Resting-state connectivity in Levodopa responsive and unresponsive Parkinson’s disease patients with Freezing of Gait (4477)

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. Disclosure: Dr. Mishra has nothing to disclose. Dr. Sreenivisan has nothing to disclose. Dr. Zhuang has nothing to disclose. Dr. Longhurst has nothing to disclose. Dr. Yang has nothing to disclose. Dr. Cordes has nothing to disclose. Dr. Ritter has nothing to disclose. Dr. Caldwell has nothing to disclose. Dr. Cummings has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Acadia%2C%20Accera%2C%20Actinogen%2C%20AgeneBio%2C%20Alkahest%2C%20Allergan%2C%20Alzheon%2C%20Avanir%2C%20Axsome%2C%20Binomics%2C%20BiOasis%20Technologies%2C%20Biogen%2C%20Bracket%2C%20Denali%2C%20Diadem%2C%20EIP%20Pharma%2C%20Eisai%2C%20Genentech%2C%20Gr. Dr. Cummings has received royalty, license fees, or contractual rights payments from Neuropsychiatric%2520Inventory. Dr. Cummings has received research support from Avid%20and%20Teva.Dr. Mari has nothing to disclose. Dr. Litvan has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Lundbeck Advisory Board. Dr. Litvan has received personal compensation in an editorial capacity for Frontiers in Neurology and Sunovion. Dr. Litvan has received research support from Abbvie, Biogen, and Roche.Dr. Bluett has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Abbvie pharmaceuticals; amneal pharmaceuticals; biogen.