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 proofof-concept study demonstrates that neural interface systems can be used effectively to bridge damaged neural pathways functionally and promote recovery after brain injury.brain-machine-brain interface | neural plasticity | traumatic brain injury | closed-loop | long-term potentiation T he view of the brain as a collection of independent anatomical modules, each with discrete functions, is currently undergoing radical change. New evidence from neurophysiological and neuroanatomical experiments in animals, as well as neuroimaging studies in humans, now suggests that normal brain function can be best appreciated in the context of the complex arrangements of functional and structural interconnections among brain areas. Although mechanistic details are still under refinement, synchronous discharge of neurons in widespread areas of the cerebral cortex appears to be an emergent property of neuronal networks that functionally couple remote locations (1). It is now recognized that not only are discrete regions of the brain damaged in injury or disease but, perhaps more importantly, the interconnections among uninjured areas are disrupted, potentially leading to many of the functional impairments that persist after brain injury (2). Likewise, plasticity of brain interconnections may partially underlie recovery of function after injury (3).Technological efforts to restore brain function after injury have focused primarily on modulating the excitability of focal regions in uninjured parts of the brain (4). Purportedly, increasing the excitability of neurons involved in adaptive plasticity expands the neural substrate potentially involved in functional recovery. However, no methods are yet available to alter the functional connectivity between spared brain regions directly, with the intent to restore normal communication patterns. The present paper tests the hypothesis that an artificial communication link between uninjured regions of the...

The purpose of this study was to examine neuronal activity levels in the hindlimb area of motor cortex following spinal cord injury (SCI) in rats and compare the results with measurements in normal rats. Fifteen male Fischer-344 rats received a 200 Kdyn contusion injury in the thoracic cord at level T9-T10. After a minimum of 4 weeks following SCI, intracortical microstimulation (ICMS) and single-unit recording techniques were used in both the forelimb and hindlimb motor areas (FLA, HLA) under ketamine anesthesia. Although movements could be evoked using ICMS in the forelimb area with relatively low current levels, no movements or electromyographical responses could be evoked from ICMS in the HLA in any of the injured rats. During the same procedure, electrophysiological recordings were obtained with a single-shank, 16-channel Michigan probe (Neuronexus) to monitor activity. Neural spikes were discriminated using principle component analysis. Neural activity (action potentials) was collected and digitized for a duration of 5 min. Despite the inability to evoke movement from stimulation of cortex, robust single-unit activity could be recorded reliably from hindlimb motor cortex in SCI rats. Activity in the motor cortex of SCI rats was significantly higher compared with uninjured rats, and increased in hindlimb and forelimb motor cortex by similar amounts. These results demonstrate that in a rat model of thoracic SCI, an increase in single-unit cortical activity can be reliably recorded for several weeks post-injury.

Object The purpose of the present study was to determine the feasibility of using a common laboratory rat strain for reliably locating cortical motor representations of the hindlimb. Methods Intracortical microstimulation techniques were used to derive detailed maps of the hindlimb motor representations in 6 adult Fischer-344 rats. Results The organization of the hindlimb movement representation, while variable across individual rats in topographic detail, displayed several commonalities. The hindlimb representation was positioned posterior to the forelimb motor representation and posterolateral to the motor trunk representation. The areal extent of the hindlimb representation across the cortical surface averaged 2.00 ± 0.50 mm2. Superimposing individual maps revealed an overlapping area measuring 0.35 mm2, indicating that the location of the hindlimb representation can be predicted reliably based on stereotactic coordinates. Across the sample of rats, the hindlimb representation was found 1.25–3.75 mm posterior to the bregma, with an average center location approximately 2.6 mm posterior to the bregma. Likewise, the hindlimb representation was found 1–3.25 mm lateral to the midline, with an average center location approximately 2 mm lateral to the midline. Conclusions The location of the cortical hindlimb motor representation in Fischer-344 rats can be reliably located based on its stereotactic position posterior to the bregma and lateral to the longitudinal skull suture at midline. The ability to accurately predict the cortical localization of functional hindlimb territories in a rodent model is important, as such animal models are being increasingly used in the development of brain-computer interfaces for restoration of function after spinal cord injury.

Nearly 6 million people in the United States are currently living with paralysis in which 23% of the cases are related to spinal cord injury (SCI). Miniaturized closed-loop neural interfaces have the potential for restoring function and mobility lost to debilitating neural injuries such as SCI by leveraging recent advancements in bioelectronics and a better understanding of the processes that underlie functional and anatomical reorganization in an injured nervous system. This paper describes our current progress towards developing a miniaturized brain-machine-spinal cord interface (BMSI) that is envisioned to convert in real time the neural command signals recorded from the brain to electrical stimuli delivered to the spinal cord below the injury level. Specifically, the paper reports on a corticospinal interface integrated circuit (IC) as a core building block for such a BMSI that is capable of low-noise recording of extracellular neural spikes from the cerebral cortex as well as muscle activation using intraspinal microstimulation (ISMS) in a rat with contusion injury to the thoracic spinal cord. The paper further presents results from a neurobiological study conducted in both normal and SCI rats to investigate the effect of various ISMS parameters on movement thresholds in the rat hindlimb. Coupled with proper signal-processing algorithms in the future for the transformation between the cortically recorded data and ISMS parameters, such a BMSI has the potential to facilitate functional recovery after an SCI by re-establishing corticospinal communication channels lost due to the injury.