Effects of microstimulation and ketamine anesthesia on neural responses in somatosensory system: a case for pairwise correlation method for data analysis.

Abstract

The neurophysiology of the somatosensory system has been under investigation for decades. The coding properties of neural populations and single units in cortical and subcortical regions have been characterized extensively using electrophysiology. Tactile stimulation produces evoked responses in the thalamus and cortical regions dedicated to processing of sensory information. The ability to evoke naturalistic neural responses as well as tactile perceptual experiences by means of microstimulation in the absence of real stimulus presented to the periphery is imperative for the development of a sensory neuroprosthesis. Three specific aims were pursued in the present study: 1. The development and validation of a novel assessment technique to quantify sensory evoked responses. 2. The investigation of effects of ketamine anesthesia on the cortical evoked responses. 3. The assessment of the feasibility of microstimulation of Ventroposterior Lateral (VPL) nucleus of the thalamus as a way to produce naturalistic responses in the primary somatosensory cortex. Brief tactile stimulation of various hand locations produces characteristic responses in both thalamic and cortical multi-neuron populations. These responses were used to create somatotopic maps of the hand regions in awake animals with chronically implanted electrode arrays in the SI cortex and in anesthetized animals during acute preparations. In the first Aim, method based on the analysis of correlation was developed to compare the firing recorded on individual electrodes during different stimuli presentations to determine which neural populations showed most activation during an evoked response. The procedure required relatively short duration of stimulation sessions. The effects of anesthesia on neural coding were studied in the second Aim using ketamine anesthetized monkeys. Ketamine anesthesia is easily induced, relatively short lasting, and generally safe. In awake chronically implanted monkeys properties of neural responses to tactile stimulation were assessed. Receptive fields (RF) corresponding to five digits were identified using recordings from an electrode array placed in area 1 of SI. Cortical stimulation fields (SF) representing signal flow from each receptive field were identified. Neural responses under ketamine anesthesia were reassessed using the same mapping techniques. The responses recorded during the maintenance phase of anesthesia were similar to responses evoked under awake condition. Most changes in the neural responses occurred during induction and recovery phases. Overall, ketamine produced responses of shorter duration compared to the awake condition. In the final Aim, isofluorane/fentanyl anesthetized monkeys had microelectrode arrays acutely implanted in the VPL thalamus and area1, 3b, and 2 of SI. Recordings were used to estimate the sizes of SFs in the thalamus and cortex. Thalamic neural representations were associated with RFs that typically spanned several digits, while cortical recordings were associated with smaller RFs. Microstimulation of the VPL (1ms single pulses, 50A) resulted in the activation of somatotopically appropriate cortical neural ensembles. The responses in the VPL and cortex were characterized by the presence of High Frequency Oscillations (HFO) (up to 800Hz). The presence of the HFOs was observed following both tactile and electrical stimulation. In summary, techniques for analyzing evoked multiunit responses were developed and used to explore cortical and thalamic responses to tactile stimulation, the effects of ketamine anesthesia on such responses, and parameters for thalamic stimulation to simulate tactile “sensation” in cortex.