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Author Notes:

Jon T. Willie, 1365 Clifton Road NE, Suite B6200, Atlanta, Georgia 30322, USA. Phone:404.727.2354; Email: jon.t.willie@emory.edu.

KRB, HSM, DLD, and JTW conceived the study.

KRB, CSI, NPP, and JTW designed the study methodology.

KRB, JRM, KSC, and SH performed the formal analysis.

KRB, CSI, NPP, REF, and JTW performed experiments.

KRB and JTW wrote the original draft of the manuscript.

KRB, JTW, JRM, REF, KSC, CSI, NPP, ACW, HSM, DLD, and SH wrote, edited, and reviewed the manuscript.

JTW, HSM, and DLD supervised the study.

We would like to thank the following individuals for their significant contributions to the development of this article: John Gale, Robert Gross, Grant Lynde, Joel Zivot, Camille Steger, and Taylor Shade of the Emory University School of Medicine.

We would also like to thank the patients for participating in the current study.

KRB, JTW, NPP, and CSI are named inventors on a patent filing based on the work described herein (US Patent Application no. 16121599 [pending]

HSM receives fees from the licensing of intellectual property to St. Jude Medical Inc.; DLD receives grant funding from Medtronic Inc. and honoraria from NeuroPace Inc.; and JTW serves as a consultant for Medtronic Inc., MRI Interventions Inc., and NeuroPace Inc.


Research Funding:

This project was supported by a Young Investigator Award from the American Foundation for Suicide Prevention to KRB (YIG-0-015-13); by the Emory University Department of Neurosurgery; by the National Center for Advancing Translational Sciences of the National Institutes of Health (UL1TR002378); and by a KL2 Scholars award to KRB (KL2TR002381); an Exploratory and Developmental Research Award from the National Institute of Neurological Disease and Stroke (R21NS104953) for KRB and JTW; a Mentored Research Award (K01MH116364) for KRB; a Mentored Clinical Research Award (K08NS105929) for NPP;and by Research Program awards to DLD (R01NS088748, K02NS070960).


  • Science & Technology
  • Life Sciences & Biomedicine
  • Medicine, Research & Experimental
  • Research & Experimental Medicine

Cingulum stimulation enhances positive affect and anxiolysis to facilitate awake craniotomy

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Journal Title:

Journal of Clinical Investigation


Volume 129, Number 3


, Pages 1152-1166

Type of Work:

Article | Final Publisher PDF


BACKGROUND. Awake neurosurgery requires patients to converse and respond to visual or verbal prompts to identify and protect brain tissue supporting essential functions such as language, primary sensory modalities, and motor function. These procedures can be poorly tolerated because of patient anxiety, yet acute anxiolytic medications typically cause sedation and impair cortical function. METHODS. In this study, direct electrical stimulation of the left dorsal anterior cingulum bundle was discovered to reliably evoke positive affect and anxiolysis without sedation in a patient with epilepsy undergoing research testing during standard inpatient intracranial electrode monitoring. These effects were quantified using subjective and objective behavioral measures, and stimulation was found to evoke robust changes in local and distant neural activity. RESULTS. The index patient ultimately required an awake craniotomy procedure to confirm safe resection margins in the treatment of her epilepsy. During the procedure, cingulum bundle stimulation enhanced positive affect and reduced the patient’s anxiety to the point that intravenous anesthetic/anxiolytic medications were discontinued and cognitive testing was completed. Behavioral responses were subsequently replicated in 2 patients with anatomically similar electrode placements localized to an approximately 1-cm span along the anterior dorsal cingulum bundle above genu of the corpus callosum. CONCLUSIONS. The current study demonstrates a robust anxiolytic response to cingulum bundle stimulation in 3 patients with epilepsy.

Copyright information:

© 2019, American Society for Clinical Investigation.

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