder

Objective To explore the association of peripheral catechol-O-methyl-transferase (COMT)gene expression and obsessive-compulsive disorder(OCD)in Han Chinese.Methods Peripheral blood samples were collected from individuals with OCD(n=35)and age-and sex-matched healthy subjects (n=31).Relative COMT gene expression levels were examined with real-time quantitative reverse transcription PCR in peripheral blood of all the subjects.Structured clinical interview for the 4th Edition of Diagnostic and Statistical Manual of Mental Disorder axisⅡ(SCID-Ⅱ)was used to assess the co-morbidity of OCD and obsessive-compulsive personality disorders(OCPD).The Yale-Brown Obsessive-Compulsive Scale(Y-BOCS)was used to evaluate the severity of obsessive compulsive symptoms.Results The COMT gene expression levels were significantly decreased in the OCD group compared with healthy control group (t=2.56,P＜0.05).The OCD patients showed a 32%down-regulation of COMT gene expression.A significant lower COMT gene expression was observed in non-OCPD patients(n=15)in comparison with healthy controls(t=2.41.P＜0.05),while there was,no significant difference between OCPD patients (n=20)and healthy controls(t=1.50,P＞0.05).The rates of COMT gene expression down-regulation in OCD patients with OCPD and ones without OCPD were 14%and 56%respectively.There was no significant correlation between COMT expression level and the Y-BOCS score(r=0.09,P=0.62).Conclusions These results suggest that COMT gene expression down-regulation is associated with OCD,and the OCD patients with and without OCPD may have different genetic background. Key words: Obsessive-compulsive disorder; Compulsive personality disorder; Catechol Omethyl transferase; Gene expression

Background: Obsessive-compulsive disorder (OCD) is a psychiatric disorder with high clinical heterogeneity manifested by the presence of obsessions and/or compulsions. The classification of the symptom dimensional subtypes is helpful for further exploration of the pathophysiological mechanisms underlying the clinical heterogeneity of OCD. Washing and checking symptoms are the two major symptom subtypes in OCD, but the neural mechanisms of the different types of symptoms are not yet clearly understood. The purpose of this study was to compare regional and network functional alterations between washing and checking OCD based on resting-state functional magnetic resonance imaging (rs-fMRI). Methods: In total, 90 subjects were included, including 15 patients in the washing group, 30 patients in the checking group, and 45 healthy controls (HCs). Regional homogeneity (ReHo) was used to compare the differences in regional spontaneous neural activity among the three groups, and local indicators were analyzed by receiver operating characteristic (ROC) curves as imaging markers for the prediction of the clinical subtypes of OCD. Furthermore, differently activated local brain areas, as regions of interest (ROIs), were used to explore differences in altered brain functioning between washing and checking OCD symptoms based on a functional connectivity (FC) analysis. Results: Extensive abnormalities in spontaneous brain activity involving frontal, temporal, and occipital regions were observed in the patients compared to the HCs. The differences in local brain functioning between checking and washing OCD were mainly concentrated in the bilateral middle frontal gyrus, right supramarginal gyrus, right angular gyrus, and right inferior occipital gyrus. The ROC curve analysis revealed that the hyperactivation right middle frontal gyrus had a better discriminatory value for checking and washing OCD. Furthermore, the seed-based FC analysis revealed higher FC between the left medial superior frontal gyrus and right caudate nucleus compared to that in the healthy controls. Conclusions: These findings suggest that extensive local differences exist in intrinsic spontaneous activity among the checking group, washing group, and HCs. The neural basis of checking OCD may be related to dysfunction in the frontal–striatal network, which distinguishes OCD from washing OCD.