""""""""Divide and conquer"""""""" seems to dominate many neural analyses: There are specialized systems for analyzing different types of information. Cognition requires synthesizing their results. To plan and execute complex, goal-directed behaviors we must learn """"""""the rules of the game"""""""": predictive relationships between disparate sensory events, environmental context, the possible actions and consequences. This depends on brain systems specialized for learning and memory: the prefrontal cortex (PFC), basal ganglia (BG) and hippocampal systems (HS). Damage to any of these systems, or their disconnection, impairs rule learning. Previous studies have shown that neural correlates of acquisition and/or representation of concrete (specific) rules and higher-level abstract rules (general principles) are prevalent in the PFC, a brain region central to rule-based behaviors. But our understanding is limited by our lack of knowledge about the respective contributions of, and PFC interactions with, the other critical systems: the BG and HS. The main goal of this project is to provide that knowledge. We plan to simultaneously study neural activity from up to 28 electrodes implanted these systems while monkeys larn and follow concrete rules )conditional visuomoter associations between an object and a saccade direction) and follow abstract rules (matching and non-matching rules applied to new stimuli). This will afford a precise assessment of the respective contributions of the PFC, BG, and GS to complex goal-directed behaviors and insight into the underlying neural circuitry.
Our specific aims are: 1. To compare and contrast the neural representation of concrete rules in the PFC with anatomically and functionally-related systems (BG and HS). 2. To assess the relative contributions of PFC, BG and HS to rule acquisition by comparing neural correlates of their learning. 3. To compare and contrast the neural representation of abstract rules in the PFC with the BG, and HS. As rule learning is fundamental to all higher-order behavior, data from this project has the potential to impact on our understanding of a wide range of behaviors and human and human disorders. The ability to glean rules and principles from experience is disrupted in a variety of neuropsychiatric disorders such as autism and schizophrenia. By identifying brain structures important for these abilities, discerning their relative roles, and uncovering their neural mechanisms, we can open a path to drug therapies designed to alleviate their dysfunction.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Integrative, Functional and Cognitive Neuroscience 8 (IFCN)
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Babcock, Debra J
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Massachusetts Institute of Technology
Other Basic Sciences
Other Domestic Higher Education
United States
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Jia, Nan; Brincat, Scott L; Salazar-Gómez, Andrés F et al. (2017) Decoding of intended saccade direction in an oculomotor brain-computer interface. J Neural Eng 14:046007
Puig, M Victoria; Miller, Earl K (2015) Neural Substrates of Dopamine D2 Receptor Modulated Executive Functions in the Monkey Prefrontal Cortex. Cereb Cortex 25:2980-7
Puig, M V; Antzoulatos, E G; Miller, E K (2014) Prefrontal dopamine in associative learning and memory. Neuroscience 282:217-29
Puig, M Victoria; Miller, Earl K (2012) The role of prefrontal dopamine D1 receptors in the neural mechanisms of associative learning. Neuron 74:874-86
Cromer, Jason A; Machon, Michelle; Miller, Earl K (2011) Rapid association learning in the primate prefrontal cortex in the absence of behavioral reversals. J Cogn Neurosci 23:1823-8
Warden, Melissa R; Miller, Earl K (2010) Task-dependent changes in short-term memory in the prefrontal cortex. J Neurosci 30:15801-10
Siegel, Markus; Warden, Melissa R; Miller, Earl K (2009) Phase-dependent neuronal coding of objects in short-term memory. Proc Natl Acad Sci U S A 106:21341-6
Buschman, Timothy J; Miller, Earl K (2009) Serial, covert shifts of attention during visual search are reflected by the frontal eye fields and correlated with population oscillations. Neuron 63:386-96
Histed, Mark H; Pasupathy, Anitha; Miller, Earl K (2009) Learning substrates in the primate prefrontal cortex and striatum: sustained activity related to successful actions. Neuron 63:244-53
Fusi, Stefano; Asaad, Wael F; Miller, Earl K et al. (2007) A neural circuit model of flexible sensorimotor mapping: learning and forgetting on multiple timescales. Neuron 54:319-33

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