Dysfunctional cortical gradient topography in treatment resistant major depression

Abstract

Background Treatment-Resistant Depression (TRD) refers to patients with major depressive disorder who do not remit after two or more antidepressant trials. TRD is common and highly debilitating, but its neurobiological basis remains poorly understood. Recent neuroimaging studies have revealed cortical connectivity gradients that dissociate primary sensorimotor areas from higher-order associative cortices. This fundamental topography determines cortical information flow and is affected by psychiatric disorders. We examined how TRD impacts this hierarchical cortical organization. Methods We analyzed resting-state fMRI data from a mindfulness-based intervention study in 56 TRD patients and 28 healthy controls. Using novel gradient extraction tools, measures of cortical gradient dispersion within and between functional brain networks were derived, compared across groups, and associated with graph theoretical measures of network topology. Within TRD, baseline cortical gradient dispersion measures were correlated with baseline clinical measures (anxiety, depression, mindfulness), as well as with changes in these measures following treatment with either mindfulness-based therapy or a health enhancement program. Results Cortical gradient dispersion was reduced within major intrinsic brain networks in TRD. Reduced cortical gradient dispersion correlated with increased network modularity assessed through graph theory-based measures of network topology. Lower dispersion among Default Mode Network regions, a transmodal system linked to depression symptomatology, related to current levels of trait anxiety, depression, and mindfulness, but not to changes in these domains following treatment. Conclusions Our findings reveal widespread alterations in cortical gradient architecture in TRD, implicating a significant role for the Default Mode Network in mediating depression, anxiety, and lower mindfulness in patients.

Exploring the embodied mind: functional connectome fingerprinting of meditation expertise

“…This network is composed of the inferior frontal sulcus, regions of the dorsolateral prefrontal cortex, the anterior insula, the dorsal anterior cingulate, the pre-supplementary motor area, and the intraparietal sulcus. Previous studies have demonstrated that these gradients can be influenced by various factors, including disorders such as depression (19) and autistic spectrum disorder (20), as well as cognitive and psycho-affective training (21). Interestingly, psychedelics, such as psilocybin (22) and N,N-Dimethyltryptamine (DMT) (23) can induce ego dissolution and are correlated to a collapse of the cognitive hierarchy as measured by the first gradient.…”