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Abstract Details

Intrinsic Connectivity Network Disruption in Progressive Supranuclear Palsy
Behavioral Neurology
S54 - (-)
002
The advent of task-free functional MRI (fMRI) has enabled researchers to identify large-scale intrinsic connectivity networks (ICNs) in humans by mapping regions with temporally correlated low frequency blood oxygen level-dependent signal fluctuations. ICN mapping has been used to link healthy human network architectures to the cortically-predominant atrophy patterns seen in Alzheimer's disease and frontotemporal dementia. Early degeneration in typical PSP, however, targets subcortical and brainstem structures that have been less well characterized with ICN methods. We hypothesized that ICN analysis would identify a PSP-related network in healthy subjects and that patients with PSP would show connectivity breakdowns within this ICN. We further sought to explore relationships between connectivity disruption and clinical impairment.
Using task-free fMRI, we mapped intrinsic connectivity to the dorsal midbrain tegmentum (dMT), a region which shows focal atrophy in PSP. Two healthy control groups (1 young, 1 older) were used to define and replicate the normal connectivity pattern, and patients with PSP were compared to an independent matched healthy control group on measures of network connectivity.
Healthy young and older subjects showed a convergent pattern of connectivity to the dMT, including brainstem, cerebellar, diencephalic, basal ganglia, and cortical regions involved in skeletal, oculomotor, and executive control. Patients with PSP showed significant connectivity disruptions within this network, particularly within cortico-subcortical and cortico-brainstem interactions. Patients with more severe functional impairment showed lower mean dMT network connectivity scores.
This study defines a PSP-related intrinsic connectivity network in the healthy brain and demonstrates the sensitivity of network-based imaging methods to PSP-related physiological and clinical changes.
Authors/Disclosures
Raquel Gardner, MD (Sheba Medical Center)
PRESENTER 		Dr. Gardner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BrainBox. The institution of Dr. Gardner has received research support from NIH. The institution of Dr. Gardner has received research support from DoD.
Ettore Beghi, MD, FAAN No disclosure on file
Adam L. Boxer, MD, PhD (University of California, San Francisco) An immediate family member of Dr. Boxer has received personal compensation for serving as an employee of Kaiser Permanente. Dr. Boxer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ono. Dr. Boxer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Oscotec. Dr. Boxer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Boxer has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Arrowhead. Dr. Boxer has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Neurocrine Biosciences. Dr. Boxer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Switch. Dr. Boxer has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Arvinas. Dr. Boxer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Alector. Dr. Boxer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Boxer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Boxer has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Transposon. Dr. Boxer has stock in Alector. Dr. Boxer has stock in Arvinas. Dr. Boxer has stock in Neurovanda. The institution of Dr. Boxer has received research support from Biogen. The institution of Dr. Boxer has received research support from Eisai. The institution of Dr. Boxer has received research support from Regeneron. The institution of Dr. Boxer has received research support from NIH. The institution of Dr. Boxer has received research support from Bluefield Project. Dr. Boxer has received research support from Rainwater Charitable Foundation.
No disclosure on file
Jacob Mirsky, MA No disclosure on file
Christine C. Guo, PhD No disclosure on file
No disclosure on file
Hilary W. Heuer (UCSF Memory and Aging Center) No disclosure on file
No disclosure on file
Juan Zhou, PhD (National University of Singapore) No disclosure on file
Joel Kramer, PhD (UCSF Medical Center) The institution of Dr. Kramer has received research support from tau consortium. Dr. Kramer has received publishing royalties from a publication relating to health care.
Bruce L. Miller, MD, FAAN (University of California, San Francisco) Dr. Miller has nothing to disclose.
William W. Seeley, MD Dr. Seeley has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GLG Council. Dr. Seeley has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Guidepoint Global Consulting. Dr. Seeley has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BridgeBio. Dr. Seeley has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Seeley has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lyterian Therapeutics. The institution of Dr. Seeley has received research support from NIH. The institution of Dr. Seeley has received research support from Rainwater Charitable Foundation. The institution of Dr. Seeley has received research support from Bluefield Project to Cure FTD. The institution of Dr. Seeley has received research support from Chan-Zuckerberg Initiative.