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

Clemens Neudorfer, Gavin J.B. Elias, Martin Jakobs, Alexandre Boutet, Jürgen Germann, Keshav Narang, Aaron Loh, Michelle Paff, Andreas Horn, Walter Kucharczyk, Wissam Deeb, Bryan Salvato, Leonardo Almeida, Kelly D. Foote, Paul B. Rosenberg, David F. Tang-Wai, William S. Anderson, Zoltan Mari, Francisco A. Ponce, David A. WolkAnna D. Burke, Stephen Salloway, Marwan N. Sabbagh, M. Mallar Chakravarty, Gwenn S. Smith, Constantine G. Lyketsos, Michael S. Okun, Andres M. Lozano

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)2837-2851
Number of pages15
Issue number9
StatePublished - Sep 1 2021


  • Alzheimer's disease
  • autonomic nervous system
  • deep brain stimulation
  • hypothalamus
  • metabolic diseases

ASJC Scopus subject areas

  • Clinical Neurology


Dive into the research topics of 'Mapping autonomic, mood and cognitive effects of hypothalamic region deep brain stimulation'. Together they form a unique fingerprint.

Cite this