| Most of the information geting from the world comes from the visual system.As one of the most important sensory systems of human,structural or functional damage at any site of visual processing pathway may lead to visual impairment,or even blindness.As a rapidly developing therapeutic strategy,neural electrical stimulation is promising for some diseases that could not be cured or relieved by conventional drug or surgery.In the field of artificial visual restoration,especially in the treatment of incurable degenerative retinal diseases,invasive retinal electrical stimulation(retinal prosthesis)is an increasing popular and effective strategy to partially restore visual function,and achieves great progress in recent years.At the same time,noninvasive retinal electrical stimulation has been demonstrated to have the neuroprotective effective and emerged as a potential treatment to improve retinal cell survival against several ophthalmic diseases.It has also been introduced to evaluate the residual function of retina in the clinic to preoperatively screen suitable candidate for implantation of retinal prostheses.Although artificial visual percepts could be evoked by retinal electrical stimulating,there are still many differences when compared with normal visual perception.Systematic and objective comparison of visual pathway response evoked by visual electrical stimulation of retina could be benefit to understand the neuromechanisms.Focusing on these issues and based on the optical imaging methods,we used transcorneal electrical stimulation(TES)as the stimulation method and cats as the experimental model to investigate the visual pathway response evoked by TES and the difference with those evoked by visual stimulation.It is still unknown whether electrical stimulation of retina could generate a comparable pattern of cortical responses similar to those induced by visual stimulation.A directly comparison between the spatiotemporal patterns of cortical responses evoked by visual and electrical stimulation is needed.In this study,cortical responses evoked by visual stimulation and TES were compared with each other.Based on the Optical imaging of Intrinsic Signals(OIS),we recorded the hemodynamic responses at visual cortex of cat.Results showed that the response latency evoked by TES was shorter than that responding to visual stimulation,and the peak time were not significantly different.Compared with full-field visual stimulation,the hemodynamic response in Area 18 to TES with the intensity above 1.2 mA was significantly stronger.The cortical response evoked by visual stimulation was retinotopically organized,whereas those elicited by TES was preferentially located in Area 18.Only when the TES intensity increased above 3.6 mA,Area 17 was activated.The threshold needed to activate Area 17 was significant higher than that to activate Area 18.Given the abrupt change of activated regions around Area 17/18 border,we suggested that the cortical activation to TES are not only influenced by the distribution of electrical field in the retina,but also related to the electrical activating threshold of different retinal neurons.In this part of study,we investigated the spatiotemporal properties of cortical responses evoked by TES and visual stimulation,and discussed the possible neuromechanisms during the processing of extrinsic electrical stimulation in the visual pathway.The results could facilitate the understanding of underlying mechanisms of prosthetic vision,and promote the application of TES in clinic.Retina is an elaborate neural tissue with multi-layer structures,and the properties of responses to electrical stimulation of different types of retinal neurons are different.However,the response pattern of retina is still unclear now.It is important to evaluate the exact responses to electrical stimulation in different retinal layers.Limited by the electrical artifacts,most of previous studies recorded the electrophysiological response of in vitro retina,or used the responses in the succeeding visual pathway to represent the activation of retina.Benefiting from the excellent axial resolution,we utilized the Optical Coherence Tomography(OCT)to record the responses evoked by TES in different retinal layers,and compared them with those evoked by visual stimulaiton.According to our results,both positive and negative Intrinsic Optical Signals(IOSs)could be evoked by TES in three segmented retinal layers,especially in the inner retina and subretinal space.The TES-induced IOSs correlated with TES intensity.The response latencies were all within 85 ms in three layers,and the rising time of IOSs increased with the increment of current intensity.Significant decay of IOSs were caused by the injection of neurotoxin in the three divided layers,peculiarly in the inner retina.We suggested that the TES-induced IOSs detected by OCT mainly originated from the activation of retinal neurons.The IOSs evoked by visual stimulation kept increasing until several hundred milliseconds after the end of stimulation,whereas those elicited by TES kept at a relative stable level during the stimulation period.We speculated that the IOSs induced by TES were highly synchronized to the electrical field generated at the retina.The results of this part probed the intrinsic responses in differet retinal layers,and could shed some light on the mechanisms of retinal electrical stimulation.In this study,we investigated the spatiotemporal properties of visual cortical and retinal responses evoked by transcorneal electrical stimulation,and compared them with those evoked by visual stimulation.The differences of visual pathway response induced by this two stimulation could shed light on the neuromechanisms of retinal electrical stimulation.The results of this study could also promote the application of retinal electrical stimulation in the treatment of ophthalmology diseases and restoring of visual function,especially for the clinical application of the noninvasive TES. |
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