Normative intracranial EEG maps epileptogenic tissues in focal epilepsy.

Planning surgery for patients with medically refractory epilepsy often requires recording seizures using intracranial EEG. Quantitative measures derived from interictal intracranial EEG yield potentially appealing biomarkers to guide these surgical procedures; however, their utility is limited by the sparsity of electrode implantation as well as the normal confounds of spatiotemporally varying neural activity and connectivity. We propose that comparing intracranial EEG recordings to a normative atlas of intracranial EEG activity and connectivity can reliably map abnormal regions, identify targets for invasive treatment and increase our understanding of human epilepsy. Merging data from the Penn Epilepsy Center and a public database from the Montreal Neurological Institute, we aggregated interictal intracranial EEG retrospectively across 166 subjects comprising >5000 channels. For each channel, we calculated the normalized spectral power and coherence in each canonical frequency band. We constructed an intracranial EEG atlas by mapping the distribution of each feature across the brain and tested the atlas against data from novel patients by generating a z-score for each channel. We demonstrate that for seizure onset zones within the mesial temporal lobe, measures of connectivity abnormality provide greater distinguishing value than univariate measures of abnormal neural activity. We also find that patients with a longer diagnosis of epilepsy have greater abnormalities in connectivity. By integrating measures of both single-channel activity and inter-regional functional connectivity, we find a better accuracy in predicting the seizure onset zones versus normal brain (area under the curve = 0.77) compared with either group of features alone. We propose that aggregating normative intracranial EEG data across epilepsy centres into a normative atlas provides a rigorous, quantitative method to map epileptic networks and guide invasive therapy. We publicly share our data, infrastructure and methods, and propose an international framework for leveraging big data in surgical planning for refractory epilepsy.

Policies Restricting Overlapping Surgeries Negatively Impact Access to Care, Clinical Efficiency, and Hospital Revenue: A Forecasting Model for Surgical Scheduling.

OBJECTIVE: To model the financial impact of policies governing the scheduling of overlapping surgeries, and to identify optimal solutions that maximize operating efficiency that satisfy the fiduciary duty to patients. BACKGROUND: Hospitals depend on procedural revenue to maintain financial health as the recent pandemic has revealed. Proposed policies governing the scheduling of overlapping surgeries may dramatically impact hospital revenue. To date, the potential financial impact has not been modeled. METHODS: A linear forecasting model based on a logic matrix decision tree enabled an analysis of surgeon productivity annualized over a fiscal year. The model applies procedural and operational variables to policy constraints limiting surgical scheduling. Model outputs included case and financial metrics modeled over 1000-surgeon-year simulations. case metrics included annual case volume, case mix, operating room (OR) utilization, surgeon utilization, idle time, and staff overtime hours. Financial outputs included annual revenue, expenses, and contribution margin. RESULTS: The model was validated against surgical data. case and financial metrics decreased as a function of increasingly restrictive scheduling scenarios, with the greatest contribution margin loses ($1,650,000 per surgeon-year) realized with the introduction of policies mandating that a second patient could not enter the OR until the critical portion of the first surgery was completed. We identify an optimal scheduling scenario that maximizes surgeon efficiency, minimizes OR idle time and revenue loses, and satisfies ethical obligations to patients. CONCLUSIONS: Hospitals may expect significant financial loses with the introduction of policies restricting OR scheduling. We identify an optimal solution that maximizes efficiency while satisfying ethical duty to patients. This forecast is immediately relevant to any hospital system that depends upon procedural revenue.

Learning active sensing strategies using a sensory brain-machine interface.

Diverse organisms, from insects to humans, actively seek out sensory information that best informs goal-directed actions. Efficient active sensing requires congruity between sensor properties and motor strategies, as typically honed through evolution. However, it has been difficult to study whether active sensing strategies are also modified with experience. Here, we used a sensory brain-machine interface paradigm, permitting both free behavior and experimental manipulation of sensory feedback, to study learning of active sensing strategies. Rats performed a searching task in a water maze in which the only task-relevant sensory feedback was provided by intracortical microstimulation (ICMS) encoding egocentric bearing to the hidden goal location. The rats learned to use the artificial goal direction sense to find the platform with the same proficiency as natural vision. Manipulation of the acuity of the ICMS feedback revealed distinct search strategy adaptations. Using an optimization model, the different strategies were found to minimize the effort required to extract the most salient task-relevant information. The results demonstrate that animals can adjust motor strategies to match novel sensor properties for efficient goal-directed behavior.

Alzheimer-like amyloid and tau alterations associated with cognitive deficit in temporal lobe epilepsy.

Temporal lobe epilepsy represents a major cause of drug-resistant epilepsy. Cognitive impairment is a frequent comorbidity, but the mechanisms are not fully elucidated. We hypothesized that the cognitive impairment in drug-resistant temporal lobe epilepsy could be due to perturbations of amyloid and tau signalling pathways related to activation of stress kinases, similar to those observed in Alzheimer's disease. We examined these pathways, as well as amyloid-ß and tau pathologies in the hippocampus and temporal lobe cortex of drug-resistant temporal lobe epilepsy patients who underwent temporal lobe resection (n = 19), in comparison with age- and region-matched samples from neurologically normal autopsy cases (n = 22). Post-mortem temporal cortex samples from Alzheimer's disease patients (n = 9) were used as positive controls to validate many of the neurodegeneration-related antibodies. Western blot and immunohistochemical analysis of tissue from temporal lobe epilepsy cases revealed increased phosphorylation of full-length amyloid precursor protein and its associated neurotoxic cleavage product amyloid-ß*56. Pathological phosphorylation of two distinct tau species was also increased in both regions, but increases in amyloid-ß1-42 peptide, the main component of amyloid plaques, were restricted to the hippocampus. Furthermore, several major stress kinases involved in the development of Alzheimer's disease pathology were significantly activated in temporal lobe epilepsy brain samples, including the c-Jun N-terminal kinase and the protein kinase R-like endoplasmic reticulum kinase. In temporal lobe epilepsy cases, hippocampal levels of phosphorylated amyloid precursor protein, its pro-amyloidogenic processing enzyme beta-site amyloid precursor protein cleaving enzyme 1, and both total and hyperphosphorylated tau expression, correlated with impaired preoperative executive function. Our study suggests that neurodegenerative and stress-related processes common to those observed in Alzheimer's disease may contribute to cognitive impairment in drug-resistant temporal lobe epilepsy. In particular, we identified several stress pathways that may represent potential novel therapeutic targets.

Primate somatosensory cortical neurons are entrained to both spontaneous and peripherally evoked spindle oscillations.

Recurrent thalamocortical circuits produce a number of rhythms critical to brain function. In slow-wave sleep, spindles (7-16 Hz) are a prominent spontaneous oscillation generated by thalamic circuits and triggered by cortical slow waves. In wakefulness and under anesthesia, brief peripheral sensory stimuli can evoke 10-Hz reverberations due potentially to similar thalamic mechanisms. Functionally, sleep spindles and peripherally evoked spindles may play a role in memory consolidation and perception, respectively. Yet, rarely have the circuits involved in these two rhythms been compared in the same animals and never in primates. Here, we investigated the entrainment of primary somatosensory cortex (S1) neurons to both rhythms in ketamine-sedated macaques. First, we compared spontaneous spindles in sedation and natural sleep to validate the model. Then, we quantified entrainment with spike-field coherence and phase-locking statistics. We found that S1 neurons entrained to spontaneous sleep spindles were also entrained to the evoked spindles, although entrainment strength and phase systematically differed. Our results indicate that the spindle oscillations triggered by top-down spontaneous cortical activity and bottom-up peripheral input share a common cortical substrate.NEW & NOTEWORTHY Brief sensory stimuli evoke 10-Hz oscillations in thalamocortical neuronal activity and in perceptual thresholds. The mechanisms underlying this evoked rhythm are not well understood but are thought to be similar to those generating sleep spindles. We directly compared the entrainment of cortical neurons to both spontaneous spindles and peripherally evoked oscillations in sedated monkeys. We found that the entrainment strengths to each rhythm were positively correlated, although with differing entrainment phases, implying involvement of similar networks.

Virtual resection predicts surgical outcome for drug-resistant epilepsy.

Patients with drug-resistant epilepsy often require surgery to become seizure-free. While laser ablation and implantable stimulation devices have lowered the morbidity of these procedures, seizure-free rates have not dramatically improved, particularly for patients without focal lesions. This is in part because it is often unclear where to intervene in these cases. To address this clinical need, several research groups have published methods to map epileptic networks but applying them to improve patient care remains a challenge. In this study we advance clinical translation of these methods by: (i) presenting and sharing a robust pipeline to rigorously quantify the boundaries of the resection zone and determining which intracranial EEG electrodes lie within it; (ii) validating a brain network model on a retrospective cohort of 28 patients with drug-resistant epilepsy implanted with intracranial electrodes prior to surgical resection; and (iii) sharing all neuroimaging, annotated electrophysiology, and clinical metadata to facilitate future collaboration. Our network methods accurately forecast whether patients are likely to benefit from surgical intervention based on synchronizability of intracranial EEG (area under the receiver operating characteristic curve of 0.89) and provide novel information that traditional electrographic features do not. We further report that removing synchronizing brain regions is associated with improved clinical outcome, and postulate that sparing desynchronizing regions may further be beneficial. Our findings suggest that data-driven network-based methods can identify patients likely to benefit from resective or ablative therapy, and perhaps prevent invasive interventions in those unlikely to do so.

Mechanistic target of rapamycin complex 1 and 2 in human temporal lobe epilepsy.

OBJECTIVE: Temporal lobe epilepsy (TLE) is a chronic epilepsy syndrome defined by seizures and progressive neurological disabilities, including cognitive impairments, anxiety, and depression. Here, human TLE specimens were investigated focusing on the mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) and complex 2 (mTORC2) activities in the brain, given that both pathways may represent unique targets for treatment. METHODS: Surgically resected hippocampal and temporal lobe samples from therapy-resistant TLE patients were analyzed by western blotting to quantify the expression of established mTORC1 and mTORC2 activity markers and upstream or downstream signaling pathways involving the two complexes. Histological and immunohistochemical techniques were used to assess hippocampal and neocortical structural abnormalities and cell-specific expression of individual biomarkers. Samples from patients with focal cortical dysplasia (FCD) type II served as positive controls. RESULTS: We found significantly increased expression of phospho-mTOR (Ser2448), phospho-S6 (Ser235/236), phospho-S6 (Ser240/244), and phospho-Akt (Ser473) in TLE samples compared to controls, consistent with activation of both mTORC1 and mTORC2. Our work identified the phosphoinositide 3-kinase and Ras/extracellular signal-regulated kinase signaling pathways as potential mTORC1 and mTORC2 upstream activators. In addition, we found that overactive mTORC2 signaling was accompanied by induction of two protein kinase B-dependent prosurvival pathways, as evidenced by increased inhibitory phosphorylation of forkhead box class O3a (Ser253) and glycogen synthase kinase 3 beta (Ser9). INTERPRETATION: Our data demonstrate that mTOR signaling is significantly dysregulated in human TLE, offering new targets for pharmacological interventions. Specifically, clinically available drugs that suppress mTORC1 without compromising mTOR2 signaling, such as rapamycin and its analogs, may represent a new group of antiepileptogenic agents in TLE patients. Ann Neurol 2018;83:311-327.

Hippocampal gamma-slow oscillation coupling in macaques during sedation and sleep.

Behavioral and neurophysiological evidence suggests that the slow (≤1 Hz) oscillation (SO) during sleep plays a role in consolidating hippocampal (HIPP)-dependent memories. The effects of the SO on HIPP activity have been studied in rodents and cats both during natural sleep and during anesthetic administration titrated to mimic sleep-like slow rhythms. In this study, we sought to document these effects in primates. First, HIPP field potentials were recorded during ketamine-dexmedetomidine sedation and during natural sleep in three rhesus macaques. Sedation produced regionally-specific slow and gamma (∼40 Hz) oscillations with strong coupling between the SO phase and gamma amplitude. These same features were seen in slow-wave sleep (SWS), but the coupling was weaker and the coupled gamma oscillation had a higher frequency (∼70 Hz) during SWS. Second, electrical stimuli were delivered to HIPP afferents in the parahippocampal gyrus (PHG) during sedation to assess the effects of sleep-like SO on excitability. Gamma bursts after the peak of SO cycles corresponded to periods of increased gain of monosynaptic connections between the PHG and HIPP. However, the two PHG-HIPP connectivity gains during sedation were both substantially lower than when the animal was awake. We conclude that the SO is correlated with rhythmic excitation and inhibition of the PHG-HIPP network, modulating connectivity and gamma generators intrinsic to this network. Ketamine-dexmedetomidine sedation produces a similar effect, but with a decreased contribution of the PHG to HIPP activity and gamma generation.

Bioresorbable silicon electronics for transient spatiotemporal mapping of electrical activity from the cerebral cortex.

Bioresorbable silicon electronics technology offers unprecedented opportunities to deploy advanced implantable monitoring systems that eliminate risks, cost and discomfort associated with surgical extraction. Applications include postoperative monitoring and transient physiologic recording after percutaneous or minimally invasive placement of vascular, cardiac, orthopaedic, neural or other devices. We present an embodiment of these materials in both passive and actively addressed arrays of bioresorbable silicon electrodes with multiplexing capabilities, which record in vivo electrophysiological signals from the cortical surface and the subgaleal space. The devices detect normal physiologic and epileptiform activity, both in acute and chronic recordings. Comparative studies show sensor performance comparable to standard clinical systems and reduced tissue reactivity relative to conventional clinical electrocorticography (ECoG) electrodes. This technology offers general applicability in neural interfaces, with additional potential utility in treatment of disorders where transient monitoring and modulation of physiologic function, implant integrity and tissue recovery or regeneration are required.

A chronic neural interface to the macaque dorsal column nuclei.

The dorsal column nuclei (DCN) of the brain stem contain secondary afferent neurons, which process ascending somatosensory information. Most of the known physiology of the DCN in primates has been acquired in acute experiments with anesthetized animals. Here, we developed a technique to implant a multielectrode array (MEA) chronically in the DCN of macaque monkeys to enable experiments with the animals awake. Two monkeys were implanted with brain-stem MEAs for 2-5 mo with no major adverse effects. Responses of the cuneate and gracile nuclei were quantified at the level of both field potentials and single units. Tactile receptive fields (RFs) were identified for 315 single units. A subset of these units had very regular spiking patterns with spike frequencies predominantly in the alpha band (8-14 Hz). The stability of the neuronal recordings was assessed with a novel analysis that identified units by their mean spike waveform and by the spike-triggered average of activity on all other electrodes in the array. Fifty-six identified neurons were observed over two or more sessions and in a few cases for as long as 1 mo. RFs of stable neurons were largely consistent across days. The results demonstrate that a chronic DCN implant in a macaque can be safe and effective, yielding high-quality unit recording for several months. The unprecedented access to these nuclei in awake primates should lead to a better understanding of their role in sensorimotor behavior.

Dynamic Network Drivers of Seizure Generation, Propagation and Termination in Human Neocortical Epilepsy.

The epileptic network is characterized by pathologic, seizure-generating 'foci' embedded in a web of structural and functional connections. Clinically, seizure foci are considered optimal targets for surgery. However, poor surgical outcome suggests a complex relationship between foci and the surrounding network that drives seizure dynamics. We developed a novel technique to objectively track seizure states from dynamic functional networks constructed from intracranial recordings. Each dynamical state captures unique patterns of network connections that indicate synchronized and desynchronized hubs of neural populations. Our approach suggests that seizures are generated when synchronous relationships near foci work in tandem with rapidly changing desynchronous relationships from the surrounding epileptic network. As seizures progress, topographical and geometrical changes in network connectivity strengthen and tighten synchronous connectivity near foci-a mechanism that may aid seizure termination. Collectively, our observations implicate distributed cortical structures in seizure generation, propagation and termination, and may have practical significance in determining which circuits to modulate with implantable devices.

Theta and high-frequency activity mark spontaneous recall of episodic memories.

Humans possess the remarkable ability to search their memory, allowing specific past episodes to be re-experienced spontaneously. Here, we administered a free recall test to 114 neurosurgical patients and used intracranial theta and high-frequency activity (HFA) to identify the spatiotemporal pattern of neural activity underlying spontaneous episodic retrieval. We found that retrieval evolved in three electrophysiological stages composed of: (1) early theta oscillations in the right temporal cortex, (2) increased HFA in the left hemisphere including the medial temporal lobe (MTL), left inferior frontal gyrus, as well as the ventrolateral temporal cortex, and (3) motor/language activation during vocalization of the retrieved item. Of these responses, increased HFA in the left MTL predicted recall performance. These results suggest that spontaneous recall of verbal episodic memories involves a spatiotemporal pattern of spectral changes across the brain; however, high-frequency activity in the left MTL represents a final common pathway of episodic retrieval.

Lateral Transorbital Endoscopic Access to the Hippocampus, Amygdala, and Entorhinal Cortex: Initial Clinical Experience.

BACKGROUND/AIMS: Transorbital approaches traditionally have focused on skull base and cavernous sinus lesions medial to the globe. Lateral orbital approaches to the temporal lobe have not been widely explored despite several theoretical advantages compared to open craniotomy. Recently, we demonstrated the feasibility of the lateral transorbital technique in cadaveric specimens with endoscopic visualization. We describe our initial clinical experience with the endoscope-assisted lateral transorbital approach to lesions in the temporal lobe. METHODS: Two patients with mesial temporal lobe pathology presenting with seizures underwent surgery. The use of a transpalpebral or Stallard-Wright eyebrow incision enabled access to the intraorbital compartment, and a lateral orbital wall 'keyhole' opening permitted visualization of the anterior temporal pole. RESULTS: This approach afforded adequate access to the surgical target and surrounding structures and was well tolerated by the patients. To the best of our knowledge, this report constitutes the first case series describing the endoscope-assisted lateral transorbital approach to the temporal lobe. We discuss the limits of exposure, the nuances of opening and closing, and comparisons to open craniotomy. CONCLUSION: Further prospective investigation of this approach is warranted for comparison to traditional approaches to the mesial temporal lobe.

Myo-cortical crossed feedback reorganizes primate motor cortex output.

The motor system is capable of adapting to changed conditions such as amputations or lesions by reorganizing cortical representations of peripheral musculature. To investigate the underlying mechanisms we induced targeted reorganization of motor output effects by establishing an artificial recurrent connection between a forelimb muscle and an unrelated site in the primary motor cortex (M1) of macaques. A head-fixed computer transformed forelimb electromyographic activity into proportional subthreshold intracortical microstimulation (ICMS) during hours of unrestrained volitional behavior. This conditioning paradigm stimulated the cortical site for a particular muscle in proportion to activation of another muscle and induced robust site- and input-specific reorganization of M1 output effects. Reorganization was observed within 25 min and could be maintained with intermittent conditioning for successive days. Control stimulation that was independent of muscle activity, termed "pseudoconditioning," failed to produce reorganization. Preconditioning output effects were gradually restored during volitional behaviors following the end of conditioning. The ease of changing the relationship between cortical sites and associated muscle responses suggests that under normal conditions these relations are maintained through physiological feedback loops. These findings demonstrate that motor cortex outputs may be reorganized in a targeted and sustainable manner through artificial afferent feedback triggered from controllable and readily recorded muscle activity. Such cortical reorganization has implications for therapeutic treatment of neurological injuries.

An open-source automated platform for three-dimensional visualization of subdural electrodes using CT-MRI coregistration.

OBJECTIVE: Visualizing implanted subdural electrodes in three-dimensional (3D) space can greatly aid in planning, executing, and validating resection in epilepsy surgery. Coregistration software is available, but cost, complexity, insufficient accuracy, or validation limit adoption. We present a fully automated open-source application, based on a novel method using postimplant computerized tomography (CT) and postimplant magnetic resonance (MR) images, for accurately visualizing intracranial electrodes in 3D space. METHODS: CT-MR rigid brain coregistration, MR nonrigid registration, and prior-based segmentation were carried out on seven patients. Postimplant CT, postimplant MR, and an external labeled atlas were then aligned in the same space. The coregistration algorithm was validated by manually marking identical anatomic landmarks on the postimplant CT and postimplant MR images. Following coregistration, distances between the center of the landmark masks on the postimplant MR and the coregistered CT images were calculated for all subjects. Algorithms were implemented in open-source software and translated into a "drag and drop" desktop application for Apple Mac OS X. RESULTS: Despite postoperative brain deformation, the method was able to automatically align intrasubject multimodal images and segment cortical subregions, so that all electrodes could be visualized on the parcellated brain. Manual marking of anatomic landmarks validated the coregistration algorithm with a mean misalignment distance of 2.87 mm (standard deviation 0.58 mm)between the landmarks. Software was easily used by operators without prior image processing experience. SIGNIFICANCE: We demonstrate an easy to use, novel platform for accurately visualizing subdural electrodes in 3D space on a parcellated brain. We rigorously validated this method using quantitative measures. The method is unique because it involves no preprocessing, is fully automated, and freely available worldwide. A desktop application, as well as the source code, are both available for download on the International Epilepsy Electrophysiology Portal (https://www.ieeg.org) for use and interactive refinement.

Dichotomous frequency-dependent phase synchrony in the sensorimotor network characterizes simplistic movement.

It is hypothesized that disparate brain regions interact via synchronous activity to control behavior. The nature of these interconnected ensembles remains an area of active investigation, and particularly the role of high frequency synchronous activity in simplistic behavior is not well known. Using intracranial electroencephalography, we explored the spectral dynamics and network connectivity of sensorimotor cortical activity during a simple motor task in seven epilepsy patients. Confirming prior work, we see a "spectral tilt" (increased high-frequency (HF, 70-100 Hz) and decreased low-frequency (LF, 3-33 Hz) broadband oscillatory activity) in motor regions during movement compared to rest, as well as an increase in LF synchrony between these regions using time-resolved phase-locking. We then explored this phenomenon in high frequency and found a robust but opposite effect, where time-resolved HF broadband phase-locking significantly decreased during movement. This "connectivity tilt" (increased LF synchrony and decreased HF synchrony) displayed a graded anatomical dependency, with the most robust pattern occurring in primary sensorimotor cortical interactions and less robust pattern occurring in associative cortical interactions. Connectivity in theta (3-7 Hz) and high beta (23-27 Hz) range had the most prominent low frequency contribution during movement, with theta synchrony building gradually while high beta having the most prominent effect immediately following the cue. There was a relatively sharp, opposite transition point in both the spectral and connectivity tilt at approximately 35 Hz. These findings support the hypothesis that task-relevant high-frequency spectral activity is stochastic and that the decrease in high-frequency synchrony may facilitate enhanced low frequency phase coupling and interregional communication. Thus, the "connectivity tilt" may characterize behaviorally meaningful cortical interactions.

Magnetic Resonance Imaging-Guided Frameless Stereotactic Injections of the Bilateral Cerebellar Dentate Nuclei in Nonhuman Primates: Technical Note.

BACKGROUND AND OBJECTIVES: Nonhuman primates (NHPs) are important preclinical models for evaluating therapeutics because of their anatomophysiological similarities to humans, and can be especially useful for testing new delivery targets. With the growing promise of cell and gene therapies for the treatment of neurological diseases, it is important to ensure the accurate and safe delivery of these agents to target structures in the brain. However, a standard guideline or method has not been developed for stereotactic targeting in NHPs. In this article, we describe the safe use of a magnetic resonance imaging-guided frameless stereotactic system to target bilateral cerebellar dentate nuclei for accurate, real-time delivery of viral vector in NHPs. METHODS: Seventeen rhesus macaques (Macaca mulatta) underwent stereotactic surgery under real-time MRI guidance using the ClearPoint® system. Bilateral cerebellar dentate nuclei were targeted through a single parietal entry point with a transtentorial approach. Fifty microliters of contrast-impregnated infusate was delivered to each dentate nucleus, and adjustments were made as necessary according to real-time MRI monitoring of delivery. Perioperative clinical outcomes and postoperative volumes of distribution were recorded. RESULTS: All macaques underwent bilateral surgery successfully. Superficial pin site infection occurred in 4/17 (23.5%) subjects, which resolved with antibiotics. Two episodes of transient neurological deficit (anisocoria and unilateral weakness) were recorded, which did not require additional postoperative treatment and resolved over time. Volume of distribution of infusate achieved satisfactory coverage of target dentate nuclei, and only 1 incidence (2.9%) of cerebrospinal fluid penetration was recorded. Mean volume of distribution was 161.22 ± 39.61 mm3 (left, 173.65 ± 48.29; right, 148.80 ± 23.98). CONCLUSION: MRI-guided frameless stereotactic injection of bilateral cerebellar dentate nuclei in NHPs is safe and feasible. The use of this technique enables real-time modification of the surgical plan to achieve adequate target coverage and can be readily translated to clinical use.

A BIOCOMPATIBLE GLASS-ENCAPSULATED TRIAXIAL FORCE SENSOR FOR IMPLANTABLE TACTILE SENSING APPLICATIONS.

This paper reports a microfabricated triaxial capacitive force sensor. The sensor is fully encapsulated with inert and biocompatible glass (fused silica) material. The sensor comprises two glass plates, on which four capacitors are located. The sensor is intended for subdermal implantation in fingertips and palms and providing tactile sensing capabilities for patients with paralyzed hands. Additional electronic components, such as passives and IC chips, can also be integrated with the sensor in a hermetic glass package to achieve an implantable tactile sensing system. Through attachment to a human palm, the sensor has been shown to respond appropriately to typical hand actions, such as squeezing or picking up a bottle.

An implantable wireless tactile sensing system.

The sense of touch is critical to dexterous use of the hands and thus an essential component to efforts to restore hand function after amputation or paralysis. Prosthetic systems have focused on wearable tactile sensors. But wearable sensors are suboptimal for neuroprosthetic systems designed to reanimate a patient's own paralyzed hand. Here, we developed an implantable tactile sensing system intended for subdermal placement. The system is composed of a microfabricated capacitive force sensor, a custom integrated circuit supporting wireless powering and data transmission, and a laser-fused hermetic silica package. The miniature device was validated through simulations, benchtop testing, and ex vivo testing in a primate hand. The sensor implanted in the fingertip accurately measured skin forces with a resolution of 4.3 mN. The output from this novel sensor could be encoded in the brain with microstimulation to provide tactile feedback. More broadly, the materials, system design, and fabrication approach establish new foundational capabilities for various applications of implantable sensing systems.

An implantable, wireless, battery-free system for tactile pressure sensing.

The sense of touch is critical to dexterous use of the hands and thus an essential component of efforts to restore hand function after amputation or paralysis. Prosthetic systems have addressed this goal with wearable tactile sensors. However, such wearable sensors are suboptimal for neuroprosthetic systems designed to reanimate a patient's own paralyzed hand. Here, we developed an implantable tactile sensing system intended for subdermal placement. The system is composed of a microfabricated capacitive pressure sensor, a custom integrated circuit supporting wireless powering and data transmission, and a laser-fused hermetic silica package. The miniature device was validated through simulations, benchtop assessment, and testing in a primate hand. The sensor implanted in the fingertip accurately measured applied skin forces with a resolution of 4.3 mN. The output from this novel sensor could be encoded in the brain with microstimulation to provide tactile feedback. More broadly, the materials, system design, and fabrication approach establish new foundational capabilities for various applications of implantable sensing systems.