Estimating Risk for Future Intracranial, Fully Implanted, Modular Neuroprosthetic Systems: A Systematic Review of Hardware Complications in Clinical Deep Brain Stimulation and Experimental Human Intracortical Arrays

Abstract

Objective A new age of neuromodulation is emerging: one of restorative neuroengineering and neuroprosthetics. As novel device systems move toward regulatory evaluation and clinical trials, a critical need arises for evidence‐based identification of potential sources of hardware‐related complications to assist in clinical trial design and mitigation of potential risk. Materials and Methods The objective of this systematic review is to provide a detailed safety analysis for future intracranial, fully implanted, modular neuroprosthetic systems. To achieve this aim, we conducted an evidence‐based analysis of hardware complications for the most established clinical intracranial modular system, deep brain stimulation (DBS), as well as the most widely used intracranial human experimental system, the silicon‐based (Utah) array. Results Of 2328 publications identified, 240 articles met the inclusion criteria and were reviewed for DBS hardware complications. The most reported adverse events were infection (4.57%), internal pulse generator malfunction (3.25%), hemorrhage (2.86%), lead migration (2.58%), lead fracture (2.56%), skin erosion (2.22%), and extension cable malfunction (1.63%). Of 433 publications identified, 76 articles met the inclusion criteria and were reviewed for Utah array complications. Of 48 human subjects implanted with the Utah array, 18 have chronic implants. Few specific complications are described in the literature; hence, implant duration served as a lower bound for complication‐free operation. The longest reported duration of a person with a Utah array implant is 1975 days (~5.4 years). Conclusions Through systematic review of the clinical and human‐trial literature, our study provides the most comprehensive safety review to date of DBS hardware and human neuroprosthetic research using the Utah array. The evidence‐based analysis serves as an important reference for investigators seeking to identify hardware‐related safety data, a necessity to meet regulatory requirements and to design clinical trials for future intracranial, fully implanted, modular neuroprosthetic systems.

Neural stimulation and recording performance in human somatosensory cortex over 1500 days

“…It is well known that signal quality deteriorates on recording electrodes over long periods of time [5], [10]- [12], [14], [15]. In this study, we found similar decreases in signal quality over time on both stimulated and non-stimulated electrodes.…”

“…The stability of microelectrode arrays in motor cortex has been well studied in non-human primates [10]–[12]. Additionally, there are several reports on signal quality and stability for electrodes implanted in human motor cortex [5], [13]–[15]. Although intersubject variability is high, signals can be reliably recorded for up to 3-5 years when devices do not fail, although the quality of these recordings deteriorates over time.…”

Electrode Materials for Chronic Electrical Microstimulation

“…Comprehensive analysis of failure modes for various styles of electrode arrays have been extensively studied and reviewed. [ 30,75–77 ] Aside from the most frequently occurring mechanical failure of the I/O connector, other failure mechanisms include mechanical defects from fabrication, chemical, physicochemical and electrochemical reactions, and the interaction of mechanical and chemical stresses. [ 78 ] All of these failures can be characterized by varying amounts of fracture, dissolution and delamination of the electrode sites and/or insulation over the implantation duration.…”

“…Additionally, the implantation of an electrode array into the neural tissue triggers foreign body responses such as inflammation and neuronal loss (reported in detail in refs. [ 30–32 ] ). Numerous investigations have shed light on the vascular and cellular pathways and time course of the foreign body response to neural recording devices.…”

Classifying Intracortical Brain-Machine Interface Signal Disruptions Based on System Performance and Applicable Compensatory Strategies: A Review

“…Less is known about the longevity of MEAs in humans due to the limited number of studies utilizing chronic implants. The few clinical trials that have investigated the functionality of intracortical BMIs beyond 4 years post-implant have reported sustained usability (Hochberg et al, 2012 ; Bockbrader, 2019 ; Bockbrader et al, 2019 ; Hughes et al, 2020 ), while most other clinical studies had planned MEA explantation dates that occurred prior to MEA malfunction (Bullard et al, 2020 ). While the useable life of MEAs for BMI control is likely longer in humans than has been reported in NHP studies, chronic declines in signal quality are evident in human trials (Perge et al, 2014 ; Zhang et al, 2018 ; Hughes et al, 2020 ).…”