Mesut Sahin

Non-rectangular waveforms for neural stimulation with practical electrodes

Historically the rectangular pulse waveform has been the choice for neural stimulation. The strength-duration curve is thus defined for rectangular pulses. Not much attention has been paid to alternative waveforms to determine if the pulse shape has an effect on the strength-duration relation. Similarly the charge injection capacity of neural electrodes has also been measured with rectangular pulses. In this study we questioned if non-rectangular waveforms can generate a stronger stimulation effect, when applied through practical electrodes, by minimizing the neural activation threshold and maximizing the charge injection capacity of the electrode. First, the activation threshold parameters were studied with seven different pulse shapes using computer simulations of a local membrane model. These waveforms were rectangular, linear increase and decrease, exponential increase and decrease, Gaussian, and sinusoidal. The chronaxie time was found to be longer with all the non-rectangular pulses and some provided more energy efficient stimulation than the rectangular waveform. Second, the charge injection capacity of titanium nitride microelectrodes was measured experimentally for the same waveforms. Linearly decreasing ramp provided the best charge injection for all pulse widths tested from 0.02 to 0.5 ms. Finally, the most efficient waveform that maximized the charge injection capacity of the electrode while providing the lowest threshold charge for neural activation was searched. Linear and exponential decrease, and Gaussian waveforms were found to be the most efficient pulse shapes.

Dilation of the oropharynx via selective stimulation of the hypoglossal nerve

The functional effects of selective hypoglossal nerve (HG) stimulation with a multi-contact peripheral nerve electrode were assessed using images of the upper airways and the tongue in anesthetized beagles. A biphasic pulse train of 50 Hz frequency and 2 s duration was applied through each one of the tripolar contact sets of the nerve electrode while the pharyngeal images were acquired into a computer. The stimulation current was limited to 20% above the activation threshold for maximum selectivity. The images showed that various contact sets could generate several different activation patterns of the tongue muscles resulting in medial and/or lateral dilation and closing of the airways at the tongue root. Some of these patterns translated into an increase in the oropharyngeal size while others did not have any effect. The pharyngeal sizes were not statistically different during stimulation either between the two different positions of the head (30 degrees and 60 degrees), or when the lateral contacts were compared with the medial ones. The contacts that had the least effect generated an average of 53 +/- 15% pharyngeal dilation relative to the best contacts, indicating that the results are marginally sensitive to the contact position around the HG nerve trunk. These results suggest that selective HG nerve stimulation can be a useful technique to produce multiple tongue activation patterns that can dilate the pharynx. This may in turn increase the size of the patient population who can benefit from HG nerve stimulation as a treatment method for obstructive sleep apnea.

Selective stimulation of the canine hypoglossal nerve using a multi-contact cuff electrode.

Electrical activation of the tongue protrusor muscle has been demonstrated as an effective technique for alleviating upper airway (UAW) obstructions and is considered a potential treatment for obstructive sleep apnea (OSA). Recent studies, however, have shown marked improvements in UAW patency by coactivating the tongue protrudor and retractor muscles. As such, selective stimulation of the hypoglossal nerve (XII) using a single implantable device presents an attractive approach for treating OSA. In order to demonstrate the feasibility of such a device, the maximum achievable stimulation selectivity of the Flat Interface Nerve Electrode (FINE) was investigated. The XII nerve of beagles was stimulated with an acutely implanted FINE, while the corresponding neural and muscular responses were recorded and analyzed. The overall performance of the FINE, as depicted by the average of the maximum target-specific selectivity values, S(i), confirmed that high degrees of selectivity can be achieved at both the fascicular and muscular levels: 0.93 ± 0.03 (n = 5) and 0.88 ± 0.03 (n = 4), respectively. The results of this study demonstrate the feasibility of the FINE for selective stimulation of the XII nerve branches and the innervated tongue muscles.

Improved nerve cuff electrode recordings with subthreshold anodic currents

A method has been developed for improving the signal amplitudes of the recordings obtained with nerve cuff electrodes. The amplitude of the electroneurogram (ENG) has been shown to increase with increasing distance between the contacts when cuff electrodes are used to record peripheral nerve activity. The effect is directly related to the propagation speed of the action potentials. Computer simulations have shown that the propagation velocity of action potentials in a length of a nerve axon can be decreased by subthreshold extracellular anodic currents. Slowing the action potentials is analogous to increasing the cuff length in that both result in longer intercontact delays, thus, larger signal outputs. This phenomenon is used to increase the amplitudes of whole nerve recordings obtained with a short cuff electrode. Computer simulations predicting the slowing effect of anodic currents as well as the experimental verification of this effect are presented. The increase in the amplitude of compound action potentials (CAPs) is demonstrated experimentally in an in vitro preparation. This method can be used to improve the signal-to-noise ratios when recording from short nerve segments where the cuff length is limited.

Floating light-activated microelectrical stimulators tested in the rat spinal cord

Microelectrodes of neural stimulation utilize fine wires for electrical connections to driving electronics. Breakage of these wires and the neural tissue response due to their tethering forces are major problems encountered with long-term implantation of microelectrodes. The lifetime of an implant for neural stimulation can be substantially improved if the wire interconnects are eliminated. Thus, we proposed a floating light-activated microelectrical stimulator (FLAMES) for wireless neural stimulation. In this paradigm, a laser beam at near infrared (NIR) wavelengths will be used as a means of energy transfer to the device. In this study, microstimulators of various sizes were fabricated, with two cascaded GaAs p-i-n photodiodes, and tested in the rat spinal cord. A train of NIR pulses (0.2 ms, 50 Hz) was sent through the tissue to wirelessly activate the devices and generate the stimulus current. The forces elicited by intraspinal stimulation were measured from the ipsilateral forelimb with a force transducer. The largest forces were around 1.08 N, a significant level of force for the rat forelimb motor function. These in vivo tests suggest that the FLAMES can be used for intraspinal microstimulation even for the deepest implant locations in the rat spinal cord. The power required to generate a threshold arm movement was investigated as the laser source was moved away from the microstimulator. The results indicate that the photon density does not decrease substantially for horizontal displacements of the source that are in the same order as the beam radius. This gives confidence that the stimulation threshold may not be very sensitive to small displacement of the spinal cord relative to the spine-mounted optical power source.

Chronic tissue response to untethered microelectrode implants in the rat brain and spinal cord

OBJECTIVE Microelectrodes implanted in the central nervous system (CNS) often fail in long term implants due to the immunological tissue response caused by tethering forces of the connecting wires. In addition to the tethering effect, there is a mechanical stress that occurs at the device-tissue interface simply because the microelectrode is a rigid body floating in soft tissue and it cannot reshape itself to comply with changes in the surrounding tissue. In the current study we evaluated the scar tissue formation to tetherless devices with two significantly different geometries in the rat brain and spinal cord in order to investigate the effects of device geometry. APPROACH One of the implant geometries resembled the wireless, floating microstimulators that we are currently developing in our laboratory and the other was a (shank only) Michigan probe for comparison. Both electrodes were implanted into either the cervical spinal cord or the motor cortices, one on each side. MAIN RESULTS The most pronounced astroglial and microglial reactions occurred within 20 μm from the device and decreased sharply at larger distances. Both cell types displayed the morphology of non-activated cells past the 100 μm perimeter. Even though the aspect ratios of the implants were different, the astroglial and microglial responses to both microelectrode types were very mild in the brain, stronger and yet limited in the spinal cord. SIGNIFICANCE These observations confirm previous reports and further suggest that tethering may be responsible for most of the tissue response in chronic implants and that the electrode size has a smaller contribution with floating electrodes. The electrode size may be playing primarily an amplifying role to the tethering forces in the brain whereas the size itself may induce chronic response in the spinal cord where the movement of surrounding tissues is more significant.

Selective recording with a multi-contact nerve cuff electrode

A multi-contact cylindrical nerve cuff electrode was evaluated for its ability to record neural signals selectively in an in vitro preparation, Three branches of a Beagle hypoglossal nerve are stimulated sequentially while compound action potentials (CAP) are recorded from its trunk with the multi-contact cuff electrode. A selectivity index (SI) is defined and applied to the CAP recorded from the 4 sets of tripolar contacts (12 contacts in total) that are equally spaced around the cuff. The results show that the cuff can record selectively from different fascicles, but these effects are small. Connecting the contacts of the opposite set together while recording from a tripole improved the selectivity. The signal amplitudes from various contacts are consistent with the location of the fascicles relative to the contacts.

Feasibility of Neural Stimulation With Floating-Light-Activated Microelectrical Stimulators

Neural microstimulation is becoming a powerful tool for the restoration of impaired functions in the central nervous system. Microelectrode arrays with fine wire interconnects have traditionally been used in the development of these neural prosthetic devices. However, these interconnects are usually the most vulnerable part of the neuroprosthetic implant that can eventually cause the device to fail. In this paper, we investigate the feasibility of floating-light-activated microelectrical stimulators (FLAMES) for wireless neural stimulation. A computer model was developed to simulate the micro stimulators for typical requirements of neural activation in the human white and gray matters. First, the photon densities due to a circular laser beam were simulated in the neural tissue at near-infrared (NIR) wavelengths. Temperature elevation in the tissue was calculated and the laser power was retrospectively adjusted to 325 and 250 mW/cm2 in the gray and white matters, respectively, to limit ΔT to 0.5°C. Total device area of the FLAMES increased with all parameters considered but decreased with the output voltage. We conclude that the number of series photodiodes in the device can be used as a free parameter to minimize the device size. The results suggest that floating, optically activated stimulators are feasible at submillimeter sizes for the activation of the brain cortex or the spinal cord.

An interface for nerve recording and stimulation with cuff electrodes

A nerve cuff electrode interface capable of both stimulating and recording from a nerve is described. The interface also rejects the EMG contamination in the recordings using reactive components without adding noise to the ENG signal. A transformer is added to the design for noise matching and the signal-to-noise ratio improvement is evaluated for a specific amplifier (AMP-O1).

Differential effects of ketamine/xylazine anesthesia on the cerebral and cerebellar cortical activities in the rat

Cerebellum is a highly organized structure with a crystalline morphology that has always intrigued neuroscientists. Much of the cerebellar research has been conducted in anesthetized animals, particularly using ketamine/xylazine combination in rats. It is not clear how and to what extent the cerebellar cortical circuitry is affected by this anesthesia. In this study, we recorded spontaneous and evoked potentials from the cerebellar surface with chronically implanted, flexible-substrate, multielectrode arrays in rats and compared them to the signals simultaneously recorded from the motor cortex with similar electrodes. The power spectra and the intercontact coherence plots of the spontaneous activity in the awake-quiet animals extended up to 800 Hz in the cerebellum and only up to 200 Hz in the motor cortex. Ketamine/xylazine anesthesia suppressed most of the activity in the cerebellar cortex, which was in clear contrast to the motor cortex. In the awake cerebellum, large coherence values were observed between contact pairs as far apart as ∼2 mm. Otherwise, there was not a discernable relation between the coherence and the intercontact distance. These results suggest that the surface electrodes can provide much more detailed information about the state of neural circuits when they are used on the cerebellar cortex compared with the cerebral areas. This may be due to the proximity of the molecular layer cells to the pial surface in the cerebellum.