Angelique C Paulk1, Rina Zelmann2, Britni Crocker3, Alik S Widge4, Darin D Dougherty5, Emad N Eskandar6, Daniel S Weisholtz7, R Mark Richardson8, G Rees Cosgrove9, Ziv M Williams8, Sydney S Cash2. 1. Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA; Center for Neurotechnology and Neurorecovery, Department of Neurology, Massachusetts General Hospital, Boston, MA, USA. Electronic address: apaulk@mgh.harvard.edu. 2. Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA; Center for Neurotechnology and Neurorecovery, Department of Neurology, Massachusetts General Hospital, Boston, MA, USA. 3. Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA; Harvard-MIT Health Sciences and Technology, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA. 4. Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, 02129, USA. 5. Center for Neurotechnology and Neurorecovery, Department of Neurology, Massachusetts General Hospital, Boston, MA, USA; Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, 02129, USA. 6. Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA. 7. Department of Neurology, Brigham and Women's Hospital, Boston, MA, 02114, USA. 8. Center for Neurotechnology and Neurorecovery, Department of Neurology, Massachusetts General Hospital, Boston, MA, USA; Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA. 9. Department of Neurosurgery, Brigham and Women's Hospital, Boston, MA, 02114, USA.
Abstract
BACKGROUND: Electrical neuromodulation via direct electrical stimulation (DES) is an increasingly common therapy for a wide variety of neuropsychiatric diseases. Unfortunately, therapeutic efficacy is inconsistent, likely due to our limited understanding of the relationship between the massive stimulation parameter space and brain tissue responses. OBJECTIVE: To better understand how different parameters induce varied neural responses, we systematically examined single pulse-induced cortico-cortico evoked potentials (CCEP) as a function of stimulation amplitude, duration, brain region, and whether grey or white matter was stimulated. METHODS: We measured voltage peak amplitudes and area under the curve (AUC) of intracranially recorded stimulation responses as a function of distance from the stimulation site, pulse width, current injected, location relative to grey and white matter, and brain region stimulated (N = 52, n = 719 stimulation sites). RESULTS: Increasing stimulation pulse width increased responses near the stimulation location. Increasing stimulation amplitude (current) increased both evoked amplitudes and AUC nonlinearly. Locally (<15 mm), stimulation at the boundary between grey and white matter induced larger responses. In contrast, for distant sites (>15 mm), white matter stimulation consistently produced larger responses than stimulation in or near grey matter. The stimulation location-response curves followed different trends for cingulate, lateral frontal, and lateral temporal cortical stimulation. CONCLUSION: These results demonstrate that a stronger local response may require stimulation in the grey-white boundary while stimulation in the white matter could be needed for network activation. Thus, stimulation parameters tailored for a specific anatomical-functional outcome may be key to advancing neuromodulatory therapy.
BACKGROUND: Electrical neuromodulation via direct electrical stimulation (DES) is an increasingly common therapy for a wide variety of neuropsychiatric diseases. Unfortunately, therapeutic efficacy is inconsistent, likely due to our limited understanding of the relationship between the massive stimulation parameter space and brain tissue responses. OBJECTIVE: To better understand how different parameters induce varied neural responses, we systematically examined single pulse-induced cortico-cortico evoked potentials (CCEP) as a function of stimulation amplitude, duration, brain region, and whether grey or white matter was stimulated. METHODS: We measured voltage peak amplitudes and area under the curve (AUC) of intracranially recorded stimulation responses as a function of distance from the stimulation site, pulse width, current injected, location relative to grey and white matter, and brain region stimulated (N = 52, n = 719 stimulation sites). RESULTS: Increasing stimulation pulse width increased responses near the stimulation location. Increasing stimulation amplitude (current) increased both evoked amplitudes and AUC nonlinearly. Locally (<15 mm), stimulation at the boundary between grey and white matter induced larger responses. In contrast, for distant sites (>15 mm), white matter stimulation consistently produced larger responses than stimulation in or near grey matter. The stimulation location-response curves followed different trends for cingulate, lateral frontal, and lateral temporal cortical stimulation. CONCLUSION: These results demonstrate that a stronger local response may require stimulation in the grey-white boundary while stimulation in the white matter could be needed for network activation. Thus, stimulation parameters tailored for a specific anatomical-functional outcome may be key to advancing neuromodulatory therapy.
Authors: Britni Crocker; Lauren Ostrowski; Ziv M Williams; Darin D Dougherty; Emad N Eskandar; Alik S Widge; Catherine J Chu; Sydney S Cash; Angelique C Paulk Journal: Neuroimage Date: 2021-04-30 Impact factor: 6.556
Authors: Uma R Mohan; Andrew J Watrous; Jonathan F Miller; Bradley C Lega; Michael R Sperling; Gregory A Worrell; Robert E Gross; Kareem A Zaghloul; Barbara C Jobst; Kathryn A Davis; Sameer A Sheth; Joel M Stein; Sandhitsu R Das; Richard Gorniak; Paul A Wanda; Daniel S Rizzuto; Michael J Kahana; Joshua Jacobs Journal: Brain Stimul Date: 2020-05-21 Impact factor: 8.955
Authors: Jeff M Bronstein; Michele Tagliati; Ron L Alterman; Andres M Lozano; Jens Volkmann; Alessandro Stefani; Fay B Horak; Michael S Okun; Kelly D Foote; Paul Krack; Rajesh Pahwa; Jaimie M Henderson; Marwan I Hariz; Roy A Bakay; Ali Rezai; William J Marks; Elena Moro; Jerrold L Vitek; Frances M Weaver; Robert E Gross; Mahlon R DeLong Journal: Arch Neurol Date: 2010-10-11
Authors: Sydney S Cash; Alik S Widge; Ishita Basu; Ali Yousefi; Britni Crocker; Rina Zelmann; Angelique C Paulk; Noam Peled; Kristen K Ellard; Daniel S Weisholtz; G Rees Cosgrove; Thilo Deckersbach; Uri T Eden; Emad N Eskandar; Darin D Dougherty Journal: Nat Biomed Eng Date: 2021-11-01 Impact factor: 29.234