Page 86 - MEGIN Book Of Abstracts - 2023

Clinic, UNMC, Omaha, NE, USA; Department of Radiology, neuroimaging applications, as oscillatory slowing has
UNMC, Omaha, NE, USA also been extensively documented in other patient
populations, most notably Parkinson's disease, with
ABSTRACT An extensive electrophysiological literature divergent spectral and spatial features.
has proposed a pathological 'slowing' of neuronal ac-
tivity in patients on the Alzheimer's disease spectrum. Keywords: magnetoencephalography, mild cognitive
Supported by numerous studies reporting increases in impairment, neural oscillations, spontaneous activity
low-frequency and decreases in high-frequency neural
oscillations, this pattern has been suggested as a stable Brain: a journal of neurology (2022), Vol. 145, No. 6
biomarker with potential clinical utility. However, no (35088842) (8 citations)
spatially resolved metric of such slowing exists, stymie-
ing efforts to understand its relation to proteinopathy
and clinical outcomes. Further, the assumption that this Neuronal synchrony abnormalities associated with
slowing is occurring in spatially overlapping popula- subclinical epileptiform activity in early-onset
tions of neurons has not been empirically validated. In Alzheimer's disease (2022)
the current study, we collected cross-sectional resting
state measures of neuronal activity using magnetoen- Ranasinghe, Kamalini G; Kudo, Kiwamu; Hinkley,
cephalography from 38 biomarker-confirmed patients Leighton; Beagle, Alexander; Lerner, Hannah; Mizuiri,
on the Alzheimer's disease spectrum and 20 cognitively Danielle; Findlay, Anne; Miller, Bruce L; Kramer, Joel H;
normal biomarker-negative older adults. From these Gorno-Tempini, Maria Luisa; Rabinovici, Gil D; Rankin,
data, we compute and validate a new metric of spatially Katherine P; Garcia, Paul A; Kirsch, Heidi E; Vossel, Keith;
resolved oscillatory deviations from healthy ageing Nagarajan, Srikantan S
for each patient on the Alzheimer's disease spectrum.
Using this Pathological Oscillatory Slowing Index, we Memory and Aging Center, Department of Neurology, Univer-
show that patients on the Alzheimer's disease spec- sity of California San Francisco, San Francisco, CA, USA; Medi-
trum exhibit robust neuronal slowing across a network cal Imaging Business Center, Ricoh Company, Ltd, Kanazawa
of temporal, parietal, cerebellar and prefrontal cortices. 920-0177, Japan; Department of Radiology and Biomedical
This slowing effect is shown to be directly relevant Imaging, University of California San Francisco, San Fran-
to clinical outcomes, as oscillatory slowing in tempo- cisco, CA, USA; Epilepsy Center, Department of Neurology,
ral and parietal cortices significantly predicted both University of California San Francisco, San Francisco, CA,
general (i.e. Montreal Cognitive Assessment scores) USA; Mary S. Easton Center for Alzheimer's Disease Research,
and domain-specific (i.e. attention, language and Department of Neurology, David Geffen School of Medicine,
processing speed) cognitive function. Further, regional University of California Los Angeles, Los Angeles, CA 90095,
amyloid-β accumulation, as measured by quantitative USA
18F florbetapir PET, robustly predicted the magnitude
of this pathological neural slowing effect, and the ABSTRACT Since the first demonstrations of network
strength of this relationship between amyloid-β burden hyperexcitability in scientific models of Alzheimer's
and neural slowing also predicted attentional impair- disease, a growing body of clinical studies have identi-
ments across patients. These findings provide empirical fied subclinical epileptiform activity and associated
support for a spatially overlapping effect of oscillatory cognitive decline in patients with Alzheimer's disease.
neural slowing in biomarker-confirmed patients on the An obvious problem presented in these studies is lack
Alzheimer's disease spectrum, and link this effect to of sensitive measures to detect and quantify network
both regional proteinopathy and cognitive outcomes in hyperexcitability in human subjects. In this study we
a spatially resolved manner. The Pathological Oscilla- examined whether altered neuronal synchrony can
tory Slowing Index also represents a novel metric that be a surrogate marker to quantify network hyperex-
is of potentially high utility across a number of clinical citability in patients with Alzheimer's disease. Using

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