A number of disorders including schizophrenia, Alzheimer's disease, and age-related memory loss are marked by correlated memory impairment and neurological dysfunction in the medial temporal lobe (MIL) and prefrontal cortex (RFC). Studies of focal brain damage suggest these two structures play distinct, specific roles in memory. The MIL is crucial for encoding information about facts, events, and relations between them into long-term memory, a capacity referred to as declarative memory in humans and relational memory in animals. RFC is thought to be involved in executive control of declarative/relational memory encoding and retrieval. The long-term goal of my research program is to understand how neural representations and computations in these and related structures give rise to declarative/relational memory. The initial aim of this proposal is to compare neural coding in MTL and PFC as macaques learn novel associations between pairs of visual objects (i.e., """"""""Object A means choose Object B""""""""), a simple but well- controlled test of relational memory that is severely impaired by MTL or PFC lesions. Single-neuron and local field potential signals will be sampled with multielectrode arrays from both structures simultaneously during the same learning episodes. These experiments will reveal where neural correlates of relational memory are strongest, where they first appear during learning, their direction of flow during associative retrieval, and how they specifically relate to behavioral learning.
A second aim of this project is to test for potential correlates of relational memory in another structure, the striatum. Competing hypotheses of striatal function propose that it either: (a) is not involved in relational learning, but is critical only for simpler forms of stimulus-response learning, or (b) performs general computations used for both simple and complex cognitive functions. This experiment will test which of these hypotheses best explains striatal function in learning and memory, and will show how striatal coding differs from that of the MTL and PFC. The results of our proposed experiments will produce critical new insights about neural organization and coding for declarative/relational memory. This knowledge of normal neural function in learning and memory will also lay a foundation for understanding how its dysfunction produces memory impairment in many debilitating disorders, for creating better animal models of these disorders, and eventually for developing novel treatments.
|Brincat, Scott L; Miller, Earl K (2016) Prefrontal Cortex Networks Shift from External to Internal Modes during Learning. J Neurosci 36:9739-54|
|Brincat, Scott L; Miller, Earl K (2015) Frequency-specific hippocampal-prefrontal interactions during associative learning. Nat Neurosci 18:576-81|