Sensory restoration by epidural stimulation of the lateral spinal cord in upper-limb amputees.
ABSTRACT: Restoring somatosensory feedback to people with limb amputations is crucial to improve prosthetic control. Multiple studies have demonstrated that peripheral nerve stimulation and targeted reinnervation can provide somatotopically relevant sensory feedback. While effective, the surgical procedures required for these techniques remain a major barrier to translatability. Here, we demonstrate in four people with upper-limb amputation that epidural spinal cord stimulation (SCS), a common clinical technique to treat pain, evoked somatosensory percepts that were perceived as emanating from the missing arm and hand. Over up to 29 days, stimulation evoked sensory percepts in consistent locations in the missing hand regardless of time since amputation or level of amputation. Evoked sensations were occasionally described as naturalistic (e.g. touch or pressure), but were often paresthesias. Increasing stimulus amplitude increased the perceived intensity linearly, without increasing area of the sensations. These results demonstrate the potential of SCS as a tool to restore somatosensation after amputations.
Project description:Amputation in adults is associated with an extensive remapping of cortical topography in primary and secondary sensorimotor areas. Here, we used tactile residual limb stimulation and 3T functional magnetic resonance imaging in humans to investigate functional connectivity changes in the sensorimotor network of patients with long-term lower limb traumatic amputations with phantom sensation, but without pain. We found a pronounced reduction of inter-hemispheric functional connectivity between homologous sensorimotor cortical regions in amputees, including the primary (S1) and secondary (S2) somatosensory areas, and primary (M1) and secondary (M2) motor areas. We additionally observed an intra-hemispheric increased functional connectivity between primary and secondary somatosensory regions, and between the primary and premotor areas, contralateral to amputation. These functional connectivity changes in specialized small-scale sensory-motor networks improve our understanding of the functional impact of lower limb amputation in the brain. Our findings in a selective group of patients with phantom limb sensations, but without pain suggest that disinhibition of neural inputs following traumatic limb amputation disrupts sensorimotor topology, unbalancing functional brain network organization. These findings step up the description of brain plasticity related with phantom sensations by showing that pain is not critical for sensorimotor network changes after peripheral injury.
Project description:The perception of somatosensation requires the integration of multimodal information, yet the effects of vision and posture on somatosensory percepts elicited by neural stimulation are not well established. In this study, we applied electrical stimulation directly to the residual nerves of trans-tibial amputees to elicit sensations referred to their missing feet. We evaluated the influence of congruent and incongruent visual inputs and postural manipulations on the perceived size and location of stimulation-evoked somatosensory percepts. We found that although standing upright may cause percept size to change, congruent visual inputs and/or body posture resulted in better localization. We also observed visual capture: the location of a somatosensory percept shifted toward a visual input when vision was incongruent with stimulation-induced sensation. Visual capture did not occur when an adopted posture was incongruent with somatosensation. Our results suggest that internal model predictions based on postural manipulations reinforce perceived sensations, but do not alter them. These characterizations of multisensory integration are important for the development of somatosensory-enabled prostheses because current neural stimulation paradigms cannot replicate the afferent signals of natural tactile stimuli. Nevertheless, multisensory inputs can improve perceptual precision and highlight regions of the foot important for balance and locomotion.
Project description:Sensory feedback is a critical aspect of motor control rehabilitation following paralysis or amputation. Current human studies have demonstrated the ability to deliver some of this sensory information via brain-machine interfaces, although further testing is needed to understand the stimulation parameters effect on sensation. Here, we report a systematic evaluation of somatosensory restoration in humans, using cortical stimulation with subdural mini-electrocorticography (mini-ECoG) grids. Nine epilepsy patients undergoing implantation of cortical electrodes for seizure localization were also implanted with a subdural 64-channel mini-ECoG grid over the hand area of the primary somatosensory cortex (S1). We mapped the somatotopic location and size of receptive fields evoked by stimulation of individual channels of the mini-ECoG grid. We determined the effects on perception by varying stimulus parameters of pulse width, current amplitude, and frequency. Finally, a target localization task was used to demonstrate the use of artificial sensation in a behavioral task. We found a replicable somatotopic representation of the hand on the mini-ECoG grid across most subjects during electrical stimulation. The stimulus-evoked sensations were usually of artificial quality, but in some cases were more natural and of a cutaneous or proprioceptive nature. Increases in pulse width, current strength and frequency generally produced similar quality sensations at the same somatotopic location, but with a perception of increased intensity. The subjects produced near perfect performance when using the evoked sensory information in target acquisition tasks. These findings indicate that electrical stimulation of somatosensory cortex through mini-ECoG grids has considerable potential for restoring useful sensation to patients with paralysis and amputation.
Project description:Pioneering work with nonhuman primates and recent human studies established intracortical microstimulation (ICMS) in primary somatosensory cortex (S1) as a method of inducing discriminable artificial sensation. However, these artificial sensations do not yet provide the breadth of cutaneous and proprioceptive percepts available through natural stimulation. In a tetraplegic human with two microelectrode arrays implanted in S1, we report replicable elicitations of sensations in both the cutaneous and proprioceptive modalities localized to the contralateral arm, dependent on both amplitude and frequency of stimulation. Furthermore, we found a subset of electrodes that exhibited multimodal properties, and that proprioceptive percepts on these electrodes were associated with higher amplitudes, irrespective of the frequency. These novel results demonstrate the ability to provide naturalistic percepts through ICMS that can more closely mimic the body's natural physiological capabilities. Furthermore, delivering both cutaneous and proprioceptive sensations through artificial somatosensory feedback could improve performance and embodiment in brain-machine interfaces.
Project description:Myoelectric devices are controlled by electromyographic signals generated by contraction of residual muscles, which thus serve as biological amplifiers of neural control signals. Although nerves severed by amputation continue to carry motor control information intended for the missing limb, loss of muscle effectors due to amputation prevents access to this important control information. Targeted Muscle Reinnervation (TMR) was developed as a novel strategy to improve control of myoelectric upper limb prostheses. Severed motor nerves are surgically transferred to the motor points of denervated target muscles, which, after reinnervation, contract in response to neural control signals for the missing limb. TMR creates additional control sites, eliminating the need to switch the prosthesis between different control modes. In addition, contraction of target muscles, and operation of the prosthesis, occurs in reponse to attempts to move the missing limb, making control easier and more intuitive. TMR has been performed extensively in individuals with high-level upper limb amputations and has been shown to improve functional prosthesis control. The benefits of TMR are being studied in individuals with transradial amputations and lower limb amputations. TMR is also being investigated in an ongoing clinical trial as a method to prevent or treat painful amputation neuromas.
Project description:Following arm amputation the region that represented the missing hand in primary somatosensory cortex (S1) becomes deprived of its primary input, resulting in changed boundaries of the S1 body map. This remapping process has been termed 'reorganisation' and has been attributed to multiple mechanisms, including increased expression of previously masked inputs. In a maladaptive plasticity model, such reorganisation has been associated with phantom limb pain (PLP). Brain activity associated with phantom hand movements is also correlated with PLP, suggesting that preserved limb functional representation may serve as a complementary process. Here we review some of the most recent evidence for the potential drivers and consequences of brain (re)organisation following amputation, based on human neuroimaging. We emphasise other perceptual and behavioural factors consequential to arm amputation, such as non-painful phantom sensations, perceived limb ownership, intact hand compensatory behaviour or prosthesis use, which have also been related to both cortical changes and PLP. We also discuss new findings based on interventions designed to alter the brain representation of the phantom limb, including augmented/virtual reality applications and brain computer interfaces. These studies point to a close interaction of sensory changes and alterations in brain regions involved in body representation, pain processing and motor control. Finally, we review recent evidence based on methodological advances such as high field neuroimaging and multivariate techniques that provide new opportunities to interrogate somatosensory representations in the missing hand cortical territory. Collectively, this research highlights the need to consider potential contributions of additional brain mechanisms, beyond S1 remapping, and the dynamic interplay of contextual factors with brain changes for understanding and alleviating PLP.
Project description:Electrical stimulation of sensory nerves is a powerful tool for studying neural coding because it can activate neural populations in ways that natural stimulation cannot. Electrical stimulation of the nerve has also been used to restore sensation to patients who have suffered the loss of a limb. We have used long-term implanted electrical interfaces to elucidate the neural basis of perceived intensity in the sense of touch. To this end, we assessed the sensory correlates of neural firing rate and neuronal population recruitment independently by varying two parameters of nerve stimulation: pulse frequency and pulse width. Specifically, two amputees, chronically implanted with peripheral nerve electrodes, performed each of three psychophysical tasks-intensity discrimination, magnitude scaling, and intensity matching-in response to electrical stimulation of their somatosensory nerves. We found that stimulation pulse width and pulse frequency had systematic, cooperative effects on perceived tactile intensity and that the artificial tactile sensations could be reliably matched to skin indentations on the intact limb. We identified a quantity we termed the activation charge rate (ACR), derived from stimulation parameters, that predicted the magnitude of artificial tactile percepts across all testing conditions. On the basis of principles of nerve fiber recruitment, the ACR represents the total population spike count in the activated neural population. Our findings support the hypothesis that population spike count drives the magnitude of tactile percepts and indicate that sensory magnitude can be manipulated systematically by varying a single stimulation quantity.
Project description:The hand area of the primary somatosensory cortex contains detailed finger topography, thought to be shaped and maintained by daily life experience. Here we utilise phantom sensations and ultra high-field neuroimaging to uncover preserved, though latent, representation of amputees' missing hand. We show that representation of the missing hand's individual fingers persists in the primary somatosensory cortex even decades after arm amputation. By demonstrating stable topography despite amputation, our finding questions the extent to which continued sensory input is necessary to maintain organisation in sensory cortex, thereby reopening the question what happens to a cortical territory once its main input is lost. The discovery of persistent digit topography of amputees' missing hand could be exploited for the development of intuitive and fine-grained control of neuroprosthetics, requiring neural signals of individual digits.
Project description:Bilateral activation of somatosensory areas after unilateral stimulation is assumed to be mediated by crosshemispheric connections. Despite evidence of bilateral activity in response to unilateral stimulation, neurologically intact humans do not experience bilateral percepts when stimulated on one side of the body. This may be due to active suppression of ipsilateral neural activity by inhibitory mechanisms whose functioning is poorly understood. We describe an individual with left fronto-parietal damage who experiences bilateral sensations in response to unilateral tactile stimulation-a rarely reported condition known as synchiria (previously described in visual, auditory, and somatosensory modalities). Presumably, the phantom sensations result from normal bilateral crosshemispheric activation, combined with a failure of inhibitory mechanisms to prevent bilateral perceptual experiences. Disruption of these mechanisms provides a valuable opportunity to examine their internal functioning. We find that the synchiria rate is affected by hand position relative to multiple reference frames. Specifically, synchiria decreases as the hands move from right (contralesional) to left (ipsilesional) space in trunk- and head-centered reference frames and disappears when the hands are crossed. These findings provide novel evidence that mechanisms that inhibit bilateral percepts operate in multiple reference frames.
Project description:OBJECTIVE:Direct electrical stimulation (DES) is a clinical gold standard for human brain mapping and readily evokes conscious percepts, yet the neurophysiological changes underlying these percepts are not well understood. APPROACH:To determine the neural correlates of DES, we stimulated the somatosensory cortex of ten human participants at frequency-amplitude combinations that both elicited and failed to elicit conscious percepts, meanwhile recording neural activity directly surrounding the stimulation site. We then compared the neural activity of perceived trials to that of non-perceived trials. MAIN RESULTS:We found that stimulation evokes distributed high gamma activity, which correlates with conscious perception better than stimulation parameters themselves. SIGNIFICANCE:Our findings suggest that high gamma activity is a reliable biomarker for perception evoked by both natural and electrical stimuli.