Mapping autonomic, mood and cognitive effects of hypothalamic region deep brain stimulation.

TitleMapping autonomic, mood and cognitive effects of hypothalamic region deep brain stimulation.
Publication TypeJournal Article
Year of Publication2021
AuthorsNeudorfer C, Elias GJB, Jakobs M, Boutet A, Germann J, Narang K, Loh A, Paff M, Horn A, Kucharczyk W, Deeb W, Salvato B, Almeida L, Foote KD, Rosenberg PB, Tang-Wai DF, Anderson WS, Mari Z, Ponce FA, Wolk DA, Burke AD, Salloway S, Sabbagh MN, Chakravarty MM, Smith GS, Lyketsos CG, Okun MS, Lozano AM
JournalBrain
Volume144
Issue9
Pagination2837-2851
Date Published2021 10 22
ISSN1460-2156
KeywordsAffect, Aged, Autonomic Nervous System, Body Temperature, Brain Mapping, Cognition, Deep Brain Stimulation, Electrodes, Implanted, Female, Humans, Hypothalamus, Male, Middle Aged, Prospective Studies, Tachycardia
Abstract

Because of its involvement in a wide variety of cardiovascular, metabolic and behavioural functions, the hypothalamus constitutes a potential target for neuromodulation in a number of treatment-refractory conditions. The precise neural substrates and circuitry subserving these responses, however, are poorly characterized to date. We sought to retrospectively explore the acute sequelae of hypothalamic region deep brain stimulation and characterize their neuroanatomical correlates. To this end we studied-at multiple international centres-58 patients (mean age: 68.5 ± 7.9 years, 26 females) suffering from mild Alzheimer's disease who underwent stimulation of the fornix region between 2007 and 2019. We catalogued the diverse spectrum of acutely induced clinical responses during electrical stimulation and interrogated their neural substrates using volume of tissue activated modelling, voxel-wise mapping, and supervised machine learning techniques. In total 627 acute clinical responses to stimulation-including tachycardia, hypertension, flushing, sweating, warmth, coldness, nausea, phosphenes, and fear-were recorded and catalogued across patients using standard descriptive methods. The most common manifestations during hypothalamic region stimulation were tachycardia (30.9%) and warmth (24.6%) followed by flushing (9.1%) and hypertension (6.9%). Voxel-wise mapping identified distinct, locally separable clusters for all sequelae that could be mapped to specific hypothalamic and extrahypothalamic grey and white matter structures. K-nearest neighbour classification further validated the clinico-anatomical correlates emphasizing the functional importance of identified neural substrates with area under the receiving operating characteristic curves between 0.67 and 0.91. Overall, we were able to localize acute effects of hypothalamic region stimulation to distinct tracts and nuclei within the hypothalamus and the wider diencephalon providing clinico-anatomical insights that may help to guide future neuromodulation work.

DOI10.1093/brain/awab170
Alternate JournalBrain
PubMed ID33905474
PubMed Central IDPMC8557336
Grant ListP30 AG066507 / AG / NIA NIH HHS / United States
# 164235 / / CIHR / Canada