Article ; Online: Unraveling the mechanisms of deep-brain stimulation of the internal capsule in a mouse model.
2023 Volume 14, Issue 1, Page(s) 5385
Abstract: Deep-brain stimulation (DBS) is an effective treatment for patients suffering from otherwise therapy-resistant psychiatric disorders, including obsessive-compulsive disorder. Modulation of cortico-striatal circuits has been suggested as a mechanism of ... ...
Abstract | Deep-brain stimulation (DBS) is an effective treatment for patients suffering from otherwise therapy-resistant psychiatric disorders, including obsessive-compulsive disorder. Modulation of cortico-striatal circuits has been suggested as a mechanism of action. To gain mechanistic insight, we monitored neuronal activity in cortico-striatal regions in a mouse model for compulsive behavior, while systematically varying clinically-relevant parameters of internal-capsule DBS. DBS showed dose-dependent effects on both brain and behavior: An increasing, yet balanced, number of excited and inhibited neurons was recruited, scattered throughout cortico-striatal regions, while excessive grooming decreased. Such neuronal recruitment did not alter basic brain function such as resting-state activity, and only occurred in awake animals, indicating a dependency on network activity. In addition to these widespread effects, we observed specific involvement of the medial orbitofrontal cortex in therapeutic outcomes, which was corroborated by optogenetic stimulation. Together, our findings provide mechanistic insight into how DBS exerts its therapeutic effects on compulsive behaviors. |
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MeSH term(s) | Animals ; Mice ; Internal Capsule ; Disease Models, Animal ; Compulsive Behavior ; Brain ; Corpus Striatum |
Language | English |
Publishing date | 2023-09-04 |
Publishing country | England |
Document type | Journal Article ; Research Support, Non-U.S. Gov't |
ZDB-ID | 2553671-0 |
ISSN | 2041-1723 ; 2041-1723 |
ISSN (online) | 2041-1723 |
ISSN | 2041-1723 |
DOI | 10.1038/s41467-023-41026-x |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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