Alterations in resting-state local 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

Local versus long-range connectivity patterns of auditory disturbance in schizophrenia

Abnormal interhemispheric functional connectivity correlates with several neurologic and psychiatric conditions, including depression, obsessive-compulsive disorder, schizophrenia, and stroke. Abnormal interhemispheric functional connectivity also correlates with abuse of cannabis and cocaine. In the current report, we evaluated whether tobacco abuse (i.e., cigarette smoking) is associated with altered interhemispheric connectivity. To that end, we examined resting state functional connectivity (RSFC) using magnetic resonance imaging (MRI) in short term tobacco deprived and smoking as usual tobacco smokers, and in non-smoker controls. Additionally, we compared diffusion tensor imaging (DTI) in the same subjects to study differences in white matter. The data reveal a significant increase in interhemispheric functional connectivity in sated tobacco smokers when compared to controls. This difference was larger in frontal regions, and was positively correlated with the average number of cigarettes smoked per day. In addition, we found a negative correlation between the number of DTI streamlines in the genual corpus callosum and the number of cigarettes smoked per day. Taken together, our results implicate changes in interhemispheric functional and anatomical connectivity in current cigarette smokers.

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.

Emerging evidences suggest that cognitive deficits in individuals with mild cognitive impairment (MCI) are associated with disruptions in brain functional connectivity (FC). This systematic review and meta-analysis aimed to comprehensively evaluate alterations in FC between MCI individuals and healthy control (HC) using functional near-infrared spectroscopy (fNIRS). Thirteen studies were included in qualitative analysis, with two studies synthesized for quantitative meta-analysis. Overall, MCI patients exhibited reduced resting-state FC, predominantly in the prefrontal, parietal, and occipital cortex. Meta-analysis of two studies revealed a significant reduction in resting-state FC from the right prefrontal to right occipital cortex (standardized mean difference [SMD]=-.56; p<.001), left prefrontal to left occipital cortex (SMD=-.68; p<.001), and right prefrontal to left occipital cortex (SMD=-.53; p<.001) in MCI patients compared to HC. During naming animal-walking task, MCI patients exhibited enhanced FC in the prefrontal, motor, and occipital cortex, whereas a decrease in FC was observed in the right prefrontal to left prefrontal cortex during calculating-walking task. In working memory tasks, MCI predominantly showed increased FC in the medial and left prefrontal cortex. However, a decreased in prefrontal FC and a shifted in distribution from the left to the right prefrontal cortex were noted in MCI patients during a verbal frequency task. In conclusion, fNIRS effectively identified abnormalities in FC between MCI and HC, indicating disrupted FC as potential markers for the early detection of MCI. Future studies should investigate the use of task- and region-specific FC alterations as a sensitive biomarker for MCI.

Background and objectivesGlaucoma is one of the leading irreversible causes of blindness worldwide, and previous studies have shown that there is abnormal functional connectivity (FC) in the visual cortex of glaucoma patients. The thalamus is a relay nucleus for visual signals; however, it is not yet clear how the FC of the thalamus is altered in glaucoma. This study investigated the alterations in thalamic FC in patients with primary angle-closure glaucoma (PACG) by using resting-state functional MRI (rs-fMRI). We hypothesized that PACG patients have abnormal FC between the thalamus and visual as well as extravisual brain regions.MethodsClinically confirmed PACG patients and age- and gender-matched healthy controls (HCs) were evaluated by T1 anatomical and functional MRI on a 3 T scanner. Thirty-four PACG patients and 33 HCs were included in the rs-fMRI analysis. All PACG patients underwent complete ophthalmological examinations; included retinal nerve fiber layer thickness (RNFLT), intraocular pressure (IOP), average cup-to-disc ratio (A-C/D), and vertical cup-to-disc ratio (V-C/D). After the MRI data were preprocessed, the bilateral thalamus was chosen as the seed point; and the differences in resting-state FC between groups were evaluated. The brain regions that significantly differed between PACG patients and HCs were identified, and the correlations were then evaluated between the FC coefficients of these regions and clinical variables.ResultsCompared with the HCs, the PACG patients showed decreased FC between the bilateral thalamus and right transverse temporal gyrus, between the bilateral thalamus and left anterior cingulate cortex, and between the left thalamus and left insula. Concurrently, increased FC was found between the bilateral thalamus and left superior frontal gyrus in PACG patients. The FC between the bilateral thalamus and left superior frontal gyrus was positively correlated with RNFLT and negatively correlated with the A-C/D and V-C/D. The FC between the left thalamus and left insula was negatively correlated with IOP.ConclusionExtensive abnormal resting-state functional connections between the thalamus and visual and extravisual brain areas were found in PACG patients, and there were certain correlations with clinical variables, suggesting that abnormal thalamic FC plays an important role in the progression of PACG.

Disorder-specific cerebellar-cerebral functional connectivity in OCD relative to GAD: A seed-based fMRI analysis.

Dynamic functional connectivity (FC) analyses have provided ample information on the disturbances of global functional brain organization in patients with schizophrenia. However, our understanding about the dynamics of local FC in never-treated first episode schizophrenia (FES) patients is still rudimentary. Dynamic Regional Phase Synchrony (DRePS), a newly developed dynamic local FC analysis method that could quantify the instantaneous phase synchronization in local spatial scale, overcomes the limitations of commonly used sliding-window methods. The current study performed a comprehensive examination on both the static and dynamic local FC alterations in FES patients (N = 74) from healthy controls (HCs, N = 41) with resting-state functional magnetic resonance imaging using DRePS, and compared the static local FC metrics derived from DRePS with those calculated from two commonly used regional homogeneity (ReHo) analysis methods that are defined based on Kendall's coefficient of concordance (KCC-ReHo) and frequency coherence (Cohe-ReHo). Symptom severities of FES patients were assessed with a set of clinical scales. Cognitive functions of FES patients and HCs were assessed with the MATRICS consensus cognitive battery. Group-level analysis revealed that compared with HCs, FES patients exhibited increased static local FC in right superior, middle temporal gyri, hippocampus, parahippocampal gyrus, putamen, and bilateral caudate nucleus. Nonetheless, the dynamic local FC metrics did not show any significant differences between the two groups. The associations between all local FC metrics and clinical characteristics manifested scores were explored using a relevance vector machine. Results showed that the Global Assessment of Functioning score highest in past year and the Brief Visuospatial Memory Test-Revised task score were statistically significantly predicted by a combination of all static and dynamic features. The diagnostic abilities of different local FC metrics and their combinations were compared by the classification performance of linear support vector machine classifiers. Results showed that the inclusion of zero crossing ratio of DRePS, one of the dynamic local FC metrics, alongside static local FC metrics improved the classification accuracy compared to using static metrics alone. These results enrich our understanding of the neurocognitive mechanisms underlying schizophrenia, and demonstrate the potential of developing diagnostic biomarker for schizophrenia based on DRePS.

Long-range cortical functional connectivity is often reduced in autism spectrum disorders (ASD), but the nature of local cortical functional connectivity in ASD has remained elusive. We used magnetoencephalography to measure task-related local functional connectivity, as manifested by coupling between the phase of alpha oscillations and the amplitude of gamma oscillations, in the fusiform face area (FFA) of individuals diagnosed with ASD and typically developing individuals while they viewed neutral faces, emotional faces, and houses. We also measured task-related long-range functional connectivity between the FFA and the rest of the cortex during the same paradigm. In agreement with earlier studies, long-range functional connectivity between the FFA and three distant cortical regions was reduced in the ASD group. However, contrary to the prevailing hypothesis in the field, we found that local functional connectivity within the FFA was also reduced in individuals with ASD when viewing faces. Furthermore, the strength of long-range functional connectivity was directly correlated to the strength of local functional connectivity in both groups; thus, long-range and local connectivity were reduced proportionally in the ASD group. Finally, the magnitude of local functional connectivity correlated with ASD severity, and statistical classification using local and long-range functional connectivity data identified ASD diagnosis with 90% accuracy. These results suggest that failure to entrain neuronal assemblies fully both within and across cortical regions may be characteristic of ASD.

BackgroundClinically, schizophrenia has a strong association with imbalances in emotional control. Previous study indicated that the emotional deficits in schizophrenia stems from disturbances in the amygdala networks, which may serve as a pivotal etiological factor in schizophrenia.1 Furthermore, it has been observed that different levels of anxiety were correlated with distinct patterns of functional connectivity (FC) strength between the amygdala and the dorsomedial prefrontal cortex2. Thus, we hypothesized that patients with schizophrenia(S) and prodromal(P) participants may have abnormal resting-state FC in the right amygdala networks when compared with healthy controls (HC), and this dysfunctional connectivity may be associated with different levels of anxiety.Aim & ObjectivesThe study aims to explore aberrant resting-state FC in the right amygdala networks of schizophrenia patients and prodromal participants with different anxiety levels.Method86 participants (26 schizophrenia patients, 25 prodromal subjects, and 35 HCs) were included in this study. The anxiety levels of the participants were assessed by The STAI Scale in Chinese Mandarin. Participants with trait scores exceeding 60 was considered as high anxiety level. Each participant underwent a whole-brain anatomical scan and 200 continuous whole-brain resting-state fMRI scans. The images were preprocessed using DPARSF. The seed region of right amygdala was placed at MNI coordinates x=22, y=-6, and z=-18 as a 3mm radius spheres. The average time-activity series were extracted from the seed region, and FC maps (r-to-z value converted) of seed region were generated. The statistical analyses for standardized FC maps were conducted using SPM12. The flexible factorial design was utilized with group and anxiety factor as between-subject factors. The changes were deemed as significant if the family-wise error rate corrected cluster p <0.05 (the cluster forming threshold is in uncorrected voxel p <0.005).ResultsFor the group effect, a significant increased FC between the amygdala and the middle frontal gyrus (MFG) has been found in the S group compared to HC, whereas the P group revealed FC values between them. For the anxiety effect, a significantly increased FC has been found in ventrolateral prefrontal cortex (vlPFC) between subjects with high and low anxiety, in both P and HC groups. The high anxiety subjects in P and HC groups revealed positive FC in vlPFC, while low anxiety subjects revealed negative FC in vlPFC. Moreover, high anxiety subjects exhibited a positive FC between amygdala and precuneus in the S group, whereas negative FC in precuneus were observed in both P and HC groups. Notably, the P group revealed FC value between S and HC groups.Discussion & ConclusionWe found altered FCs in MFG and precuneus in both S and P groups, which may be associated with the progress from normal to illness onset. Moreover, altered FC has been also found in the vlPFC between different anxiety levels in P and HC groups. Considering the precuneus and vlPFC were involved in emotional control, the FC changes between the right amygdala and these emotion-modulating regions highlight the intricate relationship between anxiety and pathophysiological changes in schizophrenia and prodrome. Future researches are needed to include longitudinal studies to track FC changes in amygdala of high anxiety individuals transitioning from the prodrome to diagnosed schizophrenia.

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.

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BackgroundPatients with amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) show functional and structural connectivity alterations in the default mode network (DMN) while cerebrovascular disease (CeVD) shows functional and structural connectivity changes in the executive control network (ECN). Such disruptions are associated with memory and executive function impairment, respectively. Concurrent AD and CeVD pathology is associated with a higher rate of cognitive decline and differential neurodegenerative patterns. Together, such findings are likely reflective of different underlying pathology in AD with and without CeVD. However, few studies have examined the effect of CeVD on network functional connectivity (task-free functional magnetic resonance imaging (fMRI)) and structural connectivity (diffusion MRI) of the DMN and ECN in aMCI and AD using a hypothesis-driven multiple seed-based approach.MethodsWe examined functional and structural connectivity network changes in 39 aMCI, 50 aMCI+CeVD, 47 AD, 47 AD+CeVD, and 65 healthy controls (HCs) and their associations with cognitive impairment in the executive/attention and memory domains.ResultsWe demonstrate divergent DMN and ECN functional connectivity changes in CeVD and non-CeVD subjects. Compared with controls, intra-DMN hippocampal functional connectivity reductions were observed in both AD and AD+CeVD, while intra-DMN parietal and medial prefrontal-parietal functional connectivity was higher in AD+CeVD and aMCI+CeVD, but lower in AD. Intra-ECN frontal functional connectivity increases and fronto-parietal functional connectivity decreases occurred in CeVD but not non-CeVD subjects. Such functional connectivity alterations were related with cognitive impairment in a dissociative manner: intra-DMN functional connectivity changes were associated with worse cognition primarily in non-CeVD groups, while intra-ECN functional connectivity changes were associated with worse cognition primarily in CeVD groups. Additionally, CeVD and non-CeVD groups showed overlapping and distinct alterations in inter-network DMN-ECN functional connectivity depending on disease severity. In contrast to functional connectivity, CeVD groups had greater network structural connectivity damage compared with non-CeVD groups in both aMCI and AD patients. Network structural connectivity damage was associated with worse cognition.ConclusionsWe demonstrate differential functional and structural network changes between aMCI and AD patients with and without CeVD through diverging and deleterious network-based degeneration underlying domain-specific cognitive impairment.

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

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.