Direct and Indirect Activation of Cortical Neurons by Electrical Microstimulation

1 Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts; 2 Max Planck Institute for Biological Cybernetics, Tuebingen; and 3 Department of Cognitive Neurology, Hertie-Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany Submitted 5 February 2006; accepted in final form 30 April 2006 ABSTRACT Electrical microstimulation has been used to elucidate cortical function. This review discusses neuronal excitability and effective current spread estimated by using three different methods: 1 ) single-cell recording, 2 ) behavioral methods, and 3 ) functional magnetic resonance imaging (fMRI). The excitability properties of the stimulated elements in neocortex obtained using these methods were found to be comparable. These properties suggested that microstimulation activates the most excitable elements in cortex, that is, by and large the fibers of the pyramidal cells. Effective current spread within neocortex was found to be greater when measured with fMRI compared with measures based on single-cell recording or behavioral methods. The spread of activity based on behavioral methods is in close agreement with the spread based on the direct activation of neurons (as opposed to those activated synaptically). We argue that the greater activation with imaging is attributed to transynaptic spread, which includes subthreshold activation of sites connected to the site of stimulation. The definition of effective current spread therefore depends on the neural event being measured. Address for reprint requests and other correspondence: E. J. Tehovnik, Massachusetts Institute of Techology, Bldg. 46-6041, Cambridge, MA 02139 (E-mail: tehovnik{at}mit.edu )