Abstract
Within multiscale brain dynamics, the structure–function relationship between cellular changes at a lower scale and coordinated oscillations at a higher scale is not well understood. This relationship may be particularly relevant for understanding functional impairments after a mild traumatic brain injury (mTBI) when current neuroimaging methods do not reveal morphological changes to the brain common in moderate to severe TBI such as diffuse axonal injury or gray matter lesions. Here, we created a physiology-based model of cerebral cortex using a publicly released modeling framework (GEneral NEural SImulation System) to explore the possibility that performance deficits characteristic of blast-induced mTBI may reflect dysfunctional, local network activity influenced by microscale neuronal damage at the cellular level. We operationalized microscale damage to neurons as the formation of pores on the neuronal membrane based on research using blast paradigms, and in our model, pores were simulated by a change in membrane conductance. We then tracked changes in simulated electrical activity. Our model contained 585 simulated neurons, comprised of 14 types of cortical and thalamic neurons each with its own compartmental morphology and electrophysiological properties. Comparing the functional activity of neurons before and after simulated damage, we found that simulated pores in the membrane reduced both action potential generation and local field potential (LFP) power in the 1–40 Hz range of the power spectrum. Furthermore, the location of damage modulated the strength of these effects: pore formation on simulated axons reduced LFP power more strongly than did pore formation on the soma and the dendrites. These results indicate that even small amounts of cellular damage can negatively impact functional activity of larger scale oscillations, and our findings suggest that multiscale modeling provides a promising avenue to elucidate these relationships.
Highlights
Human cognitive performance relies critically on cerebral cortical electrical activity within the 1–100 Hz frequency range [1,2,3,4,5], and in vivo neural activity can be measured as potential differences in the electric field which manifest itself as current in a recording electrode [1]
We used a physiology-based model of cerebral cortex built in the GEneral NEural SImulation System (GENESIS) simulation framework to explore the possibility that performance deficits characteristic of blast-induced mild traumatic brain injury (mTBI) may reflect dysfunctional, local network activity influenced by microscale neuronal damage at the cellular level
We compared the functional activity of neurons before and after simulated damage and found that simulated pores in the membrane reduced both action potential (AP) generation and local field potential (LFP) power in the 1–40 Hz range of the power spectrum, a range implicated in research on task performance
Summary
Human cognitive performance relies critically on cerebral cortical electrical activity within the 1–100 Hz frequency range [1,2,3,4,5], and in vivo neural activity can be measured as potential differences in the electric field which manifest itself as current in a recording electrode [1]. Electrical activity is commonly recorded as electroencephalography (EEG), where electrodes are placed on the outside of the head/skull, or electrocorticogram, where electrodes are placed directly on the cortical surface of the brain. Both of these electrophysiological monitoring methods record the integrated activity of millions of neurons simultaneously, and any disruption to neurons that degrades large-scale brain activity within these frequency ranges has the potential to impair cognitive performance [6, 7]. Our simulations explore the possibility that negative effects of mTBI could be due to microscale neuronal damage occurring across many neurons simultaneously, and it is their cumulative impact that disrupts coordinated cortical oscillations
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