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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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 1

Location of stimulated electrodes in the index patient.

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Location of stimulated electrodes in the index patient. (A) Postimplanta...
(A) Postimplantation lateral skull radiograph showing relative positions of the intracranial electrodes; red and blue volumes indicated by a black arrow highlight the contact pair yielding anxiolytic benefit. (B–D) Postimplantation MRI demonstrating positions of stimulated cingulate contacts; coronal slices in B and C correspond to the anode (red) and cathode (blue) of stimulation-eliciting anxiolysis and mirth. Cingulate gray matter stimulation utilized contacts 1–2 (yellow, green), cingulum bundle stimulation eliciting anxiolysis and mirth utilized contacts 3–4 (red, blue), cingulum bundle stimulation eliciting mirth and motor activation utilized contacts 5–6 (purple, magenta). The recording site for single-channel and coherence electrophysiological analyses was contact 5 (purple). (E–G) Sagittal views of deterministic tractography seeded at all tested contact pairs using modeled bipolar volumes of tissue activated via artificial neural nets based on 1.5 mA, 130 Hz, 300-μs pulse width stimulation. (E) Contacts 1 (anode; yellow) and 2 (cathode; green). (F) Contacts 3 (anode; red) and 4 (cathode; blue). (G) Contacts 5 (anode; purple) and 6 (cathode; pink). SFG, superior frontal gyrus; PCS, paracingulate sulcus, CG, cingulate gyrus; CC, corpus callosum; LV, lateral ventricle; Cd, caudate; Put, putamen; M1, primary motor cortex; S1, primary sensory cortex.