RESUMEN
BACKGROUND: After an acquired injury to the motor cortex, the ability to generate skilled movements is impaired, leading to long-term motor impairment and disability. While rehabilitative therapy can improve outcomes in some individuals, there are no treatments currently available that are able to fully restore lost function. OBJECTIVE: We previously used activity-dependent stimulation (ADS), initiated immediately after an injury, to drive motor recovery. The objective of this study was to determine if delayed application of ADS would still lead to recovery and if the recovery would persist after treatment was stopped. METHODS: Rats received a controlled cortical impact over primary motor cortex, microelectrode arrays were implanted in ipsilesional premotor and somatosensory areas, and a custom brain-machine interface was attached to perform the ADS. Stimulation was initiated either 1, 2, or 3 weeks after injury and delivered constantly over a 4-week period. An additional group was monitored for 8 weeks after terminating ADS to assess persistence of effect. Results were compared to rats receiving no stimulation. RESULTS: ADS was delayed up to 3 weeks from injury onset and still resulted in significant motor recovery, with maximal recovery occurring in the 1-week delay group. The improvements in motor performance persisted for at least 8 weeks following the end of treatment. CONCLUSIONS: ADS is an effective method to treat motor impairments following acquired brain injury in rats. This study demonstrates the clinical relevance of this technique as it could be initiated in the post-acute period and could be explanted/ceased once recovery has occurred.
Asunto(s)
Trastornos Motores , Masculino , Animales , Ratas , Factores de Tiempo , Trastornos Motores/etiología , Trastornos Motores/terapia , Corteza Motora , Lesiones Traumáticas del Encéfalo/complicaciones , Recuperación de la Función , Conducta Animal , Terapia por Estimulación EléctricaRESUMEN
Neural interface systems are becoming increasingly more feasible for brain repair strategies. This paper tests the hypothesis that recovery after brain injury can be facilitated by a neural prosthesis serving as a communication link between distant locations in the cerebral cortex. The primary motor area in the cerebral cortex was injured in a rat model of focal brain injury, disrupting communication between motor and somatosensory areas and resulting in impaired reaching and grasping abilities. After implantation of microelectrodes in cerebral cortex, a neural prosthesis discriminated action potentials (spikes) in premotor cortex that triggered electrical stimulation in somatosensory cortex continuously over subsequent weeks. Within 1 wk, while receiving spike-triggered stimulation, rats showed substantially improved reaching and grasping functions that were indistinguishable from prelesion levels by 2 wk. Post hoc analysis of the spikes evoked by the stimulation provides compelling evidence that the neural prosthesis enhanced functional connectivity between the two target areas. This proof-of-concept study demonstrates that neural interface systems can be used effectively to bridge damaged neural pathways functionally and promote recovery after brain injury.
Asunto(s)
Potenciales de Acción/fisiología , Lesiones Encefálicas/terapia , Interfaces Cerebro-Computador , Corteza Motora/fisiología , Destreza Motora/fisiología , Prótesis Neurales , Animales , Modelos Lineales , Masculino , Vías Nerviosas/fisiología , Ratas , Ratas Long-EvansRESUMEN
This paper reports on the design, analysis, implementation, and testing of a 1.5-to-5 V converter as part of a battery-powered activity-dependent intracortical microstimulation (ICMS) system-on-chip (SoC) that converts extracellular neural spikes recorded from one cortical area to electrical stimuli delivered to another cortical area in real time. The highly integrated voltage converter is intended to generate a 5-V supply for the stimulating back-end on the SoC from a miniature primary battery that powers the entire system. It is implemented in AMS 0.35 µm two-poly four-metal (2P/4M) complementary metal-oxide-semiconductor (CMOS) technology, employs only one external capacitor (1 µF) for storage, and delivers a maximum dc load current of ~88 µA with power efficiency of 31% with its output voltage adjusted to 5.05 V. This current drive capability affords simultaneous stimulation on all eight channels of the SoC with current amplitude up to ~100 µA and average stimulus rate >500 Hz, which is comfortably higher than firing rate of cortical neurons (<150 spikes per second). The measurement results also agree favorably with theoretical derivations from the analysis of converter operation.
Asunto(s)
Estimulación Encefálica Profunda/instrumentación , Suministros de Energía Eléctrica , Neuroestimuladores Implantables , Potenciales de Acción , Animales , Ingeniería Biomédica , Corteza Cerebral/fisiología , Corteza Cerebral/cirugía , Sistemas de Computación , Diseño de Equipo , Modelos Neurológicos , Ratas , Procesamiento de Señales Asistido por ComputadorRESUMEN
This paper reports on a miniaturized system for spike-triggered intracortical microstimulation (ICMS) in an ambulatory rat. The head-mounted microdevice comprises a previously developed application-specific integrated circuit fabricated in 0.35-µm two-poly four-metal complementary metal-oxide-semiconductor technology, which is assembled and packaged on a miniature rigid-flex substrate together with a few external components for programming, supply regulation, and wireless operation. The microdevice operates autonomously from a single 1.55-V battery, measures 3.6 cm × 1.3 cm × 0.6 cm, weighs 1.7 g (including the battery), and is capable of stimulating as well as recording the neural response to ICMS in biological experiments with anesthetized laboratory rats. Moreover, it has been interfaced with silicon microelectrodes chronically implanted in the cerebral cortex of an ambulatory rat and successfully delivers electrical stimuli to the second somatosensory area when triggered by neural activity from the rostral forelimb area with a user-adjustable spike-stimulus time delay. The spike-triggered ICMS is further shown to modulate the neuronal firing rate, indicating that it is physiologically effective.
Asunto(s)
Corteza Cerebral/fisiología , Estimulación Eléctrica/instrumentación , Electrodos Implantados , Microtecnología/instrumentación , Prótesis Neurales , Potenciales de Acción/fisiología , Animales , Corteza Cerebral/cirugía , Estimulación Eléctrica/métodos , Cabeza/cirugía , Microelectrodos , Ratas , Ratas Long-Evans , Caminata , Tecnología InalámbricaRESUMEN
Finite impulse response (FIR) and infinite impulse response (IIR) temporal filtering techniques are investigated to assess the feasibility of very-large-scale-integrated (VLSI) implementation of a subtraction-based stimulus artifact rejection (SAR) algorithm in implantable, closed-loop neuroprostheses. The two approaches are compared in terms of their system architectures, overall performances, and the associated computational costs. Pre-recorded neural data from an Aplysia californica are used to demonstrate the functionality of the proposed implementations. Digital building blocks for an FIR-based system are also simulated in a 0.18-microm CMOS technology, showing a total power consumption of <5microW from a 1-V supply and a die area of 1.5 mm2. An IIR-based system can further reduce the required power consumption and die area.