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Intracranial electrical stimulation of corticolimbic sites modulates arousal in humans.

Publication ,  Journal Article
Fan, JM; Lee, AM; Sellers, KK; Woodworth, K; Makhoul, GS; Liu, TX; Henderson, C; Astudillo Maya, DA; Martinez, R; Zamanian, H; Speidel, BA ...
Published in: Brain Stimul
2023

BACKGROUND: Humans routinely shift their sleepiness and wakefulness levels in response to emotional factors. The diversity of emotional factors that modulates sleep-wake levels suggests that the ascending arousal network may be intimately linked with networks that mediate mood. Indeed, while animal studies have identified select limbic structures that play a role in sleep-wake regulation, the breadth of corticolimbic structures that directly modulates arousal in humans remains unknown. OBJECTIVE: We investigated whether select regional activation of the corticolimbic network through direct electrical stimulation can modulate sleep-wake levels in humans, as measured by subjective experience and behavior. METHODS: We performed intensive inpatient stimulation mapping in two human participants with treatment resistant depression, who underwent intracranial implantation with multi-site, bilateral depth electrodes. Stimulation responses of sleep-wake levels were measured by subjective surveys (i.e. Stanford Sleepiness Scale and visual-analog scale of energy) and a behavioral arousal score. Biomarker analyses of sleep-wake levels were performed by assessing spectral power features of resting-state electrophysiology. RESULTS: Our findings demonstrated three regions whereby direct stimulation modulated arousal, including the orbitofrontal cortex (OFC), subgenual cingulate (SGC), and, most robustly, ventral capsule (VC). Modulation of sleep-wake levels was frequency-specific: 100Hz OFC, SGC, and VC stimulation promoted wakefulness, whereas 1Hz OFC stimulation increased sleepiness. Sleep-wake levels were correlated with gamma activity across broad brain regions. CONCLUSIONS: Our findings provide evidence for the overlapping circuitry between arousal and mood regulation in humans. Furthermore, our findings open the door to new treatment targets and the consideration of therapeutic neurostimulation for sleep-wake disorders.

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Published In

Brain Stimul

DOI

EISSN

1876-4754

Publication Date

2023

Volume

16

Issue

4

Start / End Page

1072 / 1082

Location

United States

Related Subject Headings

  • Wakefulness
  • Sleepiness
  • Sleep
  • Neurology & Neurosurgery
  • Humans
  • Electric Stimulation
  • Arousal
  • Animals
  • 42 Health sciences
  • 32 Biomedical and clinical sciences
 

Citation

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Fan, J. M., Lee, A. M., Sellers, K. K., Woodworth, K., Makhoul, G. S., Liu, T. X., … Krystal, A. D. (2023). Intracranial electrical stimulation of corticolimbic sites modulates arousal in humans. Brain Stimul, 16(4), 1072–1082. https://doi.org/10.1016/j.brs.2023.06.017
Fan, Joline M., A Moses Lee, Kristin K. Sellers, Kai Woodworth, Ghassan S. Makhoul, Tony X. Liu, Catherine Henderson, et al. “Intracranial electrical stimulation of corticolimbic sites modulates arousal in humans.Brain Stimul 16, no. 4 (2023): 1072–82. https://doi.org/10.1016/j.brs.2023.06.017.
Fan JM, Lee AM, Sellers KK, Woodworth K, Makhoul GS, Liu TX, et al. Intracranial electrical stimulation of corticolimbic sites modulates arousal in humans. Brain Stimul. 2023;16(4):1072–82.
Fan, Joline M., et al. “Intracranial electrical stimulation of corticolimbic sites modulates arousal in humans.Brain Stimul, vol. 16, no. 4, 2023, pp. 1072–82. Pubmed, doi:10.1016/j.brs.2023.06.017.
Fan JM, Lee AM, Sellers KK, Woodworth K, Makhoul GS, Liu TX, Henderson C, Astudillo Maya DA, Martinez R, Zamanian H, Speidel BA, Khambhati AN, Rao VR, Sugrue LP, Scangos KW, Chang EF, Krystal AD. Intracranial electrical stimulation of corticolimbic sites modulates arousal in humans. Brain Stimul. 2023;16(4):1072–1082.
Journal cover image

Published In

Brain Stimul

DOI

EISSN

1876-4754

Publication Date

2023

Volume

16

Issue

4

Start / End Page

1072 / 1082

Location

United States

Related Subject Headings

  • Wakefulness
  • Sleepiness
  • Sleep
  • Neurology & Neurosurgery
  • Humans
  • Electric Stimulation
  • Arousal
  • Animals
  • 42 Health sciences
  • 32 Biomedical and clinical sciences