Implantable Direct Current Neural Modulation: Theory, Feasibility, and Efficacy

Implantable neuroprostheses such as cochlear implants, deep brain stimulators, spinal cord stimulators, and retinal implants use charge-balanced alternating current (AC) pulses to recover delivered charge and thus mitigate toxicity from electrochemical reactions occurring at the metal-tissue interface. At low pulse rates, these short duration pulses have the effect of evoking spikes in neural tissue in a phase-locked fashion. When the therapeutic goal is to suppress neural activity, implants typically work indirectly by delivering excitation to populations of neurons that then inhibit the target neurons, or by delivering very high pulse rates that suffer from a number of undesirable side effects. Direct current (DC) neural modulation is an alternative methodology that can directly modulate extracellular membrane potential. This neuromodulation paradigm can excite or inhibit neurons in a graded fashion while maintaining their stochastic firing patterns. DC can also sensitize or desensitize neurons to input. When applied to a population of neurons, DC can modulate synaptic connectivity. Because DC delivered to metal electrodes inherently violates safe charge injection criteria, its use has not been explored for practical applicability of DC-based neural implants. Recently, several new technologies and strategies have been proposed that address this safety criteria and deliver ionic-based direct current (iDC). This, along with the increased understanding of the mechanisms behind the transcutaneous DC-based modulation of neural targets, has caused a resurgence of interest in the interaction between iDC and neural tissue both in the central and the peripheral nervous system. In this review we assess the feasibility of in-vivo iDC delivery as a form of neural modulation. We present the current understanding of DC/neural interaction. We explore the different design methodologies and technologies that attempt to safely deliver iDC to neural tissue and assess the scope of application for direct current modulation as a form of neuroprosthetic treatment in disease. Finally, we examine the safety implications of long duration iDC delivery. We conclude that DC-based neural implants are a promising new modulation technology that could benefit from further chronic safety assessments and a better understanding of the basic biological and biophysical mechanisms that underpin DC-mediated neural modulation

Restoring Sensation of Gravitoinertial Acceleration through Prosthetic Stimulation of the Utricle and Saccule

Individuals with bilateral vestibular hypofunction suffer reduced quality of life due to loss of postural and ocular reflexes essential to maintaining balance and visual acuity during head movements. Vestibular stimulation has demonstrated success in restoring sensation of angular head rotations using electrical stimulation of the semi-circular canals (SCCs). Efforts toward utricle and saccule stimulation to restore sensation of gravitoinertial acceleration have been limited due to the complexity of the otolith end organs and otolith-ocular reflexes (OORs). Four key pieces of technology were developed to extend prosthetic stimulation to the utricle and saccule: a low-noise scleral coil system to record binocular 3D eye movements; a motion platform control system for automated presentation of rotational and translational stimuli; custom electrode arrays with fifty contacts targeting the SCCs, utricle and saccule; and a general-purpose neuroelectronic stimulator for vestibular and other neuromodulation applications. Using these new technologies, OORs were first characterized in six chinchillas to establish OOR norms during translations and static tilts. Results led to creation of a model that infers the axis of head tilt from measured binocular eye movements and thereby provides a context and means to assess the selectivity of prosthetic utricle and saccule stimulation. The model confirms the expectation that excitation of the left utricle and saccule primarily encodes tilts that bring the left ear down. Three of the chinchillas were implanted with electrode arrays in the left ear. Step changes in pulse rate were delivered to utricle and saccule electrodes near the maculae while measuring 3D binocular eye movements with the animal stationary in darkness. These stimuli elicited sustained ocular counter-roll responses that increased in magnitude as pulse rate or amplitude increased. Bipolar stimulation via neighboring electrodes elicited slow-rising or delayed onset of ocular counter-rolls (consistent with normal translational OOR low-pass filter behavior). Two chinchillas showed different direction of electrically-evoked ocular counter-roll between utricle versus saccule stimulation. Only near-neighbor bipolar electrode combinations elicited eye responses compensatory for tilts other than the ‘usual’ left ear down, suggesting the need for distributing multiple bipolar electrode pairs across the maculae to achieve selective stimulation and restore 3D sensation of gravitoinertial acceleration

VLSI Circuits for Bidirectional Neural Interfaces

Medical devices that deliver electrical stimulation to neural tissue are important clinical tools that can augment or replace pharmacological therapies. The success of such devices has led to an explosion of interest in the field, termed neuromodulation, with a diverse set of disorders being targeted for device-based treatment. Nevertheless, a large degree of uncertainty surrounds how and why these devices are effective. This uncertainty limits the ability to optimize therapy and gives rise to deleterious side effects. An emerging approach to improve neuromodulation efficacy and to better understand its mechanisms is to record bioelectric activity during stimulation. Understanding how stimulation affects electrophysiology can provide insights into disease, and also provides a feedback signal to autonomously tune stimulation parameters to improve efficacy or decrease side-effects. The aims of this work were taken up to advance the state-of-the-art in neuro-interface technology to enable closed-loop neuromodulation therapies. Long term monitoring of neuronal activity in awake and behaving subjects can provide critical insights into brain dynamics that can inform system-level design of closed-loop neuromodulation systems. Thus, first we designed a system that wirelessly telemetered electrocorticography signals from awake-behaving rats. We hypothesized that such a system could be useful for detecting sporadic but clinically relevant electrophysiological events. In an 18-hour, overnight recording, seizure activity was detected in a pre-clinical rodent model of global ischemic brain injury. We subsequently turned to the design of neurostimulation circuits. Three critical features of neurostimulation devices are safety, programmability, and specificity. We conceived and implemented a neurostimulator architecture that utilizes a compact on-chip circuit for charge balancing (safety), digital-to-analog converter calibration (programmability) and current steering (specificity). Charge balancing accuracy was measured at better than 0.3%, the digital-to-analog converters achieved 8-bit resolution, and physiological effects of current steering stimulation were demonstrated in an anesthetized rat. Lastly, to implement a bidirectional neural interface, both the recording and stimulation circuits were fabricated on a single chip. In doing so, we implemented a low noise, ultra-low power recording front end with a high dynamic range. The recording circuits achieved a signal-to-noise ratio of 58 dB and a spurious-free dynamic range of better than 70 dB, while consuming 5.5 μW per channel. We demonstrated bidirectional operation of the chip by recording cardiac modulation induced through vagus nerve stimulation, and demonstrated closed-loop control of cardiac rhythm