Network localization of functional brain changes associated with ketamine's therapeutic effects in depression.

A systematic review of 18 multimodal neuroimaging studies (440 depressed individuals, 174 healthy controls) mapped brain locations linked to ketamine's antidepressant effects onto a functional brain network. The network primarily involved regions of the default mode, ventral attention, and frontoparietal networks. This network was robust under parameter perturbations and leave-one-study-out validation, and was specific to depression compared to other mental disorders. A ketamine-specific circuit, including the subgenual cingulate cortex and dorsolateral prefrontal cortex, overlapped with optimal brain stimulation sites for depression. These findings reconcile inconsistent results and suggest a network-level mechanism for ketamine's therapeutic effects.

Study at a glance

Abstract

Although numerous studies have attempted to identify the functional pathways underlying the rapid antidepressant effects of ketamine, their findings remain inconsistent, limiting our understanding of the neural mechanisms involved. This study aims to delineate a specific brain circuit by integrating diverse functional findings related to ketamine's efficacy in depression. We conducted a systematic review of multimodal neuroimaging studies reporting brain locations associated with ketamine's effects on depression. Using functional connectivity network mapping and a large-scale normative connectome database, we mapped these locations onto a ketamine functional brain network. We tested the robustness of this network by evaluating its stability under parameter perturbations and leave-one-study-out validation, and assessed its specificity for depression relative to other mental disorders. We further identified the ketamine-specific brain circuit compared with an antidepressant functional brain network constructed using the same methodology. Our review included 18 multimodal neuroimaging studies with 440 depression individuals and 174 healthy controls. The heterogeneous brain locations localized to a connected network primarily involving regions implicated in the default mode, ventral attention, and frontoparietal networks. This network demonstrated robustness to minor perturbations and validation, and was specifically linked to depression. Compared with the antidepressant functional brain network, the ketamine-specific brain circuit predominantly encompassed brain regions such as the subgenual cingulate cortex and dorsolateral prefrontal cortex, which aligned with optimal brain stimulation sites for depression. These findings help reconcile seemingly inconsistent neuroimaging results and provide new insights into the neuropathology of ketamine's therapeutic effects from a network perspective.