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Emma Pineau1, Keying Chen2, Margaret M Koletar2

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Summary
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Brain activation pattern variability increases with age and cognitive decline in Alzheimer's disease models. This variability may serve as a neurophysiological marker for cognitive reserve, offering new insights into Alzheimer's disease progression.

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Area of Science:

  • Neuroscience
  • Neuroimaging
  • Alzheimer's Disease Research

Background:

  • Cognitive reserve in Alzheimer's disease (AD) remains poorly understood.
  • Neuronal variability in response to stimulation is a known phenomenon but not studied brain-wide.
  • Hypothesized link between neuronal variability, vascular reactivity, and blood oxygenation-level dependent (BOLD) functional magnetic resonance imaging (fMRI) patterns.

Purpose of the Study:

  • Investigate brain-wide neuronal and vascular reactivity variability.
  • Explore the relationship between fMRI activation pattern variability and cognitive reserve.
  • Utilize a transgenic rat model of AD to study these phenomena.

Main Methods:

  • Employed a protracted BOLD fMRI protocol with repetitive somatosensory stimulation.
  • Used transgenic Fischer 344 rats (TGF344-AD) modeling AD pathology.
  • Analyzed trial-by-trial voxel-level response variability and quantified spatial/temporal variability using Pearson's correlation.

Main Results:

  • Brain activation pattern variability increased with age and cognitive impairment.
  • Categorized animals into young, cognitively maintained aged, and cognitively impaired aged groups.
  • Demonstrated group-wise differences in activation pattern variability correlating with cognitive performance.

Conclusions:

  • The developed assay is sensitive to group-wise differences in activation pattern variability.
  • Activation pattern variability correlates with cognitive performance in the studied AD model.
  • fMRI activation pattern variability may be a robust neurophysiological correlate of cognitive reserve.