title: Deep brain stimulation in rats: different targets induce similar antidepressant-like effects but influence different circuits.
abstract: Recent studies in patients with treatment-resistant depression have shown similar results with the use of deep brain stimulation (DBS) in the subcallosal cingulate gyrus (SCG), ventral capsule/ventral striatum (VC/VS) and nucleus accumbens (Acb). As these brain regions are interconnected, one hypothesis is that by stimulating these targets one would just be influencing different relays in the same circuitry. We investigate behavioral, immediate early gene expression, and functional connectivity changes in rats given DBS in homologous regions, namely the ventromedial prefrontal cortex (vmPFC), white matter fibers of the frontal region (WMF) and nucleus accumbens. We found that DBS delivered to the vmPFC, Acb but not WMF induced significant antidepressant-like effects in the FST (31%, 44%, and 17% reduction in immobility compared to controls). Despite these findings, stimulation applied to these three targets induced distinct patterns of regional activity and functional connectivity. While animals given vmPFC DBS had increased cortical zif268 expression, changes after Acb stimulation were primarily observed in subcortical structures. In animals receiving WMF DBS, both cortical and subcortical structures at a distance from the target were influenced by stimulation. In regard to functional connectivity, DBS in all targets decreased intercorrelations among cortical areas. This is in contrast to the clear differences observed in subcortical connectivity, which was reduced after vmPFC DBS but increased in rats receiving Acb or WMF stimulation. In conclusion, results from our study suggest that, despite similar antidepressant-like effects, stimulation of the vmPFC, WMF and Acb induces distinct changes in regional brain activity and functional connectivity.
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON M5T 1R8, Canada; Division of Neurosurgery, Toronto Western Hospital, 399 Bathurst Street, Toronto, ON M5T 2S8, Canada. Electronic address: Clement.Hamani@camh.net.
authors.forename: Clement
authors.initials: C
authors.lastname: Hamani
authors.affiliation: Disciplina de Neurofisiologia, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Beatriz O
authors.initials: BO
authors.lastname: Amorim
authors.affiliation: Kimel Family Translational Imaging Genetics Laboratory, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Canada; Department of Psychiatry, University of Toronto, Toronto, Canada.
authors.forename: Anne L
authors.initials: AL
authors.lastname: Wheeler
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON M5T 1R8, Canada.
authors.forename: Mustansir
authors.initials: M
authors.lastname: Diwan
authors.affiliation: Department of Neurology, Biotechnology & Bioengineering Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: Klaus
authors.initials: K
authors.lastname: Driesslein
authors.affiliation: Disciplina de Neurofisiologia, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Luciene
authors.initials: L
authors.lastname: Covolan
authors.affiliation: Department of Neurology, Biotechnology & Bioengineering Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Butson
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON M5T 1R8, Canada; Department of Psychiatry, University of Toronto, Toronto, Canada.
authors.forename: José N
authors.initials: JN
authors.lastname: Nobrega
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000033:anatomy & histology* / Q000502:physiology*; D003198:Computer Simulation; D046690:Deep Brain Stimulation / Q000379:methods*; D003863:Depression / Q000628:therapy*; D004195:Disease Models, Animal; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism; D005106:Exploratory Behavior; D005786:Gene Expression Regulation / Q000502:physiology; D008297:Male; D008959:Models, Neurological; D009415:Nerve Net / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013550:Swimming / Q000523:psychology; D013997:Time Factors
chemical_list: D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat
keywords: Anterior capsule; Connectivity; Deep brain stimulation; Depression; Nucleus accumbens; Prefrontal cortex