Dual activation of the reward system using sensory-based intervention and non-invasive brain stimulation in depression: A way to move forward?

Major depressive disorder (MDD) is characterized by symptoms such as low mood and anhedonia related to altered dopamine transmission in the reward system. In addition, approximately one-third of patients with MDD develop treatment-resistance to the pharmaceutical treatment, necessitating alternative therapeutic strategies. While non-invasive brain stimulation (NIBS) holds promise for improving treatment-resistant MDD, remission rates are still relatively modest. It has been demonstrated that NIBS effects not only depend of the stimulation properties but are also “state-dependent”, meaning that when patients engage in specific tasks or states that involve similar neural networks targeted by NIBS, a synergistic and additive therapeutic effect may occur. Therefore, a recent strategy to improve treatment outcomes is to combine NIBS with other types of interventions targeting the same network.

Numerous studies have demonstrated a clinically meaningful antidepressant effects when NIBS are combined with psychotherapy, cognitive-behavioral approaches, or cognitive remediation programs for patients with MDD. However, widespread use of this combination may be hindered by barriers such as cost and accessibility for both clinicians and patients. Alternatively, sensory-based interventions alone (such as music therapy or exposure to specific odors) represent a promising, easy-to-implement, cost-effective and innovative therapeutic approach for MDD. These interventions are known to activate the meso-cortico-limbic system, triggering dopamine release, or modulating dopaminergic tone in various brain structures, similar to what is observed with NIBS. In this paper, the hypothesis that combining sensory-based interventions with NIBS is a compelling approach to alleviating MDD symptoms is tested. Specifically, it is hypothesized that the dual activation of the reward system induced by sensory-based interventions, combined with the concurrent application of NIBS, will result in a synergistic effect, ultimately leading to enhanced alleviation of MDD symptoms.