Department of Neurology, School of Medicine
More than one million Americans suffer from Parkinsons Disease (PD). In the Sigvardt lab, research involves an integration of clinical studies, analysis of human electrophysiological data, and computational modeling focused on understanding the pathophysiology of Parkinsons Disease. The cardinal symptoms of PD are tremor, rigidity, bradykinesia, and postural instability. These symptoms are a consequence of the degeneration of the pars compacta of the substantia nigra with subsequent loss of dopaminergic innervation and changes in neuronal activity in the basal ganglia. However, little is understood about how these changes result in the primary motor symptoms of the disease. Following the discovery of levodopa for the treatment of PD, surgical treatment was all but abandoned in the US. However, once it was recognized that disease progression included intractable motor complications of levodopa therapy, surgical treatment was re-examined. It is now well-established that unilateral pallidotomy relieves contralateral tremor and dyskinesia and improves "off medication" motor function. More recently, it has been reported that implantation of a stimulating electrode into internal segment of the globus pallidus (GPi) or the subthalamic nucleus (STN) relieve Parkinsonian motor symptoms, as well as drug- induced dyskinesias. However, the mechanisms underlying these effects are not understood. Furthermore, the role of the basal ganglia in the control of movement remains to be established. These facts underscore the need for directly studying basal ganglia function in PD patients. The surgical treatment of PD provides an excellent opportunity to explore the relationship between the pathophysiology of the basal ganglia and the symptoms of the disease.
To establish this relationship, the Sigvardt lab is pursuing four separate but integrated lines of clinical and basic research: 1). determining the severity of the constellation of Parkinsonian motor and cognitive symptoms in individual PD patients using a battery of standard neurological rating scales; 2). characterizing the spatiotemporal dynamics of neural activity in the basal ganglia of individual PD patients who have undergone microelectrode-guided surgical procedures; 3). constructing a relational database of the results of the quantitative assessment of PD symptoms and the pathophysiology of the disease to determine the neuronal correlates in the pallidum and subthalamic nucleus of the primary cognitive and motor symptoms of PD, and 4) developing computational models of basal ganglia circuitry that include the dynamic properties of the neural activity and the dynamic aspects of the motor symptoms. The goal of our work is to use the results of these studies to better understand the neural mechanisms underlying the motor and cognitive symptoms of PD.
While PD is typically thought of as a motor disorder, cognitive and psychological symptoms are often observed, though not always well characterized. Furthermore, despite the demonstrated benefit of surgery and DBS for parkinsonian motor symptoms, little information exists about their effects on non-motor symptoms, the role of the basal ganglia in cognitive function, and the relationship between the motor and cognitive symptoms of the disease. Again, a study of PD patients undergoing surgical treatment provides a unique opportunity to address these issues. Patients undergoing surgical treatment volunteer, with informed consent, to participate in our studies of their performance on a number of simple cognitive and motor tasks. The results of these behavioral studies, combined with the results of the quantitative assessment of their motor and cognitive symptoms before and after surgery, may lead to a provide better understanding of the effects of PD on cognition as well as insight into the role of the basal ganglia in specific aspects of cognitive function.
Grad Group Affiliations
Specialties / Focus
- Medical Neuroscience
- Systems Neuroscience
- Center for Neuroscience
- Research Collaborators: Chris Higginson, Ph.D., Department of Psychology, Loyola College of Maryland; Leonid Rubchinsky, Ph.D., Department of Mathematical Sciences, Indiana University Purdue University Indianapololis; Undergraduate Research Assistants: Abhi Ray; Research Associate: Margaret Sanders
- Clinical Neuroscience Program
- Conrad Pappas, M.D., Ph.D., Vicki L. Wheelock, M.D.,Christine Na-Lee, C.N.P.
Honors and Awards
- Swedish Medical Research Council Fellow
- NIH Postdoctoral Fellowship
- Society for Neuroscience
- Movement Disorders Society
- 1974 PhD Zoology University of Iowa
- 1968 BS Zoology University of Iowa
Hurtado J.M., L.L. Rubchinsky, K.A. Sigvardt, V.L. Wheelock and C.T. Pappas. 2005. Temporal evolution of oscillations and synchrony in GPi/muscle pairs in Parkinson's disease. Journal of Neurophysiology.93:1569-84. Epub Oct 20, 2004.
Higginson, C. I., Wheelock, V. L., Carroll, K. E., Pappas, C. T. E., & Sigvardt, K. A. 2005. Recognition memory in Parkinsons disease with and without dementia: Evidence inconsistent with the retrieval deficit hypothesis. Journal of Clinical and Experimental Neuropsychology. 27:516-528.
Shook, S.K., E.A. Franz, C.I. Higginson, and K.A. Sigvardt. 2005. Dopamine dependency of intradimensional and extradimensional switching operations in Parkinson's patients. Neuropsychologia 43:1990-1999. [Epub: 27 April 2005.]
Hurtado, J.M., L.L. Rubchinsky, and K.A. Sigvardt. 2004. Statistical method for detection of phase- locking episodes in neural oscillations. Journal of Neurophysiology. 91:1883-98. Erratum in: Journal of Neurophysiology. 2005. 93:1820.
Rubchinsky, L.L. N. Kopell, and K.A. Sigvardt. 2003. Modeling facilitation and inhibition of competing motor programs in basal ganglia subthalmic nucleus-pallidal circuits. Proceedings of the National Academy of Sciences U.S.A. 100:14427-14432.
Higginson, C.I., D.S. King, D. Levine, V.L. Wheelock, N.O. Khamphay and K.A. Sigvardt. 2003. The Relationship between executive function and verbal memory in Parkinson's Disease. Brain and Cognition 52:343-352.
Hurtado, J.M., J.-P. Lachaux, D. J. Beckley, C.M. Gray and K.A. Sigvardt. 2000. Inter- and intra-limb oscillator coupling in Parkinsonian tremor. Movement Disorders 15:683-691.
Miller, W.L. and K.A. Sigvardt. 2000. The extent and role of multisegmental coupling in the lamprey spinal locomotor pattern generator. Journal of Neurophysiology. 83:465-476.
Hurtado, J.M., C.M Gray, L.B. Tamas, and K.A. Sigvardt. 1999. Dynamics of tremor-related oscillations in the human globus pallidus: a single case study. Proceedings of the National Academy of Sciences U.S.A. 96:1674-1679.
Miller, W.L. and K.A. Sigvardt. 1998. Spectral analysis of oscillatory neural circuits. Journal of Neuroscience Methods 80:113-128.