Post-Stroke Longitudinal Alterations of Inter-Hemispheric Correlation and Hemispheric Dominance in Mouse Pre-Motor Cortex

Limited restoration of function is known to occur
spontaneously after an ischemic injury to the primary motor cortex.
Evidence suggests that Pre-Motor Areas (PMAs) may “take over”
control of the disrupted functions. However, little is known about functional
reorganizations in PMAs. Forelimb movements in mice can be driven by
two cortical regions, Caudal and Rostral Forelimb Areas (CFA
and RFA), generally accepted as primary motor and pre-motor
cortex, respectively. Here, we examined longitudinal changes in functional coupling
between the two RFAs following unilateral photothrombotic stroke in CFA
(mm from Bregma: +0.5 anterior, +1.25 lateral). Local field potentials (LFPs) were recorded from the RFAs
of both hemispheres in freely moving injured and naïve mice. Neural signals
were acquired at 9, 16 and 23 days after surgery (sub-acute period in stroke
animals) through one bipolar electrode per hemisphere placed in the center of RFA,
with a ground screw over the occipital bone. LFPs were pre-processed through an efficient method of
artifact removal and analysed through: spectral, cross-correlation, mutual information and Granger
causality analysis.Spectral analysis demonstrated an early decrease (day
9) in the alpha band power in both the RFAs. In the late sub-acute period (days 16
and 23), inter-hemispheric functional coupling was reduced in ischemic animals,
as shown by a decrease in the cross-correlation and mutual information measures.
Within the gamma and delta bands, correlation measures were already reduced at
day 9. Granger analysis, used as a measure of the symmetry of the inter-hemispheric causal connectivity, showed a less
balanced activity in the two RFAs after stroke, with more
frequent oscillations of hemispheric dominance.These results indicate robust electrophysiological
changes in PMAs after stroke. Specifically, we found alterations
in transcallosal connectivity, with reduced
inter-hemispheric functional coupling and a fluctuating dominance pattern. These reorganizations may underlie vicariation
of lost functions following stroke.