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Abstract Details

Effects of ATP1A3 Mutations on Brain Functional Network Connectivity
Movement Disorders
P13 - Poster Session 13 (5:30 PM-6:30 PM)
3-017
The aim of this study was to characterize the effects of ATP1A3 gene mutations of rapid-onset dystonia Parkinsonism (RDP) and alternating hemiplegia of childhood (AHC) on functional brain network connectivity. We hypothesized that different ATP1A3 gene mutations would be associated with different patterns of brain functional network connectivity compared to controls.

ATP1A3 is in the P2 family of ion transport ATPases that establish and maintain electrochemical gradients for Na+ and K+ across the plasma membrane.  Little is known about brain functional network connectivity that may underlie ATP1A3 clinical disease phenotypes, including RDP and AHC.

In this IRB-approved study, brain MRI was acquired from all participants, including 10-minutes of resting-state blood oxygen level dependent (BOLD) data. Image pre-processing included file conversion to NIFTI, brain segmentation, head motion correction, and artifact removal from the functional MRI time series data.  BOLD data were then co-registered to structural T1-images, and Automated Anatomical Labeling atlas structures used as seeds to map region-to-region connectivity.  Group-wise statistical analyses were conducted, with correction for multiple region-to-region comparisons.

Compared to controls, RDP was associated with greater connectivity (p<0.05) between postcentral gyrus-to-angular gyrus and precentral gyrus-to-temporal pole.  Compared to controls, AHC was associated with lower connectivity (p<0.05) between amygdala-to-superior frontal lobe, postcentral gyrus-to-thalamus, paracentral lobule-to-superior temporal pole, and portions of the cerebellum-to-vermis, as well as greater connectivity (p<0.05) between posterior cingulum-to-pallidum. Compared to AHC, RDP was associated with greater connectivity (p<0.05) between superior parietal lobe-to-supplementary motor area, as well as lower connectivity between inferior parietal lobe-to-orbitofrontal cortex, inferior parietal lobe-to-angular gyrus, and portions of the cerebellum-to-vermis.

ATP1A3 mutations of RDP and AHC are associated with different phenotypes of brain functional network connectivity, suggesting disruption of integrated brain circuitry.  Future studies will determine if these differences in ATP1A3-associated functional brain network phenotypes underlie different clinical manifestations of RDP and AHC.
Authors/Disclosures
Christopher T. Whitlow, MD (Wake Forest School of Medicine)
PRESENTER 		Dr. Whitlow has nothing to disclose.
No disclosure on file
Jared Cook No disclosure on file
No disclosure on file
No disclosure on file
Beverly Snively The institution of Beverly Snively has received research support from National Institutes of Health. The institution of Beverly Snively has received research support from Duke Endowment. The institution of Beverly Snively has received research support from Department of Defense. The institution of Beverly Snively has received research support from PCORI.
Ihtsham Haq, MD, FÂ鶹´«Ã½Ó³»­ (University of Miami Miller School of Medicine) The institution of Dr. Haq has received research support from NINDS. The institution of Dr. Haq has received research support from the Parkinson's Foundation.
Kathleen J. Sweadner, PhD (Massachusetts General Hospital and Harvard Medical School) The institution of Dr. Sweadner has received research support from Hope for Annabel, AHC Foundation, and CureAHC. The institution of Dr. Sweadner has received research support from the Chan-Zuckerberg Initiative.
Laurie J. Ozelius, PhD The institution of Dr. Ozelius has received research support from NIH. Dr. Ozelius has received intellectual property interests from a discovery or technology relating to health care.
Allison Brashear, MD, MBA, FÂ鶹´«Ã½Ó³»­ (Univeristy of Buffalo) Dr. Brashear has received personal compensation for serving as an employee of McKnight Brain Res Found. Dr. Brashear has received personal compensation for serving as an employee of American Board of Psychiatry and Neurology. Dr. Brashear has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for ABPN. Dr. Brashear has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for McKnight Brain Research Foundation i. Dr. Brashear has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for Care Directions- start up . Dr. Brashear has stock in Caredirections . The institution of Dr. Brashear has received research support from NINDS. Dr. Brashear has received publishing royalties from a publication relating to health care. Dr. Brashear has received personal compensation in the range of $500-$4,999 for serving as a Special government employee and study section reviewer with NIH. Dr. Brashear has received personal compensation in the range of $0-$499 for serving as a Adminstrative board -travel reimbursement with AAMC.