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Harrington DL, Shen Q, Theilmann RJ, et al. Altered Functional Interactions of Inhibition Regions in Cognitively Normal Parkinson's Disease. Front Aging Neurosci. 2018;10:331doi: 10.3389/fnagi.2018.00331.
Harrington, D. L., Shen, Q., Theilmann, R. J., Castillo, G. N., Litvan, I., Filoteo, J. V., Huang, M., & Lee, R. R. (2018). Altered Functional Interactions of Inhibition Regions in Cognitively Normal Parkinson's Disease. Frontiers in aging neuroscience, 10331. https://doi.org/10.3389/fnagi.2018.00331
Harrington, Deborah L, et al. "Altered Functional Interactions of Inhibition Regions in Cognitively Normal Parkinson's Disease." Frontiers in aging neuroscience vol. 10 (2018): 331. doi: https://doi.org/10.3389/fnagi.2018.00331
Harrington DL, Shen Q, Theilmann RJ, Castillo GN, Litvan I, Filoteo JV, Huang M, Lee RR. Altered Functional Interactions of Inhibition Regions in Cognitively Normal Parkinson's Disease. Front Aging Neurosci. 2018 Oct 23;10:331. doi: 10.3389/fnagi.2018.00331. eCollection 2018. PMID: 30405399; PMCID: PMC6206214.
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Front Aging Neurosci. 2018 Oct 23;10:331. doi: 10.3389/fnagi.2018.00331. eCollection 2018.

Altered Functional Interactions of Inhibition Regions in Cognitively Normal Parkinson's Disease.

Frontiers in aging neuroscience

Deborah L Harrington, Qian Shen, Rebecca J Theilmann, Gabriel N Castillo, Irene Litvan, J Vincent Filoteo, Mingxiong Huang, Roland R Lee

Affiliations

  1. Cognitive Neuroimaging Laboratory, Research Service, VA San Diego Healthcare System, San Diego, CA, United States.
  2. Department of Radiology, University of California, San Diego, La Jolla, CA, United States.
  3. Department of Neurosciences, University of California, San Diego, La Jolla, CA, United States.
  4. Psychology Service, VA San Diego Healthcare System, San Diego, CA, United States.
  5. Department of Psychiatry, University of California, San Diego, La Jolla, CA, United States.
  6. Department of Radiology, VA San Diego Healthcare System, San Diego, CA, United States.

PMID: 30405399 PMCID: PMC6206214 DOI: 10.3389/fnagi.2018.00331

Abstract

Deficient inhibitory control in Parkinson's disease (PD) is often observed in situations requiring inhibition of impulsive or prepotent behaviors. Although activation of the right-hemisphere frontal-basal ganglia response inhibition network is partly altered in PD, disturbances in interactions of these regions are poorly understood, especially in patients without cognitive impairment. The present study investigated context-dependent connectivity of response inhibition regions in PD patients with normal cognition and control participants who underwent fMRI while performing a stop signal task. PD participants were tested off antiparkinsonian medication. To determine if functional disturbances depended on underlying brain structure, aberrant connectivity was correlated with brain volume and white-matter tissue diffusivity. We found no group differences in response inhibition proficiency. Yet the PD group showed functional reorganization in the long-range connectivity of inhibition regions, despite preserved within network connectivity. Successful inhibition in PD differed from the controls by strengthened connectivity of cortical regions, namely the right dorsolateral prefrontal cortex, pre-supplementary motor area and right caudal inferior frontal gyrus, largely with ventral and dorsal attention regions, but also the substantia nigra and default mode network regions. Successful inhibition in controls was distinguished by strengthened connectivity of the right rostral inferior frontal gyrus and subcortical inhibition nodes (right caudate, substantia nigra, and subthalamic nucleus). In both groups, the strength of context-dependent connectivity correlated with various indices of response inhibition performance. Mechanisms that may underlie aberrantly stronger context-specific connectivity include reduced coherence within reorganized systems, compensatory mechanisms, and/or the reorganization of intrinsic networks. In PD, but not controls, abnormally strengthened connectivity was linked to individual differences in underlying brain volumes and tissue diffusivity, despite no group differences in structural variables. The pattern of structural-functional associations suggested that subtle decreases in tissue diffusivity of underlying tracts and posterior cortical volumes may undermine the enhancement of normal cortical-striatal connectivity or cause strengthening in cortical-cortical connectivity. These novel findings demonstrate that functionally reorganized interactions of inhibition regions predates the development of inhibition deficits and clinically significant cognitive impairment in PD. We speculate that altered interactions of inhibition regions with attention-related networks and the dopaminergic system may presage future decline in inhibitory control.

Keywords: Parkinson’s disease; brain volume; cognition; context-dependent connectivity; diffusion tensor imaging; response inhibition; task-activated functional MRI

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