Failure in a population: Tauopathy disrupts homeostatic set-points in emergent dynamics despite stability in the constituent neurons.

Homeostatic regulation of neuronal activity is essential for robust computation; set-points, such as firing rate, are actively stabilized to compensate for perturbations. The disruption of brain function central to neurodegenerative disease likely arises from impairments of computationally essential set-points. Here, we systematically investigated the effects of tau-mediated neurodegeneration on all known set-points in neuronal activity. We continuously tracked hippocampal neuronal activity across the lifetime of a mouse model of tauopathy. We were unable to detect effects of disease in measures of single-neuron firing activity. By contrast, as tauopathy progressed, there was disruption of network-level neuronal activity, quantified by measuring neuronal pairwise interactions and criticality, a homeostatically controlled, ideal computational regime. Deviations in criticality correlated with symptoms, predicted underlying anatomical pathology, occurred in a sleep-wake-dependent manner, and could be used to reliably classify an animal's genotype. This work illustrates how neurodegeneration may disrupt the computational capacity of neurobiological systems.

Quasicriticality explains variability of human neural dynamics across life span.

Aging impacts the brain's structural and functional organization and over time leads to various disorders, such as Alzheimer's disease and cognitive impairment. The process also impacts sensory function, bringing about a general slowing in various perceptual and cognitive functions. Here, we analyze the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) resting-state magnetoencephalography (MEG) dataset-the largest aging cohort available-in light of the quasicriticality framework, a novel organizing principle for brain functionality which relates information processing and scaling properties of brain activity to brain connectivity and stimulus. Examination of the data using this framework reveals interesting correlations with age and gender of test subjects. Using simulated data as verification, our results suggest a link between changes to brain connectivity due to aging and increased dynamical fluctuations of neuronal firing rates. Our findings suggest a platform to develop biomarkers of neurological health.

Evidence for Quasicritical Brain Dynamics.

Much evidence seems to suggest the cortex operates near a critical point, yet a single set of exponents defining its universality class has not been found. In fact, when critical exponents are estimated from data, they widely differ across species, individuals of the same species, and even over time, or depending on stimulus. Interestingly, these exponents still approximately hold to a dynamical scaling relation. Here we show that the theory of quasicriticality, an organizing principle for brain dynamics, can account for this paradoxical situation. As external stimuli drive the cortex, quasicriticality predicts a departure from criticality along a Widom line with exponents that decrease in absolute value, while still holding approximately to a dynamical scaling relation. We use simulations and experimental data to confirm these predictions and describe new ones that could be tested soon.