The neurophysiological underpinnings of brain resilience: a BOLD fMRI deep phenotyping study

Motivation: Basal plasticity leads to time-dependent stochasticity in neurons' responsiveness to stimuli. Stochasticity results in neuronal activity variance that has been described at single-cell resolution; however, mesoscopic scale measures are lacking. Goal(s): We set out to quantify response variability to stimulation as detected by BOLD fMRI and quantify the extent to which this variability is correlated to age and cognitive decline. Approach: Long (3-hour) imaging protocols provide deep within-subject characterization of response variability in the transgenic F344AD rat model. Results: On a whole brain level, greater variability correlates with age and degree of cognitive impairment. Impact: The development of a non-invasive MRI assay to assess brain resilience is an important step towards bettering our understanding of why individuals are differentially susceptible to cognitive decline due to Alzheimer's disease pathology.