# Individual trajectories for recovery of neocortical activity in disorders of consciousness

## TL;DR

This study uses brain simulations to show how weakened thalamo-cortical connections in unconscious patients can be strengthened to restore normal brain rhythms, aiding recovery.

## Contribution

The study introduces personalized biophysical modeling to identify recovery pathways in disorders of consciousness.

## Key findings

- Unconscious patients show reduced excitatory corticothalamic synaptic strength.
- Strengthening these connections in models restores normal brain rhythms in some patients.
- Recovery extent correlates with cerebral glucose uptake measured by PET.

## Abstract

The evolution from disturbed brain activity to physiological brain rhythms can precede recovery in patients with disorders of consciousness (DoC). Accordingly, intriguing questions arise: What are the pathophysiological factors associated to disrupted brain rhythms in patients with DoC, and are there potential pathways for individual patients with DoC to return to normal brain rhythms? We addressed these questions at the individual subject level using biophysical simulations based on electroencephalography (EEG). The main findings are that unconscious patients exhibit a loss of excitatory corticothalamic synaptic strength. Synaptic plasticity in this excitatory corticothalamic circuitry facilitates the return of physiological brain rhythms, characterized by the reappearance of spectral peaks and flattening of the aperiodic (1/f) component of the power spectrum, in the selection of patients with DoC, particularly in those who are minimally conscious. The extent to which this occurred was correlated with cerebral glucose uptake. The current findings emphasize the importance of excitatory thalamocortical activity in reestablishing normal brain rhythms after brain injury and show that biophysical modelling of the corticothalamic circuitry could help select patients who might be potentially receptive to treatment and undergo plasticity.

Following acute brain injury, some patients remain in a disorder of consciousness (DoC), ranging from unresponsive wakefulness to minimal awareness. Clinicians track recovery using electroencephalography (EEG), a technique that measures the electrical rhythms of the brain. Normal brains exhibit typical alpha and theta rhythms; in DoC, these rhythms are less apparent. We posed two challenging questions: which features of the brain’s wiring are most disrupted in DoC, and by what biological pathways can normal rhythms recover? Using a biophysical model fitted to each patient’s EEG, we found that the primary deficit lies in weakened excitatory connections from the thalamus to the cortex. This pathway helps organize widespread cortical activity. When we allowed these thalamo-cortical connections to strengthen in the model (a form of synaptic plasticity), physiological rhythms reappeared in a subset of subjects, but not when cortical connections were strengthened in isolation. The extent of modelled recovery was correlated with cerebral glucose metabolism as measured by PET, implying an association between maintained brain energy and the capacity for plasticity. Our findings show that simulating personalized thalamo-cortical dynamics from common EEG would allow identification of patients with most favorable response to recovery-promoting treatments.