Abstract Details

Title Effects of ATP1A3 Mutations on Default Mode Network Connectivity

Topic Movement Disorders

Presentation(s) N1 - Neuroscience in the Clinic: Child Neurology: Emerging Understanding of the Epilepsy-Movement Disorder Spectrum Across the Lifespan (5:00 PM-5:15 PM)

Poster/Presentation
Number 002

Background 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 network connectivity associated with ATP1A3 disease phenotypes, including RDP and AHC.

Objective

The purpose 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 brain default mode network (DMN) connectivity, which has been implicated in other forms of dystonia. We hypothesized that ATP1A3 gene mutations would be associated with decreases in DMN connectivity compared to controls.

Design/Methods

Twenty-three patients with ATP1A3 mutations of RDP or AHC, as well as seven age/sex matched controls were recruited for this IRB approved study. Brain magnetic resonance imaging (MRI) data were acquired from all participants, including 10-minutes of resting-state BOLD data. Image pre-processing included file conversion to NIFTI format, brain segmentation, head motion correction, and artifact removal from functional MRI time-series data. BOLD data were then co-registered to structural T1 images, and a DMN seed created from the orthogonal slices of spatial cross-correlation of independent component analysis spatial maps, which were used to extract individual DMNs for estimating changes in connectivity strength. T-tests were conducted to examine between-group differences.

Results

There were statistically significant (p<0.05) between-group decreases in DMN connectivity strength. In particular, there were decreases between DMN and superior temporal gyrus among participants with ATP1A3 mutations compared to controls.

Conclusions Differences between patients with ATP1A3 mutations and controls in DMN connectivity suggest disruption of integrated functional brain circuitry, and reveal similarities with other forms of dystonia. Non-invasive neuroimaging allows quantitative measurement of brain function that may provide insights into brain phenotypes of ATP1A3-related disease, and lead to the development of imaging biomarkers for future treatment or prevention trials.

Authors/Disclosures
Christopher T. Whitlow, MD (Wake Forest School of Medicine) PRESENTER	Dr. Whitlow has nothing to disclose.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Jared Cook	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, FAAN (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. The institution of Dr. Haq has received research support from NIMH.
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, FAAN (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.

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