The Mechanism Of Spatiotemporal Response Pattern To Transcorneal Electrical Stimulation In Visual Cortices Investigated By Intrinsic Optical Imaging

Visual system is one of the most important sensory systems of human to get information from the world.Disease along the visual pathway may lead to blindness,which has a huge impact on people's life.Neuroscientists hope to restore vision by electrically stimulating visual pathway of the blind people,therefore,electrical stimulation of visual pathway was proposed.With the clinical application of retinal prosthesis,electrical stimulation of the retina has achieved great success.Researchers now are paying more attention to the preoperative evaluation of visual function and postoperative rehabilitation strategies.Transcorneal electrical stimulation(TcES)can noninvasively activate the retina and is expected to play a potential role in artificial vision.At present,the use of phosphenes evoked by TcES has been used to assess residual visual function and screen suitable candidates before implanting retinal prostheses.Compared with the subjective measure of phosphenes,objective and quantitative study of the cortical response not only promotes the application of TcES in assessment and screening of patients,but also helps understand the neural mechanism induced by electrical stimulation.Focusing on this issue,we studied the visual cortical responses using optical intrinsic signal(OIS)imaging and multi-electrode array recordings.Main research contents of this dissertation are as follows.As a noninvasive stimulation,how the hemodynamic response changes in visual cortex after TcES and what kind of parameters can effectivelly evoke the cortical response are still unknown.To answer these questions,an objective and quantitative measurement of cortical response is required.By using multi-wavelength OIS,the spatiotemporal changes in hemoglobin oxygenation and cerebral blood volume(CBV)were simultaneously recorded.We systematically investigated different effects of TcES parameter on cortical response.Silver-ball electrode array was used to record evoked field potentials(EFPs)in the visual cortex.Results showed that the largest OIS responses were obtained when the stimulus frequencies were about 10–20 Hz.With the increase of stimulus electric charge,the OIS amplitudes and response areas increased and tended to saturate.Meanwhile,the response regions expanded from the cortical regions representing peripheral visual field to the regions representing central visual field,while TcES mainly activates the peripheral retina.Electrophysiological recordings showed strong EFPs in OIS response region.This research established foundation for investigating the cortical response to TcES,and improved understanding of the mechanisms underlying prosthetic vision,which promoted the application of TcES.This study showed that TcES could evoke an antagonistic spatial pattern of positive OIS response(POR)and negative OIS response(NOR),however,the mechanisms of NOR were still controversial.For more comprehensive information of cortical response,we must also focus on the NOR.To understand the mechanisms for negative response,we used laser speckle contrast imaging(LSCI)and microelectrode array recordings to study the cerebral blood flow(CBF)and neurophysiological changes.We found that the onset time and peak time of negative hemodynamic responses(including oximetric,volumetric and CBF signals)were always more delayed than those of positive hemodynamic responses.With the increase of pulse width,the NOR increased firstly and then decreased.CBF in the NOR region decreased while CBF in the POR region increased.A high degree of linear correlation between oximetric and volumetric signals was found.Electrophysiological recordings demonstrated that decrease and increase of neuronal activities coexisted in the NOR regions.Hence,the NOR in this study was associated with the decrease of CBF,which may be due to the imbalance between neuronal excitation and inhibition.In this study,we also found peripheral grating stimuli could evoke negative response.However,we did not observe significant decrease of neuronal activities in the negative response regions.This result suggest that the negative response does not necessarily originate in decreased neuronal activity.Complex interplay of hemodynamic responses among adjacent cortical areas should be considered when interpreting the negative response as decreases in neuronal activity.These results would be of help for the interpretation of negative hemodynamic response.These results provided the experimental basis to TcES-induced cortical response,which promoted the application of TcES in visual function assessment and candidate selection.The revealing of the neural mechanisms underlying negative hemodynamic response made the brain function imaging techniques serve the clinic and scientific research better.