Sam E. John

Minimally invasive endovascular stent-electrode array for high-fidelity, chronic recordings of cortical neural activity

High-fidelity intracranial electrode arrays for recording and stimulating brain activity have facilitated major advances in the treatment of neurological conditions over the past decade. Traditional arrays require direct implantation into the brain via open craniotomy, which can lead to inflammatory tissue responses, necessitating development of minimally invasive approaches that avoid brain trauma. Here we demonstrate the feasibility of chronically recording brain activity from within a vein using a passive stent-electrode recording array (stentrode). We achieved implantation into a superficial cortical vein overlying the motor cortex via catheter angiography and demonstrate neural recordings in freely moving sheep for up to 190 d. Spectral content and bandwidth of vascular electrocorticography were comparable to those of recordings from epidural surface arrays. Venous internal lumen patency was maintained for the duration of implantation. Stentrodes may have wide ranging applications as a neural interface for treatment of a range of neurological conditions.

Suprachoroidal electrical stimulation: effects of stimulus pulse parameters on visual cortical responses

OBJECTIVE Neural responses to biphasic constant current pulses depend on stimulus pulse parameters such as polarity, duration, amplitude and interphase gap. The objective of this study was to systematically evaluate and optimize stimulus pulse parameters for a suprachoroidal retinal prosthesis. APPROACH Normally sighted cats were acutely implanted with platinum electrode arrays in the suprachoroidal space. Monopolar stimulation comprised of monophasic and biphasic constant current pulses with varying polarity, pulse duration and interphase gap. Multiunit responses to electrical stimulation were recorded in the visual cortex. MAIN RESULTS Anodal stimulation elicited cortical responses with shorter latencies and required lower charge per phase than cathodal stimulation. Clinically relevant retinal stimulation required relatively larger charge per phase compared with other neural prostheses. Increasing the interphase gap of biphasic pulses reduced the threshold of activation; however, the benefits of using an interphase gap need to be considered in light of the pulse duration and polarity used and other stimulation constraints. Based on our results, anodal first biphasic pulses between 300-1200 µs are recommended for suprachoroidal retinal stimulation. SIGNIFICANCE These results provide insights into the efficacy of different pulse parameters for suprachoroidal retinal stimulation and have implications for the design of safe and clinically relevant stimulators for retinal prostheses.

An automated system for rapid evaluation of high-density electrode arrays in neural prostheses

The success of high-density electrode arrays for use in neural prostheses depends on efficient impedance monitoring and fault detection. Conventional methods of impedance testing and fault detection are time consuming and not always suited for in vivo assessment of high-density electrode arrays. Additionally, the ability to evaluate impedances and faults such as open and short circuits, both in vitro and in vivo, are important to ensure safe and effective stimulation. In this work we describe an automated system for the rapid evaluation of high-density electrode arrays. The system uses a current pulse similar to that used to stimulate neural tissue and measures the voltage across the electrode in order to calculate the impedance. The switching of the system was validated by emulating a high-density electrode array using light-emitting diodes and a resistor-capacitor network. The system was tested in vitro and in vivo using a range of commercially available and in-house developed electrode arrays. The system accurately identified faults in an 84-electrode array in less than 20 s and reliably measured impedances up to 110 kΩ using a 200 µA, 250 µs per phase current pulse. This system has direct application for screening high-density electrode arrays in both clinical and experimental settings.

The evolution of endovascular electroencephalography: historical perspective and future applications

Current standard practice requires an invasive approach to the recording of electroencephalography (EEG) for epilepsy surgery, deep brain stimulation (DBS), and brain-machine interfaces (BMIs). The development of endovascular techniques offers a minimally invasive route to recording EEG from deep brain structures. This historical perspective aims to describe the technical progress in endovascular EEG by reviewing the first endovascular recordings made using a wire electrode, which was followed by the development of nanowire and catheter recordings and, finally, the most recent progress in stent-electrode recordings. The technical progress in device technology over time and the development of the ability to record chronic intravenous EEG from electrode arrays is described. Future applications for the use of endovascular EEG in the preoperative and operative management of epilepsy surgery are then discussed, followed by the possibility of the techniques future application in minimally invasive operative approaches to DBS and BMI.

7T-fMRI: Faster temporal resolution yields optimal BOLD sensitivity for functional network imaging specifically at high spatial resolution

&NA; Recent developments in accelerated imaging methods allow faster acquisition of high spatial resolution images. This could improve the applications of functional magnetic resonance imaging at 7 Tesla (7T‐fMRI), such as neurosurgical planning and Brain Computer Interfaces (BCIs). However, increasing the spatial and temporal resolution will both lead to signal‐to‐noise ratio (SNR) losses due to decreased net magnetization per voxel and T1‐relaxation effect, respectively. This could potentially offset the SNR efficiency gains made with increasing temporal resolution. We investigated the effects of varying spatial and temporal resolution on fMRI sensitivity measures and their implications on fMRI‐based BCI simulations. We compared temporal signal‐to‐noise ratio (tSNR), observed percent signal change (%&Dgr;S), volumes of significant activation, Z‐scores and decoding performance of linear classifiers commonly used in BCIs across a range of spatial and temporal resolution images acquired during an ankle‐tapping task. Our results revealed an average increase of 22% in %&Dgr;S (p=0.006) and 9% in decoding performance (p=0.015) with temporal resolution only at the highest spatial resolution of 1.5×1.5×1.5 mm3, despite a 29% decrease in tSNR (p<0.001) and plateaued Z‐scores. Further, the volume of significant activation was indifferent (p>0.05) across spatial resolution specifically at the highest temporal resolution of 500 ms. These results demonstrate that the overall BOLD sensitivity can be increased significantly with temporal resolution, granted an adequately high spatial resolution with minimal physiological noise level. This shows the feasibility of diffuse motor‐network imaging at high spatial and temporal resolution with robust BOLD sensitivity with 7T‐fMRI. Importantly, we show that this sensitivity improvement could be extended to an fMRI application such as BCIs. Graphical abstract Figure. No caption available. HighlightsObserved BOLD contrast increases with shorter TR only at high spatial resolution.Decoding performance increases with shorter TR only at high spatial resolution.These occur despite the decrease in tSNR.Faster TRs reduce physiological noise, undersampling effect and increase SNR efficiency.Higher temporal resolution improves BOLD sensitivity, only at high spatial resolution.

Consistency of Long-Term of Subdural Electrocorticography in Humans

Objective: Subdural electrocorticography (ECoG) can provide a robust control signal for a brain–computer interface (BCI). However, the long-term recording properties of ECoG are poorly understood as most ECoG studies in the BCI field have only used signals recorded for less than 28 days. We assessed human ECoG recordings over durations of many months to investigate changes to recording quality that occur with long-term implantation. Methods: We examined changes in signal properties over time from 15 ambulatory humans who had continuous subdural ECoG monitoring for 184–766 days. Results: Individual electrodes demonstrated varying changes in frequency power characteristics over time within individual patients and between patients. Group level analyses demonstrated that there were only small changes in effective signal bandwidth and spectral band power across months. High-gamma signals could be recorded throughout the study, though there was a decline in signal power for some electrodes. Conclusion: ECoG-based BCI systems can robustly record high-frequency activity over multiple years, albeit with marked intersubject variability. Significance: Group level results demonstrated that ECoG is a promising modality for long-term BCI and neural prosthesis applications.

Suitability of nitinol electrodes in neural prostheses such as endovascular neural interfaces

A major challenge facing neural prostheses is the development of electrodes that are well tolerated by the brain and body. A novel way to circumvent the need to perform an invasive craniotomy and penetration of the blood-brain barrier to implant electrodes, is to guide electrodes up into the cerebral veins and place electrodes on the vessel walls adjacent to neuronal populations. To aid in the development of these stent based devices, microelectrodes manufactured from Nitinol would allow electrodes to be implanted via a catheter and then once deployed, alter their shape to conform to the vessel walls. However, there is a paucity of data on whether Nitinol is a suitable material to record neural signals. Here we show that Nitinol is tolerated by the body and that it can effectively measure neural signals. Specifically, we electrochemically evaluate Nitinol electrodes in blood and record visually evoked potentials from sheep.A major challenge facing neural prostheses is the development of electrodes that are well tolerated by the brain and body. A novel way to circumvent the need to perform an invasive craniotomy and penetration of the blood-brain barrier to implant electrodes, is to guide electrodes up into the cerebral veins and place electrodes on the vessel walls adjacent to neuronal populations. To aid in the development of these stent based devices, microelectrodes manufactured from Nitinol would allow electrodes to be implanted via a catheter and then once deployed, alter their shape to conform to the vessel walls. However, there is a paucity of data on whether Nitinol is a suitable material to record neural signals. Here we show that Nitinol is tolerated by the body and that it can effectively measure neural signals. Specifically, we electrochemically evaluate Nitinol electrodes in blood and record visually evoked potentials from sheep.

Optimized partial-coverage functional analysis pipeline (OPFAP): a semi-automated pipeline for skull stripping and co-registration of partial-coverage, ultra-high-field functional images

ObjectiveUltra-high-field functional MRI (UHF-fMRI) allows for higher spatiotemporal resolution imaging. However, higher-resolution imaging entails coverage limitations. Processing partial-coverage images using standard pipelines leads to sub-optimal results. We aimed to develop a simple, semi-automated pipeline for processing partial-coverage UHF-fMRI data using widely used image processing algorithms.Materials and methodsWe developed automated pipelines for optimized skull stripping and co-registration of partial-coverage UHF functional images, using built-in functions of the Centre for Functional Magnetic Resonance Imaging of the Brains (FMRIB’s) Software library (FSL) and advanced normalization tools. We incorporated the pipelines into the FSL’s functional analysis pipeline and provide a semi-automated optimized partial-coverage functional analysis pipeline (OPFAP).ResultsCompared to the standard pipeline, the OPFAP yielded images with 15 and 30% greater volume of non-zero voxels after skull stripping the functional and anatomical images, respectively (all p = 0.0004), which reflected the conservation of cortical voxels lost when the standard pipeline was used. The OPFAP yielded the greatest Dice and Jaccard coefficients (87 and 80%, respectively; all p < 0.0001) between the co-registered participant gyri maps and the template gyri maps, demonstrating the goodness of the co-registration results. Furthermore, the greatest volume of group-level activation in the most number of functionally relevant regions was observed when the OPFAP was used. Importantly, group-level activations were not observed when using the standard pipeline.ConclusionThese results suggest that the OPFAP should be used for processing partial-coverage UHF-fMRI data for detecting high-resolution macroscopic blood oxygenation level-dependent activations.

Spatially dynamic recurrent information flow across long‐range dorsal motor network encodes selective motor goals

Performing voluntary movements involves many regions of the brain, but it is unknown how they work together to plan and execute specific movements. We recorded high‐resolution ultra‐high‐field blood‐oxygen‐level‐dependent signal during a cued ankle‐dorsiflexion task. The spatiotemporal dynamics and the patterns of task‐relevant information flow across the dorsal motor network were investigated. We show that task‐relevant information appears and decays earlier in the higher order areas of the dorsal motor network then in the primary motor cortex. Furthermore, the results show that task‐relevant information is encoded in general initially, and then selective goals are subsequently encoded in specifics subregions across the network. Importantly, the patterns of recurrent information flow across the network vary across different subregions depending on the goal. Recurrent information flow was observed across all higher order areas of the dorsal motor network in the subregions encoding for the current goal. In contrast, only the top–down information flow from the supplementary motor cortex to the frontoparietal regions, with weakened recurrent information flow between the frontoparietal regions and bottom–up information flow from the frontoparietal regions to the supplementary cortex were observed in the subregions encoding for the opposing goal. We conclude that selective motor goal encoding and execution rely on goal‐dependent differences in subregional recurrent information flow patterns across the long‐range dorsal motor network areas that exhibit graded functional specialization.

An ovine model of cerebral catheter venography for implantation of an endovascular neural interface

OBJECTIVE Neural interface technology may enable the development of novel therapies to treat neurological conditions, including motor prostheses for spinal cord injury. Intracranial neural interfaces currently require a craniotomy to achieve implantation and may result in chronic tissue inflammation. Novel approaches are required that achieve less invasive implantation methods while maintaining high spatial resolution. An endovascular stent electrode array avoids direct brain trauma and is able to record electrocorticography in local cortical tissue from within the venous vasculature. The motor area in sheep runs in a parasagittal plane immediately adjacent to the superior sagittal sinus (SSS). The authors aimed to develop a sheep model of cerebral venography that would enable validation of an endovascular neural interface. METHODS Cerebral catheter venography was performed in 39 consecutive sheep. Contrast-enhanced MRI of the brain was performed on 13 animals. Multiple telescoping coaxial catheter systems were assessed to determine the largest wide-bore delivery catheter that could be delivered into the anterior SSS. Measurements of SSS diameter and distance from the motor area were taken. The location of the motor area was determined in relation to lateral and superior projections of digital subtraction venography images and confirmed on MRI. RESULTS The venous pathway from the common jugular vein (7.4 mm) to the anterior SSS (1.2 mm) was technically challenging to selectively catheterize. The SSS coursed immediately adjacent to the motor cortex (< 1 mm) for a length of 40 mm, or the anterior half of the SSS. Attempted access with 5-Fr and 6-Fr delivery catheters was associated with longer procedure times and higher complication rates. A 4-Fr catheter (internal lumen diameter 1.1 mm) was successful in accessing the SSS in 100% of cases with no associated complications. Complications included procedure-related venous dissection in two major areas: the torcular herophili, and the anterior formation of the SSS. The bifurcation of the cruciate sulcal veins with the SSS was a reliable predictor of the commencement of the motor area. CONCLUSIONS The ovine model for cerebral catheter venography has generalizability to the human cerebral venous system in relation to motor cortex location. This novel model may facilitate the development of the novel field of endovascular neural interfaces that may include preclinical investigations for cortical recording applications such as paralysis and epilepsy, as well as other potential applications in neuromodulation.