Cognitive enhancement with central thalamic electrical stimulation

doi:10.1073/pnas.0604811103

Cognitive enhancement with central thalamic electrical stimulation

*Departments of Psychiatry and
^†Neurology and Neuroscience, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021

Edited by Donald W. Pfaff, The Rockefeller University, New York, NY, and approved September 14, 2006 (received for review June 9, 2006)

Abstract

Central thalamic electrical stimulation has been proposed as a method for remediation of acquired cognitive disability. Long-standing experimental and clinical observations indicate a key role for neurons within the central thalamus in maintaining the alert waking state and facilitating attended behaviors. Here, we show that continuous high frequency (100 Hz) electrical stimulation of the central thalamus generates widespread cortical activation of c-fos across all cortical layers and a selective pattern of regulation of zif268 within the supragranular, granular, and infragranular cortical laminae. Significant elevation of both immediate early genes also is seen in the dentate gyrus of the hippocampus. Use of the same stimulation parameters is shown to facilitate untrained goal-directed seeking behavior and object recognition memory in rodents. An overall increase of exploratory motor behaviors and grooming activity also is observed, consistent with a global increase in arousal. Taken together, these studies indicate that electrical stimulation of the central thalamus may enhance cognitive performance through neocortical and hippocampal neuronal activation and specific regulation of gene expression.

Footnotes

^‡To whom correspondence should be addressed. E-mail: dah2007{at}med.cornell.edu
Author contributions: P.S., M.S., and D.G.H. performed research; N.D.S. and D.G.H. designed research; P.S., N.D.S., and D.G.H. analyzed data; and P.S., N.D.S., and D.G.H. wrote the paper.
Conflict of interest statement: N.D.S. is an inventor on the patents that have been issued to Cornell University for central thalamic brain stimulation for impaired cognitive function.
This article is a PNAS direct submission.
↵ ^§Schiff, N. D., Hudson, A. E., Purpura, K. P., 32nd Annual Meeting of the Society of Neuroscience, November 2–7, 2002, Orlando, FL, program 62.12 (abstr.).
↵ ^¶Schiff, N. D., Giacino, J., Kalmar, K., Kobylarz, E., Baker, K., Farris, S., Machado, A., Victor, J., McCagg, C., Plum, F., et al., 36th Annual Meeting of the Society of Neuroscience, October 14–18, 2006, Atlanta, GA, program 182.4 (abstr.).
Abbreviations:

ACC,

anterior cingulate cortex;

CL,

central lateral;

CP,

caudate-putamen;

I,

interval;

IR,

immunoreactivity;

mCtx,

motor cortex;

NOR,

novel object recognition;

OP,

object presentation;

OR,

object recognition;

SP,

stimulation protocol.
Freely available online through the PNAS open access option.