It has been demonstrated that after a stroke-like lesion in the cerebral cortex of non-human primates, the remaining intact tissue undergoes extensive neuro-physiological and neuroanatomical remodeling. The ability of cortical areas remote from the infarct to form new cortico-cortical connections over long distances between the frontal and parietal lobes has been demonstrated. It is likely that these novel connections play a role in functional recovery after cortical injury.
This work combines neurobiological tools with implantable device technology to develop a novel microsystem to guide post-injury axonal sprouting in order to reshape cortical connections, optimize connectivity patterns, and improve long-term functional recovery after a traumatic brain injury (TBI). Advancements in designing neuroprosthetic devices to temporally couple the activity of remote cortical locations that are not normally coactivated or interconnected were used, taking advantage of the injured brain’s ability to produce growth-promoting substances that encourage anatomical rewiring. Such temporal coupling will encourage growing axons to migrate toward and terminate in the coupled region.
A fully integrated neural recording front-end comprising a low-noise, two-stage amplification circuitry and a 10-bit successive approximation register (SAR)-based analog-to-digital converter (ADC) was fabricated using the TSMC 0.35 μm 2P/4M n-well CMOS process. The ac-coupled amplification circuitry provided a maximum mid-band ac gain of 52 dB and featured a measured input-referred voltage noise of 3.5 Vrms from 0.1 Hz to 12.8 kHz, while dissipating 78 μW from 2 V. The SAR ADC featured an effective number of bits (ENOB) of 9.4 for maximum sampling frequency of 45 kSa/s, while dissipating only 16 μW.
Monolithic circuitry was designed using standard digital cells to identify the presence of large action potentials in the recorded digitized data with a spike discrimination algorithm based on two programmable threshold levels and time-amplitude windows. Detected spikes were then used to trigger the back-end microstimulator with a programmable delay. A first-order digital high-pass filter was also designed to remove any dc/low-frequency signal components prior to spike discrimination. The measured power consumption was less than 1 μW with a 1.5-V supply and ADC sampling frequency of 35 kSa/s.
A high-output-impedance current microstimulator was fabricated using the TSMC 0.35 μm CMOS process. It delivered a maximum current of 94.5 μA to the target cortical tissue with current efficiency of 86% and voltage compliance of 4.7 V with a 5-V supply. The stimulus current could be programmed via a 6-bit digital-to-analog converter (DAC) with accuracy better than 0.47 LSB.
A cross-coupled, voltage-controlled oscillator (VCO) for digital frequency shift-keyed (FSK) transmission based on an earlier design was developed. The oscillator tank employed a surface-mount, high-Q, off-chip inductor for low-power operation at a frequency near 433 MHz. The tank varactors were implemented using PMOS capacitors with source/drain/bulk connected to each other. To have flexibility in selecting a suitable _F for the FSK transmitter, the varactors were divided into two sets of binary-weighted capacitors that could be externally controlled with three bits. Using this tuning scheme, _F could be varied in the range of 2-14 MHz in steps of 2 MHz.
Rapid progress is being made toward developing smart prosthetic platforms for altering plasticity in the injured brain, leading to future therapeutic interventions for TBI that are guided by the underlying mechanisms for long-range functional and structural plasticity in the cerebral cortex. This first-generation integrated device was tested successfully in an anesthetized rat model by recording neural spikes from the somatosensory cortex of the brain, and stimulating the primary motor cortex that resulted in clear wrist movements. Behavioral assessments of reaching, retrieval of small food items, and locomotion demonstrate that deficits persist during the five-week recovery period following injury. Work is still ongoing for system assembly and packaging in the form of a miniature implantable device to test the system on long-range intracortical connectivity formation post-TBI.
This work was done by Pedram Mohseni, Ph.D., of Case Western Reserve University for the Army Medical Research and Materiel Command. For more information, download the Technical Support Package (free white paper) at www.medicaldesignbriefs.com/briefs. ARL-0103
This Brief includes a Technical Support Package (TSP).
Implantable Microsystems for Anatomical Rewiring of Brain Circuitry
(reference ARL-0103) is currently available for download from the TSP library.
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