Intra-Operative Behavioral Tasks in Awake Humans Undergoing Deep Brain Stimulation Surgery

Summary

Deep brain stimulation surgery offers a unique opportunity to examine information encoding in the awake human brain. This article will describe intra-operative methods used to perform cognitive and behavioral tasks while simultaneously acquiring physiological data such as EMG, single-unit neuronal activity and/or local field potentials.

Abstract

Deep brain stimulation (DBS) is a surgical procedure that directs chronic, high frequency electrical stimulation to specific targets in the brain through implanted electrodes. Deep brain stimulation was first implemented as a therapeutic modality by Benabid et al. in the late 1980s, when he used this technique to stimulate the ventral intermediate nucleus of the thalamus for the treatment of tremor ¹. Currently, the procedure is used to treat patients who fail to respond adequately to medical management for diseases such as Parkinson’s, dystonia, and essential tremor. The efficacy of this procedure for the treatment of Parkinson’s disease has been demonstrated in well-powered, randomized controlled trials ². Presently, the U.S. Food and Drug Administration has approved DBS as a treatment for patients with medically refractory essential tremor, Parkinson’s disease, and dystonia. Additionally, DBS is currently being evaluated for the treatment of other psychiatric and neurological disorders, such as obsessive compulsive disorder, major depressive disorder, and epilepsy.

DBS has not only been shown to help people by improving their quality of life, it also provides researchers with the unique opportunity to study and understand the human brain. Microelectrode recordings are routinely performed during DBS surgery in order to enhance the precision of anatomical targeting. Firing patterns of individual neurons can therefore be recorded while the subject performs a behavioral task. Early studies using these data focused on descriptive aspects, including firing and burst rates, and frequency modulation ³. More recent studies have focused on cognitive aspects of behavior in relation to neuronal activity ^4,5. This article will provide a description of the intra-operative methods used to perform behavioral tasks and record neuronal data with awake patients during DBS cases. Our exposition of the process of acquiring electrophysiological data will illuminate the current scope and limitations of intra-operative human experiments.

Protocol

1. Subject Recruitment and Consent Following clinical evaluation and consent for subthalamic nucleus (STN) deep brain stimulation (DBS) for refractory Parkinson Disease, each patient’s information is reviewed in order to determine if he/she meets the criteria for the intra-operative study (Defined in an Institutional Review Board approved protocol at the Massachusetts General Hospital). If it is determined that the subject meets the study criteria, a physician member of the study group (not the ope…

Discussion

Deep Brain Stimulation surgery offers a valuable opportunity to examine the activity of individual neurons in the human brain. To date this opportunity has permitted numerous descriptive studies that characterize the activities of different deep nuclei. More recently, intra-operative tasks have become more sophisticated in order to address various aspects of behavior and cognition. The intent of the current protocol is to provide a guide for implementing successful intra-operative behavioral tasks. The goals of the ta…

Materials

Material Name	Type	Company	Catalogue Number	Comment
Behavioral Rig
PC with dual Video Out		Dell Computers*	Optiplex 745
Digital Boards		National Instruments**	PCI-6229
Connector Board		National Instruments**	BNC-2090a
Software		The MathWorks	Matlab 2007b***
Behavioral Software		Eskandar Lab	www.Monkeylogic.net
Acquisition Rig
PC		Dell Computers *	Optiplex 745
Digital Boards		Cambridge Electronic Designs*	Power 1401
Software		Cambridge Electronic Designs*	Spike2
Signal Processing		Alpha-Omega Engineering*	Micro-Guide Pro
Analysis
Neuonal Signal post-processing		Plexon *	Offline Sorter
Software		The MathWorks *	Matlab 2007b
Button Box		Refer to ‘Button Assembly’

*Denotes that this items can be substitute for by comparable equipment or software;
** Denotes that substitute National Instruments components can be used (refer to www.Monkeylogic.net for compatibility);
*** Refer to www.Monkeylogic.net for specific required Matlab toolboxs.