Toward a Structural and Functional Basis for Changes in Brain Signal Variability with Age (Emmy Noether Group 6th year extension application)
Final Report Abstract
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 primary 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. Strikingly however, because longitudinal change-change relations between brain and behaviour are notoriously difficult to detect, our findings provide even greater weight to understanding cognitive aging in the context of brain signal variability; (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. These cross-sectional effects directly address many of the key goals of my Emmy Noether proposal (variability, functional connectivity, dopamine, and task modulation/flexibility) and will be followedup using five-year longitudinal data that have been recently collected. Further, my group has achieved substantial results in relation to flexible/goal-directed modulation of brain signal variability, showing broadly that modulation of signal variability is required to adjust to varying environmental demands. We have also pursued extensive optimization of the estimation of signal variability, utilized a priori computational modeling to better embed our hypotheses regarding the nature of brain signal variability effects in relation to cognitive aging, and continue to develop a host of open-source code/tools for utilizing signal variability approaches in cognitive neuroscience. Overall, we have been highly successful in pursuing and meeting many of our originally proposed research objectives (having already published multiple papers in top journals in the field), but also in adapting our research foci and strategy when required. Without question, the extraordinary flexibility and support of the Emmy Noether program has made our unique constellation of results and approaches possible.
Publications
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Brain signal variability is modulated as a function of internal and external demand in younger and older adults. NeuroImage, 169, 510-523.
Grady, Cheryl L. & Garrett, Douglas D.
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Local temporal variability reflects functional integration in the human brain. NeuroImage, 183, 776-787.
Garrett, Douglas D.; Epp, Samira M.; Perry, Alistair & Lindenberger, Ulman
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Humans strategically shift decision bias by flexibly adjusting sensory evidence accumulation. eLife, 8.
Kloosterman, Niels A.; de Gee, Jan Willem; Werkle-Bergner, Markus; Lindenberger, Ulman; Garrett, Douglas D. & Fahrenfort, Johannes Jacobus
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Boosts in brain signal variability track liberal shifts in decision bias. eLife, 9.
Kloosterman, Niels A.; Kosciessa, Julian Q.; Lindenberger, Ulman; Fahrenfort, Johannes Jacobus & Garrett, Douglas D.
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Functional Connectivity within and beyond the Face Network Is Related to Reduced Discrimination of Degraded Faces in Young and Older Adults. Cerebral Cortex, 30(12), 6206-6223.
Grady, Cheryl L.; Rieck, Jenny R.; Nichol, Daniel & Garrett, Douglas D.
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Higher performers upregulate brain signal variability in response to more feature-rich visual input. NeuroImage, 217, 116836.
Garrett, Douglas D.; Epp, Samira M.; Kleemeyer, Maike; Lindenberger, Ulman & Polk, Thad A.
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Standard multiscale entropy reflects neural dynamics at mismatched temporal scales: What’s signal irregularity got to do with it?. PLOS Computational Biology, 16(5), e1007885.
Kosciessa, Julian Q.; Kloosterman, Niels A. & Garrett, Douglas D.
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Behavior needs neural variability. Neuron, 109(5), 751-766.
Waschke, Leonhard; Kloosterman, Niels A.; Obleser, Jonas & Garrett, Douglas D.
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Lost Dynamics and the Dynamics of Loss: Longitudinal Compression of Brain Signal Variability is Coupled with Declines in Functional Integration and Cognitive Performance. Cerebral Cortex, 31(11), 5239-5252.
Garrett, Douglas D.; Skowron, Alexander; Wiegert, Steffen; Adolf, Janne; Dahle, Cheryl L.; Lindenberger, Ulman & Raz, Naftali
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Thalamocortical excitability modulation guides human perception under uncertainty. Nature Communications, 12(1).
Kosciessa, Julian Q.; Lindenberger, Ulman & Garrett, Douglas D.
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Moment-to-Moment Brain Signal Variability Reliably Predicts Psychiatric Treatment Outcome. Biological Psychiatry, 91(7), 658-666.
Månsson, Kristoffer N.T.; Waschke, Leonhard; Manzouri, Amirhossein; Furmark, Tomas; Fischer, Håkan & Garrett, Douglas D.
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The impact of the human thalamus on brain-wide information processing. Nature Reviews Neuroscience, 24(7), 416-430.
Shine, James M.; Lewis, Laura D.; Garrett, Douglas D. & Hwang, Kai
