Neuroprosthetics aims at restoring impaired or lost neurological and mental functions by exploiting technological advances in implantable and wearable devices. The performance of implantable devices, such as neural interfaces, relies upon the synergy between biology and machines. Should this synergy lack, numerous undesirable consequences might occur, such as rejection, infection, or malfunctioning. Several material properties like softness, electrochemical behaviour, biocompatibility, and biodegradability are among the features affecting the reliability of neural interfaces. In this review, the authors describe modern polymeric substrates and organic-based electrodes, offering the best combination of such characteristics. Their versatility in merging different properties derives from the accessible control over their molecular structure and blending. Compared to inorganic materials, organic materials have superior mechanical compliance with the soft tissue, and conjugated polymers also have an advantageous electrochemical transport mechanism at the interface with electrolytic solutions, involving both ionic and electronic conductivities. Hence, all-polymer neural interfaces would be convenient for a multitude of benefits, including low-cost manufacturing, increased biocompatibility, lightweight, transparency, and affinity with green electronics. This review also highlights materials strategies supporting the development of safe electronic interfaces based on organic materials and beneficial for various applications neuroprosthetics.

Electrical stimulation has been used for decades in devices such as pacemakers, cochlear implants and more recently for deep brain and retinal stimulation and electroceutical treatment of disease. However, current spread from the electrodes limits the precision of neural activation, leading to a low quality therapeutic outcome or undesired side-effects. Alternative methods of neural stimulation such as optical stimulation offer the potential to deliver higher spatial resolution of neural activation. Direct optical stimulation is possible with infrared light, while visible light can be used to activate neurons if the neural tissue is genetically modified with a light sensitive ion channel. Experimentally, both methods have resulted in highly precise stimulation with little spread of activation at least in the cochlea, each with advantages and disadvantages. Infrared neural stimulation does not require modification of the neural tissue, but has very high power requirements. Optogenetics can achieve precision of activation with lower power, but only in conjunction with targeted insertion of a light sensitive ion channel into the nervous system via gene therapy. This review will examine the advantages and limitations of optical stimulation of neural tissue, using the cochlea as an exemplary model and recent developments for retinal and deep brain stimulation.

Retinal degenerative diseases, such as retinitis pigmentosa, begin with damage to the photoreceptor layer of the retina. In the absence of presynaptic input from photoreceptors, networks of electrically coupled AII amacrine and cone bipolar cells have been observed to exhibit oscillatory behaviour and result in spontaneous firing of ganglion cells. This ganglion cell activity could interfere with external stimuli provided by retinal prosthetic devices and potentially degrade their performance. In this work, the authors computationally investigate stimulus waveform designs, which can improve the performance of retinal prostheses by suppressing undesired spontaneous firing of ganglion cells and generating precise temporal spiking patterns. They utilise a multi-scale computational model for electrical stimulation of degenerated retina based on the admittance method and NEURON simulation environments. They present a class of asymmetric biphasic pulses that can generate precise ganglion cell firing patterns with up to 55% lower current requirements compared to traditional symmetric biphasic pulses. This lower current results in activation of only proximal ganglion cells, provides more focused stimulation and lowers the risk of tissue damage.

Deep brain stimulation (DBS) is an effective treatment for many people living with Parkinson's disease (PD). Although the primary treatment for PD is based on medications, disease progression eventually leads to inadequate symptom control. DBS provides benefits by alleviating motor dysfunctions such as muscle rigidity and tremor. DBS devices deliver electric pulse trains into specific brain regions via implanted electrodes. Existing DBS systems usually provide continuous stimulation with constant settings of parameters such as the amount of charge delivered per pulse. However, PD is characterised by fluctuations in the severity and frequency of impairments. DBS would be improved if stimulation settings were adjusted automatically in response to each patient's ever-changing needs. This requires a device incorporating sensing of signals that estimate the severity of motor impairment linked to an adaptive control algorithm that optimises therapeutic stimulation. Several types of signals are candidates for this function. Spontaneous local field potentials recorded by the DBS electrodes have shown promise in some experimental studies of adaptive DBS. More recently, DBS-evoked potentials have been reported. In particular, evoked resonant neural activity has properties including a larger amplitude than spontaneous potentials, suggesting it may be a suitable feedback signal to control adaptive DBS.

Advances in technology and improvement of efficacy for many neuromodulation applications have been achieved without understanding the relationship between the stimulation parameters and the neural activity which is generated in the nervous system. It is the neural activity that ultimately drives the therapeutic benefit and the advent of evoked compound action potential recording allows this activity to be directly measured and quantified. Closed-loop control adjusts the stimulation parameters to maintain a predetermined level of neural recruitment and has been shown to provide improved pain relief in individuals with spinal cord stimulators. However, no mechanism that relates more consistent neural recruitment to patient outcomes has been proposed. The authors propose a hypothesis that may explain the difference in efficacy between open- and closed-loop operational modes by considering the relationship between measured neural recruitment with hypothetical dose and side effect response curves. This provides a rational basis for directing clinical research and improving therapeutic systems.

Implantable motor neuroprosthetic systems can restore function to individuals with significant disabilities, such as spinal cord injury, stroke, cerebral palsy, and multiple sclerosis. Neuroprostheses provide restored functionality by electrically activating paralysed muscles in coordinated patterns that replicate (enable) controlled movement that was lost through injury or disease. It is important to consider the general topology of the implanted system itself. The authors demonstrate that the wired multipoint implant technology is practical and feasible as a basis for the development of implanted multi-function neuroprosthetic systems. The advantages of a centralised power supply are significant. Heating due to recharge can be mitigated by using an actively cooled external recharge coil. Using this approach, the time required to perform a full recharge was significantly reduced. This approach has been demonstrated as a practical option for regular clinical use of implanted neuroprostheses.

Spinal cord injury (SCI) results in the inability to empty the bladder voluntarily, and neurogenic detrusor overactivity (NDO) and detrusor sphincter dyssynergia (DSD) negatively impact both the health and quality of life of persons with SCI. Current approaches to treat bladder dysfunction in persons with SCI, including self-catheterisation and anticholinergic medications, are inadequate, and novel approaches are required to restore continence with increased bladder capacity, as well as to provide predictable and efficient on-demand voiding. Improvements in bladder function following SCI have been documented using a number of different modalities of spinal cord stimulation (SCS) in both persons with SCI and animal models, including SCS alone or SCS with concomitant activity-based training. Improvements include increased volitional voiding, voided volumes, bladder capacity, and quality of life, as well as decreases in NDO and DSD. Further, SCS is a well-developed therapy for chronic pain, and existing Food And Drug Administration (FDA)-approved devices provide a clear pathway to sustainable commercial availability and impact. However, the effective stimulation parameters and the appropriate timing and location of stimulation for SCS-mediated restoration of bladder function require further study, and studies are needed to determine underlying mechanisms of action.

Cerebral palsy (CP) is the most common form of childhood disability, and spasticity is the most common motor-manifestation. Thankfully, there has been a significant reduction in the percentage of children born with CP in recent years, but nonetheless, those afflicted children can face life long devastating disabilities. Spinal cord stimulation (SCS), an implanted device used to treat chronic neuropathic pain, has been used to treat children with spasticity. In some cases, it has been shown to produce a remarkable improvement but despite this, the technique is not commonly used. There are a number of case series, and retrospective reports of outcomes with the most successful demonstrating a nearly 1.5-point reduction in Ashworth scale, the least successful demonstrating no significant improvements. Here, the authors examine the clinical reports and propose a mechanism of action based on the current understanding of SCS. Technology development in SCS for pain management has progressed significantly since the early clinical experience with CP and some of the new technology may be able to better exploit the putative mechanism. The advent of compound action potential recording and closed-loop control could lead to new insights into the electrophysiology and how to better tune these devices to provide more substantial relief from symptoms.