Altered effective connectivity in sensorimotor cortices is a signature of severity and clinical course in depression

Abstract

Functional neuroimaging research on depression has traditionally targeted neural networks associated with the psychological aspects of depression. In this study, instead, we focus on alterations of sensorimotor function in depression. We used resting-state functional MRI data and dynamic causal modeling (DCM) to assess the hypothesis that depression is associated with aberrant effective connectivity within and between key regions in the sensorimotor hierarchy. Using hierarchical modeling of between-subject effects in DCM with parametric empirical Bayes we first established the architecture of effective connectivity in sensorimotor cortices. We found that in (interoceptive and exteroceptive) sensory cortices across participants, the backward connections are predominantly inhibitory, whereas the forward connections are mainly excitatory in nature. In motor cortices these parities were reversed. With increasing depression severity, these patterns are depreciated in exteroceptive and motor cortices and augmented in the interoceptive cortex, an observation that speaks to depressive symptomatology. We established the robustness of these results in a leave-one-out cross-validation analysis and by reproducing the main results in a follow-up dataset. Interestingly, with (nonpharmacological) treatment, depression-associated changes in backward and forward effective connectivity partially reverted to group mean levels. Overall, altered effective connectivity in sensorimotor cortices emerges as a promising and quantifiable candidate marker of depression severity and treatment response.

Static and treatment-responsive brain biomarkers of depression relapse vulnerability following prophylactic psychotherapy: Evidence from a randomized control trial

“…Functional connectivity studies support this view, as cognitive control networks including the LPFC are observed less frequently in patients remitted from MDD ( Figueroa et al, 2019 ), whereas non-relapsers tend to show increased connectivity of the LPFC with executive control regions following antidepressant discontinuation ( Berwian et al, 2020 ). While less often the focus of neuroimaging research, emerging mechanistic accounts of depression have also implicated sensorimotor dysfunction a reliable correlate of symptom burden ( Ray et al, 2021 ), which is consistent with established findings linking experiential avoidance to depression vulnerability ( Barnhofer et al, 2014 , Panayiotou et al, 2015 ). The present findings affirm the role of sensory deactivation in characterizing depression relapse vulnerability, broadening accounts of depression vulnerability to also sensorimotor deactivation as a contributing vulnerability biomarker.…”

“…Furthermore, in one of the few prospective neuroimaging studies of MDD recurrence, both PFC activation and sensory deactivation were associated with new MDD episodes over a subsequent 18-month follow-up ( Farb et al, 2011 ). In parallel, emerging connectivity studies of depression suggest that abnormal sensorimotor connectivity may be a powerful but overlooked feature of depressive symptom burden and treatment response ( Ray et al, 2021 ). While small sample sizes limit the generalizability of regional findings, such studies provide initial evidence for characterizing MDD relapse vulnerability as an over-reliance on cognitive elaboration to the detriment of sensory integration.…”

Astrocyte dysfunction drives abnormal resting-state functional connectivity in depression

“…Many studies have examined rsfMRI networks in both depressed patients and animal models, yielding highly quantitative and objective measurements that are of theranostic utility ( 2 , 32 , 38 , 39 ). However, the relationship between astrocyte dysfunction and these rsfMRI measurements in depression remained unknown.…”

“…The brain regions with notably altered rsfMRI connectivity in MDD patients and Itpr2 −/− mice can be associated with depression ( 2 , 13 , 14 , 38 , 42 ), such as mPFC, TH, Str, AMY, SsCx, VCx, SC, Hb, DRN, and Ant ( Figs. 1 and 2 ).…”

Psychological Resilience in Adolescence as a function of Genetic Risk for Major Depressive Disorder and Alzheimer’s Disease

“…Conversely, network rigidity related to poorer resilience among AD-prone adolescents. Anchored in VIS areas of greater GABA, relative to GLU, receptor density, this profile reaffirmed the importance of externally oriented processing systems to MDD pathology (e.g., [68]), as well as the role of E/I balance in supporting functional network development (69). It also underscored the importance of conducting more targeted, neurotransmitter system-specific investigations into the relationships among AD/MDD risk, resilience and incentive processing.…”