Complex negative emotions induced by electrical stimulation of the human hypothalamus

Josef Parvizi; Michael J Veit; Daniel A N Barbosa; Aaron Kucyi; Claire Perry; Jonathon J Parker; Rajat S Shivacharan; Fengyixuan Chen; Jennifer Yih; James J Gross; Robert Fisher; Jennifer A McNab; Jessica Falco-Walter; Casey H Halpern

doi:10.1016/j.brs.2022.04.008

Complex negative emotions induced by electrical stimulation of the human hypothalamus

Brain Stimul. 2022 May-Jun;15(3):615-623. doi: 10.1016/j.brs.2022.04.008. Epub 2022 Apr 9.

Affiliations

¹ Laboratory of Behavioral and Cognitive Neuroscience, Stanford University School of Medicine, Palo Alto, CA, USA; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, CA, USA; Department of Neurosurgery, Stanford University School of Medicine, Palo Alto, CA, USA. Electronic address: jparvizi@stanford.edu.
² Laboratory of Behavioral and Cognitive Neuroscience, Stanford University School of Medicine, Palo Alto, CA, USA; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, CA, USA.
³ Department of Neurosurgery, Stanford University School of Medicine, Palo Alto, CA, USA.
⁴ Laboratory of Behavioral and Cognitive Neuroscience, Stanford University School of Medicine, Palo Alto, CA, USA.
⁵ Department of Psychology, Stanford University, Palo Alto, CA, USA.
⁶ Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, CA, USA.
⁷ Department of Radiology, Stanford University School of Medicine, Palo Alto, CA, USA.

PMID: 35413481
DOI: 10.1016/j.brs.2022.04.008

Abstract

Background: Stimulation of the ventromedial hypothalamic region in animals has been reported to cause attack behavior labeled as sham-rage without offering information about the internal affective state of the animal being stimulated.

Objective: To examine the causal effect of electrical stimulation near the ventromedial region of the human hypothalamus on the human subjective experience and map the electrophysiological connectivity of the hypothalamus with other brain regions.

Methods: We examined a patient (Subject S20_150) with intracranial electrodes implanted across 170 brain regions, including the hypothalamus. We combined direct electrical stimulation with tractography, cortico-cortical evoked potentials (CCEP), and functional connectivity using resting state intracranial electroencephalography (EEG).

Results: Recordings in the hypothalamus did not reveal any epileptic abnormalities. Electrical stimulations near the ventromedial hypothalamus induced profound shame, sadness, and fear but not rage or anger. When repeated single-pulse stimulations were delivered to the hypothalamus, significant responses were evoked in the amygdala, hippocampus, ventromedial-prefrontal and orbitofrontal cortices, anterior cingulate, as well as ventral-anterior and dorsal-posterior insula. The time to first peak of these evoked responses varied and earliest propagations correlated best with the measures of resting-state EEG connectivity and structural connectivity.

Conclusion: This patient's case offers details about the affective state induced by the stimulation of the human hypothalamus and provides causal evidence relevant to current theories of emotion. The complexity of affective state induced by the stimulation of the hypothalamus and the profile of hypothalamic electrophysiological connectivity suggest that the hypothalamus and its connected structures ought to be seen as causally important for human affective experience.

Keywords: Affect; Depression; EEG; Emotion; Feelings; Hypothalamic nuclei; Subjectivity; VMH nucleus of hypothalamus.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Brain Mapping*
Electric Stimulation
Emotions / physiology
Evoked Potentials* / physiology
Humans
Hypothalamus