Altered Corticostriatal Functional Connectivity in Obsessive-compulsive Disorder

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

The relationship between Obsessive Compulsive Disorder (OCD) and Obsessive Compulsive Personality Disorder (OCPD) has been the subject of interest for some time due to the historical assumption that OCPD causes OCD. This study systematically examined the association between OCD and OCPD in terms of prevalence and clinical presentation. The specificity of the association between OCD and OCPD was investigated relative to another axis I anxiety disorder (Panic disorder). Data for this study were drawn from measures taken at initial assessment at a specialist treatment centre for anxiety disorders. Of the 359 participants included in this study, 189 had a principal diagnosis of OCD, while 170 had a principal diagnosis of Panic disorder. Measures included SCID I and II interview modules and self-report measures of anxiety, depression, and OCD syptomatology. Significantly elevated rates of OCPD were found in OCD relative to Panic disorder. Regardless of axis I disorder, individuals with comorbid OCPD reported more severe depression relative to those without. Participants with both OCD and OCPD had greater self-reported OCD symptom severity, doubting, ordering, and hoarding symptoms at assessment relative to those without OCPD. Participants with OCD and comorbid OCPD also reported significantly higher levels of alcohol consumption. There appears to be a significant and specific association between OCD and OCPD. Co-occurring OCD and OCPD is associated with greater severity of impairment in terms of certain OCD symptoms. The significant and specific association between OCD and OCPD suggests that OCPD occurs more frequently with OCD than previously suggested. A comorbid OCPD diagnosis is associated with a greater degree of depression, regardless of axis I disorder, either OCD or Panic disorder. This is an important consideration, as depression can interfere with therapeutic progress (Foa, 1979). Participants with OCD and OCPD had greater self-reported OCD severity, along with doubting, ordering, and hoarding symptoms, relative to those without OCPD. In clinical practice, where OCD symptoms are severe, and the primary OCD symptoms include doubting, ordering, and hoarding, this may indicate a need to assess for comorbid OCPD. This may be useful in terms of including relevant information in formulation with the patient, and in addressing these issues in treatment. There may have been a sampling issue, as the study compared patients from a specialist clinic for the treatment of OCD and Panic disorder. Furthermore, OCD referrals were primary, secondary, or tertiary, whereas Panic disorder referrals were primary or secondary from the immediate catchment area only. This suggests the possibility of greater severity of the OCD sample relative to Panic disorder patients. All participants who met criteria for OCD were assessed for OCPD regardless of whether or not this was indicated by the SCID II screener self-report measure, while participants with Panic disorder were interviewed for OCPD only if indicated by the SCID-II screener. Had participants with Panic disorder been assessed for OCPD regardless of whether or not this was indicated by the SCID-II screener, there is a possibility that a higher rate of OCPD in the Panic disorder sample may have been found.

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.

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.

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

The paper is devoted to graph theoretical analysis of functional connectivity matrices of 96 patients diagnosed with obsessive-compulsive disorder (OCD) and 95 healthy controls. Connectivity matrices were obtained from electroencephalography (EEG) as a solution of inverse problem, each matrix contains functional connectivity of 84 regions of interest (ROIs) corresponding to segmentation according to the Brodmann areas. The connectivity matrix was converted into a graph by applying a threshold. Small-network characteristics such as clustering coefficient and characteristic path length were computed as a function of threshold for 4 frequency bands. It was shown that the level of clustering coefficient is significantly lower for the OCD group than for healthy controls, which means loss in local integration. Characteristic path length for OCD patients was significantly higher than for controls, which indicates loss in multi-scale connections. Regression analysis was used for understanding connection between topological features of the network and severity symptoms evaluated by the Yale-Brown Obsessive-Compulsive scale (Y-BOC). Direct relation was demonstrated between the severity of the disease and local integration properties in theta band (corelation coefficient 0.1870, p-value 0.018208).

Although it was acknowledged that patients with obsessive-compulsive disorder (OCD) would exhibit cognitive inflexibility, the underlying neural mechanism has not been fully clarified. Therefore, this study aimed to investigate the neural substrates involved in cognitive inflexibility among individuals with OCD. A total of 42 patients with OCD and 48 healthy controls (HCs) completed clinical assessment and functional magnetic resonance imaging (fMRI) data collection during cued task switching. Behavioral performances and fMRI activation were compared between the OCD group and the HC group. Psychophysiological interactions (PPIs) analyses were applied to explore functional connectivity related to task switching. Pearson correlation was used to investigate the relationships among behavioral performance, fMRI activity, and obsessive-compulsive symptoms in OCD. The OCD group had a greater switch cost than HCs (χ2 = 5.89, p < .05). A significant difference in reaction time was found during switch (χ2 = 17.72, p < .001) and repeat (χ2 = 16.60, p = .018) between the two groups, while there was no significant difference in group accuracy. Comparison of group differences showed that the OCD group had increased activation in the right superior parietal cortex (rSPL) during task switching, and exhibited increased connectivity of frontoparietal network/default mode network (FPN-DMN; i.e., middle frontal gyrus [MFG]/inferior parietal cortex-precuneus, MFG-middle/posterior cingulate gyrus) and within the FPN (inferior parietal cortex-postcentral gyrus). In the OCD group, the compulsion score was positively correlated with accuracy during switch (r = .405, p = .008, FDRq <.05), and negatively correlated with activation of rSPL (r = -.328, p = .034, FDRq >.05). Patients with OCD had impaired cognitive flexibility and cautious response strategy. The neural mechanism of cognitive inflexibility in OCD may involve increased activation in the rSPL, as well as hyperconnectivity within the FPN and between the FPN and DMN.

Obsessive-compulsive disorder (OCD) is characterized by obsessions and compulsions that significantly impair functioning. Obsessive-compulsive personality disorder (OCPD) co-occurs in 17-45% of OCD patients, worsening outcomes across multiple domains. Therefore, we aimed to study the impact of OCPD in more detail by analyzing selected comorbidities, emotional aspects, and sociodemographic data. This study assessed 78 OCD patients (average age 44.9 years, 34.61% OCPD), using Y-BOCS, BABS, BPAQ, BIS-11, YMRS, HDRS-17, and ASEX. Patients with comorbid OCPD had significantly worse outcomes in symptom severity (Y-BOCS = 0.0006), treatment duration (p = 0.0127), insight (BABS, p = 0.0185), aggression (p = 0.0266), impulsivity (p = 0.0469), depression (HDRS, p = 0.0178), mania (YMRS, p = 0.0003), and sexual dysfunction (ASEX, p = 0.008). OCPD was more prevalent in unemployed individuals (p = 0.046) and older patients (p = 0.009). No significant differences were found regarding gender, education, or relationship status. Obsessions and compulsions, such as contamination (p = 0.025), somatic (p = 0.018), ruminations (p = 0.003), and obsessional slowness (p = 0.007), were more common in the OCPD group. In the group with OCPD, aggression and OCD severity were correlated with increased levels of depression, which can be considered potential correlates of bipolarity in the relationship between OCD and OCPD. In conclusion, OCPD significantly worsens clinical outcomes in OCD across emotional, behavioral, and functional dimensions.

Neurobiological models of obsessive-compulsive disorder (OCD) have emphasized the mediation of clinical symptoms by aberrant frontal-striatal circuits. A recent neurobiological model for normal human emotion perception has proposed distinct ventral and dorsal processing systems corresponding with differential levels of emotion perception. This construct appears also relevant for elucidating the pathophysiology of OCD, being an anxiety disorder. In the present paper, we present a comprehensive review of the neuroimaging literature in OCD, with the aim of critically appraising the current status of imaging-based knowledge on neurophysiological factors in the pathogenesis of OCD, along with the methodological possibilities and limitations of each imaging paradigm for OCD research. Moreover, we intend to relate these experimental findings to the frontal-striatal model and to the model of normal emotion perception. Results of imaging studies point to the need for adjustments in current models, with respect to the involvement of frontalstriatal circuits in OCD, as a ventral-dorsal dissociation may be distinguished. Moreover, data from pediatric OCD patient samples have commenced to shed light on developmental characteristics of OCD. Furthermore, longitudinal designs, in combination with pre-post treatment comparisons, are of great value for assessing the state-trait duality. Finally, the use of multimodal study designs holds great promise for the near future. Keywords: obsessive-compulsive disorder, review, pathophysiology, neurobiological models, neuroimaging

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.

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: Although abnormality of cerebellar-cerebral functional connectivity at rest in obsessive-compulsive disorder (OCD) has been hypothesized, only a few studies have investigated the neural mechanism. To verify the findings of previous studies, a large sample of patients with OCD was studied because OCD shows possible heterogeneity.Methods: Forty-seven medication-free patients with OCD and 62 healthy controls (HCs) underwent resting-state functional magnetic imaging scans. Seed-based connectivity was examined to investigate differences in cerebellar-cerebral functional connectivity in OCD patients compared with HCs. Correlations between functional connectivity and the severity of obsessive-compulsive symptoms were analyzed.Results: In OCD, we found significantly increased functional connectivity between the right lobule VI and the left precuneus, which is a component of the default mode network (DMN), compared to HCs. However, there was no correlation between the connectivity of the right lobule VI-left precuneus and obsessive-compulsive severity.Conclusions: These findings suggest that altered functional connectivity between the cerebellum and DMN might cause changes in intrinsic large-scale brain networks related to the traits of OCD.

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

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

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