Abnormal regional spontaneous neural activity in treatment‐refractory depression revealed by resting‐state fMRI

Abstract

Treatment-refractory depression (TRD) represents a large proportion of the depressive population, yet has seldom been investigated using advanced imaging techniques. To characterize brain dysfunction in TRD, we performed resting-state functional MRI (rs-fMRI) on 22 TRD patients, along with 26 matched healthy subjects and 22 patients who were depressed but not treatment-refractory (NDD) as comparison groups. Results were analyzed using a data-driven approach known as Regional Homogeneity (ReHo) analysis which measures the synchronization of spontaneous fMRI signal oscillations within spatially neighboring voxels. Relative to healthy controls, both depressed groups showed high ReHo primarily within temporo-limbic structures, and more widespread low ReHo in frontal, parietal, posterior fusiform cortices, and caudate. TRD patients showed more cerebral regions with altered ReHo than did NDD. Moderate but significant correlations between the altered regional ReHo and measures of clinical severity were observed in some identified clusters. These findings shed light on the pathophysiological mechanisms underlying TRD and demonstrate the feasibility of using ReHo as a research and clinical tool to monitor persistent cerebral dysfunction in depression, although further work is necessary to compare different measures of brain function to elucidate the neural substrates of these ReHo abnormalities.

Resting-State Connectivity Predictors of Response to Psychotherapy in Major Depressive Disorder

“…Of note, a number of findings highlight altered connectivity with middle temporal gyrus, a brain area that is involved in imitation, social cognition, and mentalizing, implicating brain regions that code for awareness, salience, and cognitive control of mental states in the pathophysiology of MDD. Additionally, pretreatment connectivity of the anterior insula and intraparietal sulcus predicted response to psychotherapy, a pattern of results consistent with other reports of pretreatment anterior insula metabolism and connectivity (Downar et al, 2013) as predictors of response to psychotherapy and parietal lobe connectivity predicting response to antidepressant medication treatment (Guo et al, 2013a;Wu et al, 2011). More generally, the present study adds to the nascent but growing body of evidence linking pretreatment neuroimaging endophenotypes to antidepressant treatment outcomes .…”

“…Thus our finding of decreased connectivity between a DAN network hub and orbitofrontal gyrus may reflect the well-replicated finding of decreased cognitive control over emotion processing in MDD and prevailing neural models of MDD that highlight decreased modulatory control of prefrontal cortical brain regions over limbic brain regions, particularly in the context of emotion processing and emotion regulation (Johnstone et al, 2007;Joormann and Gotlib, 2010;Ray et al, 2005). Additionally, recent studies investigating response to antidepressant medications in MDD highlight that treatment response is associated with increased connectivity between prefrontal cortical and limbic brain regions, possibly implicating greater inhibitory control over neural circuits that process emotions in positive treatment response (Alexopoulos et al, 2012;Lai and Wu, 2012;Lui et al, 2011;Wu et al, 2011;Yang et al, 2014). The somatic subscale as defined by Siegert et al (2009) encompasses mood (sadness), vegetative (eg, sleep, fatigue), attention/concentration, and motivation-related (interest, energy) symptoms and thus may be especially sensitive to disruptions in circuits that underlie both attention and goal-directed behaviors.…”

Voxel-wise meta-analyses of brain blood flow and local synchrony abnormalities in medication-free patients with major depressive disorder

“…In separate studies of patients with treatmentrefractory depression (TRD) compared with healthy controls, we found decreases in both regional homo geneity 17 and rCBF 10 in the inferior frontal gyrus of patients with TRD. Two restingstate studies in healthy participants have reported significantly correlated spatial variation in rCBF and regional homogeneity, both measures being rela tively high in the insula, superior temporal gyrus, posterior cingulate cortex, medial prefrontal cortex and thalamus 18 and the cortical-limbic network.…”

Resting-state fMRI studies in epilepsy

“…Subsequently, the RS-fMRI technique has been widely used to investigate synchronous brain activity in a variety of functional systems, such as the visual [11] , auditory [12] , emotional [11] , attentional [13] , language [14] , reading [15] and memory systems [16] , as well as the default mode network [17,18] . In addition, the SLFF of RSfMRI signals has been widely used to explore the changes that occur in certain brain diseases such as depression [19] ,…”