Delivery of Precision Acoustic Fields to Penetrating Neural Implants to Improve Longevity and Performance of the Neural Interface - This program evaluates the application of precision acoustic fields to penetrating neural implants to prevent
electrode impedance rise and improve implant longevity.
Problem to be solved: Chronic neural implants hold great potential for illuminating features of neural function
and treating neurological disorders. Penetrating electrode arrays provide direct access to neural signals across
the central and peripheral nervous system with high spatial resolution. A consistent point of failure for
chronically implanted microelectrode arrays is the poor longevity and functionality of these devices, an issue
that must be addressed to facilitate clinical translation of neural implant technology. One major failure mode of
electrode arrays is the host tissue’s immune response (i.e., foreign body response or FBR), which causes glial
scarring and neural cell loss near electrode sites, impairing recording quality. Efforts have been made to
minimize the brain FBR through electrode design and pharmacological treatment, but there is no optimal
solution; performance variability persists for all array types. We propose an innovative means of reducing the
FBR by using low-intensity pulsed ultrasound to acoustically promote localized neurotrophic release in cortical
tissue surrounding a neural implant. Studies will also focus on implanted transducers and provide new insights
into the possible neuroprotective effects of frequencies above conventional transcranial ultrasound studies.
Hypothesis. Application of localized ultrasonic fields of different acoustic parameters and treatment intervals
can affect release of neurotrophic factors, and can be used to mitigate glial scarring, promote neural implant
longevity, and neuron health. Aim 1 – Design and characterize head-mounted ultrasound transducer for
chronic in vivo studies. Acceptance Criteria: Acoustic stimulation is well-coupled and is thermally safe (<1°C
temperature increase in tissue model). Aim 2 – Identify ultrasonic parameters that safely stimulate acute
neurotrophin release in cortical tissue below neural activation thresholds, in an in vivo model. Acceptance
Criteria: Significantly increase neurotrophin release (e.g., BDNF) with low-intensity ultrasound stimulation, as
measured through cerebral fluid sampling via an implanted microdialysis probe and tissue histology, without
damaging neural tissue. Aim 3 – Evaluate effects of low-intensity ultrasound stimulation on long-term neural
electrode performance and glial scarring in cortical tissue in an in vivo model. Acceptance Criteria:
Significantly (α=0.05) reduce the change in electrode impedance as compared to experimental control (no
acoustic stimulation); significantly (α=0.05) improve neural recording quality (number of neural units, signal-to-
noise ratios), over a 4-week period. Aim 4 – Evaluate the effects of low-intensity ultrasound stimulation on the
microglia response to a neural implant in an in vivo model. Acceptance Criteria: Significant reduction in
microglia activation and migration within 200 µm of the electrode-tissue interface with periodic low-intensity
ultrasound stimulation over a 4-week period.
