Patrick Rousche

Microstimulation in auditory cortex provides a substrate for detailed behaviors

Sensory cortical prostheses have potential to aid people suffering from blindness, deafness and other sensory deficits. However, research to date has shown that sensation thresholds via epicortical stimulation are surprisingly large. These thresholds result in potentially deleterious electrical currents, as well as large activation volumes. Large activation volumes putatively limit the corresponding number of independent stimulation channels in a neural prosthesis. In this study, penetrating stimulation of the auditory cortex was tested for its ability to transmit salient information to behaving rat subjects. Here, we show that subjects that were previously trained to discriminate natural stimuli immediately discriminated different microstimulation cues more accurately and with shorter response latencies than the natural stimuli. Additionally, the cortical microstimulation resulted in a generalization gradient across locations within the cortex. The results demonstrate the efficacy of using closely spaced cortical microstimulation to efficiently transmit highly salient and discriminable information to a behaving subject.

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.

Single electrode micro-stimulation of rat auditory cortex: an evaluation of behavioral performance.

A combination of electrophysiological mapping, behavioral analysis and cortical micro-stimulation was used to explore the interrelation between the auditory cortex and behavior in the adult rat. Auditory discriminations were evaluated in eight rats trained to discriminate the presence or absence of a 75 dB pure tone stimulus. A probe trial technique was used to obtain intensity generalization gradients that described response probabilities to mid-level tones between 0 and 75 dB. The same rats were then chronically implanted in the auditory cortex with a 16 or 32 channel tungsten microwire electrode array. Implanted animals were then trained to discriminate the presence of single electrode micro-stimulation of magnitude 90 microA (22.5 nC/phase). Intensity generalization gradients were created to obtain the response probabilities to mid-level current magnitudes ranging from 0 to 90 microA on 36 different electrodes in six of the eight rats. The 50% point (the current level resulting in 50% detections) varied from 16.7 to 69.2 microA, with an overall mean of 42.4 (+/-8.1) microA across all single electrodes. Cortical micro-stimulation induced sensory-evoked behavior with similar characteristics as normal auditory stimuli. The results highlight the importance of the auditory cortex in a discrimination task and suggest that micro-stimulation of the auditory cortex might be an effective means for a graded information transfer of auditory information directly to the brain as part of a cortical auditory prosthesis.

A Benchtop System to Assess Cortical Neural Interface Micromechanics

A benchtop brain tissue-microelectrode insertion model system was developed to aid in improving the design of cortical neural interfaces. The model partially mimics the in vivo environment via the use of human cadaver brain specimens (nspecimen=6), or agar gel exposed to physiologically relevant mechanical oscillations. 150 mum diameter stainless-steel microelectrode wires (TS=600 MPa) implanted 3.0 cm within fixed human primary auditory cortex (ntrial>10) experienced 133plusmn8 and 64plusmn4 mN of peak and steady axial forces. When subjected to a 3 Hz, 3-mm vertical oscillation, dynamic force amplitudes (ntrial>10) of 148plusmn10 mN were measured. The model system allows the study and comparison of static and dynamic forces and their mechanical influences on proposed implanted microelectrode structures

Fast wave propagation in auditory cortex of an awake cat using a chronic microelectrode array.

We investigated fast wave propagation in auditory cortex of an alert cat using a chronically implanted microelectrode array. A custom, real-time imaging template exhibited wave dynamics within the 33-microwire array (3 mm(2)) during ten recording sessions spanning 1 month post implant. Images were based on the spatial arrangement of peri-stimulus time histograms at each recording site in response to auditory stimuli consisting of tone pips between 1 and 10 kHz at 75 dB SPL. Functional images portray stimulus-locked spiking activity and exhibit waves of excitation and inhibition that evolve during the onset, sustained and offset period of the tones. In response to 5 kHz, for example, peak excitation occurred at 27 ms after onset and again at 15 ms following tone offset. Variability of the position of the centroid of excitation during ten recording sessions reached a minimum at 31 ms post onset (sigma = 125 microm) and 18 ms post offset (sigma = 145 microm), suggesting a fine place/time representation of the stimulus in the cortex. The dynamics of these fast waves also depended on stimulus frequency, likely reflecting the tonotopicity in auditory cortex projected from the cochlea. Peak wave velocities of 0.2 m s(-1) were also consistent with those purported across horizontal layers of cat visual cortex. The fine resolution offered by microimaging may be critical for delivering optimal coding strategies used with an auditory prosthesis. Based on the initial results, future studies seek to determine the relevance of these waves to sensory perception and behavior.

Electrophysiological response dynamics during focal cortical infarction.

While the intracellular processes of hypoxia-induced necrosis and the intercellular mechanisms of post-ischemic neurotoxicity associated with stroke are well documented, the dynamic electrophysiological (EP) response of neurons within the core or periinfarct zone remains unclear. The present study validates a method for continuous measurement of the local EP responses during focal cortical infarction induced via photothrombosis. Single microwire electrodes were acutely implanted into the primary auditory cortex of eight rats. Multi-unit neural activity, evoked via a continuous 2 Hz click stimulus, was recorded before, during and after infarction to assess neuronal function in response to local, permanent ischemia. During sham infarction, the average stimulus-evoked peak firing rate over 20 min remained stable at 495.5+/-14.5 spikes s-1, indicating temporal stability of neural function under normal conditions. Stimulus-evoked peak firing was reliably reduced to background levels (firing frequency in the absence of stimulus) following initiation of photothrombosis over a period of 439+/-92 s. The post-infarction firing patterns exhibited unique temporal degradation of the peak firing rate, suggesting a variable response to ischemic challenge. Despite the inherent complexity of cerebral ischemia secondary to microvascular occlusion, complete loss of EP function consistently occurred 300-600 s after photothrombosis. The results suggest that microwire recording during photothrombosis provides a simple and highly efficacious strategy for assessing the electrophysiological dynamics of cortical infarction.

A method for monitoring intra-cortical motor cortex responses in an animal model of ischemic stroke

Neuroplasticity is believed to play a key role in functional recovery after stroke. Neuroplastic effects can be monitored at the cellular level via e.g. neurotransmitter assessment, but these studies require sacrifice of the animal. FMRI can be used to assess functional neuronal performance, but the spatial and temporal resolution is far from the single cell level. The objective was to establish an effective method for short-term analysis of single and multi-unit electrophysiological function before, during and after stroke. We instrumented one rat with a 16-ch array in the primary motor cortex (100 mum wire diameter) to monitor cortical activity. A bipolar cuff electrode was implanted around the Ulnar nerve in the contralateral forelimb to provide a controlled electrical stimulus input to the sensory-motor system. A 3 mm diameter ischemic infarct was created immediately posterior to the electrode array by light activation of a photosensitive dye (Rose Bengal, 1.3 mg/100 mg body weight) at the cortical surface. M1 activity in response to the peripheral electrical stimulus was recorded before, during and after the cortical ischemic infarct. At 425 min following ischemic infarct the peak peri-stimulus time response had decreased to 30plusmn11% (electrodes placed 1.5 mm from the infarct core) of the activity before the ischemic onset. The mean response latency increased from 30.1plusmn4.5 ms (before infarct) to 40.6plusmn8.5 ms (at 425 min). This dynamic view of neuroplasticity may eventually assist in optimizing acute stroke therapies and optimize functional recovery further

Decoding of auditory cortex signals with a LAMSTAR neural network

Abstract Objectives: Each neuron has a specific set of stimuli, which it preferentially responds to (the receptive field of the neuron). For implantable cortical prosthetic devices specific points of the cortex (or groups of neurons) have to be stimulated to create perceptions of sensory stimulus with specific attributes (such as frequency, temporal characteristics, etc). Such applications would need real time decoding of signals. Previously mathematical techniques, such as computing the receptive field (using electrophysiology data) and artificial neural networks (Kohonen network or SOM and back propagation network) have been used to decode neural signals. Methods: A Large Adaptive Memory Storage and Retrieval (LAMSTAR) neural-network-based decoder was designed to decode responses recorded from neurons in the auditory cortex. It was designed to identify the frequency of the tonal stimuli that elicited a particular discharge rate pattern recorded on two channels of a tungsten wire electrode array. Results: The network functioned efficiently as a decoder with 100% accuracy for the small sample of stimulus-response data used. Discussion: The results show that the network is effective in studying the functional organization of the auditory cortex and other sensory systems. Depending on the input sub-word, information about the kind of stimuli that activates particular parts of the sensory cortex can be studied.

Translational neural engineering: multiple perspectives on bringing benchtop research into the clinical domain

A half-day forum to address a wide range of issues related to translational neural engineering was conducted at the annual meeting of the Biomedical Engineering Society. Successful practitioners of translational neural engineering from academics, clinical medicine and industry were invited to share a diversity of perspectives and experiences on the translational process. The forum was targeted towards traditional academic researchers who may be interested in the expanded funding opportunities available for translational research that emphasizes product commercialization and clinical implementation. The seminar was funded by the NIH with support from the Rehabilitation Institute of Chicago. We report here a summary of the speaker viewpoints with particular focus on extracting successful strategies for engaging in or conducting translational neural engineering research. Daryl Kipke, PhD, (Department of Biomedical Engineering at the University of Michigan) and Molly Shoichet, PhD, (Department of Chemical Engineering at the University of Toronto) gave details of their extensive experience with product commercialization while holding primary appointments in academic departments. They both encouraged strong clinical input at very early stages of research. Neurosurgeon Fady Charbel, MD, (Department of Neurosurgery at the University of Illinois at Chicago) discussed his role in product commercialization as a clinician. Todd Kuiken, MD, PhD, (Director of the Neural Engineering for Artificial Limbs at the Rehabilitation Institute of Chicago, affiliated with Northwestern University) also a clinician, described a model of translational engineering that emphasized the development of clinically relevant technology, without a strong commercialization imperative. The clinicians emphasized the importance of communicating effectively with engineers. Representing commercial neural engineering was Doug Sheffield, PhD, (Director of New Technology at Vertis Neuroscience, Inc.) who strongly encouraged open industrial-academic partnerships as an efficient path forward in the translational process. Joe Pancrazio, PhD, a Program Director at NIHs National Institute of Neurological Disorders and Stroke, emphasized that NIH funding for translational research was aimed at breaking down scientific barriers to clinic entrance. Vivian Weil, PhD, (Director of Center for the Study of Ethics in the Professions at the Illinois Institute of Technology) a specialist on ethics in science and engineering, spoke of the usefulness of developing a code of ethics for addressing ethical aspects of translation from the bench to clinical implementation and of translation across disciplines in multi-disciplinary projects. Finally, the patient perspective was represented by Mr Jesse Sullivan. A double-arm amputee and patient of Dr Kuikens, Mr Sullivan demonstrated the critically important role of the patient in successful translational neural engineering research.

Encoding of self-paced, repetitive forelimb movements in rat primary motor cortex

Multi-unit, intra-cortical recordings from the primary motor cortex have been shown to provide information about functional movement of the body, and thus, have been used as command signals for control of an external robotic arm in rat and monkey. However, study of the M1 responses has shown that movement encoding may be dependent on both the functional and behavioral context of the intended motion. The main objective of the present work was to determine if self-paced, repetitive forelimb movements are effectively encoded in multiple-unit recordings from the primary motor cortex (M1) in freely moving, non-constrained rats. Four rats were chronically implanted with 7-channel, 50 /spl mu/m tungsten micro-wire arrays. Standard psychophysical techniques were first used to train the rats to depress a response paddle in return for a food reward. We computed peri-event time histograms and found both statistically significant excitatory (24/49) and inhibitory (9/49) pre-paddle activity up to 200 ms before a paddle hit. On average, responses from 161/spl plusmn/37 individual paddle hits were necessary in order to detect statistically significant (> 95%), excitatory pre-paddle action. Thus, while it is possible to detect self-paced, forelimb movements in multi-unit recordings of M1, the high number of repetitions required would limit the efficacy of a real-time cortical neuroprosthesis.