Background: Bilateral laser interstitial thermal therapy (LITT) anterior capsulotomy reduces symptoms in about half of patients with treatment-resistant obsessive-compulsive disorder (OCD), but the cortical correlate of non-response is unknown. Prior capsulotomy tractography has linked outcomes to lesion size without characterising the cortical disconnection profile of non-responders at individual-parcel resolution. Methods: From 47 consecutive LITT capsulotomy patients, eight had paired pre- and postoperative diffusion tensor imaging (DTI) suitable for forward differential tractography (FDT), a method we developed: four non-responders (<35% Yale-Brown Obsessive Compulsive Scale [Y-BOCS] reduction) and four responders. In DSI Studio, FDT mapped the cortical endpoints of streamlines with postoperative fractional anisotropy decrease onto the 360-region Human Connectome Project Multi-Modal Parcellation (HCP-MMP) atlas, yielding a per-patient quantitative disconnectome (qDisconnectome). Proportional disconnection was compared with exact permutation testing (all C(8,4)=70 assignments) and Mann-Whitney U tests, and a qDisconnectome score was correlated with Y-BOCS reduction (Spearman). No people with lived experience were involved in this retrospective analysis. Outcomes: Six bilateral frontopolar regions reached dual-test convergence, non-responders 4-to-20-fold higher than responders (R a10p, R 10pp, L 10pp, L 10d, L p10p, L 10v); bilateral lateral orbitofrontal cortex trended similarly (P=0·057). The qDisconnectome score correlated inversely with Y-BOCS reduction (rho=−0·91, P=0·0020), separating groups on a continuous scale. Interpretation: Bilateral frontopolar disconnection characterises non-response to LITT anterior capsulotomy. The qDisconnectome score offers a complementary, imaging-based measure of response for patients with qualifying paired DTI. Prospective validation with standardised high-resolution diffusion imaging is needed.Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Background Laser interstitial thermal therapy (LITT) hemispherotomy offers a minimally invasive alternative to open hemispheric disconnection for medically refractory epilepsy. This study used quantitative deterministic tractography to evaluate whether the pattern of tract disconnection, rather than total ablation volume, predicts seizure outcome following LITT hemispherotomy.Methods Ten patients (median age 11 years, range 6-19) with medically refractory hemispheric epilepsy underwent LITT hemispherotomy between February 2021 and June 2025. Deterministic tractography was performed on paired preoperative and postoperative diffusion tensor imaging in five patients, quantifying percent volume ablation across 17 white matter pathways in commissural, temporal/limbic, and projection categories.Results Nine of 10 patients (90%) achieved Engel Class I outcomes at a median follow-up of 24.7 months (range 8.7-60.7). Mean total hemispheric tract volume ablated was 6.9% (range 1.2-19.8%). No patient developed hydrocephalus. Mean hospital length of stay was 2.1 days. Tractographic analysis revealed that no two patients shared an identical disconnection profile. For example, Case 5 achieved seizure freedom through commissural disconnection alone with no measurable projection tract disconnection, while Case 3 had the highest total ablation volume yet failed with only 9% splenium ablation.Conclusions These data support an individualized network hypothesis for hemispheric disconnection: seizure freedom depended on ablation of patient-specific seizure propagation pathways rather than maximization of total ablation volume. Prospective integration of high-resolution tractography with preoperative seizure generator localization could enable a minimal but sufficient disconnection strategy and warrants evaluation in future studies.

Intracortical microstimulation (ICMS) of somatosensory cortex can restore a sense of touch to people with spinal cord injury. In this early feasibility clinical trial (NCT01894802), we evaluated the safety, efficacy, and longevity of ICMS because there is a paucity of such long-term studies in humans. This information is crucial to the development of clinical neuromodulation devices, particularly for restoring touch, hearing, and vision. ICMS was delivered to five participants with spinal cord injury who were each implanted with two Blackrock NeuroPort microelectrode arrays in the hand representation of Brodmann's area 1. Across implant durations spanning 2 to 10 years, we measured single-electrode detection thresholds, projected fields, quality reports, and electrode health characteristics. ICMS-related adverse events were documented throughout. More than 168 million ICMS pulses were delivered across a combined implant duration of 27 years without any serious adverse events or direct negative effects on electrode health. ICMS consistently evoked sensations localized to the hand. Rarely, sensations persisted for brief periods after stimulation offset (3 to 25 events across participants). ICMS detection thresholds increased slowly over time (about 3.5 microamperes per year), but 64 ± 13% of the electrodes still reliably evoked tactile sensations (about 21% decrease in functional electrodes), including 60% of the electrodes after 10 years in one participant. The quality and projected field coverage of ICMS-evoked sensations were both consistent. Delivering ICMS to the somatosensory cortex was safe and effective, consistently evoking informative somatosensory percepts as long as 10 years, demonstrating the clinical promise of ICMS for sensory restoration.

Abstract The hippocampus has been proposed to support visual processing and perception, challenging longstanding accounts that emphasize navigation or declarative memory. A key prediction of visual-processing accounts is that the hippocampus should exhibit similar visuospatial coding properties to those of higher-order visual neocortical areas, such as sensitivity to the size of visual stimuli and contralateral visual field biases. We tested for these properties using intracranial EEG to measure hippocampal neural activity during a retinotopic mapping task. The hippocampus exhibited characteristic slow (∼2 Hz) and fast (∼8 Hz) theta oscillations throughout the task. Fast theta was responsive to the presence but not the amount of visual stimulation. In contrast, slow theta did not generally respond to stimulus presence but scaled with the size of the visual stimulus, consistent with larger receptive fields. Slow theta also showed a contralateral bias, an effect that was specific to the right hippocampus. None of these effects were attributable to microsaccades or performance of the concurrent vigilance task. These findings provide electrophysiological evidence for visual field coding by human hippocampus, supporting accounts of hippocampal function that emphasize its role atop the visual hierarchy. Visual processing of this kind may combine with self-motion, memory, and other signals to support the broader spatial and mnemonic functions with which hippocampal theta oscillations have long been associated.

Theta oscillations are implicated in regulating information flow within cortico-hippocampal networks to support memory and cognition. However, causal evidence tying theta oscillations to network communication in humans is lacking. Here we report experimental findings using a closed-loop, phase-locking algorithm to apply direct electrical stimulation to neocortical nodes of the hippocampal network precisely timed to ongoing hippocampal theta rhythms in human neurosurgical patients. We show that repetitive stimulation of lateral temporal cortex synchronized to hippocampal theta increases hippocampal theta while it is delivered, suggesting theta entrainment of hippocampal neural activity. After stimulation, network connectivity is persistently increased relative to baseline, as indicated by theta-phase synchrony of hippocampus to neocortex and increased amplitudes of the hippocampal evoked response to isolated neocortical stimulation. These indicators of network connectivity are not affected by control stimulation delivered with approximately the same rhythm but without phase locking to hippocampal theta. These findings support the causal role of theta oscillations in routing neural signals across the hippocampal network and suggest phase-synchronized stimulation as a promising method to modulate theta- and hippocampal-dependent behaviors.

INTRODUCTION: Intracortical microstimulation (ICMS) of the somatosensory cortex can evoke basic tactile sensations in patients with paralysis or limb loss, but traditional ICMS has constrained functionality to the simplicity of induced sensations. In this paper, we demonstrate for the first time that precisely patterned and sequenced ICMS can evoke complex tactile sensations including oriented edges, 3D-indentations, and directed motion across the skin. This discovery significantly enhances the functionality and usability of bionic neuroprosthetic devices. METHODS: We conducted experiments on two participants with spinal cord injury by implanting microelectrode arrays in the hand areas of somatosensory cortex. We designed and tested novel neurostimulation paradigms using spatially and temporally patterned ICMS. Participants performed tasks to discriminate edge orientations, identify shapes, and perceive motion. Statistical significance was assessed using Fisher's Exact Test. RESULTS: Spatially patterned ICMS evoked the sensation of an edge, with participants discriminating edge orientation at 85% accuracy for C1 and 65% for C2 (p<0.05). For complex shapes, C1 identified shapes with 82% accuracy on D2 and 72% on D3 (p<0.05). C1 differentiated between concave, convex, and flat curvatures at 64% accuracy (p<0.05). Sequential ICMS evoked motion sensations, with C1 distinguishing motion direction with 76% accuracy and C2 with 78% accuracy (p<0.05). Speed discrimination was achieved with a Weber Fraction of 0.56 ± 0.09. CONCLUSIONS: Given the complexity of tactile experience and limitations of current neural interfaces, it was previously not thought possible to recreate intricate sensations. Nevertheless, we show that spatiotemporal ICMS can produce complex sensations with existing technology. This demonstrates the potential for neuroprosthetics to restore life-enhancing touch in people with paralysis or limb loss.

BACKGROUND:Temporal lobe epilepsy (TLE) is often accompanied by psychiatric manifestations, of which, anxiety is among the most common. While the effects of surgery or ablation on TLE and seizure outcomes, as well as neuropsychological outcomes, have been well studied, anxiety is an exception and has not been systematically examined. Our study aims to systematically review the changes in anxiety before and after TLE surgery. METHODS:We systematically reviewed the existing literature on anxiety in the setting of TLE. Different electronic databases were queried for studies published until 3rd June 2024. RESULTS:Eighteen studies with 1403 patients who had refractory TLE and underwent surgical treatment were included. Eight different anxiety scales were used in the included studies, with baseline anxiety rates of 5.3 % to 35.1 %. A significant reduction in anxiety was observed in studies using the Hamilton Anxiety Rating Scale, with a pooled change of -0.87 (95 % CI: -1.26, -0.48, P < 0.001) after surgery. Conversely, the State-Trait Anxiety Inventory (STAI) scores did not show significant changes, with pooled changes of -0.30 (95 % CI: -1.72, 1.12, P = 0.68) for the State (STAI-S) and 0.10 (95 % CI: -1.56, 1.77, P = 0.90) for Trait (STAI-T) anxiety types. Similarly, significant improvements in anxiety were observed on the Hospital Anxiety and Depression Scale, with a pooled change of -0.87 (95 % CI: -1.62, -0.12, P = 0.02) at the last follow-up. CONCLUSION:Our findings indicate that TLE surgery leads to a significant reduction in anxiety levels, though evidence regarding subgroup differences, such as seizure-free versus non-seizure-free patients, remains limited due to the small number of studies. Additional research is necessary to clarify these findings and further assess the broader effects of surgery on anxiety.

Intracortical microstimulation (ICMS) of somatosensory cortex evokes tactile sensations whose properties can be systematically manipulated by varying stimulation parameters. However, ICMS currently provides an imperfect sense of touch, limiting manual dexterity and tactile experience. Leveraging our understanding of how tactile features are encoded in the primary somatosensory cortex (S1), we sought to inform individuals with paralysis about local geometry and apparent motion of objects on their skin. We simultaneously delivered ICMS through electrodes with spatially patterned projected fields (PFs), evoking sensations of edges. We then created complex PFs that encode arbitrary tactile shapes and skin indentation patterns. By delivering spatiotemporally patterned ICMS, we evoked sensation of motion across the skin, the speed and direction of which could be controlled. Thus, we improved individuals’ tactile experience and use of brain-controlled bionic hands.

Precise anatomical implantation of a microelectrode array is fundamental for successful brain-computer interface (BCI) surgery, ensuring high-quality, robust signal communication between the brain and the computer interface. Robotic neurosurgery can contribute to this goal, but its application in BCI surgery has been underexplored. Here, the authors present a novel robot-assisted surgical technique to implant rigid intracortical microelectrode arrays for the BCI. Using this technique, the authors performed surgery in a 31-year-old male with tetraplegia due to a traumatic C4 spinal cord injury that occurred a decade earlier. Each of the arrays was embedded into the parenchyma with a single insertion without complication. Postoperative imaging verified that the devices were placed as intended. With the motor cortex arrays, the participant successfully accomplished 2D control of a virtual arm and hand, with a success rate of 20 of 20 attempts, and recording quality was maintained at 100 and 200 days postimplantation. Intracortical microstimulation of the somatosensory cortex arrays elicited sensations in the fingers and palm. A robotic neurosurgery technique was successfully translated into BCI device implantation as part of an early feasibility trial with the long-term goal of restoring upper-limb function. The technique was demonstrated to be accurate and subsequently contributed to high-quality signal communication.

Background:Intracortical microstimulation (ICMS) of somatosensory cortex can restore a sense of touch to people with spinal cord injury (SCI). In this early-feasibility clinical trial, we evaluate the safety, efficacy, and longevity of ICMS as there is a paucity of such long-term studies in humans. This information is crucial to the development of clinical neuromodulation devices, particularly for restoring touch, hearing, and vision. Methods:ICMS was delivered to five participants with SCI who were each implanted with two Blackrock NeuroPort microelectrode arrays in the hand representation of Brodmann's Area 1. Across implant durations spanning two to ten years, we measured single-electrode detection thresholds, projected fields, quality reports, and electrode health characteristics. ICMS-related adverse events were documented throughout. Results:Over 168 million ICMS pulses were delivered across a combined implant duration of 24 years without any serious adverse events or direct negative effects on electrode health. ICMS consistently evoked sensations localized to the hand. Rarely, sensations persisted for brief periods after stimulation offset (3-25 events across participants). ICMS detection thresholds increased slowly over time (~3.5 μA/year), but 62±15% of the electrodes still reliably evoke tactile sensations (~25% decrease in functional electrodes), including 55% of the electrodes after 10 years in one participant. The quality and projected field coverage of ICMS-evoked sensations were both consistent. Conclusions:Delivering ICMS to somatosensory cortex was safe and reliable, consistently evoking informative somatosensory percepts as long as 10 years, demonstrating the clinical promise of ICMS for sensory restoration. (Funded by NIH; ClinicalTrials.gov: NCT01894802).

Intracortical brain-computer interfaces (iBCIs) have achieved remarkable progress in restoring arm and hand movement by inferring motor intent from neural signals in primary motor cortex (M1) and realizing the intended movements in a bionic limb. However, manual interactions with objects require not only restoration of movement but also the precise application of forces on objects, which implies a different mode of limb control that has been largely overlooked. One of the major obstacles in incorporating force control is the lack of understanding of how manual forces are encoded in M1 during object interactions. To fill this gap, we recorded the neural activity in M1 as monkeys grasped sensorized objects with varying levels of force. We found that static decoders could not reliably extract force information from M1 activity, suggesting a dynamic relationship between force and neural activity. Consistent with this hypothesis, a recurrent neural network could exploit these dynamics to accurately decode time-varying forces. Next, we applied the insights gleaned from our experiments with able-bodied macaques to build decoders of manual force in a human participant with tetraplegia. First, we found that the patterns of responses in human M1 during imagined force application were similar to those in monkey M1 during physical force application. We then applied recurrent neural networks to decode force from M1 activity and showed that these allow the participants to accurately exert forces with a (brain-controlled) virtual hand.

IntroductionEssential tremor (ET) is a common neurological disease. Deep brain stimulation (DBS) to the thalamic ventral intermediate nucleus (VIM) or the adjacent structures, such as caudal zona incerta/ posterior subthalamic area (cZi/PSA), can be effective in treating medication refractory tremor. However, it is not clear whether DBS can cause cognitive changes, in which domain, and to what extent if so.MethodsWe systematically searched PubMed and the Web of Science for available publications reporting on cognitive outcomes in patients with ET who underwent DBS following the PICO (population, intervention, comparators, and outcomes) concept. The PRISMA guideline for systematic reviews was applied.ResultsTwenty relevant articles were finally identified and included for review, thirteen of which were prospective (one also randomized) studies and seven were retrospective. Cognitive outcomes included attention, memory, executive function, language, visuospatial function, and mood-related variables. VIM and cZi/PSA DBS were generally well tolerated, although verbal fluency and language production were affected in some patients. Additionally, left-sided VIM DBS was associated with negative effects on verbal abstraction, word recall, and verbal memory performance in some patients.ConclusionSignificant cognitive decline after VIM or cZi/PSA DBS in ET patients appears to be rare. Future prospective randomized controlled trials are needed to meticulously study the effect of the location, laterality, and stimulation parameters of the active contacts on cognitive outcomes while considering possible medication change post-DBS, timing, standard neuropsychological battery, practice effects, the timing of assessment, and effect size as potential confounders.

Intracranial electroencephalographic (IEEG) recording, using subdural electrodes (SDEs) and stereoelectroencephalography (SEEG), plays a pivotal role in localizing the epileptogenic zone (EZ). SDEs, employed for superficial cortical seizure foci localization, provide information on two-dimensional seizure onset and propagation. In contrast, SEEG, with its three-dimensional sampling, allows exploration of deep brain structures, sulcal folds, and bihemispheric networks. SEEG offers the advantages of fewer complications, better tolerability, and coverage of sulci. Although both modalities allow electrical stimulation, SDE mapping can tessellate cortical gyri, providing the opportunity for a tailored resection. With SEEG, both superficial gyri and deep sulci can be stimulated, and there is a lower risk of afterdischarges and stimulation-induced seizures. Most systematic reviews and meta-analyses have addressed the comparative effectiveness of SDEs and SEEG in localizing the EZ and achieving seizure freedom, although discrepancies persist in the literature. The combination of SDEs and SEEG could potentially overcome the limitations inherent to each technique individually, better delineating seizure foci. This review describes the strengths and limitations of SDE and SEEG recordings, highlighting their unique indications in seizure localization, as evidenced by recent publications. Addressing controversies in the perceived usefulness of the two techniques offers insights that can aid in selecting the most suitable IEEG in clinical practice.

Tactile feedback from brain-controlled bionic hands can be partially restored via intracortical microstimulation (ICMS) of the primary somatosensory cortex. In ICMS, the location of percepts depends on the electrode's location and the percept intensity depends on the stimulation frequency and amplitude. Sensors on a bionic hand can thus be linked to somatotopically appropriate electrodes, and the contact force of each sensor can be used to determine the amplitude of a stimulus. Here we report a systematic investigation of the localization and intensity of ICMS-evoked percepts in three participants with cervical spinal cord injury. A retrospective analysis of projected fields showed that they were typically composed of a focal hotspot with diffuse borders, arrayed somatotopically in keeping with their underlying receptive fields and stable throughout the duration of the study. When testing the participants' ability to rapidly localize a single ICMS presentation, individual electrodes typically evoked only weak sensations, making object localization and discrimination difficult. However, overlapping projected fields from multiple electrodes produced more localizable and intense sensations and allowed for a more precise use of a bionic hand.

Intracortical microstimulation (ICMS) is a method for restoring sensation to people with paralysis as part of a bidirectional brain-computer interface to restore upper limb function. Evoking tactile sensations of the hand through ICMS requires precise targeting of implanted electrodes. Here we describe the presurgical imaging procedures used to generate functional maps of the hand area of the somatosensory cortex and subsequent planning that guided the implantation of intracortical microelectrode arrays. In five participants with cervical spinal cord injury, across two study locations, this procedure successfully enabled ICMS-evoked sensations localized to at least the first four digits of the hand. The imaging and planning procedures developed through this clinical trial provide a roadmap for other brain-computer interface studies to ensure successful placement of stimulation electrodes.

Intracortical microstimulation (ICMS) is a method for restoring sensation to people with paralysis as part of a bidirectional brain-computer interface (BCI) to restore upper limb function. Evoking tactile sensations of the hand through ICMS requires precise targeting of implanted electrodes. Here we describe the presurgical imaging procedures used to generate functional maps of the hand area of the somatosensory cortex and subsequent planning that guided the implantation of intracortical microelectrode arrays. In five participants with cervical spinal cord injury, across two study locations, this procedure successfully enabled ICMS-evoked sensations localized to at least the first four digits of the hand. The imaging and planning procedures developed through this clinical trial provide a roadmap for other BCI studies to ensure the successful placement of stimulation electrodes.

BackgroundMRI guided laser interstitial thermal therapy (M-LITT) capsulotomy has proven to be efficacious in decreasing refractory obsessive-compulsive disorder (OCD) related symptomatology yet capsulotomy either via radiosurgery or radiofrequency ablation has in some patients led to increased apathy following surgery. The current case series aims to investigate objective patient-reported change in apathy, disinhibition, depression, and executive dysfunction following anterior capsulotomy via M-LITT for OCD.MethodsTen consecutive patients pre- and post-M-LITT completed measures of OCD, apathy, disinhibition, executive dysfunction, and depression (Mtime between= 1.3 years; 0.42-3.7 years). Reliable Change Index (RCI) was used to evaluate change in pre- and post-M-LITT. OCD symptom response was evaluated using percent change (Y-BOCS scores: 24-34 % reduction indicating partial response; ≥35% reduction indicating full response).ResultsPositive post-surgical change was noted in OCD symptomatology with >65% reporting a partial or full response. However, six patients endorsed increased apathy with half of the non-responders (e.g., less than <24% score reduction on Y-BOCS) reporting increases in apathy. Patients reported relatively stable disinhibition and executive dysfunction, while over half reported a decrease in depression symptoms. Two of the non-responders and one responder endorsed increased apathy despite stable or improved depression symptoms, disinhibition, and executive dysfunction.ConclusionsMost patients in the current cohort achieved full-or-partial OCD recovery. Yet, 60% of patients also reported significant increases in apathy, despite experiencing a decrease in depression symptoms, with stable disinhibition and executive dysfunction. Despite these promising improvements in OCD symptomatology following M-LITT, further investigations of the impact of surgery and lesion location on apathy levels is clearly warranted using objective, quantifiable methods.

Epileptic DisordersAccepted Articles CLINICAL VIGNETTE Paradigm found: Epileptogenic Zone Identified by fMRI in Ictal Fixation Off Sensitivity Douglas R. Nordli III, Corresponding Author Douglas R. Nordli III [email protected] University of Chicago, Department of Neurology, 5841 S Maryland Ave, Chicago, IL Correspondence mail id. Email: [email protected]Search for more papers by this authorJohn Collins, John Collins University of Chicago, Department of Radiology, 5841 S Maryland Ave, Chicago, ILSearch for more papers by this authorPeter Warnke, Peter Warnke University of Chicago, Department of Neurological Surgery, 5841 S Maryland Ave, Chicago, ILSearch for more papers by this authorDouglas R. Nordli JR, Douglas R. Nordli JR orcid.org/0000-0002-3995-5467 University of Chicago, Department of Neurology, 5841 S Maryland Ave, Chicago, ILSearch for more papers by this author Douglas R. Nordli III, Corresponding Author Douglas R. Nordli III [email protected] University of Chicago, Department of Neurology, 5841 S Maryland Ave, Chicago, IL Correspondence mail id. Email: [email protected]Search for more papers by this authorJohn Collins, John Collins University of Chicago, Department of Radiology, 5841 S Maryland Ave, Chicago, ILSearch for more papers by this authorPeter Warnke, Peter Warnke University of Chicago, Department of Neurological Surgery, 5841 S Maryland Ave, Chicago, ILSearch for more papers by this authorDouglas R. Nordli JR, Douglas R. Nordli JR orcid.org/0000-0002-3995-5467 University of Chicago, Department of Neurology, 5841 S Maryland Ave, Chicago, ILSearch for more papers by this author First published: 28 November 2023 https://doi.org/10.1002/epd2.20183 This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/epd2.20183. AboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat Supporting Information Filename Description epd220183-sup-0001-Supinfo.zipZip archive, 41.5 MB Appendix S1: Supporting Information Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. Accepted ArticlesAccepted, unedited articles published online and citable. The final edited and typeset version of record will appear in the future. RelatedInformation

Manual interactions with objects are supported by tactile signals from the hand. This tactile feedback can be restored in brain-controlled bionic hands via intracortical microstimulation (ICMS) of somatosensory cortex (S1). In ICMS-based tactile feedback, contact force can be signaled by modulating the stimulation intensity based on the output of force sensors on the bionic hand, which in turn modulates the perceived magnitude of the sensation. In the present study, we gauged the dynamic range and precision of ICMS-based force feedback in three human participants implanted with arrays of microelectrodes in S1. To this end, we measured the increases in sensation magnitude resulting from increases in ICMS amplitude and participant's ability to distinguish between different intensity levels. We then assessed whether we could improve the fidelity of this feedback by implementing "biomimetic" ICMS-trains, designed to evoke patterns of neuronal activity that more closely mimic those in natural touch, and by delivering ICMS through multiple channels at once. We found that multi-channel biomimetic ICMS gives rise to stronger and more distinguishable sensations than does its single-channel counterpart. Finally, we implemented biomimetic multi-channel feedback in a bionic hand and had the participant perform a compliance discrimination task. We found that biomimetic multi-channel tactile feedback yielded improved discrimination over its single-channel linear counterpart. We conclude that multi-channel biomimetic ICMS conveys finely graded force feedback that more closely approximates the sensitivity conferred by natural touch.