The pericontused cortex can support function early after TBI but it remains functionally isolated from normal...

Area of Science:

• Neuroscience
• Systems Neuroscience
• Neurotrauma

Background:

• Traumatic brain injury (TBI) causes altered functional connectivity (FC) in a region-dependent manner, with some brain areas becoming disconnected and others hyperconnected.
• Remote cortical regions may become hyperexcitable post-injury, potentially increasing trans-hemispheric inhibition and hindering reorganization in the injured hemisphere.

Purpose of the Study:

• To investigate the mechanisms underlying the temporary normalization of forelimb behavioral use after TBI by silencing the contralesional cortex.
• To determine if this normalization is due to restored afferent pathway FC or brain circuit reorganization.
• To probe forelimb circuit function at 1 and 4 weeks post-injury using sensorimotor task-evoked fMRI, resting-state fMRI, and structural equation modeling (SEM).

Main Methods:

• Experimental traumatic brain injury (TBI) model in rats.
• Temporary silencing of the contralesional cortex using muscimol injection versus vehicle control.
• Sensorimotor task-evoked functional magnetic resonance imaging (fMRI) to assess brain activity.
• Resting-state fMRI seed-based analysis to evaluate functional connectivity.
• Structural equation modeling (SEM) to analyze directed causal connections.

Main Results:

• Silencing the contralesional cortex at 1 and 4 weeks post-injury reduced the forelimb cortical map evoked by stimulating the unaffected forelimb.
• At 1 week, silencing also activated pericontused cortex ipsilateral to the stimulated forelimb, but this region could not be activated by direct stimulation of the injured forelimb.
• Increased interhemispheric FC at the cortical level and decreased FC in subcortical regions were observed.
• SEM analysis revealed increased corticothalamic connectivity and suggested changes involving the bilateral thalamus.

Conclusions:

• Temporary neuromodulation of the contralesional cortex can activate the pericontused cortex early after TBI, but this region remains functionally disconnected from normal afferent input.
• Altered cross-brain FC during neuromodulation, particularly at 1 week post-injury, suggests that more distributed brain activity underlies early sensorimotor function recovery.
• Hemispheric functional imbalance is causally involved in the early loss of sensorimotor function following TBI.