Jason A. Cromer - US grants

DESCRIPTION (provided by applicant): Humans must quickly and accurately redirect their gaze in order to look at new targets of interest. Thus, the gaze system must respond to sensory input with precise movement of the eyes and head to correctly position gaze on that target. The central Mesencephalic Reticular Formation (cMRF) interacts with the superior colliculus (SC) and the paramedian pontine reticular formation (PPRF) to control movement of the eyes. However, the signals carried by neurons in these regions are very different. SC neurons respond for a subset of movements, thus the SC is spatially encoded. The excitatory burst neurons (EBNs) in the PPRF change their firing rate with changes in the amplitude and velocity of the movement, thus the EBNs are temporally encoded. How a transformation from spatial to temporal encoding occurs between these two regions is not known. As a major recipient of input from the SC and with direct projections to the PPRF, the cMRF is ideally situated to perform this transformation. Indeed, neurons in the cMRF have BOTH spatial and temporal characteristics. Our current hypothesis is that cMRF pre-saccadic neurons provide the physiologic machinery to perform a spatial to temporal transformation. This proposal will examine cMRF neurons during behaviors that permit comparison of saccades of different velocities, but similar amplitudes to discern whether cMRF neurons temporally encode eye movement velocity. This will be coupled with analysis of the neurons spatial properties and antidromic stimulation to confirm downstream projections.

[unreadable] DESCRIPTION (provided by applicant): Normal cognition depends on interactions between the prefrontal cortex (RFC) and basal ganglia (BG). The cognitive impairments observed in a host of neuropsychiatric disorders including schizophrenia, Parkinson's disease, Huntington's disease, and ADHD have been linked to their dysfunction. Thus, understanding the respective contributions and collaborations between the PFC and BG will be critical to opening paths to treatment of these disorders. However, we understand little about the normal functioning of these areas because their neural activity has largely been studied separately, by different laboratories in different monkeys performing different tasks. The aim of this proposal is to advance our understanding by recording from multiple electrodes simultaneously implanted in each region while monkeys perform a cognitively demanding task that will test the hypothesis that the basal ganglia is responsible for the acquisition and implementation of simple associations while the PFC pieces such information into a higher-level representation of the entire task structure. This project will test this hypothesis by extending investigations to a novel type of goal-directed behavior. Previous studies have employed rules with a strong motor component; in contrast, I will use categorical learning. It is fundamental to cognition and can be dissociated from motor responses. Neurophysiological studies in monkeys and fMRI studies in humans indicate involvement of both the PFC and BG in categorization, but they have never been directly compared. Aim 1 of this proposal is to directly compare visual category information in PFC versus BG. This will allow us to compare the prevalence, strength, and latency of neural category information and to examine precise timing relationships within and between brain areas that can provide insight into their respective roles and how information is transferred between them. Prior studies also indicate that familiar, higher-order, motor-related rules are even more strongly represented and have a shorter latency in the premotor cortex (PMC) than the PFC. Thus, the PMC may function to consolidate information pertaining to frequently utilized tasks. But we do not know if this is only limited to rules with a motor component; non-motor rules such as visual categories have never been examined in the PMC. This is the goal of the second aim, to directly compare visual category information in premotor cortex, prefrontal cortex, and the BG. By directly comparing neural activity in these three structures, I hope to provide insight into their roles in a fundamental cognitive function - categorization. By understanding the normal functioning of these brain regions and their respective roles in cognition, we may better understand how to approach treatments for patients whose afflictions involve them. [unreadable] [unreadable] [unreadable]