Functional connectivity in the cognitive control network and the default mode network in late-life depression

Abstract

Background Abnormalities have been identified in the Cognitive Control Network (CCN) and the default mode network (DMN) during episodes of late-life depression. This study examined whether functional connectivity at rest (FC) within these networks characterize late-life depression and predict antidepressant response. Methods 26 non-demented, non-MCI older adults were studied. Of these, 16 had major depression and 10 had no psychopathology. Depressed patients were treated with escitalopram (target dose 20 mg) for 12 weeks after a 2-week placebo phase. Resting state timeseries was determined prior to treatment. FC within the CCN was determined by placing seeds in the dACC and the DLPFC bilaterally. FC within the DMN was assessed from a seed placed in the posterior cingulate. Results Low resting state FC within the CCN and high FC within the DMN distinguished depressed from normal elderly subjects. Beyond this “double dissociation”, low resting state FC within the CCN predicted low remission rate and persistence of depressive symptoms and signs, apathy, and dysexecutive behavior after treatment with escitalopram. In contrast, resting state FC within the DMN was correlated with pessimism but did not predict treatment response. Conclusions If confirmed, these findings may serve as a signature of the brain’s functional topography characterizing late-life depression and sustaining its symptoms. By identifying the network abnormalities underlying biologically meaningful characteristics (apathy, dysexecutive behavior, pessimism) and sustaining late-life depression, these findings can provide a novel target on which new somatic and psychosocial treatments can be tested.

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

“…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.…”

Relation between patterns of intrinsic network connectivity, cognitive functioning, and symptom presentation in trauma‐exposed patients with major depressive disorder

“…The vmPFC not only represents a core region of the DMN (Buckner et al., 2008), but it is also a critical region involved in self‐referential processing (Lemogne, Delaveau, Freton, Guionnet, & Fossati, 2012; Northoff et al., 2006). This finding suggests hyperconnectivity within the DMN in patients with MDD, and is consistent with previous studies in patients with depression (Alexopoulos et al., 2012; Kaiser, Andrews‐Hanna, Wager, & Pizzagalli, 2015; Sheline, Price, Yan, & Mintun, 2010) (but see de Kwaasteniet et al. (2015) and Zhu et al.…”

“…Interestingly, increased activation of the anterior insula in response to negative stimuli has been shown in MDD (Strigo et al, 2008), and increased connectivity of the dorsal mid‐insula cortex with limbic areas is positively correlated with depressive symptom severity (Avery et al., 2014) (but see Alexopoulos et al. (2012)). The right fronto‐insular cortical network, however, was found to be less active at rest in patients with MDD as compared to controls (Hamilton et al., 2012).…”

“…(2014) studied youth with remitted MDD and found that hyperconnectivity of the DMN and SN with the CCN was positively correlated with greater sustained attention on a Go/No‐Go task. In a sample of patients with late‐life depression, low resting functional connectivity within the CCN prior to treatment was related to greater dysexecutive behavior after treatment (Alexopoulos et al., 2012). To date, however, no studies have examined the relation between these core neural networks and performance on standardized neuropsychological assessments tapping frontal‐temporally mediated cognitive domains in patients with MDD and a history of trauma.…”

Molecular, Functional, and Structural Imaging of Major Depressive Disorder

“…Advanced methods for analyzing functional connectivity using MRI (for review, see [54]), such as seed-based correlation analysis, independent component analysis, regional homogeneity, and amplitude of low-frequency fluctuations, have been increasingly used. Through these techniques, aberrant functional connectivity has been identified in MDD, such as in the salience network (SN) [55,56], default mode network (DMN) [57][58][59][60], cognitive control network (CCN) [59,61], and affective network (AN) [60,62]. The SN, predominantly consisting of the anterior insular cortex and dorsal ACC, serves to assess the correlation of internal and external stimuli to produce appropriate responses and direct behaviors [63].…”