Intracranial electrical stimulation of corticolimbic sites modulates arousal in humans
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...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-07-01
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| Series: | Brain Stimulation |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1935861X23018132 |
| _version_ | 1827861406210326528 |
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| author | Joline M. Fan A. Moses Lee Kristin K. Sellers Kai Woodworth Ghassan S. Makhoul Tony X. Liu Catherine Henderson Daniela A. Astudillo Maya Rebecca Martinez Hashem Zamanian Benjamin A. Speidel Ankit N. Khambhati Vikram R. Rao Leo P. Sugrue Katherine W. Scangos Edward F. Chang Andrew D. Krystal |
| author_facet | Joline M. Fan A. Moses Lee Kristin K. Sellers Kai Woodworth Ghassan S. Makhoul Tony X. Liu Catherine Henderson Daniela A. Astudillo Maya Rebecca Martinez Hashem Zamanian Benjamin A. Speidel Ankit N. Khambhati Vikram R. Rao Leo P. Sugrue Katherine W. Scangos Edward F. Chang Andrew D. Krystal |
| author_sort | Joline M. Fan |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T13:36:27Z |
| format | Article |
| id | doaj.art-7f36f01504914a89a70166e8b3673f39 |
| institution | Directory Open Access Journal |
| issn | 1935-861X |
| language | English |
| last_indexed | 2024-03-12T13:36:27Z |
| publishDate | 2023-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain Stimulation |
| spelling | doaj.art-7f36f01504914a89a70166e8b3673f392023-08-24T04:34:48ZengElsevierBrain Stimulation1935-861X2023-07-0116410721082Intracranial electrical stimulation of corticolimbic sites modulates arousal in humansJoline M. Fan0A. Moses Lee1Kristin K. Sellers2Kai Woodworth3Ghassan S. Makhoul4Tony X. Liu5Catherine Henderson6Daniela A. Astudillo Maya7Rebecca Martinez8Hashem Zamanian9Benjamin A. Speidel10Ankit N. Khambhati11Vikram R. Rao12Leo P. Sugrue13Katherine W. Scangos14Edward F. Chang15Andrew D. Krystal16Department of Neurology, University of California, San Francisco, CA, USA; Weill Institute for Neurosciences, University of California, San Francisco, CA, USA; Corresponding author. University of California, San Francisco, Department of Neurology and Weill Institute for Neurosciences, 505 Parnassus Ave, Box 0114, San Francisco, CA, 94158, USA.Weill Institute for Neurosciences, University of California, San Francisco, CA, USA; Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, CA, USAWeill Institute for Neurosciences, University of California, San Francisco, CA, USA; Department of Neurosurgery, University of California, San Francisco, CA, USAWeill Institute for Neurosciences, University of California, San Francisco, CA, USA; Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, CA, USAWeill Institute for Neurosciences, University of California, San Francisco, CA, USA; Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, CA, USAWeill Institute for Neurosciences, University of California, San Francisco, CA, USA; Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, CA, USAWeill Institute for Neurosciences, University of California, San Francisco, CA, USA; Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, CA, USAWeill Institute for Neurosciences, University of California, San Francisco, CA, USA; Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, CA, USAWeill Institute for Neurosciences, University of California, San Francisco, CA, USA; Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, CA, USAWeill Institute for Neurosciences, University of California, San Francisco, CA, USA; Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, CA, USADepartment of Neurology, University of California, San Francisco, CA, USA; Weill Institute for Neurosciences, University of California, San Francisco, CA, USAWeill Institute for Neurosciences, University of California, San Francisco, CA, USA; Department of Neurosurgery, University of California, San Francisco, CA, USADepartment of Neurology, University of California, San Francisco, CA, USA; Weill Institute for Neurosciences, University of California, San Francisco, CA, USAWeill Institute for Neurosciences, University of California, San Francisco, CA, USA; Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, CA, USA; Department of Radiology, University of California, San Francisco, CA, USAWeill Institute for Neurosciences, University of California, San Francisco, CA, USA; Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, CA, USAWeill Institute for Neurosciences, University of California, San Francisco, CA, USA; Department of Neurosurgery, University of California, San Francisco, CA, USAWeill Institute for Neurosciences, University of California, San Francisco, CA, USA; Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, CA, USABackground: 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.http://www.sciencedirect.com/science/article/pii/S1935861X23018132ArousalNeurostimulationHuman electrophysiologySleepinessVentral capsule |
| spellingShingle | Joline M. Fan A. Moses Lee Kristin K. Sellers Kai Woodworth Ghassan S. Makhoul Tony X. Liu Catherine Henderson Daniela A. Astudillo Maya Rebecca Martinez Hashem Zamanian Benjamin A. Speidel Ankit N. Khambhati Vikram R. Rao Leo P. Sugrue Katherine W. Scangos Edward F. Chang Andrew D. Krystal Intracranial electrical stimulation of corticolimbic sites modulates arousal in humans Brain Stimulation Arousal Neurostimulation Human electrophysiology Sleepiness Ventral capsule |
| title | Intracranial electrical stimulation of corticolimbic sites modulates arousal in humans |
| title_full | Intracranial electrical stimulation of corticolimbic sites modulates arousal in humans |
| title_fullStr | Intracranial electrical stimulation of corticolimbic sites modulates arousal in humans |
| title_full_unstemmed | Intracranial electrical stimulation of corticolimbic sites modulates arousal in humans |
| title_short | Intracranial electrical stimulation of corticolimbic sites modulates arousal in humans |
| title_sort | intracranial electrical stimulation of corticolimbic sites modulates arousal in humans |
| topic | Arousal Neurostimulation Human electrophysiology Sleepiness Ventral capsule |
| url | http://www.sciencedirect.com/science/article/pii/S1935861X23018132 |
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