Delivery of Low-Intensity Pulsed Ultrasound in the Cortex to Improve Longevity and Performance of Neural Interfaces
NN TIRKO, AS ALSUBHI, JK GREASER, RS CLEMENT, KA SNOOK, RB BAGWELL, ML MULVIHILL
Actuated Medical, Inc., Bellefonte, PA
Chronic neural implants hold great potential for illuminating features of neural function, treating neurological disorders, and enabling the next generation of neuroprosthetics. Penetrating electrode arrays provide direct access to neural signals across the central and peripheral nervous system with high temporospatial resolution. However, a consistent point of failure for chronically implanted microelectrode arrays is poor longevity and variability in functionality of these devices. The foreign body response (FBR) can cause glial scarring and neural cell loss near the electrode sites. The FBR begins with electrode insertion, when damage to the blood brain barrier activates astrocytes and microglia and continues throughout the lifetime of the implant due to the persistent presence of the foreign material in the tissue. Significant efforts have been made to reduce the FBR, both at the outset of implantation by limiting initial insertion damage and over the long-term by reducing the mechanical mismatch between brain and implant, or long-term use of exogenous chemicals to suppress the FBR.
Rather than relying on temporary interventions to limit the FBR, we proposed a method to harness endogenous cortical function to improve the long-term neural interface microenvironment. Low-intensity pulsed ultrasound (LIPUS) has recently been shown to have protective and healing effects in models of cerebral disease and injury, through promotion of brain-derived neurotrophic factor (BDNF) and other neurotrophic factors that affect the anti-inflammatory response of microglia and other cells. Here, we investigate the use of sub-threshold LIPUS focused directly at the neural electrode interface to improve tissue health and increase the quality and longevity of neural recordings. A study was undertaken in which silicon shank electrodes (A4x4-5mm-100-125-703-CM16LP, NeuroNexus, Inc.) oriented at 45º from horizontal, were chronically implanted into cortical layers II/III of the motor or somatosensory cortex of rats (N=8). The effects of LIPUS on neural recording quality over 6 weeks post-implant were studied (n=4) with respect to Sham treatment (n=4). Nominal conditions used were based on the prior LIPUS research on disease and injury; stimulation (0.5 W/cm2 intensity, 1.1 MHz, 15 min. total treatment at 4% duty cycle) was administered daily Week 1, and twice weekly for Weeks 2-6 and coupled with electrophysiology recording sessions (SmartBox Pro Allego, NeuroNexus). Single unit analysis of electrophysiological data reveals strong trends in signal quality improvements in the LIPUS-treated group. More than double the electrode channels remained active throughout the 6 weeks in subjects in the LIPUS stimulation group as compared to Sham (p<0.01). Also, the channels that remained active maintained an average 4 dB higher signal-to-noise ratio (SNR) over the same time period (p<0.01). Our studies demonstrate that periodic application of localized LIPUS to tissue at the neural interface has potential to improve electrophysiology signal quality. Implications for future studies will be discussed.