Abstract Details

Title Resting-state connectivity in Levodopa responsive and unresponsive Parkinson’s disease patients with Freezing of Gait

Topic Movement Disorders

Presentation(s) P3 - Poster Session 3 (12:00 PM-1:00 PM)

Poster/Presentation
Number 3-010

Objective

To assess resting-state functional connectivity (rs-FC) in Levodopa (LD) responsive (R) and unresponsive (UR) Parkinson’s disease (PD) patients with freezing of gait (FOG) in the “clinically defined” ON state.

Background It has been suggested that dopaminergic deficiency could cause altered deactivation of the DMN connectivity which in turn affects executive task performance and subsequently may result in FOG. Studying the default mode network (DMN) using rs-functional MRI (fMRI) in PD-FOG-R and PD-FOG-UR could inform whether dopamine therapy modulates DMN connectivity differently between these groups and whether these differences are associated differentially with motor dysfunction in the two groups. Therefore, in this study, we use rs-fMRI to investigate FC in the DMN in LD-R and LD-UR PD-FOG patients.

Design/Methods 17 PD-FOG (9R (age-67.56±7.99years; 8Male); 8UR (71.75±5.37years; 5Male)), and 10 controls (70.7±2.21years; 5Male) were scanned using a 3T Skyra MRI scanner. PD participants were identified as R if the change in the Movement Disorder Society (MDS) UPDRS III score between the OFF and ON states was greater than 30%. Mean time-series were obtained from the medial prefrontal cortex, posterior cingulate cortex and bilateral inferior parietal lobule (IPL) regions. Seed based FC maps were obtained for all participants. Nonparametric statistical analysis was then conducted to obtain connectivity differences between the different groups and linear regression was used to study association between DMN FC and MDS-UPDRS III scores.

Results PD-FOG-UR patients showed hyper-connectivity as compared to controls between the left IPL and the cerebellar regions. PD-FOG-UR also showed negative relationship between left IPL and cerebellar region connectivity and MDS-UPDRS III scores.

Conclusions Our preliminary analysis suggests that dopamine therapy potentially modulates DMN connectivity differently in the PD-FOG-R group as we do not see the hyper-connectivity and the relationship to MDS-UPDRS III observed in PD-FOG-UR group. Future studies involving larger sample are underway to confirm our findings.

Authors/Disclosures
Virendra R. Mishra, PhD (The University of Alabama at Birmingham) PRESENTER	The institution of Prof. Mishra has received research support from Keep Memory Alive Young Scholar Award. The institution of Prof. Mishra has received research support from NINDS/NIA: R01NS117547-01. The institution of Prof. Mishra has received research support from NIGMS: P20GM109025.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Aaron Ritter, MD (Cleveland Clinic)	The institution of Dr. Ritter has received research support from NIH.
	No disclosure on file
Jeffrey L. Cummings, MD, FAAN	Dr. Cummings has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acadia, Actinogen, Acumen, AlphaCognition, ALZpath, Aprinoia, AriBio, Artery, Biogen, Biohaven, BioVie, BioXcel, Bristol-Myers Squib, Cassava, Cerecin, Diadem, Eisai, GAP Foundation, GemVax, Janssen, Jocasta, Karuna, Lighthouse, Lilly, Lundbeck, LSP/eqt, Mangrove Therapeutics, Merck, NervGen, New Amsterdam, Novo Nordisk, Oligomerix, ONO, Optoceutics, Otsuka, Oxford Brain Diagnostics, Prothena, ReMYND, Roche, Sage Therapeutics, Signant Health, Simcere, sinaptica, Suven, TrueBinding, Vaxxinity, and Wren pharmaceutical, assessment, and investment companies. Dr. Cummings has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Acadia, Biogen, Genentech, Grifols, Janssen, Karuna, Otsuka, reMYND, Roche, Signant Health. Dr. Cummings has stock in Artery, Vaxxinity, Behrens, Alzheon, MedAvante-Prophase, and Acumen. Dr. Cummings has received research support from NIH. Dr. Cummings has received research support from NIGMS. Dr. Cummings has received intellectual property interests from a discovery or technology relating to health care.
Zoltan Mari, MD, FAAN (Cleveland Clinic Lou Ruro Center for Brain Health)	Dr. Mari has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AbbVie. Dr. Mari has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for ACADIA. Dr. Mari has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amneal. Dr. Mari has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Parkinson Study Group. Dr. Mari has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for AbbVie. Dr. Mari has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for ACADIA. Dr. Mari has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for US World Meds. Dr. Mari has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. Dr. Mari has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Moore and Moore PLLC. Dr. Mari has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Francis Law Firm PLLC. Dr. Mari has stock in NeuroReserve. Dr. Mari has stock in Sensory Cloud. The institution of Dr. Mari has received research support from Cerevel. The institution of Dr. Mari has received research support from AbbVie. The institution of Dr. Mari has received research support from NIH. The institution of Dr. Mari has received research support from Parkinson's Foundation. The institution of Dr. Mari has received research support from Michael J Fox Foundation. The institution of Dr. Mari has received research support from LBDA. The institution of Dr. Mari has received research support from Eli Lilly.
Irene Litvan, MD, FAAN (UC San Diego Parkinson and Other Movement Disorder Center)	Dr. Litvan has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Aprinoia. Dr. Litvan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lundbeck. Dr. Litvan has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Frontiers in Neurology. Dr. Litvan has received personal compensation in the range of $50,000-$99,999 for serving as a Chief Editor with Frontiers in Neurology.
Brent R. Bluett, DO (Central California Movement Disorders)	No disclosure on file

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