The nuclei comprising the anterior striatum play a critical role in learning and motivation. Derangements of these nuclei are implicated in a broad range of diseases including depression, drug addiction, and learning disorders. Our hypothesis is that there are two streams of information processing in the anterior striatum, dorsal and ventral, that perform complementary but different roles. Specifically, we hypothesize that the dorsal stream, which includes the caudate (Cd), is involved in the executive aspects of associative learning, whereas the ventral stream, which includes the nucleus accumbens (NAc), is involved in providing motivation for the performance of learned behaviors. Recent studies in our lab have demonstrated that intermittent electrical stimulation of the Cd, can significantly enhance the rate of visual-motor learning in primates. Our group is uniquely able to investigate these structures because we are able to perform physiological recordings and electrical stimulation in both primates and humans. This project will test the overarching hypothesis that is that deep brain stimulation of the Cd and NAc can be used to enhance learning in primates and humans. In the first stage of experiments, we will we use electrical stimulation to modulate the activity of the Cd and NAc during associative learning in primates, in order to optimize the parameters for learning enhancement. In the second stage, we will use the implanted DBS devices to assess the behavioral effects of stimulation on learning and motivation. We predict that stimulation in the NAC combined with stimulation in the Cd will lead to a dramatic increase in learning enhancement in both primates and subsequently in humans. Preliminary data is very promising suggesting that the Cd and NAc play distinct roles consistent with our proposed hypothesis. Elucidating the role of these nuclei in learning and motivation will significantly advance our understanding of the brain;and is vitally important to treating disorders that have an extremely large impact on public health.

Public Health Relevance

Common brain disorders such as stroke, traumatic brain injury, and autism, result in an impaired ability to learn movements or associations. Recent work has demonstrated that electrical stimulation in the striatum, a part of the basal ganglia, can lead to enhanced learning. The goal of this proposal is to establish whether deep brain stimulation, which is currently used to treat movement disorders, can be used to enhance learning and hence be used to speed or increase functional recovery following brain injury.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZNS1-SRB-P (44))
Program Officer
Thomas, David A
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Massachusetts General Hospital
United States
Zip Code
Martinez-Rubio, Clarissa; Paulk, Angelique C; McDonald, Eric J et al. (2018) Multimodal Encoding of Novelty, Reward, and Learning in the Primate Nucleus Basalis of Meynert. J Neurosci 38:1942-1958
Lee, Karen E; Bhati, Mahendra T; Halpern, Casey H (2016) A Commentary on Attitudes Towards Deep Brain Stimulation for Addiction. J Neurol Neuromedicine 1:1-3
Sierra-Mercado, Demetrio; Deckersbach, Thilo; Arulpragasam, Amanda R et al. (2015) Decision making in avoidance-reward conflict: a paradigm for non-human primates and humans. Brain Struct Funct 220:2509-17
Sierra-Mercado, Demetrio; McAllister, Lauren M; Lee, Christopher C H et al. (2015) Controlled cortical impact before or after fear conditioning does not affect fear extinction in mice. Brain Res 1606:133-41
Patel, Shaun R; Ghose, Kaushik; Eskandar, Emad N (2014) An open source 3-d printed modular micro-drive system for acute neurophysiology. PLoS One 9:e94262
Patel, Shaun R; Sheth, Sameer A; Martinez-Rubio, Clarissa et al. (2013) Studying task-related activity of individual neurons in the human brain. Nat Protoc 8:949-57
Srinivasan, Lakshminarayan; Asaad, Wael F; Ginat, Daniel T et al. (2013) Action initiation in the human dorsal anterior cingulate cortex. PLoS One 8:e55247
Sheth, Sameer A; Mian, Matthew K; Patel, Shaun R et al. (2012) Human dorsal anterior cingulate cortex neurons mediate ongoing behavioural adaptation. Nature 488:218-21
Patel, Shaun R; Sheth, Sameer A; Mian, Matthew K et al. (2012) Single-neuron responses in the human nucleus accumbens during a financial decision-making task. J Neurosci 32:7311-5
Sheth, Sameer A; Abuelem, Tarek; Gale, John T et al. (2011) Basal ganglia neurons dynamically facilitate exploration during associative learning. J Neurosci 31:4878-85

Showing the most recent 10 out of 15 publications