Cognitive remediation therapy modulates intrinsic neural activity in patients with major depression

Abstract

BackgroundCognitive impairment is a core feature of major depressive disorder (MDD). Cognitive remediation may improve cognition in MDD, yet so far, the underlying neural mechanisms are unclear. This study investigated changes in intrinsic neural activity in MDD after a cognitive remediation trial.MethodsIn a longitudinal design, 20 patients with MDD and pronounced cognitive deficits and 18 healthy controls (HC) were examined using resting-state functional magnetic resonance imaging. MDD patients received structured cognitive remediation therapy (CRT) over 5 weeks. The whole-brain fractional amplitude of low-frequency fluctuations was computed before the first and after the last training session. Univariate methods were used to address regionally-specific effects, and a multivariate data analysis strategy was employed to investigate functional network strength (FNS).ResultsMDD patients significantly improved in cognitive function after CRT. Baseline comparisons revealed increased right caudate activity and reduced activity in the left frontal cortex, parietal lobule, insula, and precuneus in MDD compared to HC. In patients, reduced FNS was found in a bilateral prefrontal system at baseline (p < 0.05, uncorrected). In MDD, intrinsic neural activity increased in right inferior frontal gyrus after CRT (p < 0.05, small volume corrected). Left inferior parietal lobule, left insula, left precuneus, and right caudate activity showed associations with cognitive improvement (p < 0.05, uncorrected). Prefrontal network strength increased in patients after CRT, but this increase was not associated with improved cognitive performance.ConclusionsOur findings support the role of intrinsic neural activity of the prefrontal cortex as a possible mediator of cognitive improvement following CRT in MDD.

Age at illness onset and physical activity are associated with cognitive impairment in patients with current diagnosis of major depressive disorder

“…Neural correlates of cognitive remediation have been poorly investigated. The few available studies have shown changes in cerebral activation after cognitive remediation: an increased activation in lateral and medial prefrontal, superior temporal, and lateral parietal regions (Meusel et al, 2013) and a trend toward normalization of intrinsic neural activity, with an increase in the right inferior frontal gyrus (a region that has been related to cognitive processing) (Schneider et al, 2019) and a modulation of left inferior parietal lobe and caudate nucleus activity, areas of interest in MDD.…”

“…Current hypotheses accept that physical exercise induce both acute and chronic effects affecting several putative systems implicated in depression such as neuroendocrine system, neurogenesis, oxidative stress, auto-immunity and producing cortical structural changes (for a review see Schuch et al, 2016). Decreases in arousal (Lambourne et al, 2010), increased catecholamines release (McMorris et al, 2009) and brain derived neurotrophic factor (BDNF) levels (Ferris et al, 2007), changes in cerebral activation (Meusel et al, 2013;Schneider et al, 2019 ) and enhanced brain plasticity have been found after physical activity both in healthy individuals and depressive patients (Gujral et al, 2017), leading to improved performance in specific cognitive domains: attention control (Colcombe et al, 2004), spatial memory (Erickson et al, 2011) and executive functioning (Kubesch et al, 2003;Colcombe et al, 2003). This cognitive improvement is higher with moderate physical activity and when it is performed simultaneously to the cognitive task (Rathore and Lom, 2017).…”

Differentiating Melancholic and Non-melancholic Major Depressive Disorder Using Fractional Amplitude of Low-Frequency Fluctuations

“…The OFC is involved in the reward system, linking reward to happy experience (36), which contains the VS, ACC, ventral tegmental area (VTA), nucleus accumbens, and dorsolateral prefrontal cortex (36,37), contributing to impaired mood reactivity and MEL features (17,19). Schneider et al (84) found size reduction in the left IFG; Guo et al (35) observed decreased brain activity in the OFC of patients with MDD; and Bracht et al (36) detected decreased connectivity between the right VTA and the OFC in MEL patients. These results are unexpectedly different from our findings that regional activity increased in the bilateral IFG of MEL patients.…”

A meta-analysis on neural changes of cognitive training for mental disorders in executive function tasks: increase or decrease brain activation?

“…Precuneus and cuneus are related to cognitive dysfunction in patients with mental disorders [ 40 , 41 ]. Decreased activation of left precuneus after cognitive training is associated with cognitive improvement [ 42 ]. Typically, relative DMN activity decreases during task performance [ 43 ], suggesting that CT improves cognitive function by reducing neurological resources for vision.…”