Reza Tadayonnejad

Brain network dysfunction in late-life depression: a literature review.

As a common psychiatric disorder in the growing geriatric population, late-life depression (LLD) has a negative impact on the cognitive, affective, and somatic domains of the lives of the elderly individuals. Accumulating evidence from the structural and functional imaging studies on LLD supports a “network dysfunction model” rather than a “lesion pathology model” for understanding the underlying biological mechanism in this mental disorder. In this work, we used network dysfunction model as a conceptual framework for reviewing recent neuroimaging findings in LLD. Our focus was on 4 major neurocircuits that have been shown to be involved in LLD: default mood network, cognitive control network, affective/frontolimbic network, and corticostriatal circuits. Findings of LLD-related gray and white matter structural abnormalities and resting-state and task-based functional changes were discussed for each network separately. We extended our review by summarizing the latest works that apply graph theory–based network analysis techniques for testing alterations in whole-brain network properties associated with LLD.

Multimodal Brain Connectivity Analysis in Unmedicated Late-Life Depression

Late-life depression (LLD) is a common disorder associated with emotional distress, cognitive impairment and somatic complains. Structural abnormalities have been suggested as one of the main neurobiological correlates in LLD. However the relationship between these structural abnormalities and altered functional brain networks in LLD remains poorly understood. 15 healthy elderly comparison subjects from the community and 10 unmedicated and symptomatic subjects with geriatric depression were selected for this study. For each subject, 87 regions of interest (ROI) were generated from whole brain anatomical parcellation of resting state fMRI data. Whole-brain ROI-wise correlations were calculated and compared between groups. Group differences were assessed using an analysis of covariance after controlling for age, sex and education with multiple comparison correction using the false discovery rate. Structural connectivity was assessed by tract-based spatial statistics (TBSS). LLD subjects had significantly decreased connectivity between the right accumbens area (rA) and the right medial orbitofrontal cortex (rmOFC) as well as between the right rostral anterior cingulate cortex (rrACC) and bilateral superior frontal gyrus (bsSFG). Altered connectivity of rrACC with the bsSFG was significantly correlated with depression severity in depressed subjects. TBSS analysis showed a 20% reduction in fractional anisotropy (FA) in the right Forceps Minor (rFM) in depressed subjects. rFM FA values were positively correlated with rA-rmOFC and rrACC-bsFG functional connectivity values in our total study sample. Coordinated structural and functional impairment in circuits involved in emotion regulation and reward pathways play an important role in the pathophysiology of LLD.

Resting-state theta band connectivity and graph analysis in generalized social anxiety disorder

Background Functional magnetic resonance imaging (fMRI) resting-state studies show generalized social anxiety disorder (gSAD) is associated with disturbances in networks involved in emotion regulation, emotion processing, and perceptual functions, suggesting a network framework is integral to elucidating the pathophysiology of gSAD. However, fMRI does not measure the fast dynamic interconnections of functional networks. Therefore, we examined whole-brain functional connectomics with electroencephalogram (EEG) during resting-state. Methods Resting-state EEG data was recorded for 32 patients with gSAD and 32 demographically-matched healthy controls (HC). Sensor-level connectivity analysis was applied on EEG data by using Weighted Phase Lag Index (WPLI) and graph analysis based on WPLI was used to determine clustering coefficient and characteristic path length to estimate local integration and global segregation of networks. Results WPLI results showed increased oscillatory midline coherence in the theta frequency band indicating higher connectivity in the gSAD relative to HC group during rest. Additionally, WPLI values positively correlated with state anxiety levels within the gSAD group but not the HC group. Our graph theory based connectomics analysis demonstrated increased clustering coefficient and decreased characteristic path length in theta-based whole brain functional organization in subjects with gSAD compared to HC. Conclusions Theta-dependent interconnectivity was associated with state anxiety in gSAD and an increase in information processing efficiency in gSAD (compared to controls). Results may represent enhanced baseline self-focused attention, which is consistent with cognitive models of gSAD and fMRI studies implicating emotion dysregulation and disturbances in task negative networks (e.g., default mode network) in gSAD.

Thought Chart: Tracking Dynamic EEG Brain Connectivity with Unsupervised Manifold Learning

Assuming that the topological space containing all possible brain states forms a very high-dimensional manifold, this paper proposes an unsupervised manifold learning framework to reconstruct and visualize this manifold using EEG brain connectivity data acquired from a group of healthy volunteers.

Pharmacological modulation of pulvinar resting-state regional oscillations and network dynamics in major depression.

The pulvinar, the largest thalamus nucleus, has rich anatomical connections with several different cortical and subcortical regions suggesting its important involvement in high-level cognitive and emotional functions. Unfortunately, pulvinar dysfunction in psychiatric disorders particularly major depression disorder has not been thoroughly examined to date. In this study we explored the alterations in the baseline regional and network activities of the pulvinar in MDD by applying spectral analysis of resting-state oscillatory activity, functional connectivity and directed (effective) connectivity on resting-state fMRI data acquired from 20 healthy controls and 19 participants with MDD. Furthermore, we tested how pharmacological treatment with duloxetine can modulate the measured local and network variables in ten participants who completed treatment. Our results revealed a frequency-band dependent modulation of power spectrum characteristics of pulvinar regional oscillatory activity. At the network level, we found MDD is associated with aberrant causal interactions between pulvinar and several systems including default-mode and posterior insular networks. It was also shown that duloxetine treatment can correct or overcompensate the pathologic network behavior of the pulvinar. In conclusion, we suggest that pulvinar regional baseline oscillatory activity and its resting-state network dynamics are compromised in MDD and can be modulated therapeutically by pharmacological treatment.

EEG based functional connectivity reflects cognitive load during emotion regulation

Patients suffering from anxiety disorders commonly have difficulties in emotion regulation. Understanding underlying brain network dysfunction can provide insight into their pathophysiology. Electroencephalography (EEG)-based functional connectivity contains high temporal information of brain network dynamics. We acquired EEG recordings in the resting state and during a series of emotion regulation tasks (ERT) from a sample of 20 subjects with anxiety disorders and 20 healthy controls. To generate EEG-based functional connectomes, we used the weighted phase lag index (WPLI), a phase based connectivity metric. Graph theory measures of clustering coefficient (CC) and characteristic path length (CPL) were computed to characterize properties of these complex functional networks. Results showed that in the theta band network integration measured using CPL increased as the cognitive load during the emotion regulation task increased, with a complementary trend in the CC. In summary, the EEG-based functional connectome is highly dynamic and task dependent, thus may serve as a promising non-invasive biomarker for diagnosis and treatment evaluation.

Mechanisms of cognitive-behavioral therapy for obsessive-compulsive disorder involve robust and extensive increases in brain network connectivity

Cognitive-behavioral therapy (CBT) is effective for obsessive compulsive disorder (OCD); however, little is understood about its mechanisms related to brain network connectivity. We examined connectivity changes from resting-state functional magnetic resonance imaging data pre-to-post-CBT in 43 OCD participants, randomized to receive either 4 weeks of intensive CBT or 4 weeks waitlist followed by 4 weeks of CBT, and 24 healthy controls before and after 4 weeks of no treatment. Network-based-statistic analysis revealed large-magnitude increases in OCD connectivity in eight networks. Strongest increases involved connectivity between the cerebellum and caudate/putamen, and between the cerebellum and dorsolateral/ventrolateral prefrontal cortices. Connectivity increases were associated with increased resistance to compulsions. Mechanisms of CBT may involve enhanced cross-network integration, both within and outside of classical cortico-striatal-thalamo-cortical regions; those involving cerebellar to striatal and prefrontal regions may reflect acquisition of new non-compulsive goal-directed behaviors and thought patterns. Our findings have implications for identifying targets for enhancing treatment efficacy and monitoring treatment progress.

Aberrant pulvinar effective connectivity in generalized social anxiety disorder

AbstractRecent neuroimaging findings in general social anxiety disorder (gSAD) have extended our understanding of the neural mechanisms of gSAD beyond an amygdala-centric fear-based hyperactivity model to include other brain regions and networks relevant to salient cues. In particular, higher order areas compromising visual networks that process emotional and social information have been implicated. The pulvinar anchors this network and is a key regulatory node that mediates complex sensory inputs and the integration between limbic and frontal brain systems. However, the role of the pulvinar and specifically alteration of its effective connectivity with the rest of the brain has not been examined in the pathophysiology of gSAD, a disorder characterized by aberrant socio-emotional processing. The main aim of this study was to examine the pulvinar network effective connectivity in gSAD. In this study, we recruited 21 individuals with gSAD and 19 demographically matched healthy controls (HC), who performed an emotional face processing task while brain activity was recorded using functional magnetic resonance imaging (fMRI). To examine pulvinar-based network dynamics, Granger causality (GC) based effective connectivity (EC) analysis was applied on fMRI data to compare gSAD and HC. The EC analysis revealed heightened casual influential dynamics between pulvinar in higher order visual and frontal regions in gSAD. In conclusion, these preliminary data suggest a novel network-based cortico-pulvino-cortical neural mechanism in the pathophysiology of gSAD.

Pregenual Anterior Cingulate Dysfunction Associated with Depression in OCD: An Integrated Multimodal fMRI/ 1 H MRS Study

Depression is a commonly occurring symptom in obsessive-compulsive disorder (OCD), and is associated with worse functional impairment, poorer quality of life, and poorer treatment response. Understanding the underlying neurochemical and connectivity-based brain mechanisms of this important symptom domain in OCD is necessary for development of novel, more globally effective treatments. To investigate biopsychological mechanisms of comorbid depression in OCD, we examined effective connectivity and neurochemical signatures in the pregenual anterior cingulate cortex (pACC), a structure known to be involved in both OCD and depression. Resting-state functional magnetic resonance imaging (fMRI) and 1H magnetic resonance spectroscopy (MRS) data were obtained from participants with OCD (n=49) and healthy individuals of equivalent age and sex (n=25). Granger causality-based effective (directed) connectivity was used to define causal networks involving the right and left pACC. The interplay between fMRI connectivity, 1H MRS and clinical data was explored by applying moderation and mediation analyses. We found that the causal influence of the right dorsal anterior midcingulate cortex (daMCC) on the right pACC was significantly lower in the OCD group and showed significant correlation with depressive symptom severity in the OCD group. Lower and moderate levels of glutamate (Glu) in the right pACC significantly moderated the interaction between right daMCC–pACC connectivity and depression severity. Our results suggest a biochemical-connectivity-psychological model of pACC dysfunction contributing to depression in OCD, particularly involving intracingulate connectivity and glutamate levels in the pACC. These findings have implications for potential molecular and network targets for treatment of this multi-faceted psychiatric condition.

Relationships between obsessive-compulsive disorder, depression and functioning before and after exposure and response prevention therapy

Abstract Objective: Obsessive-compulsive disorder (OCD) is associated with impaired functioning and depression. Our aim was to examine relationships between OCD symptoms, depression and functioning before and after exposure and response prevention (ERP), a type of cognitive-behavioural therapy for OCD, specifically examining whether functioning, depression and other cognitive factors like rumination and worry acted as mediators. Methods: Forty-four individuals with OCD were randomised to 4 weeks of intensive ERP treatment first (n = 23) or waitlist then treatment (n = 21). We used a bootstrapping method to examine mediation models. Results: OCD symptoms, depression and functioning significantly improved from pre- to post-intervention. Functioning mediated the relationship between OCD symptoms and depression and the relationship between functioning and depression was stronger at post-treatment. Depression mediated the relationship between OCD symptoms and functioning, but only at post-intervention. Similarly, rumination mediated the relationship between OCD symptoms and depression at post-intervention. Conclusions: Our findings suggest that after ERP, relationships between depression and functioning become stronger. Following ERP, treatment that focuses on depression and functioning, including medication management for depression, cognitive approaches targeting rumination, and behavioural activation to boost functionality may be important clinical interventions for OCD patients.