Deep brain stimulation (DBS) of the subthalamic nucleus (STN) dramatically improves motor function and quality of life in PD yet may alter cognitive skills and mood (Progress Report). Our studies and others suggest that functional organization of basal ganglia-thalamocortical (BGTC) circuits and their course through STN underlies these effects. We hypothesize based on preliminary data that DBS focused in ventral STN (V-STN) selectively alters cognition and mood whereas motor benefit is widely distributed. We propose that this functional organization of STN will produce downstream effects in relevant pathways. In people with PD, we will compare the effects of unilateral monopolar DBS through selected V-STN and dorsal STN (D-STN) contacts on quantified motor, cognitive, and mood function with DBS-induced rCBF responses and presurgical MRI-based resting state functional connectivity (rs-fcMRI) networks. We found that rs-fcMRI identified key cortical and BGTC networks that are disrupted in PD and can provide an anchor for interpretation of downstream effects seen with rCBF responses. These studies have great potential to extend our understanding of the functional anatomy of the STN by delineating its role in motor, cognitive and mood behaviors in PD. These studies could reveal valuable insights into the clinical action of DBS and the pathophysiology of cognitive, mood and motor symptoms of PD. However, the importance of these studies goes beyond the specifics of DBS treatment for PD. We can take this unique opportunity to investigate the function of selected brain pathways in the region of the STN and how they affect cognitive, mood and motor function. Such basic observations have importance for understanding STN function and how impairments lead to disabilities in other basal ganglia disorders. These studies also have the potential to help refine DBS targeting, inform future development of new electrode design to shape current spread and improve programming strategies for optimal clinical benefit from STN DBS.
Parkinson disease (PD) affects nearly one million people in North American and leads to substantial disability for many. Deep brain stimulation (DBS) has been a dramatic advance, yet there are still many unknowns about how this new therapy works. This proposal has the potential to reveal valuable insights into the clinical action of DBS and the pathophysiology of non-motor as well as motor manifestations of PD. However, the importance of these studies goes well beyond the specifics of DBS treatment for PD. We also can take advantage of this unique opportunity to investigate the function of selected brain pathways and how they affect cognitive, mood and motor function. Such basic observations have importance for understanding normal function as well as how impairments lead to disabilities in other basal ganglia related disorders with motor or cognitive dysfunction.
|Norris, Scott A; Jinnah, H A; Espay, Alberto J et al. (2016) Clinical and demographic characteristics related to onset site and spread of cervical dystonia. Mov Disord 31:1874-1882|
|Eisenstein, Sarah A; Bogdan, Ryan; Love-Gregory, Latisha et al. (2016) Prediction of striatal D2 receptor binding by DRD2/ANKK1 TaqIA allele status. Synapse 70:418-31|
|Benitez, Bruno A; Davis, Albert A; Jin, Sheng Chih et al. (2016) Resequencing analysis of five Mendelian genes and the top genes from genome-wide association studies in Parkinson's Disease. Mol Neurodegener 11:29|
|Davis, Albert A; Andruska, Kristin M; Benitez, Bruno A et al. (2016) Variants in GBA, SNCA, and MAPT influence Parkinson disease risk, age at onset, and progression. Neurobiol Aging 37:209.e1-7|
|Stewart, Stephanie B; Koller, Jonathan M; Campbell, Meghan C et al. (2015) Additive global cerebral blood flow normalization in arterial spin labeling perfusion imaging. PeerJ 3:e834|
|Buddhala, Chandana; Campbell, Meghan C; Perlmutter, Joel S et al. (2015) Correlation between decreased CSF Î±-synuclein and AÎ²â‚â‚‹â‚„â‚‚ in Parkinson disease. Neurobiol Aging 36:476-84|
|Karimi, Morvarid; Tu, Zhude; Yue, Xuyi et al. (2015) Radiation dosimetry of [(18)F]VAT in nonhuman primates. EJNMMI Res 5:73|
|Yan, Ling; Hicks, Matt; Winslow, Korey et al. (2015) Secured web-based video repository for multicenter studies. Parkinsonism Relat Disord 21:366-71|
|Lucero, Carolyn; Campbell, Meghan C; Flores, Hubert et al. (2015) Cognitive reserve and Î²-amyloid pathology in Parkinson disease. Parkinsonism Relat Disord 21:899-904|
|Campbell, Meghan C; Koller, Jonathan M; Snyder, Abraham Z et al. (2015) CSF proteins and resting-state functional connectivity in Parkinson disease. Neurology 84:2413-21|
Showing the most recent 10 out of 116 publications