Year: 2025
Type: article
Abstract: Deep brain stimulation (DBS) has emerged as a widely used therapeutic option when pharmacological treatments prove ineffective or refractory for psychiatric patients. The nucleus accumbens (NAc) represents a frequently targeted site in DBS interventions due to its demonstrated safety profile and therapeutic efficacy in obsessive-compulsive disorder, major depression, and anorexia nervosa. However, limited mechanistic understanding hampers its broader clinical applicability. This study sought to delineate the distinct behavioural dimensions modulated by NAc-DBS, its impact on distinct facets of memory, and to elucidate the underlying brain-network mechanism of action. We developed a novel spatial navigation task for rats and employed a high-dimensional behavioural analysis complemented by fMRI to dissect the cognitive, behavioural and neurobiological effects of NAc-DBS. Active NAc-DBS in male rats produced a selective enhancement of long-term memory encoding without affecting memory recall or working memory. We found a small but statistically significant rewarding effect of NAc-DBS, with no detectable impact on motor or stress-related behaviours. Sustained neuronal activation in the NAc, septum, entorhinal and insular cortex demonstrated no desensitisation to chronic NAc-DBS, which triggered a functional reorganisation among dopaminergic-related structures. These findings suggest that NAc-DBS induces a functional reorganisation in the mesocorticolimbic system, potentially mimicking a dopaminergic novelty signal to enhance memory updating. This provides a mechanistic basis for the therapeutic use of NAc-DBS, particularly in improving cognitive flexibility in psychiatric disorders.
Source: Neuropsychopharmacology
Institutions: Consejo Superior de Investigaciones Científicas, Instituto de Neurociencias, Institute for Cross-Disciplinary Physics and Complex Systems, Universitat de les Illes Balears, Universidad Politécnica de Madrid, Ikerbasque, University of the Basque Country, Basque Centre for Climate Change
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $5,290
Awards: G1175115578, G1401168639, G1722358650, G1855990336, G2262748287, G2309174360, G2373305540, G2398247149, G2446644622, G252646220, G2660406951, G2692215668, G294895050, G3007729222, G300979063, G3032124924, G3480869486, G3518538256, G425668148, G430777504, G4792882789, G4805787424, G5080475149, G5362055841, G5408403652, G5421974903, G5805502524, G7084143925, G7434936867, G7920858549, G8575141037, G99296377
OpenAlex ID: W4410766124