Toward a Structural and Functional Basis for Changes in Brain Signal Variability with Age (Emmy Noether Group 6th year extension application)

• Applicant: Douglas Garrett, Ph.D.
• Subject Area: Human Cognitive and Systems Neuroscience
• Term: from 2016 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 310615419

Since the inception of the Lifespan Neural Dynamics (Emmy Noether) Group, we have made tremendous ground in measuring, understanding, and manipulating brain signal variability in the context of cognition and aging. Regarding our original Emmy Noether research targets, we have found that: (1) brain structure is a positive yet modest correlate of the level of brain signal variability expressed during aging, yet shows marked spatial differentiation when examining cross-sectional vs. longitudinal data; (2) functional connectivity is tightly and positively coupled with brain signal variability at the regional level, suggesting that signal variability expressed within brain regions is likely due to synaptic input rather than “local noise” sources. This combination of functional connectivity and local signal variability also reflects broad-scale cognition across the adult lifespan, associations that hold at cross-section and in longitudinal data; (3) dopamine continues to provide a fruitful neurochemical basis for understanding brain signal variability in the context of aging and cognition. Notably, we find that older adults who can better modulate brain signal variability under working memory load are better able to increase functional network integration, can respond faster, and express higher baseline dopamine levels. Without question however, the COVID-19 pandemic has delayed progress on several research goals outlined in my original Emmy Noether proposal. In particular, we have been delayed in addressing our primary original objective of examining the flexible modulation of signal variability under uncertainty in younger and older adults. This research objective would serve as the singular focus within our 6th year Emmy Noether Group extension. Using two unique experimental paradigms (one dataset already collected pre-pandemic) that parametrically manipulate uncertainty while participants undergo EEG and fMRI, we seek to address whether older adults are less able to: (a) modulate their "state space" by shifting from a rhythmic to a noisier neural regime under uncertainty; (b) constrain their brain states to those that are task relevant (i.e., cued). We will also estimate the extent to which uncertainty-related shifts in fMRI and EEG-based estimates of neural variability are coupled within-person, and how this coupling differs by age and performance. This work requires a comprehensive multidisciplinary (e.g., lifespan cognitive neuroscience, mathematics, statistics), multi-method (e.g., multimodal imaging; computational modelling) approach.

• DFG Programme: Independent Junior Research Groups