Perlmutter Lab

Joel S. Perlmutter, MD

The lab focuses on Parkinson disease and related disorders. We investigate mechanisms of action of deep-brain stimulation — a dramatic new treatment. These studies combine PET measures of regional cerebral blood flow, cognitive testing and quantified measures of movement. These studies have led to new insights into the mechanisms of deep brain stimulation as well as offer an opportunity for functional mapping of basal ganglia function in humans.

We have an ongoing investigation of dementia in people with Parkinson disease. This study includes cognitive, clinical, genetic and neuroimaging-based measures (PET and MRI) with subsequent comparison to post-mortem findings.

We also test new drugs that might rescue injured nigrostriatal neurons (a model of PD). For these, we use PET to measure dopamine pathways and also quantify motor behavior. We are actively developing and validating biomarkers of PD progression using nonhuman primate models. In people with PD, we develop and apply MR and PET methods for objective measures of disease severity. These measures enhance our genetic and etiologic studies of PD (for example investigating the potential of welding exposure or manganese toxicity to lead to nigrostriatal damage).

In other patient-oriented research, we have developed a biorepository linked to clinical phenotype data on a variety of movement disorders to act as a resource for ongoing and future biomarker and genetic studies. One of the new studies is a multicenter collaboration studying focal dystonias. These studies have included the development of a new resource at Washington University called the NeuroClinical Research Unit that has also provided the basis of the Brain, Behavior and Performance Unit of the CTSA at WU. The BBPU supports new patient-oriented research studies in neuropsychiatric disorders.

We also use PET to measure radioligand binding and sensorimotor processing in dystonia. We developed a new animal model of dystonia to investigate pharmacologic and physiologic changes. We use PET to investigate drug-mediated pathways in the brain and parse out the effects of selective dopaminergic agonists.

Finally, we investigate the relationship between blood flow responses in the brain with electrophysiological responses done in the same animals. These animal studies provide insights into the basic mechanisms of many of the studies that we subsequently apply to humans.

Principal investigator

Joel Perlmutter, MD

Elliot Stein Family Professor of Neurology
Section Chief, Movement Disorders
Professor, Radiology, Neuroscience, Physical Therapy and Occupational Therapy

Recent publications

  • Diagnosis and classification of blepharospasm: Recommendations based on empirical evidencefor the Dystonia Coalition Investigators, Aug 15 2022, In: Journal of the Neurological Sciences. 439, 120319.Research output: Contribution to journal › Article › peer-review
  • Protracted course progressive supranuclear palsyCouto, B., Martinez-Valbuena, I., Lee, S., Alfradique-Dunham, I., Perrin, R. J., Perlmutter, J. S., Cruchaga, C., Kim, A., Visanji, N., Sato, C., Rogaeva, E., Lang, A. E. & Kovacs, G. G., Aug 2022, In: European Journal of Neurology. 29, 8, p. 2220-2231 12 p.Research output: Contribution to journal › Article › peer-review
  • Proteinopathy and Longitudinal Cognitive Decline in Parkinson DiseaseMyers, P. S., O'Donnell, J. L., Jackson, J. J., Lessov-Schlaggar, C. N., Miller, R. L., Voegtli, E., Cruchaga, C., Benitez Viloria, B. A., Kotzbauer, P. T., Perlmutter, J. S. & Campbell, M., Jul 5 2022, In: Neurology. 99, 1, p. E66-E76Research output: Contribution to journal › Article › peer-review
  • Radiosynthesis and characterization of a carbon-11 PET tracer for receptor-interacting protein kinase 1Huang, T., Gu, J., Jiang, H., Liang, Q., Perlmutter, J. S. & Tu, Z., Jul 1 2022, In: Nuclear Medicine and Biology. 110-111, p. 18-27 10 p.Research output: Contribution to journal › Article › peer-review
  • Hold that pose: capturing cervical dystonia's head deviation severity from videoZhang, Z., Cisneros, E., Lee, H. Y., Vu, J. P., Chen, Q., Benadof, C. N., Whitehill, J., Rouzbehani, R., Sy, D. T., Huang, J. S., Sejnowski, T. J., Jankovic, J., Factor, S., Goetz, C. G., Barbano, R. L., Perlmutter, J. S., Jinnah, H. A., Berman, B. D., Richardson, S. P., Stebbins, G. T., & 2 othersComella, C. L. & Peterson, D. A., May 2022, In: Annals of Clinical and Translational Neurology. 9, 5, p. 684-694 11 p.Research output: Contribution to journal › Article › peer-review