Short-Term Effects of Gamma Stimulation on Neuroinflammation at the Tissue-Electrode Interface in Motor Cortex.

OBJECTIVES: The reliability of long-term neural recordings as therapeutic interventions for motor and sensory disorders is hampered by the brain tissue response. Previous work showed that flickering light at gamma frequencies (ie, 20-50 Hz) causes enhanced microglial recruitment in the visual cortex. The effects of gamma stimulation on glial cells surrounding implanted neural electrodes are not well understood. We hypothesized that invasive stimulation in the gamma frequency band increases microglial recruitment in the short term and reduces astrogliosis at the tissue-electrode interface. MATERIALS AND METHODS: Male Long Evans rats were implanted with dual-shank silicon microelectrode arrays into the motor cortex. After implantation, rats received one hour of 40-Hz stimulation at a constant current of 10 µA using charge-balanced, biphasic pulses on one shank, and the other shank served as the nonstimulated control. Postmortem, tissue sections were stained with ectodermal dysplasia 1 (ED1) for activated microglia, glial fibrillary acidic protein (GFAP) for astrocytes, and 4',6-diamidino-2-phenylindole (DAPI) for nonspecific nuclei. Fluorescent intensity and cell number as a function of distance from the tissue-electrode interface were used to quantify all stained sections. RESULTS: Fluorescent intensity for ED1 was nearly 40% lower for control than for stimulated sites (0-500 µm away from the implant), indicating increased microglial recruitment to the stimulated site (p < 0.05). Fluorescent intensity for GFAP was >67% higher for control than for stimulated sites (0-500 µm away from the implant), indicating reduced astrogliosis at the stimulated site (p < 0.05). No differences were observed in DAPI-stained sections between conditions. CONCLUSIONS: These results suggest that short-term gamma stimulation modulates glial recruitment in the immediate vicinity of the microelectrode. Future studies will investigate the long-term effects of gamma stimulation on glial recruitment at the tissue-electrode interface as a strategy to improve long-term recording reliability.

Bidirectional telemetry controller for neuroprosthetic devices.

We present versatile multifunctional programmable controller with bidirectional data telemetry, implemented using existing commercial microchips and standard Bluetooth protocol, which adds convenience, reliability, and ease-of-use to neuroprosthetic devices. Controller, weighing 190 g, is placed on animal's back and provides bidirectional sustained telemetry rate of 500 kb/s , allowing real-time control of stimulation parameters and viewing of acquired data. In continuously-active state, controller consumes approximately 420 mW and operates without recharge for 8 h . It features independent 16-channel current-controlled stimulation, allowing current steering; customizable stimulus current waveforms; recording of stimulus voltage waveforms and evoked neuronal responses with stimulus artifact blanking circuitry. Flexibility, scalability, cost-efficiency, and a user-friendly computer interface of this device allow use in animal testing for variety of neuroprosthetic applications. Initial testing of the controller has been done in a feline model of brainstem auditory prosthesis. In this model, the electrical stimulation is applied to the array of microelectrodes implanted in the ventral cochlear nucleus, while the evoked neuronal activity was recorded with the electrode implanted in the contralateral inferior colliculus. Stimulus voltage waveforms to monitor the access impedance of the electrodes were acquired at the rate of 312 kilosamples/s. Evoked neuronal activity in the inferior colliculus was recorded after the blanking (transient silencing) of the recording amplifier during the stimulus pulse, allowing the detection of neuronal responses within 100 mus after the end of the stimulus pulse applied in the cochlear nucleus.