Cingulum stimulation enhances positive affect and anxiolysis to facilitate awake craniotomy
Kelly R. Bijanki, … , Helen S. Mayberg, Jon T. Willie
Kelly R. Bijanki, … , Helen S. Mayberg, Jon T. Willie
Published March 1, 2019; First published December 27, 2018
Citation Information: J Clin Invest. 2019;129(3):1152-1166. https://doi.org/10.1172/JCI120110.
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Categories: Clinical Medicine Neuroscience Therapeutics

Cingulum stimulation enhances positive affect and anxiolysis to facilitate awake craniotomy

Abstract

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. TRIAL REGISTRATION. The current study was not affiliated with any formal clinical trial. FUNDING. This project was supported by the American Foundation for Suicide Prevention and the NIH.

Authors

Kelly R. Bijanki, Joseph R. Manns, Cory S. Inman, Ki Sueng Choi, Sahar Harati, Nigel P. Pedersen, Daniel L. Drane, Allison C. Waters, Rebecca E. Fasano, Helen S. Mayberg, Jon T. Willie

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Figure 2

Localization of stimulated electrodes for the 3 patients.

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Localization of stimulated electrodes for the 3 patients. (A and B) Sagi...
(A and B) Sagittal and coronal views of stimulated locations across the full patient set (n = 3). Numbers inside circular indicators on the sagittal view reflect the number of 1-mm incremental sections from the displayed section in which the contact was located, where “–” corresponds to sections more medial and “+” corresponds to sections more lateral. Red circles indicate behaviorally active contacts, whereas black circles indicate behaviorally inactive contacts. (C) Overlap of the volumes of tissue activated (red) by all behaviorally active contacts across the full patient set (n = 3), relative to the index patient’s diffusion tensor imaging data set, collapsed by side of stimulation. The VTA for all patients robustly engage the cingulum bundle to the exclusion of other fiber systems. cb, cingulum bundle; CG, cingulate gyrus; PrG, precentral gyrus; PCun, precuneus; SFG, superior frontal gyrus; Cun, cuneus; OcG, occipital gyrus; cc, corpus callosum; OFG, orbitofrontal gyrus; SG, straight gyrus; HCd, head of caudate nucleus; FStr, fundus striati; LTh, lateral thalamic nucleus; MD, mediodorsal thalamic nucleus; CM, centromedial thalamic nucleus; LD, lateral dorsal thalamic nucleus; MTG, middle temporal gyrus. The underlying anatomical drawings in A and B were adapted with permission from Elsevier (52).