Cerebral Spreading Depression Transient Disruption of Cross-Frequency Coupling in the Rat Brain: Preliminary Observations.

Normal brain function requires an integrated, simultaneous communication between brain regions in a coordinated manner. In our studies on cortical spreading depolarization (CSD) induced electrically in the rat brain while recording electrocorticography (ECoG) and delta wave activity, we found for the first time that CSD suppressed delta wave activity, which began even before the CSD was fully developed. We pursued this observation to determine whether repeated CSD suppressed delta wave activity in rats. CSD was produced by electrical stimulation of the neocortex while recording the development of CSD and changes in the coupling of low-frequency band cross coupling to four typical physiological neuronal activity frequency bands, i.e., 5-7 Hz, 8-12 Hz, 13-30 Hz, and 30-80 Hz. Band-pass filters were applied to achieve the corresponding physiological band signals. Besides the cross-frequency coupling (CFC) analysis, the distribution of delta wave density in time domain was analyzed. We calculated the delta wave density per 30 seconds but represent the density as frequency per minute. A Generalized Linear Models (GLM) was used to carry out the CFC analysis in Matlab. Because delta waves dominated the ECoG recorded, we modeled the higher-frequency amplitude envelope as a function of low-frequency phase using a spline basis. Besides the CFC analysis, we also characterized the distribution of the delta wave density in time domain. Four CFC, Theta, Alpha, Beta, and Gamma were at very small values after CSD, and after about 8 minutes, the CFC recovered to the pre-CSD level. CFC were seen to decrease before a CSD occurred at the higher-frequency bands and tended to decrease quickly. Whether the attenuated CFC by CSD has long-term consequences remains to be determined. Future studies will explore the impact of cortical CSD on CFC with deeper brain structures, including the thalamus and the caudate putamen.