Intracortical microstimulation of the somatosensory cortex offers the potential for creating a sensory neuroprosthesis to restore tactile sensation. Whereas animal studies have suggested that both cutaneous and proprioceptive percepts can be evoked using this approach, the perceptual quality of the stimuli cannot be measured in these experiments. We show that microstimulation within the hand area of the somatosensory cortex of a person with long-term spinal cord injury evokes tactile sensations perceived as originating from locations on the hand and that cortical stimulation sites are organized according to expected somatotopic principles. Many of these percepts exhibit naturalistic characteristics (including feelings of pressure), can be evoked at low stimulation amplitudes, and remain stable for months. Further, modulating the stimulus amplitude grades the perceptual intensity of the stimuli, suggesting that intracortical microstimulation could be used to convey information about the contact location and pressure necessary to perform dexterous hand movements associated with object manipulation.

High frequency alternating current (HFAC) sinusoidal waveforms can block conduction in mammalian peripheral nerves. A mammalian axon model was used to simulate the response of nerves to HFAC conduction block. Sinusoidal waveforms from 1 to 40 kHz were delivered to eight simulated axon diameters ranging from 7.3 to 16 microm. Conduction block was obtained between 3 to 40 kHz. The minimum peak to peak current at which block was obtained, defined as the block threshold, increased with increasing frequency. Block threshold varied inversely with axon diameter. Upon initiation, the HFAC waveform produced one or more action potentials. These simulation results closely parallel previous experimental results of high frequency motor block of the rat sciatic and cat pudendal nerve. During HFAC block, the axons showed a dynamic steady state depolarization of multiple nodes, strongly suggesting a depolarization mechanism for HFAC conduction block.

The purpose of this study was to prospectively investigate the agreement between the epileptogenic zone(s) (EZ) localization by resting-state functional magnetic resonance imaging (rs-fMRI) and the seizure onset zone(s) (SOZ) identified by intracranial electroencephalogram (ic-EEG) using novel differentiating and ranking criteria of rs-fMRI abnormal independent components (ICs) in a large consecutive heterogeneous pediatric intractable epilepsy population without an a priori alternate modality informing EZ localization or prior declaration of total SOZ number. The EZ determination criteria were developed by using independent component analysis (ICA) on rs-fMRI in an initial cohort of 350 pediatric patients evaluated for epilepsy surgery over a 3-year period. Subsequently, these rs-fMRI EZ criteria were applied prospectively to an evaluation cohort of 40 patients who underwent ic-EEG for SOZ identification. Thirty-seven of these patients had surgical resection/disconnection of the area believed to be the primary source of seizures. One-year seizure frequency rate was collected postoperatively. Among the total 40 patients evaluated, agreement between rs-fMRI EZ and ic-EEG SOZ was 90% (36/40; 95% confidence interval [CI], 0.76–0.97). Of the 37 patients who had surgical destruction of the area believed to be the primary source of seizures, 27 (73%) rs-fMRI EZ could be classified as true positives, 7 (18%) false positives, and 2 (5%) false negatives. Sensitivity of rs-fMRI EZ was 93% (95% CI 78–98%) with a positive predictive value of 79% (95% CI, 63–89%). In those with cryptogenic localization-related epilepsy, agreement between rs-fMRI EZ and ic-EEG SOZ was 89% (8/9; 95% CI, 0.52–99), with no statistically significant difference between the agreement in the cryptogenic and symptomatic localization-related epilepsy subgroups. Two children with negative ic-EEG had removal of the rs-fMRI EZ and were seizure free 1 year postoperatively. Of the 33 patients where at least 1 rs-fMRI EZ agreed with the ic-EEG SOZ, 24% had at least 1 additional rs-fMRI EZ outside the resection area. Of these patients with un-resected rs-fMRI EZ, 75% continued to have seizures 1 year later. Conversely, among 75% of patients in whom rs-fMRI agreed with ic-EEG SOZ and had no anatomically separate rs-fMRI EZ, only 24% continued to have seizures 1 year later. This relationship between extraneous rs-fMRI EZ and seizure outcome was statistically significant (p = 0.01). rs-fMRI EZ surgical destruction showed significant association with postoperative seizure outcome. The pediatric population with intractable epilepsy studied prospectively provides evidence for use of resting-state ICA ranking criteria, to identify rs-fMRI EZ, as developed by the lead author (V.L.B.). This is a high yield test in this population, because no seizure nor particular interictal epilepiform activity needs to occur during the study. Thus, rs-fMRI EZ detected by this technique are potentially informative for epilepsy surgery evaluation and planning in this populatio...

Recent advancement in electrocorticography (ECoG)-based brain-computer interface technology has sparked a new interest in providing somatosensory feedback using ECoG electrodes, i.e., cortical surface electrodes. We conducted a 28-day study of cortical surface stimulation in an individual with arm paralysis due to brachial plexus injury to examine the sensation produced by electrical stimulation of the somatosensory cortex. A high-density ECoG grid was implanted over the somatosensory and motor cortices. Stimulation through cortical surface electrodes over the somatosensory cortex successfully elicited arm and hand sensations in our participant with chronic paralysis. There were three key findings. First, the intensity of perceived sensation increased monotonically with both pulse amplitude and pulse frequency. Second, changing pulse width changed the type of sensation based on qualitative description provided by the human participant. Third, the participant could distinguish between stimulation applied to two neighboring cortical surface electrodes, 4.5 mm center-to-center distance, for three out of seven electrode pairs tested. Taken together, we found that it was possible to modulate sensation intensity, sensation type, and evoke sensations across a range of locations from the fingers to the upper arm using different stimulation electrodes even in an individual with chronic impairment of somatosensory function. These three features are essential to provide effective somatosensory feedback for neuroprosthetic applications.

One outstanding challenge for machine learning in diagnostic biomedical imaging is algorithm interpretability. A key application is the identification of subtle epileptogenic focal cortical dysplasias (FCDs) from structural MRI. FCDs are difficult to visualize on structural MRI but are often amenable to surgical resection. We aimed to develop an open-source, interpretable, surface-based machine-learning algorithm to automatically identify FCDs on heterogeneous structural MRI data from epilepsy surgery centres worldwide. The Multi-centre Epilepsy Lesion Detection (MELD) Project collated and harmonized a retrospective MRI cohort of 1015 participants, 618 patients with focal FCD-related epilepsy and 397 controls, from 22 epilepsy centres worldwide. We created a neural network for FCD detection based on 33 surface-based features. The network was trained and cross-validated on 50% of the total cohort and tested on the remaining 50% as well as on 2 independent test sites. Multidimensional feature analysis and integrated gradient saliencies were used to interrogate network performance. Our pipeline outputs individual patient reports, which identify the location of predicted lesions, alongside their imaging features and relative saliency to the classifier. On a restricted ‘gold-standard’ subcohort of seizure-free patients with FCD type IIB who had T1 and fluid-attenuated inversion recovery MRI data, the MELD FCD surface-based algorithm had a sensitivity of 85%. Across the entire withheld test cohort the sensitivity was 59% and specificity was 54%. After including a border zone around lesions, to account for uncertainty around the borders of manually delineated lesion masks, the sensitivity was 67%. This multicentre, multinational study with open access protocols and code has developed a robust and interpretable machine-learning algorithm for automated detection of focal cortical dysplasias, giving physicians greater confidence in the identification of subtle MRI lesions in individuals with epilepsy.

Objective: The purpose of this study is to investigate the outcomes of epilepsy surgery targeting the subcentimeter-sized resting state functional magnetic resonance imaging (rs-fMRI) epileptogenic onset zone (EZ) in hypothalamic hamartoma (HH). Methods: Fifty-one children with HH-related intractable epilepsy received anatomical MRI-guided stereotactic laser ablation (SLA) procedures. Fifteen of these children were control subjects (CS) not guided by rs-fMRI. Thirty-six had been preoperatively guided by rs-fMRI (RS) to determine EZs, which were subsequently targeted by SLA. The primary outcome measure for the study was a predetermined goal of 30% reduction in seizure frequency and improvement in class I Engel outcomes 1 year postoperatively. Quantitative and qualitative volumetric analyses of total HH and ablated tissue were also assessed. Results: In the RS group, the EZ target within the HH was ablated with high accuracy (>87.5% of target ablated in 83% of subjects). There was no difference between the groups in percentage of ablated hamartoma volume (P = 0.137). Overall seizure reduction was higher in the rs-fMRI group: 85% RS versus 49% CS (P = 0.0006, adjusted). The Engel Epilepsy Surgery Outcome Scale demonstrated significant differences in those with freedom from disabling seizures (class I), 92% RS versus 47% CS, a 45% improvement (P = 0.001). Compared to prior studies, there was improvement in class I outcomes (92% vs 76%-81%). No postoperative morbidity or mortality occurred. Significance: For the first time, surgical SLA targeting of subcentimeter-sized EZs, located by rs-fMRI, guided surgery for intractable epilepsy. Our outcomes demonstrated the highest seizure freedom rate without surgical complications and are a significant improvement over prior reports. The approach improved freedom ---

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Context: Spinal cord injury (SCI) results in a loss of function and sensation below the level of the lesion. Neuroprosthetic technology has been developed to help restore motor and autonomic functions as well as to provide sensory feedback. Findings: This paper provides an overview of neuroprosthetic technology that aims to address the priorities for functional restoration as defined by individuals with SCI. We describe neuroprostheses that are in various stages of preclinical development, clinical testing, and commercialization including functional electrical stimulators, epidural and intraspinal microstimulation, bladder neuroprosthesis, and cortical stimulation for restoring sensation. We also discuss neural recording technologies that may provide command or feedback signals for neuroprosthetic devices. Conclusion/clinical relevance: Neuroprostheses have begun to address the priorities of individuals with SCI, although there remains room for improvement. In addition to continued technological improvements, closing the loop between the technology and the user may help provide intuitive device control with high levels of performance.