Project Grant F31NS147616

NEURAL COMPUTATIONS IN THE CEREBELLUM DURING MOTOR PLANNING - PROJECT SUMMARY/ABSTRACT THE CEREBELLUM IS TRADITIONALLY VIEWED AS A MOTOR CONTROL STRUCTURE, BUT IT ALSO PLAYS A CRITICAL ROLE IN PLANNING AND OTHER EXECUTIVE FUNCTIONS, AS SHOWN BOTH BY CLINICAL AND ELECTROPHYSIOLOGICAL STUDIES. ADDITIONALLY, CEREBELLAR ABNORMALITIES HAVE BEEN LINKED TO COMMON COGNITIVE DISORDERS SUCH AS AUTISM, SCHIZOPHRENIA, AND DEMENTIA. HOWEVER, THE SPECIFIC COMPUTATIONS PERFORMED BY THE CEREBELLUM DURING COGNITIVE CONTROL ARE POORLY UNDERSTOOD, SO CLINICIANS ARE LIMITED IN THEIR ABILITY TO DIAGNOSE AND TREAT COGNITIVE DEFICITS CAUSED BY CEREBELLAR DYSFUNCTION. CLINICIANS HAVE SUGGESTED THAT THE CEREBELLUM MAY PLAY A SIMILAR ROLE DURING COGNITIVE CONTROL AS IT DOES DURING MOVEMENT, IN WHICH IT REGULATES MUSCLE ACTIVITY AND MAINTAINS ENDPOINT ACCURACYN.22 - 24 . A RECENT STUDY FROM OUR LAB ON THE ROLE OF PURKINJE CELLS (P-CELLS ), THE OUTPUT CELLS OF THE CEREBELLAR CORTEX, DURING MOVEMENT CONTROL REVEALED THAT EACH P-CELL CAN BE ASSIGNED A POTENT VECTOR THAT QUANTIFIES ITS FUNCTIONAL EFFECT ON THE BEHAVIOR. WHEN P-CELL ACTIVITY WAS ORGANIZED BY THEIR POTENT VECTORS, A POPULATION VECTOR WAS REVEALED THAT SHOWED HOW THE POPULATION OF CELLS COORDINATES THEIR ACTIVITIES TO ENSURE MOVEMENT ACCURACY. THUS, POTENT VECTORS CAN EXPLAIN CEREBELLAR COMPUTATION DURING MOVEMENT THIS IDEA, ALONG WITH THE IDEA OF SHARED CEREBELLAR COMPUTATIONS FOR MOVEMENT AND COGNITION, LEADS US TO THE FOLLOWING HYPOTHESIS: CEREBELLAR ACTIVITY DURING COGNITION WILL BE ORGANIZED VIA POTENT VECTORS. TO EXPLORE THIS HYPOTHESIS, I HAVE DESIGNED AN ELECTROPHYSIOLOGICAL EXPERIMENT IN WHICH I WILL RECORD FROM THE CEREBELLUM OF TWO MARMOSET MONKEYS WHILE THEY COMPLETE A SACCADE INHIBITION TASK. MY PRELIMINARY RESULTS FROM 27 SESSIONS HAVE REVEALED THAT SACCADE INHIBITION MANIFESTS AS A RACE BETWEEN TWO COMPETING NEURAL PROCESSES, ONE OF WHICH INITIATES A SACCADE TO THE TARGET, WHILE THE OTHER TRIGGERS MICROSACCADES TO MAINTAIN FIXATION. THE NEURONS THAT IMPLEMENT THESE PROCESSES SEND INPUTS TO THE CEREBELLUM VIA MOSSY FIBERS. THIS RESEARCH PROPOSAL WILL TEST WHETHER POTENT VECTORS CAN BE FOUND THAT REVEAL HOW THE P-CELL POPULATION ACTIVITY MODULATES THESE TWO COMPETING SACCADE INITIATION PROCESSES. IF OUR HYPOTHESIS IS CORRECT, WE WOULD IMPROVE OUR OVERALL UNDERSTANDING OF HOW THE CEREBELLUM CONTRIBUTES TO COGNITIVE TASKS AND PROVIDE FURTHER EVIDENCE FOR THE IDEA THAT CEREBELLAR CONTROL OF MOVEMENT AND COGNITION ARE ANALOGOUS. THE TRAINING PLAN FOR THE PROPOSED WORK WILL FOLLOW AN APPROACH THAT DR. SHADMEHR HAS USED TO GUIDE MANY OF HIS STUDENTS TO SUCCESSFUL CAREERS AS TENURE-TRACK SCIENTISTS. I WILL LEARN TO UNDERSTAND THE LITERATURE, DESIGN HYPOTHESIS DRIVEN EXPERIMENTS, COLLECT AND ANALYZE DATA, DEVELOP QUANTITATIVE INTERPRETATIONS OF THE DATA, AND COMMUNICATE MY WORK. DR. SHADMEHR WILL HOLD WEEKLY MEETINGS WITH ME TO PROVIDE GUIDANCE. DR. SHADMEHR'S LAB IS A PART OF JOHNS HOPKINS' TOP-RANKED DEPARTMENT OF BIOMEDICAL ENGINEERING, SO I WILL HAVE ACCESS TO STATE-OF-THE-ART FACILITIES AND OPPORTUNITIES TO RECEIVE FEEDBACK FROM EXPERT CLINICIANS AND SCIENTISTS.