Evidence map›Paper›PMID 33905474›Full record

Trial reportBrain : a journal of neurology2021

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 and 18 more

Open access · bronzeAbstract readClinical TrialMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Brain : a journal of neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 2 pooled it
1.9field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 2 syntheses or guidelines pooled it, 27 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. A human subcortical connectome at 400 μm resolution.bioRxiv : the preprint server for biology · 2026
    Article
  4. Explainability in AI-enabled medical neurotechnology: a scoping review.Journal of neuroengineering and rehabilitation · 2026
    Article
  5. Review
  6. Biomarker changes associated with fornix deep brain stimulation in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
  7. Article
  8. Frontiers in neurology · 2025
    Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
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  15. Review
  16. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

28 authors at 11 institutions in 3 countries.

Clemens NeudorferDivision of Neurosurgery, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, ON, Canada.ORCID 0000-0002-3153-1045
Gavin J B EliasDivision of Neurosurgery, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, ON, Canada.
Martin JakobsDivision of Neurosurgery, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, ON, Canada.
Alexandre BoutetDivision of Neurosurgery, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, ON, Canada.ORCID 0000-0001-6942-5195
Jürgen GermannDivision of Neurosurgery, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, ON, Canada.ORCID 0000-0003-0995-8226
Keshav NarangDivision of Neurosurgery, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, ON, Canada.ORCID 0000-0001-7128-2461
Aaron LohDivision of Neurosurgery, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, ON, Canada.
Michelle PaffDivision of Neurosurgery, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, ON, Canada.
Andreas HornMovement Disorders and Neuromodulation Unit, Department for Neurology, Charité - University Medicine Berlin, Berlin, Germany.ORCID 0000-0002-0695-6025
Walter KucharczykJoint Department of Medical Imaging, University of Toronto, Toronto, ON, Canada.
Wissam DeebNorman Fixel Institute for Neurological Diseases, Departments of Neurology and Neurosurgery, University of Florida Health, Gainesville, FL, USA.
Bryan SalvatoFlorida State University, Tallahassee, FL, USA.ORCID 0000-0001-8339-2238
Leonardo AlmeidaNorman Fixel Institute for Neurological Diseases, Departments of Neurology and Neurosurgery, University of Florida Health, Gainesville, FL, USA.
Kelly D FooteNorman Fixel Institute for Neurological Diseases, Departments of Neurology and Neurosurgery, University of Florida Health, Gainesville, FL, USA.
Paul B RosenbergSchool of Medicine, Department of Psychiatry and Behavioural Sciences, Johns Hopkins University, Baltimore, MD, USA.
David F Tang-WaiDepartment of Neurology, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, ON, Canada.
William S AndersonDepartment of Neurosurgery, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Zoltan MariCleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, USA.
Francisco A PonceDepartment of Neurosurgery, Barrow Neurological Institute, Phoenix, AZ, USA.
David A WolkDepartment of Neurology, University of Pennsylvania, Philadelphia, PA, USA.
Anna D BurkeDepartment of Neurology, Barrow Neurological Institute, Phoenix, AZ, USA.
Stephen SallowayDepartment of Psychiatry and Human Behaviour and Neurology, Alpert Medical School of Brown University, Providence, RI, USA.
Marwan N SabbaghCleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, USA.
M Mallar ChakravartyCerebral Imaging Centre, Douglas Research Centre, Montreal QC, Canada.
Gwenn S SmithSchool of Medicine, Department of Psychiatry and Behavioural Sciences, Johns Hopkins University, Baltimore, MD, USA.
Constantine G LyketsosSchool of Medicine, Department of Psychiatry and Behavioural Sciences, Johns Hopkins University, Baltimore, MD, USA.
Michael S OkunNorman Fixel Institute for Neurological Diseases, Departments of Neurology and Neurosurgery, University of Florida Health, Gainesville, FL, USA.
Andres M LozanoDivision of Neurosurgery, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, ON, Canada.
University Health Network · CAJohns Hopkins University · USUniversity of Florida Health · USBarrow Neurological Institute · USCleveland Clinic · USBrown University · USCharité - Universitätsmedizin Berlin · DEFlorida State University · USMcGill University · CAUniversity of Pennsylvania · USUniversity of Toronto · CA

Funding

Research Education ComponentP30AG066507 · NIA · JOHNS HOPKINS UNIVERSITY · PI MARILYN S. ALBERT · 2020 to 2026
$29.3M
CIHR # 164235NIA NIH HHS P30 AG066507
6 · The paper itself

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.

Indexed as

AffectAgedAutonomic Nervous SystemBody TemperatureBrain MappingCognitionDeep Brain StimulationElectrodes, ImplantedFemaleHumansHypothalamusMaleMiddle AgedProspective StudiesTachycardiaAlzheimer’s diseaseautonomic nervous systemdeep brain stimulationhypothalamusmetabolic diseases

Identifiers

PMID33905474
PMCPMC8557336
OpenAlexW3159189061

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.