The goals of the Starr laboratory are to understand (1) brain network abnormalities underlying disorders of movement and (2) how therapeutic interventions correct those abnormalities. The disorders studied include Parkinson’s disease, primary and secondary dystonias, essential tremor, and Huntington’s disease. The general approach involves combined cortical and basal ganglia recording in humans. This research effort is complementary to our existing high-volume clinical program, in which approximately 80 new patients per year undergo placement of DBS electrodes. Data gathered are used to confirm, refute, or expand upon existing models of basal ganglia and cortical function and dysfunction, to identify possible new surgical targets, and to provide a better understanding of the mechanism of action of brain stimulation.
Specific questions addressed are:
1) How do basal ganglia diseases disrupt cortical function, with emphasis on cortical oscillatory activity and synchronization of neuronal population spiking to the motor beta rhythm?
2) How do therapeutic interventions such as DBS normalize cortical function?
3) Can cortical signals be used for feedback control to improve the efficacy of DBS?
Acute intraoperative recording of cortical and basal ganglia local field potentials. During surgery for implantation of permanent DBS leads, temporary cortical strip electrodes (electrocorticography, ECoG) are introduced into the subdural space via the standard surgical exposure used for DBS implantation. Basal ganglia and cortical LFPs are recorded at rest, during computer-controlled movement tasks, and during acute therapeutic stimulation. Intraoperative CT is used in conjunction with structural MRI to accurately localize recording sites, and diffusion tensor imaging acquired preoperatively may be used to relate cortical findings to the anatomy of specific fiber tracts.
Intraoperative high resolution ECoG recordings
Acute intraoperative recording of single unit activity in combination with cortical recording. Neurons are recorded at rest, during voluntary limb movement, and during passive (investigator-imposed) limb movement. Units are analyzed for discharge rate, pattern, oscillatory activity, and peri-movement changes in activity. Targets include the subthalamic nucleus (STN), globus pallidus internus (GPi), and globus pallidus externus (GPe). We are especially interested in the relationship of single unit basal ganglia discharge to cortical oscillatory activity.
Interictal electrocorticography in patients undergoing invasive video-ECoG monitoring. In human studies that involve placement of invasive electrodes, true normal control data are not available. However, ECoG data recorded in epilepsy patients, from cortical areas not involved with the epileptic focus, can be considered as a "control" group and be compared to subjects with movement disorders to provide insight into those patterns of brain activity that are specific to subjects with basal ganglia disease.
Chronic invasive brain recording from a permanently implanted device that both delivers therapeutic stimulation and stores local field potentials (Medtronic Activa PC+S) then wirelessly transmits data used in our research studies.
Noninvasive electrophysiological analyses using scalp electroencephalography.
Selected recent publications
Miocinovic S, de Hemptinne C, Qasim SE, Ostrem JL, Starr PA. Motor cortex electrocorticography reveals similar patterns of synchronization in isolated dystonia and Parkinson's disease. JAMA Neurology, In Press.
Swann NC, de Hemptinne C, Aron AR, Ostrem JL, Knight RT, Starr PA. Elevated synchrony in Parkinson disease detected with electroencephalography. Ann Neurol. 2015 Aug 20. doi: 10.1002/ana.24507. [Epub ahead of print]
de Hemptinne C, Swann NC, Ostrem JL, Ryapolova-Webb ES, San Luciano M, Galifianakis NB, Starr PA. Therapeutic deep brain stimulation reduces cortical phase-amplitude coupling in Parkinson's disease. Nat Neurosci. 2015 May;18(5):779-86. doi: 10.1038/nn.3997.
de Hemptinne C, Ryapolova-Webb ES, Air EL, Garcia PA, Miller KJ, Ojemann JG, Ostrem JL, Galifianakis NB, Starr PA. Exaggerated phase-amplitude coupling in the primary motor cortex in Parkinson disease. PNAS 110:4780-4785, 2013
Shimamoto SA, Ryapolova-Webb ES, Ostrem JL, Galifianakis NB, Miller KJ, Starr PA. Subthalamic nucleus neurons are synchronized to primary motor cortex local field potentials in Parkinson's disease. J Neurosci 33:7220-7233, 2013
Crowell AL, Ryapolova-Webb ES, Ostrem JL, Galifianakis NB, Shimamoto S, Lim DA, Starr PA. Oscillations in sensorimotor cortex in movement disorders: an electrocorticography study, Brain 135 (Pt 2):615-30, 2012.
Alzforum: Deep Brain Stimulation: It’s All About the Rhythm
IEE.org: How Brain Pacemakers Treat Parkinson's Disease
MIT Tech Quarterly Review: Why Zapping the Brain Helps Parkinson’s Patients
UCSF News: How Deep-Brain Stimulation Reshapes Neural Circuits in Parkinson’s Disease
New York Times: Clues to How an Electric Treatment for Parkinson's Works
Nature Neuroscience News and Views: Good vibrations with deep brain stimulation ,
Listen to the April 2015 Nature Neuroscience podcast, available at: http://www.nature.com/neurosci/neuropod/archive.html