Bradley S. Folley - US grants

DESCRIPTION (provided by applicant): The basal ganglia have long been known to play an important role in movement disorders. These nuclei have been important targets to the surgical treatment of Parkinson's disease (PD) and other movement disorders. A growing body of evidence demonstrates that parallel circuits through the basal ganglia also play an important role in processes of cognition and in the generation of emotional states. Over the past decade, deep brain stimulation (DBS) has become an increasingly important tool in the treatment of movement disorders. It has been demonstrated to substantially improve standardized motor scores and quality of life measures for patients suffering from Parkinson's disease, essential tremor and dystonia1-5. Despite these successes there is increasing evidence that DBS can cause subtle alterations in the processing of emotion and, in rare cases, can lead to clinically significant depression, mania or compulsive behaviors7-12. The proposed mechanism of these effects is coincidental stimulation of neighboring affective and cognitive circuits13. The evidence for these circuits, however is based largely on rodent and primate data and it remains unclear how the cognitive and affective circuits are organized in the human basal ganglia. The undertaking of DBS surgery requires extensive recording of human neurophysiology. Recordings made from neurons in the basal ganglia allow us to precisely determine the local physiological anatomy so that electrodes are placed with precision in the required nuclei. Microelectrode recording also provides a unique opportunity to gather information about the functioning of the nuclei encountered and to determine their role in specific emotional behaviors. Subsequently the placement of DBS electrodes provides the opportunity to transiently and reversibly perturb the system and examine its effect on subtle tasks of emotional discrimination and mood induction. By these paradigms we propose to study, in detail, the behavioral properties of neurons in the basal ganglia to determine their role in the processing of emotion. In this way we hope to substantiate the theories that have been described on parallel cognitive/emotional circuits, and to expand understanding on the physiological properties of these circuits. An expanded knowledge of the physiology of emotional circuits will be of significant benefit to the thousands of patients undergoing DBS surgery for Parkinson's disease. A more precise mapping of emotional effects will undoubtedly reduce side-effects and improve treatment precision. Furthermore, as the field of functional neurosurgery begins to treat intractable psychiatric disease with DBS, it is of critical importance that we refine our understanding of the neurophysiology of frontal-subcortical emotional networks and thereby improve our ability to generate safe and effective therapies. PUBLIC HEALTH RELEVANCE: Parkinson's disease is associated with significant emotional perturbations. Further, it is well established that the medications and deep brain stimulation surgeries used to treat the disease are often complicated by changes in emotional behavior. A precise neurophysiological characterization of the distinct emotional responses of the neuronal circuits that underlie the disease will make future PD treatments safer and may suggest improved therapies for treating intractable mood disorders.