. 2025 Feb 4;167(1):33.

doi: 10.1007/s00701-025-06430-w.

Deep brain stimulation of the hypothalamic region: a systematic review

Mohammad Mofatteh^{1

2}, Abdulkadir Mohamed^{3

4}, Mohammad Sadegh Mashayekhi^{5

6}, Georgios P Skandalakis^{7

8}, Clemens Neudorfer^{9

10

11

12}, Saman Arfaie^{13

14

15

16}, ArunSundar MohanaSundaram¹⁷, Mohammadmahdi Sabahi¹⁸, Ayush Anand¹⁹, Rabii Aboulhosn²⁰, Xuxing Liao²¹, Andreas Horn^{22

23

24}, Keyoumars Ashkan^{25

26

27

28

29}

Affiliations

¹ School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, UK. mmofatteh01@qub.ac.uk.
² Neuro International Collaboration (NIC), London, UK. mmofatteh01@qub.ac.uk.
³ Medical Sciences Division, University of Oxford, Oxford, UK.
⁴ Neuro International Collaboration (NIC), Oxford, UK.
⁵ Faculty of Medicine, Division of Neurosurgery, University of Ottawa, Ottawa, ON, Canada.
⁶ Neuro International Collaboration (NIC), Vancouver, Ottawa, ON, Canada.
⁷ Department of Neurosurgery, Evangelismos General Hospital, National and Kapodistrian University of Athens, Athens, Greece.
⁸ Section of Neurosurgery, Dartmouth Hitchcock Medical Center, Lebanon, NH, USA.
⁹ Brain Modulation Lab, Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA.
¹⁰ Harvard Medical School, Boston, MA, USA.
¹¹ Center for Brain Circuit Therapeutics Department of Neurology Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA.
¹² Movement Disorder and Neuromodulation Unit, Department of Neurology, Charité -Universitätsmedizin Berlin, corporate member of, Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany.
¹³ Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada.
¹⁴ Division of Neurosurgery, Department of Clinical Neurological Sciences, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada.
¹⁵ Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA, USA.
¹⁶ Neuro International Collaboration (NIC), Montreal, QC, Canada.
¹⁷ School of Pharmacy, Sathyabama Institute of Science and Technology, Chennai, Tamilnadu, India.
¹⁸ Department of Neurological Surgery, Pauline Braathen Neurological Center, Cleveland Clinic Florida, Weston, FL, USA.
¹⁹ Koirala Institute of Health Sciences, B. P, Dharan, Nepal.
²⁰ School of Medicine, University of Aberdeen, Aberdeen, UK.
²¹ Department of Neurosurgery, First People's Hospital of Foshan, Foshan, Guangdong Province, China.
²² Movement Disorder and Neuromodulation Unit, Department of Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
²³ Center for Brain Circuit Therapeutics, Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA.
²⁴ Departments of Neurology and Neurosurgery, Massachusetts General Hospital, Boston, MA, USA.
²⁵ Neuro International Collaboration (NIC), London, UK.
²⁶ School of Biomedical Engineering and Imaging Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK.
²⁷ King's Health Partners Academic Health Sciences Centre, London, UK.
²⁸ Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
²⁹ Department of Neurosurgery, King's College Hospital NHS Foundation Trust, London, UK.

PMID: 39904782
PMCID: PMC11794333
DOI: 10.1007/s00701-025-06430-w

Deep brain stimulation of the hypothalamic region: a systematic review

Mohammad Mofatteh et al. Acta Neurochir (Wien). 2025.

. 2025 Feb 4;167(1):33.

doi: 10.1007/s00701-025-06430-w.

Authors

Affiliations

¹ School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, UK. mmofatteh01@qub.ac.uk.
² Neuro International Collaboration (NIC), London, UK. mmofatteh01@qub.ac.uk.
³ Medical Sciences Division, University of Oxford, Oxford, UK.
⁴ Neuro International Collaboration (NIC), Oxford, UK.
⁵ Faculty of Medicine, Division of Neurosurgery, University of Ottawa, Ottawa, ON, Canada.
⁶ Neuro International Collaboration (NIC), Vancouver, Ottawa, ON, Canada.
⁷ Department of Neurosurgery, Evangelismos General Hospital, National and Kapodistrian University of Athens, Athens, Greece.
⁸ Section of Neurosurgery, Dartmouth Hitchcock Medical Center, Lebanon, NH, USA.
⁹ Brain Modulation Lab, Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA.
¹⁰ Harvard Medical School, Boston, MA, USA.
¹¹ Center for Brain Circuit Therapeutics Department of Neurology Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA.
¹² Movement Disorder and Neuromodulation Unit, Department of Neurology, Charité -Universitätsmedizin Berlin, corporate member of, Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany.
¹³ Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada.
¹⁴ Division of Neurosurgery, Department of Clinical Neurological Sciences, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada.
¹⁵ Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA, USA.
¹⁶ Neuro International Collaboration (NIC), Montreal, QC, Canada.
¹⁷ School of Pharmacy, Sathyabama Institute of Science and Technology, Chennai, Tamilnadu, India.
¹⁸ Department of Neurological Surgery, Pauline Braathen Neurological Center, Cleveland Clinic Florida, Weston, FL, USA.
¹⁹ Koirala Institute of Health Sciences, B. P, Dharan, Nepal.
²⁰ School of Medicine, University of Aberdeen, Aberdeen, UK.
²¹ Department of Neurosurgery, First People's Hospital of Foshan, Foshan, Guangdong Province, China.
²² Movement Disorder and Neuromodulation Unit, Department of Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
²³ Center for Brain Circuit Therapeutics, Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA.
²⁴ Departments of Neurology and Neurosurgery, Massachusetts General Hospital, Boston, MA, USA.
²⁵ Neuro International Collaboration (NIC), London, UK.
²⁶ School of Biomedical Engineering and Imaging Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK.
²⁷ King's Health Partners Academic Health Sciences Centre, London, UK.
²⁸ Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
²⁹ Department of Neurosurgery, King's College Hospital NHS Foundation Trust, London, UK.

PMID: 39904782
PMCID: PMC11794333
DOI: 10.1007/s00701-025-06430-w

Abstract

Background: Deep brain stimulation (DBS) has been successfully used for the treatment of circuitopathies including movement, anxiety, and behavioral disorders. The hypothalamus is a crucial integration center for many peripheral and central pathways relating to cardiovascular, metabolic, and behavioral functions and constitutes a potential target for neuromodulation in treatment-refractory conditions. To conduct a systematic review, investigating hypothalamic targets in DBS, their indications, and the primary clinical findings.

Methods: PubMed, Scopus, and Web of Science databases were searched in accordance with the PRISMA guideline to identify papers published in English studying DBS of the hypothalamus in humans.

Results: After screening 3,148 papers, 34 studies consisting of 412 patients published over two decades were included in the final review. Hypothalamic DBS was indicated in refractory headaches (n = 238, 57.8%), aggressive behavior (n = 100, 24.3%), mild Alzheimer's disease (n = 58, 14.1%), trigeminal neuralgia in multiple sclerosis (n = 5, 1.2%), Prader-Willi syndrome (n = 4, 0.97%), and atypical facial pain (n = 3, 0.73%). The posterior hypothalamus was the most common DBS target site across 30 studies (88.2%). 262 (63.6%) participants were males, and 110 (26.7%) were females. 303 (73.5%) patients were adults whereas 33 (8.0%) were pediatrics. The lowest mean age of participants was 15.25 ± 4.6 years for chronic refractory aggressiveness, and the highest was 68.5 ± 7.9 years in Alzheimer's disease patients. The mean duration of the disease ranged from 2.2 ± 1.7 (mild Alzheimer's disease) to 19.8 ± 10.1 years (refractory headaches). 213 (51.7%) patients across 29 studies (85.3%) reported symptom improvements which ranged from 23.1% to 100%. 25 (73.5%) studies reported complications, most of which were associated with higher voltage stimulations.

Conclusions: DBS of the hypothalamus is feasible in selected patients with various refractory conditions ranging from headaches to aggression in both pediatric and adult populations. Future large-scale studies with long-term follow-up are required to validate the safety and efficacy data and extend these findings.

Keywords: Aggression; DBS; Deep brain stimulation; Hypothalamic nuclei; Hypothalamus; Refractory headaches.

PubMed Disclaimer

Conflict of interest statement

Declarations. Informed consent: N/A. Competing interests: The authors declare no competing interests. Research involving human participants and/or animals: This article does not contain any studies with animals or human participants performed by any of the authors. Ethical approval was not required as this study is a systematic review of published data.

Figures

**Fig. 1**
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flowchart demonstrating search, screen, inclusion, and exclusion process for the current study. DBS, deep brain stimulation

**Fig. 2**
Anatomical relationship between the hypothalamus and surrounding gray and white matter structures. A Frontal, B superior, C right-sided, and D left-sided view of the hypothalamus (red) and surrounding structures (gray) overlaid on a 100 μm resolution, 7 T brain scan in Montreal Neurological Institute (MNI) 152 space

**Fig. 3**
3D reconstruction of hypothalamic nuclei and their anatomical relationships. A Oblique posterior view featuring the outer surface of hypothalamic nuclei and B medial view featuring the inner surface of hypothalamic nuclei. Hypothalamic nuclei, which have been previously targeted in the literature are featured in yellow. AN, arcuate nucleus; DM, LH, lateral hypothalamus; PA, paraventricular nucleus; PE, periventricular nucleus; PH, posterior hypothalamus; *SCh*, suprachiasmatic nucleus

See this image and copyright information in PMC

References

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Deep brain stimulation of the hypothalamic region: a systematic review

Affiliations

Deep brain stimulation of the hypothalamic region: a systematic review

Authors

Affiliations

Abstract

Conflict of interest statement

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Medical