The goal of the Starr laboratory is to understand the pathophysiology of movement disorders. The disorders studied include Parkinson’s disease, primary and secondary dystonia, essential tremor, and Huntington’s disease. The general approach is to record electrical activity in humans undergoing microelectrode-guided basal ganglia surgery in the awake state. This research effort is complementary to our existing high-volume clinical program, in which approximately 80 new patients per year undergo placement of deep brain stimulators. Data gathered are used to confirm, refute, or expand upon existing models of basal ganglia function and dysfunction, to identify possible new surgical targets, and to provide a better understanding of the mechanism of action of brain stimulation.
Current Research Projects
Single unit analysis of basal ganglia activity in humans
To place stimulators accurately into basal ganglia targets, single-unit microelectrode recording is routinely used to confirm or to refine the final intra-operative target prior to permanent stimulator placement. Under a long-standing human studies protocol, recordings are collected and analyzed off-line in our laboratory. Neurons are recorded at rest, during voluntary limb movement, and during passive (investigator-imposed) limb movement. For voluntary movement, a binary choice arm movement task is used to study responses during movement planning, initiation, and execution. Units are discriminated with spike sorting software, and analyzed for discharge rate, pattern, oscillatory activity, and peri-movement changes in activity. Targets studied include the subthalamic nucleus (STN), globus pallidus internus (GPi), globus pallidus externus (GPe), and pedunculopontine nucleus (PPN). Prior work of the laboratory has characterized the physiology of the GPi in a variety of movement disorders, and is now focusing on structures of the indirect pathway (GPe and STN) in Parkinsons’s disease and dystonia.
Cortical and basal ganglia local field potentials in humans
In this project, we record local field potentials (LFP)s simultaneously from the surface and deep structures of the brain in humans undergoing DBS implantation in the awake state. The local field potential represents synchronized sub- and supra- threshold synaptic activity, and is a particularly good technique for analysis of oscillatory activity. In the past ten years, several laboratories have proposed that Parkinson’s disease is characterized by abnormal brain oscillations in the basal ganglia nuclei. Our work now extends this approach to other disorders (essential tremor and dystonia). In addition, by performing simultaneous electrocorticography (Ecog) over the primary motor, primary sensory, and premotor cortices, we are able to evaluate the contribution of the cortex to oscillatory behavior. Our goal is to determine how basal ganglia oscillation frequency distinguishes different movement disorders, and to determine the extent to which characteristic oscillation frequencies in the basal ganglia are reflected in cortical potentials recorded by Ecog. LFPs are analyzed in the frequency domain, focusing on power spectral density at rest and during movement, time varying power spectral density during simple motor tasks, and cortex-basal ganglia coherence. For cortical recordings, subjects without movement disorders are available as “normal” controls: patients undergoing corticography for epilepsy or cortical mapping for pain procedures.
Behavioral and electrophysiological analyses in animal models of movement disorders
In collaboration of with the laboratory of Dr. Krys Bankiewicz (UCSF), and Dr. Nutan Sharma (Massachusetts General Hospital), we are exploring an animal model of DYT1+ dystonia created by convection-enhanced delivery to the brain of viral vectors expressing the mutant Tor1A gene. The focus is on recording basal ganglia activity in normal subjects versus subjects in which the mutant gene is expressed.