Neural Basis of Human Working Memory

PROJECT SUMMARY Working memory, the ability to maintain information in mind over a period of seconds, is compromised in several mental illnesses and neurological conditions, including schizophrenia. The prefrontal cortex has been thought of as the primary site of working memory maintenance, though conflicting results have been obtained from human imaging and animal neurophysiological studies. To resolve this question, we will obtain neurophysiological recordings from human patients implanted with intracranial electrodes prior to epilepsy surgery and isolate spiking activity and local field potentials. The patients will perform working memory tasks closely modeled after tasks used in the non-human primate neurophysiological literature, requiring maintenance in memory of visual spatial, and shape information. We will thus be able to address the neural basis of memory at the level of neuronal firing in the human prefrontal cortex and other cortical areas, and compare our findings with the large literature of similar studies in non-human primate animal models. Specifically, we will address whether neuronal spiking in the prefrontal cortex exhibits selectivity for spatial locations objects held in memory or plays a more general supervisory or control role. Further, we will test predictions of competing models of working memory by using electrical stimulation to perturb neural activity and behavior. We will characterize the selectivity of sites isolated from each electrode contact when different stimuli are held in working memory, and we will apply electrical stimulation at either high (gamma) or low (beta) frequencies to disrupt or reinforce the memory of the stimulus. Results from these experiments will inform strategies for effective remediation of working memory deficits in patient populations.