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

Clemens Neudorfer, Toronto Western Hospital University of Toronto
Gavin J.B. Elias, Toronto Western Hospital University of Toronto
Martin Jakobs, Toronto Western Hospital University of Toronto
Alexandre Boutet, Toronto Western Hospital University of Toronto
Jürgen Germann, Toronto Western Hospital University of Toronto
Keshav Narang, Toronto Western Hospital University of Toronto
Aaron Loh, Toronto Western Hospital University of Toronto
Michelle Paff, Toronto Western Hospital University of Toronto
Andreas Horn, Charité – Universitätsmedizin Berlin
Walter Kucharczyk, University of Toronto
Wissam Deeb, University of Florida Health
Bryan Salvato, Florida State University
Leonardo Almeida, University of Florida Health
Kelly D. Foote, University of Florida Health
Paul B. Rosenberg, Johns Hopkins School of Medicine
David F. Tang-Wai, Toronto Western Hospital University of Toronto
William S. Anderson, Johns Hopkins School of Medicine
Zoltan Mari, Cleveland Clinic Lou Ruvo Center for Brain Health
Francisco A. Ponce, Barrow Neurological InstituteFollow
David A. Wolk, University of Pennsylvania
Anna D. Burke, Barrow Neurological InstituteFollow
Stephen Salloway, The Warren Alpert Medical School
Marwan N. Sabbagh, Cleveland Clinic Lou Ruvo Center for Brain HealthFollow
M. Mallar Chakravarty, Le Centre de Recherche Douglas
Gwenn S. Smith, Johns Hopkins School of Medicine
Constantine G. Lyketsos, Johns Hopkins School of Medicine
Michael S. Okun, University of Florida Health
Andres M. Lozano, Toronto Western Hospital University of Toronto

Document Type

Article

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.

Publication Date

9-1-2021

Publication Title

Brain

ISSN

00068950

E-ISSN

14602156

Volume

144

Issue

9

First Page

2837

Last Page

2851

PubMed ID

33905474

Digital Object Identifier (DOI)

10.1093/brain/awab170

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