Semantic Recollection in Parkinson’s Disease: Functional Reconfiguration and MAPT Variants
Decline in semantic cognition in early stages of Parkinson’s disease (PD) is a leading risk factor for future dementia, yet the underlying neural mechanisms are not understood. The present study addressed this gap by investigating the functional connectivity of regions involved in semantic recollect...
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doaj-39daa308b7d049109f35f30018402c3e2021-09-20T14:12:01ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652021-09-011310.3389/fnagi.2021.727057727057Semantic Recollection in Parkinson’s Disease: Functional Reconfiguration and MAPT VariantsDeborah L. Harrington0Deborah L. Harrington1Qian Shen2Qian Shen3Vida Sadeghi4Mingxiong Huang5Mingxiong Huang6Irene Litvan7Xiangyu Wei8Roland R. Lee9Roland R. Lee10Research and Radiology Services, VA San Diego Healthcare System, San Diego, CA, United StatesDepartment of Radiology, University of California, San Diego, La Jolla, CA, United StatesResearch and Radiology Services, VA San Diego Healthcare System, San Diego, CA, United StatesDepartment of Radiology, University of California, San Diego, La Jolla, CA, United StatesResearch and Radiology Services, VA San Diego Healthcare System, San Diego, CA, United StatesResearch and Radiology Services, VA San Diego Healthcare System, San Diego, CA, United StatesDepartment of Radiology, University of California, San Diego, La Jolla, CA, United StatesDepartment of Neurosciences, University of California, San Diego, La Jolla, CA, United StatesResearch and Radiology Services, VA San Diego Healthcare System, San Diego, CA, United StatesResearch and Radiology Services, VA San Diego Healthcare System, San Diego, CA, United StatesDepartment of Radiology, University of California, San Diego, La Jolla, CA, United StatesDecline in semantic cognition in early stages of Parkinson’s disease (PD) is a leading risk factor for future dementia, yet the underlying neural mechanisms are not understood. The present study addressed this gap by investigating the functional connectivity of regions involved in semantic recollection. We further examined whether microtubule-associated protein tau (MAPT) risk variants, which may accelerate cognitive decline, altered the strength of regional functional connections. Cognitively normal PD and healthy elder controls underwent fMRI while performing a fame-discrimination task, which activates the semantic network. Analyses focused on disturbances in fame-modulated functional connectivity in PD for regions that govern semantic recollection and interrelated processes. Group differences were found in multiple connectivity features, which were reduced into principal components that reflected the strength of fame-modulated regional couplings with other brain areas. Despite the absence of group differences in semantic cognition, two aberrant connectivity patterns were uncovered in PD. One pattern was related to a loss in frontal, parietal, and temporal connection topologies that governed semantic recollection in older controls. Another pattern was characterized by functional reconfiguration, wherein frontal, parietal, temporal and caudate couplings were strengthened with areas that were not recruited by controls. Correlations between principal component scores and cognitive measures suggested that reconfigured frontal coupling topologies in PD supported compensatory routes for accessing semantic content, whereas reconfigured parietal, temporal, and caudate connection topologies were detrimental or unrelated to cognition. Increased tau transcription diminished recruitment of compensatory frontal topologies but amplified recruitment of parietal topologies that were unfavorable for cognition. Collectively, the findings provide a new understanding of early vulnerabilities in the functional architecture of regional connectivity during semantic recollection in cognitively normal PD. The findings also have implications for tracking cognitive progression and selecting patients who stand to benefit from therapeutic interventions.https://www.frontiersin.org/articles/10.3389/fnagi.2021.727057/fullParkinson’s diseasesemantic networkcognitionfMRIfunctional connectivityMAPT gene |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Deborah L. Harrington Deborah L. Harrington Qian Shen Qian Shen Vida Sadeghi Mingxiong Huang Mingxiong Huang Irene Litvan Xiangyu Wei Roland R. Lee Roland R. Lee |
spellingShingle |
Deborah L. Harrington Deborah L. Harrington Qian Shen Qian Shen Vida Sadeghi Mingxiong Huang Mingxiong Huang Irene Litvan Xiangyu Wei Roland R. Lee Roland R. Lee Semantic Recollection in Parkinson’s Disease: Functional Reconfiguration and MAPT Variants Frontiers in Aging Neuroscience Parkinson’s disease semantic network cognition fMRI functional connectivity MAPT gene |
author_facet |
Deborah L. Harrington Deborah L. Harrington Qian Shen Qian Shen Vida Sadeghi Mingxiong Huang Mingxiong Huang Irene Litvan Xiangyu Wei Roland R. Lee Roland R. Lee |
author_sort |
Deborah L. Harrington |
title |
Semantic Recollection in Parkinson’s Disease: Functional Reconfiguration and MAPT Variants |
title_short |
Semantic Recollection in Parkinson’s Disease: Functional Reconfiguration and MAPT Variants |
title_full |
Semantic Recollection in Parkinson’s Disease: Functional Reconfiguration and MAPT Variants |
title_fullStr |
Semantic Recollection in Parkinson’s Disease: Functional Reconfiguration and MAPT Variants |
title_full_unstemmed |
Semantic Recollection in Parkinson’s Disease: Functional Reconfiguration and MAPT Variants |
title_sort |
semantic recollection in parkinson’s disease: functional reconfiguration and mapt variants |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Aging Neuroscience |
issn |
1663-4365 |
publishDate |
2021-09-01 |
description |
Decline in semantic cognition in early stages of Parkinson’s disease (PD) is a leading risk factor for future dementia, yet the underlying neural mechanisms are not understood. The present study addressed this gap by investigating the functional connectivity of regions involved in semantic recollection. We further examined whether microtubule-associated protein tau (MAPT) risk variants, which may accelerate cognitive decline, altered the strength of regional functional connections. Cognitively normal PD and healthy elder controls underwent fMRI while performing a fame-discrimination task, which activates the semantic network. Analyses focused on disturbances in fame-modulated functional connectivity in PD for regions that govern semantic recollection and interrelated processes. Group differences were found in multiple connectivity features, which were reduced into principal components that reflected the strength of fame-modulated regional couplings with other brain areas. Despite the absence of group differences in semantic cognition, two aberrant connectivity patterns were uncovered in PD. One pattern was related to a loss in frontal, parietal, and temporal connection topologies that governed semantic recollection in older controls. Another pattern was characterized by functional reconfiguration, wherein frontal, parietal, temporal and caudate couplings were strengthened with areas that were not recruited by controls. Correlations between principal component scores and cognitive measures suggested that reconfigured frontal coupling topologies in PD supported compensatory routes for accessing semantic content, whereas reconfigured parietal, temporal, and caudate connection topologies were detrimental or unrelated to cognition. Increased tau transcription diminished recruitment of compensatory frontal topologies but amplified recruitment of parietal topologies that were unfavorable for cognition. Collectively, the findings provide a new understanding of early vulnerabilities in the functional architecture of regional connectivity during semantic recollection in cognitively normal PD. The findings also have implications for tracking cognitive progression and selecting patients who stand to benefit from therapeutic interventions. |
topic |
Parkinson’s disease semantic network cognition fMRI functional connectivity MAPT gene |
url |
https://www.frontiersin.org/articles/10.3389/fnagi.2021.727057/full |
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