Fig 1.
ICMS map, optogenetic MEP recording and schematic of stroke location and electrodes position.
A-C) Mean maps of forelimb movements evoked in all animals at 20,40 and 60 μA current threshold in naïve mice (n = 9). Coordinates for lesion and electrode implantation were based on this map. The color bar represents the probability to elicit a forelimb movement after stimulation of a specific site. D) Representative MEP recorded from the forelimb contra-lateral to the stimulated RFA. The blue line at time 0 represents the light stimulation. E) Stroke was unilaterally induced in CFA whereas bipolar electrodes were inserted in both RFAs: recording (El1 and El2) and reference (Ref1 and Ref2) electrodes. A surgical screw (Ground) was placed in the occipital bone and used as ground reference.
Fig 2.
A) and B) Two examples of typical recording artifacts, both indicated by the horizontal red line. Each artifact is characterized by a large deviation of the signal from its mean value.
Fig 3.
A) The raw ipsi-lateral LFP signal recorded from a single animal shows several artifacts, i.e. large deviations from the average of the signal. B) Same as A) but for the contra-lateral LFP signal. C) The cleaned ipsi-lateral LFP signal after the application of the artifact removal algorithm. D) Same as C) but for the contra-lateral LFP signal.
Fig 4.
Representative differences in LFPs after stroke on frequency oscillations and correlation.
A) A window of 15 seconds of two raw signals recorded at day 9 in control and stroke animals, red and blue trace respectively, is shown. B) The same signals after pass band filtering between 8 − 12 Hz, corresponding to α frequency, is shown. The power of the signal from the stroke animal (red) is higher compared to the control (blue), in agreement with the result shown in Fig 5A and 5B. C) A window of 15 seconds of two raw signals recorded at day 16 in control and stroke animals, red and blue trace respectively, is shown. D) The same signals after pass band filtering between 0.5 − 4 Hz, corresponding to δ frequency, are shown. In this case, the power of the stroke signal (red) is lower compared to the control (blue), in agreement with the result in Fig 5C. E) and F) A window of 3 seconds from the two raw LFPs, simultaneously recorded in the ipsi-lateral and contra-lateral RFA of a control (Panel E) and stroke (Panel F) animals at day 16. The two traces of the control animal show a high correlation, as reported in Fig 6A and 6B. On the other hand, the signals recorded simultaneously from the two RFAs of the stroke animal show a lower correlation compared with the control case, as reported in Fig 6A and 6B.
Fig 5.
Time evolution after stroke of the mean relative powers of α and δ spectral bands.
Only bands showing significant differences in stroke vs. naïve animals are shown. A) Values of the relative power of the α = (8 − 12) Hz band for the ipsi-lesional are shown. The result for day 9 shows significant statistical differences between stroke and control (p < 0.05). B) Values of the relative power α = (8 − 12) Hz band for the contra-lateral hemisphere is shown. As in the case of the ipsi-lesional hemisphere, significant statistical differences were found at day 9 (p < 0.05). C) Significant reduction of the δ band in the contralesional hemisphere, 16 days after stroke. For all panels the error bars represent the corresponding standard errors.
Fig 6.
Time evolution after stroke of the mean linear and non-linear inter-hemispheric correlation measures.
A) Cross correlation between the ipsi-lateral and contra-lateral hemisphere. Days 16 and 23 show significant statistical differences, p < 0.01 and p < 0.05, respectively. B) Longitudinal evolution of mutual information. Statistically significant differences between stroke and controls are present at days 16 (p < 0.01) and 23 (p < 0.05). For all panels the error bars represent the corresponding standard errors.
Fig 7.
Time evolution after stroke of the inter-hemispheric correlation on δ = (0.5 − 4) Hz and γ = (30 − 50) Hz bands.
A) Cross correlation between the ipsi-lateral and contra-lateral hemisphere for signals having frequencies on γ = (30 − 50) Hz band. The differences are highly significant at day 16 p < 0.001. B) Same as A) but using the mutual information measure. C) Values of the mutual information on δ = (0.5 − 4) Hz band. Note the significant reduction in stroke mice, already apparent at day 9. For all panels the error bars represent the corresponding standard errors.
Fig 8.
Mean values of and frequency of hemispheric dominance fHD.
A) Level of symmetry of the inter-hemispheric interaction evaluated through the values of . The first week does not present significant statistical differences. On the other hand, days 16 and 23 highlight significant statistical differences p < 0.01 and p < 0.05, respectively (two-way repeated measures Anova). B) Frequency of hemispheric dominance fHD (expressed in percentage) at days 16 post surgery. The distributions are zoomed in the ranges 0 − 10% and 80 − 100% to magnify the variation of fHD. The frequency distributions of stroke and control mice are significantly different (p < 0.05 χ2-test). C) Same as B) but for 23 post surgery. Also in this case the frequency distributions are significantly different between stroke and control mice (p < 0.05 χ2-test). For the top panel the error bars represent the corresponding standard errors.
Fig 9.
Schematic of the experimental protocol and summary of the results and possible interpretations.
A) The experimental layout is described in all of its parts: the stroke induction in CFA (or sham treatment) was followed by the positioning of the bipolar electrodes into the two RFAs. The LFPs were then recorded 9,16 and 23 days after surgery in the freely moving animals. B) The overall results are presented following the proposed separation in an early (day 9) and a late sub-acute period (days 16 and 23). The possible biological interpretation is also reported.