Neural interface for a cortical vision prosthesis

Journal ArticleThe development of a cortically based vision prosthesis has been hampered by a lack of basic experiments on phosphene psychophysics. This basic research has been hampered by the lack of a means to safely stimulate large numbers of cortical neurons. Recently, a number of laboratories have developed arrays of silicon microelectrodes that could enable such basic studies on phosphene psychophysics. This paper describes one such array, the Utah electrode array, and summarizes neurosurgical, physiological and histological experiments that suggest that such an array could be implanted safely in visual cortex. We also summarize a series of chronic behavioral experiments that show that modest levels of electrical currents passed into cortex via this array can evoke sensory percepts. Pending the successful outcome of biocompatibility studies using such arrays, high count arrays of penetrating microelectrodes similar to this design could provide a useful tool for studies of the psychophysics of phosphene perception in human volunteers. Such studies could provide a proof-of-concept for cortically based artificial vision

Cortical microstimulation in auditory cortex of rat elicits best-frequency dependent behaviors

Electrical activation of the auditory cortex has been shown to elicit an auditory sensation; however, the perceptual effects of auditory cortical microstimulation delivered through penetrating microelectrodes have not been clearly elucidated. This study examines the relationship between electrical microstimulus location within the adult rat auditory cortex and the subsequent behavior induced. Four rats were trained on an auditory frequency discrimination task and their lever-pressing behavior in response to stimuli of intermediate auditory frequencies was quantified. Each trained rat was then implanted with a microwire array in the auditory cortex of the left hemisphere. Best frequencies (BFs) of each electrode in the array were determined by both local field potential and multi-unit spike-rate activity evoked by pure tone stimuli. A cross-dimensional psychophysical generalization paradigm was used to evaluate cortical microstimulation-induced behavior. Using the BFs of each electrode, the microstimulation-induced behavior was evaluated relative to the auditory-induced behavior. Microstimulation resulted in behavior that was dependent on the BFs of the electrodes used for stimulation. These results are consistent with recent reports indicating that electrophysiological recordings of neural responses to sensory stimuli may provide insight into the sensation generated by electrical stimulation of the same sensory neural tissue.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/49183/2/jne5_2_005.pd

CD44 modulates Smad1 activation in the BMP-7 signaling pathway

Bone morphogenetic protein 7 (BMP-7) regulates cellular metabolism in embryonic and adult tissues. Signal transduction occurs through the activation of intracellular Smad proteins. In this paper, using a yeast two-hybrid screen, Smad1 was found to interact with the cytoplasmic domain of CD44, a receptor for the extracellular matrix macromolecule hyaluronan. Coimmunoprecipitation experiments confirmed the interaction of Smad1 with full-length CD44—interactions that did not occur when CD44 receptors truncated within the cytoplasmic domain were tested. Chondrocytes overexpressing a truncated CD44 on a background of endogenous full-length CD44 no longer exhibited Smad1 nuclear translocation upon BMP-7 stimulation. Further, pretreatment of chondrocytes with Streptomyces hyaluronidase to disrupt extracellular hyaluronan–cell interactions inhibited BMP-7–mediated Smad1 phosphorylation, nuclear translocation of Smad1 or Smad4, and SBE4–luciferase reporter activation. These results support a functional link between the BMP signaling cascade and CD44. Thus, changes in hyaluronan–cell interactions may serve as a means to modulate cellular responsiveness to BMP

COMMUNICATION: Multi-site incorporation of bioactive matrices into MEMS-based neural probes

Methods are presented to incorporate polymer-based bioactive matrices into micro-fabricated implantable microelectrode arrays. Using simple techniques, hydrogels infused with bioactive molecules are deposited within wells in the substrate of the device. This method allows local drug delivery without increasing the footprint of the device. In addition, each well can be loaded individually, allowing spatial and temporal control over diffusion gradients in the microenvironment of the implanted neural interface probe. In vivo testing verified the following: diffusion of the bioactive molecules, integration of the bioactive molecules with the intended neural target and concurrent extracellular recording using nearby electrodes. These results support the feasibility of using polymer gels to deliver bioactive molecules to the region close to microelectrode shanks. This technique for microdrug delivery may serve as a means to intervene with the initial phases of the neuroinflammatory tissue response to permanently implanted microelectrode arrays.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/49187/2/jne5_4_l03.pd

Development of a Three Dimensional Neural Sensing Device by a Stacking Method

This study reports a new stacking method for assembling a 3-D microprobe array. To date, 3-D array structures have usually been assembled with vertical spacers, snap fasteners and a supporting platform. Such methods have achieved 3-D structures but suffer from complex assembly steps, vertical interconnection for 3-D signal transmission, low structure strength and large implantable opening. By applying the proposed stacking method, the previous techniques could be replaced by 2-D wire bonding. In this way, supporting platforms with slots and vertical spacers were no longer needed. Furthermore, ASIC chips can be substituted for the spacers in the stacked arrays to achieve system integration, design flexibility and volume usage efficiency. To avoid overflow of the adhesive fluid during assembly, an anti-overflow design which made use of capillary action force was applied in the stacking method as well. Moreover, presented stacking procedure consumes only 35 minutes in average for a 4 × 4 3-D microprobe array without requiring other specially made assembly tools. To summarize, the advantages of the proposed stacking method for 3-D array assembly include simplified assembly process, high structure strength, smaller opening area and integration ability with active circuits. This stacking assembly technique allows an alternative method to create 3-D structures from planar components

Multifunctional Nanobiomaterials for Neural Interfaces

Neural electrodes are designed to interface with the nervous system and provide control signals for neural prostheses. However, robust and reliable chronic recording and stimulation remains a challenge for neural electrodes. Here, a novel method for the fabrication of soft, low impedance, high charge density, and controlled releasing nanobiomaterials that can be used for the surface modification of neural microelectrodes to stabilize the electrode/tissue interface is reported. The fabrication process includes electrospinning of anti-inflammatory drug-incorporated biodegradable nanofibers, encapsulation of these nanofibers by an alginate hydrogel layer, followed by electrochemical polymerization of conducting polymers around the electrospun drug-loaded nanofibers to form nanotubes and within the alginate hydrogel scaffold to form cloud-like nanostructures. The three-dimensional conducting polymer nanostructures significantly decrease the electrode impedance and increase the charge capacity density. Dexamethasone release profiles show that the alginate hydrogel coating slows down the release of the drug, significantly reducing the burst effect. These multifunctional materials are expected to be of interest for a variety of electrode/tissue interfaces in biomedical devices.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/61888/1/573_ftp.pd

Perceived intensity of somatosensory cortical electrical stimulation

Artificial sensations can be produced by direct brain stimulation of sensory areas through implanted microelectrodes, but the perceptual psychophysics of such artificial sensations are not well understood. Based on prior work in cortical stimulation, we hypothesized that perceived intensity of electrical stimulation may be explained by the population response of the neurons affected by the stimulus train. To explore this hypothesis, we modeled perceived intensity of a stimulation pulse train with a leaky neural integrator. We then conducted a series of two-alternative forced choice behavioral experiments in which we systematically tested the ability of rats to discriminate frequency, amplitude, and duration of electrical pulse trains delivered to the whisker barrel somatosensory cortex. We found that the model was able to predict the performance of the animals, supporting the notion that perceived intensity can be largely accounted for by spatiotemporal integration of the action potentials evoked by the stimulus train

An alginate hydrogel dura mater replacement for use with intracortical electrodes

The collagenous dura mater requires a secure closure following implantation of neural prosthetic devices to avoid complications due to cerebrospinal fluid leakage and infections. Alginate was previously suggested for use as a dural sealant. The liquid application and controllable gelling conditions enable alginate to conform to the unique geometries of a neural prosthetic device and the surrounding dura mater to create a barrier with the external environment. In this study, we evaluated the use of alginate as a method to securely reclose a dural defect and seal around an untethered microscale neural probe in the rabbit model. After 3 days and 3 weeks, the sealing strength of alginate remained eight times greater than normal rabbit intracranial pressure and similar in both the presence and absence of a penetrating neural probe. For time points up to 3 months, there was no significant difference in dura mater fibrosis or thickness between alginate and controls. Application of alginate to a dural defect results in a watertight seal that remains intact while the dura mater reforms. These findings indicate that alginate is an effective tool for sealing around microscale neural probes and suggests broader application as a sealant for larger neural prosthetic devices. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78236/1/31733_ftp.pd

Spatial characterization of interictal high frequency oscillations in epileptic neocortex

Interictal high frequency oscillations (HFOs), in particular those with frequency components in excess of 200 Hz, have been proposed as important biomarkers of epileptic cortex as well as the genesis of seizures. We investigated the spatial extent, classification and distribution of HFOs using a dense 4 × 4 mm2 two dimensional microelectrode array implanted in the neocortex of four patients undergoing epilepsy surgery. The majority (97%) of oscillations detected included fast ripples and were concentrated in relatively few recording sites. While most HFOs were limited to single channels, ∼10% occurred on a larger spatial scale with simultaneous but morphologically distinct detections in multiple channels. Eighty per cent of these large-scale events were associated with interictal epileptiform discharges. We propose that large-scale HFOs, rather than the more frequent highly focal events, are the substrates of the HFOs detected by clinical depth electrodes. This feature was prominent in three patients but rarely seen in only one patient recorded outside epileptogenic cortex. Additionally, we found that HFOs were commonly associated with widespread interictal epileptiform discharges but not with locally generated ‘microdischarges’. Our observations raise the possibility that, rather than being initiators of epileptiform activity, fast ripples may be markers of a secondary local response