Compensating functional connectivity changes due to connectome alterations via dynome modifications
Poster No:
1439
Submission Type:
Abstract Submission
Authors:
Demian Battaglia1, Samy Castro2, Benitez Stulz Sophie3, Anagh Pathak1, Matthieu Aguilera2
Institutions:
1University of Strasbourg, Strasbourg, France, 2University of Strasbourg, Strasbourg, Bas Rhin, 3Aix-Marseille University, Marseille, France
First Author:
Co-Author(s):
Introduction:
Neurological pathologies as e.g. Alzheimer's Disease or Multiple Sclerosis are often associated to neurodegenerative processes affecting the strength and the transmission speed of long-range inter-regional fiber tracts. Such degradation of Structural Connectivity (SC) impacts on large-scale brain dynamics and the associated Functional Connectivity (FC) and dynamic Functional Connectivity (dFC) , eventually perturbing network computations and cognitive performance. Functional Connectivity however is not bound to merely mirror Structural Connectivity, but rather reflects the complex coordinated dynamics of many regions. What if, by restoring brain dynamics, perturbed by ongoing degenerative processes, functional impairments could be restored even if structural degeneration is not reverted?
Here, we first use analytical characterizations of toy models and computational simulations of connectome-based whole-brain models, we predict that suitable modulations of regional dynamics could precisely compensate for the effects of structural degradation, as if the original Structural Connectivity strengths and speeds of conduction were effectively restored. The required dynamical changes are widespread and aspecific (i.e. they do not need to be restricted to specific regions) so that they could be potentially implemented via neuromodulation or pharmacological therapy, globally shifting regional excitability and/or excitation/inhibition balance.
Specifically, we provide evidence in favour for our hypothesis, considering the case of brain dynamics fluidity loss in early Alzheimer's disease, in which it has been shown that non-invasive sensory stimulation protocols restoring fluidity also restore memory performance, despite lack of a clear structural determinant for the effects.
Here, we first use analytical characterizations of toy models and computational simulations of connectome-based whole-brain models, we predict that suitable modulations of regional dynamics could precisely compensate for the effects of structural degradation, as if the original Structural Connectivity strengths and speeds of conduction were effectively restored. The required dynamical changes are widespread and aspecific (i.e. they do not need to be restricted to specific regions) so that they could be potentially implemented via neuromodulation or pharmacological therapy, globally shifting regional excitability and/or excitation/inhibition balance.
Specifically, we provide evidence in favour for our hypothesis, considering the case of brain dynamics fluidity loss in early Alzheimer's disease, in which it has been shown that non-invasive sensory stimulation protocols restoring fluidity also restore memory performance, despite lack of a clear structural determinant for the effects.
Methods:
- We use connectome-based modelling. Models embed a SC matrix derived from an average over an healthy subject cohort, previously used in Hansen et al. (2015). Regional dynamics is modeled by a delayed rectified linear transfer function. Inter-regional connection strengths and conduction speed, or local excitability and E/I balance are free parameters that can be freely adjusted to modify dynamical regime. The initial dynamic working point is chosen to maximize fit with generic rs BOLD FC matrices, obtained averaging over the same subjects used to construct the SC.
- Mock neurodegeneration is simulated weakening or slowing down inter-regional tracts, or disregulating local excitability.
- Fluidity is assessed on BOLD via speed of dFC reconfiguraiton and on EEG via microstate dwell time and inverse persistence non-linear time-series analyses.
- Mock neurodegeneration is simulated weakening or slowing down inter-regional tracts, or disregulating local excitability.
- Fluidity is assessed on BOLD via speed of dFC reconfiguraiton and on EEG via microstate dwell time and inverse persistence non-linear time-series analyses.
Results:
- FC, dFC speed and brain dynamics fluidity induced by simulated neurodegeneration or disregulation of system parameters can be reversed by suitable modifications of local dynamics, applied globally and aspecifically, as a neuromodulatory change or pharmacological treatment could do.
- These local dynamics changes do not have to be guessed blindly but insight from toy models which are analytically solvable can provide precious guidance.
- Memory deficits in early AD with absence of Amyloid plaques correlate with reduced rs/task EEG and rs fMRI BOLD in mutant mice. Analogously reduced fluidity corresponds to reduced cognitive performance in human aging, and its maintainance to maintained performance (mechanisms for cognitive reserve?)
- Restoring of dynamic fluidity corresponds to recovered cognitive performance in absence of proved reversal of physiopathological processes supposedly causing the cognitive impairments.
- These local dynamics changes do not have to be guessed blindly but insight from toy models which are analytically solvable can provide precious guidance.
- Memory deficits in early AD with absence of Amyloid plaques correlate with reduced rs/task EEG and rs fMRI BOLD in mutant mice. Analogously reduced fluidity corresponds to reduced cognitive performance in human aging, and its maintainance to maintained performance (mechanisms for cognitive reserve?)
- Restoring of dynamic fluidity corresponds to recovered cognitive performance in absence of proved reversal of physiopathological processes supposedly causing the cognitive impairments.
Conclusions:
In conclusions, theoretical and data-driven computational modelling suggest that, in the future therapeutic interventions could be designed to "repair brain dynamics" rather than structure (or in other words, the "software" rather than the "hardware") to boost functional connectivity and its dynamics without having to block or revert neurodegenerative and other physiopathological processes.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 2
Modeling and Analysis Methods:
fMRI Connectivity and Network Modeling 1
Keywords:
Aging
Cognition
Computational Neuroscience
Degenerative Disease
Electroencephaolography (EEG)
FUNCTIONAL MRI
Memory
Modeling
Other - Sensory stimulation
1|2Indicates the priority used for review
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Aguilera, M., et al. (2024). 40 Hz light stimulation restores early brain dynamics alterations and associative memory in Alzheimer’s disease model mice. bioRxiv, 2024.10.21.619392. https://doi.org/10.1101/2024.10.21.619392