During the previous funding period we began studying learning in the caudate and the globus pallidus internus. We more clearly elucidated that the caudate is involved in executive aspects of learning, rapdily making new associations between the visaul cues, specific motor movements, and reward. We discovered that intermittent electrical micro-stimulation of the caudate leads to enhanced learning beyond normal rates . We found that the globus pallidus internus plays a key role in learning by initially faciliatating exploration, while later maximizing consolidation of learned associations. These results were published in a series of articles in Nature Neuroscience and the Journal of Neuroscience. We also made a number of novel preliminary findings that form the basis of the current proposal. We found that, the nucleus accumbens has a very different pattern of neuronal activity than the caudate suggesting a role in motivation. We also found that intermittent electrical stimulation in the ventral striatum or nucleus accumbens seems to ehance motivation. We can now posit a two stream model of the anterior striatum, where the dorsal striatum is involved in the executive aspects of learning, while the ventral striatum plays a role in the motivation to learn. The goal of the current proposal is to explicitly address two hypotheses. The first hypothesis is that there are two streams of processing in the anterior striatum, one critical to learning and the other for motivation. In this regard, our goal is to demonstrate that he dorsal module, Caudate (Cd) and dorsal lateral prefrontal cortex (DLPFC), is involved in the executive aspects of learning, that is the rapid association of visual cues and motor responses, while the ventral module, nucleus accumbens core (NAcc) and orbital-frontal cortex (OFC), plays a complementary role, by providing the motivation to perform learning behavior. The second hypothesis is that the dorsal and ventral modules also play important and complementary roles in working-memory, which is an essential component of associative learning. In regard to working-memory, our hypothesis is that the Cd is critical in gating relevant visual images, while the NAcc is critical in linking reward value with remembered images. We will employ a multi-modal approach using neuron physiology, connectivity analysis, and microstimulation. These results will be extremely important for optimizing and generating treatments for a broad range of neurological and psychiatric disorders.

Public Health Relevance

Disabilities due to brain injury or stroke include, cognitive, memory and emotional deficits. These severely reduce the quality of life for the disabled, and represent a major public health issue. The primary goal of this proposal is to develop a better understanding of the role of the dorsal and ventral striatum and learning and memory and to assess whether intermittently stimulating these areas has the potential to provide a treatment for patients with learning disabilities due to brain injury, stroke, or other brain disorders.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
Project #
Application #
Study Section
Neurobiology of Learning and Memory Study Section (LAM)
Program Officer
Steinmetz, Michael A
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Massachusetts General Hospital
United States
Zip Code
Katnani, Husam A; Patel, Shaun R; Kwon, Churl-Su et al. (2016) Temporally Coordinated Deep Brain Stimulation in the Dorsal and Ventral Striatum Synergistically Enhances Associative Learning. Sci Rep 6:18806
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
Mian, Matthew K; Sheth, Sameer A; Patel, Shaun R et al. (2014) Encoding of rules by neurons in the human dorsolateral prefrontal cortex. Cereb Cortex 24:807-16
Gale, John T; Lee, Kendall H; Amirnovin, Ramin et al. (2013) Electrical stimulation-evoked dopamine release in the primate striatum. Stereotact Funct Neurosurg 91:355-63
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
Lewis, Laura D; Weiner, Veronica S; Mukamel, Eran A et al. (2012) Rapid fragmentation of neuronal networks at the onset of propofol-induced unconsciousness. Proc Natl Acad Sci U S A 109:E3377-86
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
Asaad, Wael F; Eskandar, Emad N (2011) Encoding of both positive and negative reward prediction errors by neurons of the primate lateral prefrontal cortex and caudate nucleus. J Neurosci 31:17772-87

Showing the most recent 10 out of 20 publications