Citation

Pallikaras V, Shizgal P. Brain Sci. 2022; 12(8).

Copyright

(Copyright © 2022, Switzerland Molecular Diversity Preservation International (MDPI) AG)

DOI

10.3390/brainsci12081052

PMID

unavailable

Abstract

Major depressive disorder is a leading cause of disability and suicide worldwide. Consecutive rounds of conventional interventions are ineffective in a significant sub-group of patients whose disorder is classified as treatment-resistant depression. Significant progress in managing this severe form of depression has been achieved through the use of deep brain stimulation of the medial forebrain bundle (MFB). The beneficial effect of such stimulation appears strong, safe, and enduring. The proposed neural substrate for this promising clinical finding includes midbrain dopamine neurons and a subset of their cortical afferents. Here, we aim to broaden the discussion of the candidate circuitry by exploring potential implications of a new "convergence" model of brain reward circuitry in rodents. We chart the evolution of the new model from its predecessors, which held that midbrain dopamine neurons constituted an obligatory stage of the final common path for reward seeking. In contrast, the new model includes a directly activated, non-dopaminergic pathway whose output ultimately converges with that of the dopaminergic neurons. On the basis of the new model and the relative ineffectiveness of dopamine agonists in the treatment of depression, we ask whether non-dopaminergic circuitry may contribute to the clinical efficacy of deep brain stimulation of the MFB. © 2022 by the authors.

Language: en

Keywords

human; suicide; depression; dopamine; nuclear magnetic resonance imaging; psychophysiology; neurotransmission; nonhuman; electrostimulation; psychostimulant agent; monoamine; monotherapy; brain depth stimulation; orbital cortex; Article; locus ceruleus; dopamine receptor stimulating agent; self stimulation; pulse rate; nerve excitability; antidepressant activity; personalized medicine; treatment resistant depression; dopaminergic nerve cell; myelination; treatment-resistant depression; medial forebrain bundle; tractography; experimental behavioral test; binocular convergence; brain-stimulation reward; central gray matter; convergence model; intracranial self-stimulation test; laterodorsal tegmental nucleus; mesencephalon reticular formation; monoaminergic nerve; neuroscientist; optogenetics; reward seeking behavior