| Background Burst suppression(BS)is a special EEG pattern characterized by alternating high amplitude electrical discharges separated by variable periods of low electrical activity with a duration on the order of seconds,which can be induced by a variety of factors.Studies have shown that burst suppression induced by controllable methods(such as cooling or anesthesia)is an effective neuroprotective method.On the contrary,burst suppression with the "same burst pattern" can be used to predict the poor prognosis of brain injury.The EEG pattern BS is one of the common characteristics of some epileptic encephalopathy.Similar to it is isoflurane,a common inhaled general anesthetic that has also been reported to have neuroprotective effects.However,there are still some controversies about this protective effect,and its effects may be dose-related.Inhalational anesthetic-induced burst suppression(BS)is classically considered a bilaterally synchronous rhythm.However,local asynchrony has been predicted in theoretical studies and reported in patients with pre-existing focal pathology.Objective Therefore we used high-speed wide-field calcium imaging to study the spatiotemporal dynamics of isoflurane-induced BS in rats,to further explore the neurophysiological characteristics of the cortical activity in the isoflurane-induced BS,such as the rhythm,origin,and transmission,and compare them with the state after 4-AP injection.The mesoscopic mechanism of burst suppression is expected to provide the possibility for BS and the application of isoflurane in neuroprotection and epileptic focus location.Methods: Healthy male SD rats(200~350g)was stained with Calcium dye by convectionenhanced delivery to create smooth,continuous loading of a large area of the cortical surface.After staining,the skull over both hemispheres was removed.The onset site and propagation characteristics of bursts were analyzed by MATLAB.To study the role of the thalamus,TTX was injected to silence the VBC in some experiments.In another group of rats,an acute seizure focus was created in the cortex with 4-AP injection and the VBC was excited by electric stimulation.The characteristics of calcium signal and LFP were measured and compared with the previous data to study the role of the thalamus in BS and epilepsy.Focal seizures were induced by 4-AP injection in the somatosensory cortex,to explore the changes in cortical activity after an epileptic seizure.Results Through time-frequency and power analysis of the local LFP and the calcium signal,we found that they have high temporal synchronization,and the burst frequency is mainly in the delta band(0-3Hz).Through the analysis of the spatial characteristics of calcium imaging of unilateral neocortex,we found that isoflurane-induced BS is not synchronized throughout the brain,but is rapidly transmitted from a focal onset site to the whole field of view.The propagation time is usually within 100 ms.The initiation site of a burst suppression is mainly randomly distributed along the edge of the field of imaging.Through the analysis of the calcium single burst wave,we found the bursts consist of multiple propagating waves with variable degrees of propagation.Then we analyzed the calcium signal of bilateral cortical calcium imaging and found the crosshemisphere delay was,comparable to the propagation speed within one hemisphere,indicating that,on average,a similar number of synapses needed to be crossed in each scenario.Through the analysis of the calcium imaging spatial characteristics of the bilateral cerebral cortex,we found that there is no preference for the origin side,and 81.2% of the burst showed mirroring propagation patterns,suggesting a critical role of the cross-hemisphere fiber projection(such as the corpus callosum).By analyzing the burst frequency and onset site of calcium imaging after thalamic TTX injection,we found that the burst frequency was significantly reduced,and TTX injection caused the cortical burst onset sites to shift away from the hemisphere whose thalamus was inactivated.After induction of focal seizures with 4-AP,we observed three types of LFP and calcium waves.Among them,epileptic waves have different origins from burst waves and herald spikes.VBC electrical stimulation can induce both bursts and seizures in the neocortex,suggesting that the thalamus may play an important role in cortical bursts and seizures through thalamic-cortical projections.Conclusions 1.In the cortex,the onset site of the burst is not evenly distributed.In the field of view,bursts are usually initiated from the periphery of the field of view.2.Bursts in the interictal period are often initiated from the area outside the seizure acute seizure focus.3.Cortical bursts and focal seizures can be triggered by thalamic-cortical projections.4.Burst propagation sequences are preserved between hemispheres.After the origin of the local cortex burst,it quickly spread to the entire hemispheres and quickly spread to the opposite side through the intermediate structure.5.Bursts consist of multiple propagating waves with variable degrees of propagation,and the propagation mode of the burst has changed during the entire propagation process,which may be caused by the gradual attenuation of energy and transmitter. |
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