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Stability of Sensory Topographies in Adult Cortex
Abstract
Textbooks teach us that the removal of sensory input to sensory cortex, e.g. following
arm amputation, results in massive reorganisation in the adult brain. Here, we
critically examine evidence for functional reorganisation of sensory cortical
representations, focusing on the sequelae of arm amputation on somatosensory
topographies. Based on literature from human and non-human primates, we conclude
that the cortical representation of the limb remains remarkably stable despite the loss
of its main peripheral input. Furthermore, the purportedly massive reorganisation
results primarily from potentiation of new pathways in subcortical structures and does
not produce novel functional sensory representations. We discuss the implications of
the stability of sensory representations on the development of upper-limb
neuroprostheses.
... Neuroprostheses for enabling sensations have been developed for different sensory modalities, including the very successful auditory implants and visual prostheses which are rapidly developing using stimulation of the retina (Ayton et al., 2020), visual nerve (Finn and LoPresti, 2002), thalamus (Panetsos et al., 2011) and cortex (Fernandez, 2018) to generate visual sensations. Progress has been made in the development of sensorized hand prostheses for the amputees, as well (Soghoyan et al., 2023;Bensmaia et al., 2023;Raspopovic et al., 2021;Makin and Bensmaia, 2017). Yet, more research is needed for improving the practicality of these systems. ...
... Cuberovic et al. (2019) reported similar shifts likely caused by neural plasticity. It should be noted, however, that Makin and Bensmaia (2017) argued that cortical maps of the body are not as plastic as suggested by the other literature, even in the amputees many years after limb loss. These conflicting results raise an important question: what drives plasticity in some neuroprosthetic systems but not in others? ...
... Based on our present findings, we have more positive expectations compared to those of Makin and Bensmaia (2017) regarding the possibility of evoking of neural plasticity by the use of a neuroprosthesis. Yet, the exact mechanisms and brain regions involved remain to be elucidated and combining neurophysiological recordings with the participants' reports should help to clarify this issue. ...
Limb amputation results in such devastating consequences as loss of motor and sensory functions and phantom limb pain (PLP). Neurostimulation-based approaches have been developed to treat this condition, which provide artificial somatosensory feedback such as peripheral nerve stimulation (PNS), spinal cord stimulation (SCS), and transcutaneous electrical nerve stimulation (TENS). Yet, the effectiveness of different neurostimulation methods has been rarely tested in the same participants. Meanwhile, such tests would help to select the most effective method or a combination of methods and could contribute to the development of multisensory limb prostheses. In this study, two transhumeral amputees were implanted with stimulating electrodes placed in the medial nerve and over the spinal cord epidurally. PNS and SCS were tested in each participant as approaches to enable tactile and proprioceptive sensations and suppress PLP. Both PNS and SCS induced sensation in different parts of the phantom hand, which correlated with cortical responses detected with electroencephalographic (EEG) recordings. The sensations produced by PNS more often felt natural compared to those produced by SCS. Еvoked response potentials (ERPs) were more lateralized and adapted faster for PNS compared to SCS. In the tasks performed with the bionic hand, neurostimulation-induced sensations enabled discrimination of object size. As the participants practiced with neurostimulation, they improved on the object-size discrimination task and their sensations became more natural. А combination of PNS and TENS enabled sensations that utilized both tactile and proprioceptive information. This combination was effective to convey the perception of object softness. In addition to enabling sensations, neurostimulation led to a decrease in PLP.
Clinical trial registration
https://clinicaltrials.gov/, identifier, #NCT05650931.
... Classical studies posited that amputation and spinal cord injury modify the topography of body parts in S1, with intact body parts taking over cortical areas originally dedicated to the amputated part (Merzenich et al., 1984;Qi et al., 2000;Pons et al., 1991;Jain et al., 2008). However, recent human neuroimaging studies and sensory BCI studies have challenged the extent of this remapping, arguing that sensory topographies largely persist even after complete sensory loss (Makin and Bensmaia, 2017;Kikkert et al., 2021;Flesher et al., 2016;Armenta Salas et al., 2018). Thus, the level of plasticity in the adult nervous system is still an ongoing investigation. ...
... A frequent (Flesher et al., 2016;Armenta Salas et al., 2018;Stavisky et al., 2019;Willett et al., 2020;Fifer et al., 2022;Chivukula et al., 2021;Andersen and Aflalo, 2022) discussion question is: how well do these findings generalize to the brains of able-bodied individuals? Specifically, do the observed phenomena result from partial reorganization (Kambi et al., 2014;Nardone et al., 2013) after spinal cord injury, or do they reflect intact motor circuits, preserved from before injury (Makin and Bensmaia, 2017)? intervals indicate ± standard error of the mean (SEM) bootstrapped across 10 sessions. ...
... However, the authors also recognized that the amputated body part might persist in latent somatosensory maps. Since then, preserved, latent somatosensory representations have been demonstrated in studies of amputation (Makin and Bensmaia, 2017;Kikkert et al., 2016;Wesselink et al., 2019;Bruurmijn et al., 2017) and even paralysis (Kikkert et al., 2021;Flesher et al., 2016;Armenta Salas et al., 2018;Fifer et al., 2022). ...
Neural plasticity allows us to learn skills and incorporate new experiences. What happens when our lived experiences fundamentally change, such as after a severe injury? To address this question, we analyzed intracortical population activity in the posterior parietal cortex (PPC) of a tetraplegic adult as she controlled a virtual hand through a brain-computer interface (BCI). By attempting to move her fingers, she could accurately drive the corresponding virtual fingers. Neural activity during finger movements exhibited robust representational structure similar to fMRI recordings of able-bodied individuals' motor cortex, which has previously been shown to reflect able-bodied usage patterns. The finger representational structure was consistent throughout multiple sessions, even though the structure contributed to BCI decoding errors. Within individual BCI movements, the representational structure was dynamic, first resembling muscle activation patterns and then resembling the anticipated sensory consequences. Our results reveal that motor representations in PPC reflect able-bodied motor usage patterns even after paralysis, and BCIs can re-engage these representations to restore lost motor functions.
... The findings described above suggesting widespread reorganization are seemingly contradictory with evidence from functional magnetic resonance imaging (fMRI), transcranial magnetic stimulation (TMS), and peripheral intracortical stimulation techniques in humans that suggest a persistent functional representation of missing body parts after amputation [reviewed in (25)] and deafferentation (26,27). We (28,29) and others (30,31) have shown that, even decades after amputation of a hand, phantom hand movements evoke activity patterns in S1 that are largely indistinguishable from normal hand movement. ...
... First, the somatosensory cortex and the motor system are tightly linked (52,53), and motor commands, unaffected by our nerve block, are also routed to S1. We have previously argued for a role for the motor system in stabilizing S1 organization following (long-term) amputation (25), and similar mechanisms could facilitate the persistent representation observed here. According to this interpretation, the S1 inputs contributing to the maintained representation of the deafferented finger (or limb) may be distinct from the afferent inputs comprising the "remapped" (surviving) representations [see e.g., (54)]. ...
... When taking these representational motifs into consideration, we find that a drastic and highly localized change to the periphery causes hand-wide and largely homogeneous suppression of cortical hand representation. Our findings are consistent with mounting recent evidence, demonstrating that the representation of an insensate or even an amputated hand is stable and can be evoked by S1 stimulation (25). Beyond advancing our understanding of the underlying representational structure of hand representation and (lack of) reorganization, which, in itself, may not generalize to long-term input loss, our study makes two additional contributions that are generalizable. ...
Electrophysiological studies in monkeys show that finger amputation triggers local remapping within the deprived primary somatosensory cortex (S1). Human neuroimaging research, however, shows persistent S1 representation of the missing hand’s fingers, even decades after amputation. Here, we explore whether this apparent contradiction stems from underestimating the distributed peripheral and central representation of fingers in the hand map. Using pharmacological single-finger nerve block and 7-tesla neuroimaging, we first replicated previous accounts (electrophysiological and other) of local S1 remapping. Local blocking also triggered activity changes to nonblocked fingers across the entire hand area. Using methods exploiting interfinger representational overlap, however, we also show that the blocked finger representation remained persistent despite input loss. Computational modeling suggests that both local stability and global reorganization are driven by distributed processing underlying the topographic map, combined with homeostatic mechanisms. Our findings reveal complex interfinger representational features that play a key role in brain (re)organization, beyond (re)mapping.
... The effect of ICMS intensity on PF size is qualitatively consistent with the proposed neural determinants of the PF. Each volume of cortex maps onto a patch of skin; the greater the volume of cortex activated (amplitude modulation 19,20 ) or the number of activated neurons within that cortical volume (frequency modulation 21 ), the greater the corresponding swath of skin. ...
... Indeed, attempts to modify the PFs of electrodes implanted in the nerves-leveraging both cortical and subcortical plasticity-failed to change the PF location 20 . The idea of major post-injury cortical reorganization 16 has lost favour recently, with the changes in observed cortical activity being explained by existing lateral connectivity instead 21,22 . This work furthers the notion that the underlying somatotopy does not change because of injury, as direct stimulation evokes percepts in the expected locations. ...
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.
... Pre-operative fMRI, MEG, or ECOG can be used to identify the digit representations and thus guide the placement of arrays of stimulating electrodes (Flesher et al., 2016;Foldes et al., 2021). Critically, studies involving limited numbers of patients and electrodes have shown that PFs are relatively stable over time (Flesher et al., 2016;Ortiz-Catalan et al., 2020a), suggesting that the somatotopic map is stable, even after deafferentation caused by spinal cord injury or amputation (Kikkert et al., 2021(Kikkert et al., , 2016Makin and Bensmaia, 2017). ...
... ;https://doi.org/10.1101https://doi.org/10. /2023 to modify the PFs of electrodes implanted in the nerves -which leverage any subcortical plasticity -have failed to systematically change the PF location (Ortiz-Catalan et al., 2020a), consistent with the theory that body maps are rigid in adulthood (Makin and Bensmaia, 2017). ...
When we interact with objects, signals from the hand convey information about the objects and our interactions with them. A basic feature of these interactions, the locations of contacts between the hand and object, is often only available via the sense of touch. Information about locations of contact between a brain-controlled bionic hand and an object can in principle be signaled via intracortical microstimulation (ICMS) of somatosensory cortex (S1), which evokes touch sensations that are localized to a specific patch of skin. To provide intuitive location information, tactile sensors on the robotic hand drive ICMS through electrodes that evoke sensations at skin locations matching sensor locations. This approach requires that ICMS-evoked sensations be focal, stable, and distributed over the hand. To systematically investigate the localization of ICMS-evoked sensations, we analyzed the projected fields (PFs) of ICMS-evoked sensations-their spatial extent-from reports obtained over multiple years from three participants implanted with micro-electrode arrays in S1. First, we found that PFs vary widely in their size, are highly stable, and are distributed over large swaths of each participant's hand. Second, PFs increase in size as the amplitude and frequency of ICMS increases. Third, leveraging participants with residual sensation, we found that PF locations match the locations of the receptive fields (RFs) of the neurons near the stimulating electrode. Furthermore, PFs tended to be subsumed by the corresponding RFs. Fourth, multi-channel stimulation yielded a PF that reflected an approximately additive combination of the PFs of the component channels. By stimulating through electrodes with largely overlapping PFs, then, we could evoke more focal sensations, experienced primarily at the intersection of the component PFs. To assess the functional consequence of this phenomenon, we implemented multi-channel ICMS-based feedback in a bionic hand and demonstrated that the resulting sensations are more localizable than are those evoked via single-channel ICMS.
... Furthermore, the importance of sensory feedback in intact motor control underlies the hypothesis that dexterity in BMI applications might also be significantly improved with sensory feedback, especially with the manipulation of objects in sensorized robotic hands. Evidence of somatotopical organization within S1 existing years after injury, amputation, or cortical inactivity (Kikkert et al. 2021, Makin & Bensmaia 2017) adds credence to the possibility of restoring naturalistic sensations. Actual somatosensations could be evoked by stimulating these networks to recreate missing sensory feedback in the sensorimotor control loop. ...
... Twelve years after sensory deafferentation of the upper limb of NHPs, it was found through the use of microelectrode mapping experiments (Pons et al. 1991) that the cortical maps of the body in S1 were substantially reorganized. However, M1 remains functional in humans years after spinal cord injury (Hochberg et al. 2006), and stimulation of S1 produces topographically organized sensations to the deafferented regions of cortex (Armenta , Flesher et al. 2016, Makin & Bensmaia 2017. These results suggest that a good deal of the structure remains after spinal cord lesions. ...
Traditional brain–machine interfaces decode cortical motor commands to control external devices. These commands are the product of higher-level cognitive processes, occurring across a network of brain areas, that integrate sensory information, plan upcoming motor actions, and monitor ongoing movements. We review cognitive signals recently discovered in the human posterior parietal cortex during neuroprosthetic clinical trials. These signals are consistent with small regions of cortex having a diverse role in cognitive aspects of movement control and body monitoring, including sensorimotor integration, planning, trajectory representation, somatosensation, action semantics, learning, and decision making. These variables are encoded within the same population of cells using structured representations that bind related sensory and motor variables, an architecture termed partially mixed selectivity. Diverse cognitive signals provide complementary information to traditional motor commands to enable more natural and intuitive control of external devices.
... Amputation was classically thought to modify the topography of body parts in S1, with intact body parts taking over cortical areas originally dedicated to the amputated part [6][7][8] . However, recent human neuroimaging studies have challenged the extent of this remapping, arguing that sensory topographies in S1 largely persist even after complete sensory loss 9 . Thus, the level of plasticity in the adult nervous system is still an ongoing investigation. ...
... If, as previously thought, sensory deprivation drives cortical reorganization and any group of neurons can learn to control a prosthetic 42,43 , the specific implant location would not affect BCI performance. Our results and others 2,9,12,23,24,38 suggest that such a stance is oversimplified. Although experience does shape neural organization 6,14,24 , representations may be remarkably persistent once formed 24 . ...
A bstract
Neural plasticity allows us to learn skills and incorporate new experiences. What happens when our lived experiences fundamentally change, such as after a severe injury? To address this question, we analyzed intracortical population activity in a tetraplegic adult as she controlled a virtual hand through a brain-computer interface (BCI). By attempting to move her fingers, she could accurately drive the corresponding virtual fingers. Neural activity during finger movements exhibited robust representational structure and dynamics that matched the representational structure, previously identified in able-bodied individuals. The finger representational structure was consistent during extended use, even though the structure contributed to BCI decoding errors. Our results suggest that motor representations are remarkably stable, even after complete paralysis. BCIs re-engage these preserved representations to restore lost motor functions.
... Amputation was classically thought to modify the topography of body parts in S1, with intact body parts taking over cortical areas originally dedicated to the amputated part [6][7][8] . However, recent human neuroimaging studies have challenged the extent of this remapping, arguing that sensory topographies in S1 largely persist even after complete sensory loss 9 . Thus, the level of plasticity in the adult nervous system is still an ongoing investigation. ...
... If, as previously thought, sensory deprivation drives cortical reorganization and any group of neurons can learn to control a prosthetic 42,43 , the specific implant location would not affect BCI performance. Our results and others 2,9,12,23,24,38 suggest that such a stance is oversimplified. Although experience does shape neural organization 6,14,24 , representations may be remarkably persistent once formed 24 . ...
Neural plasticity allows us to learn skills and incorporate new experiences. What happens when our lived experiences fundamentally change, such as after a severe injury? To address this question, we analyzed intracortical population activity in a tetraplegic adult as she controlled a virtual hand through a brain-computer interface (BCI). By attempting to move her fingers, she could accurately drive the corresponding virtual fingers. Neural activity during finger movements exhibited robust representational structure and dynamics that matched the representational structure, previously identified in able-bodied individuals. The finger representational structure was consistent during extended use, even though the structure contributed to BCI decoding errors. Our results suggest that motor representations are remarkably stable, even after complete paralysis. BCIs re-engage these preserved representations to restore lost motor functions.
... This remapping demonstrates the brain's ability to adapt to sensory loss and has been proposed as a factor in altered body perception during both waking and dreaming states. On the other side, Makin et al. argue that cortical representations of the amputated limb can remain relatively stable even decades after amputation (Makin & Bensmaia, 2017). This stability may explain the persistent phantom limb sensations and the frequent depiction of intact limbs in dreams. ...
Recent neuroscience advances emphasize the complex relationship between the physical body and dreams during sleep, as these two bodies share many neurological and physiological components. Understanding how significant bodily changes, like amputations, affect dream body perception opens a window to investigate the contribution of memory and somatosensory processing in dream formation. This sleep laboratory PSG study aimed to collect dream reports from amputees through REM awakenings and assess the subjective body perception in their dreams. We compared these results with dream content from two control populations experiencing temporary body perception changes: muscle soreness and electrical muscle stimulation (EMS). The dream reports indicate mixed body perception, both as an intact body and post-amputation, especially in recent amputees. In addition, more temporary changes in body perception, such as those from muscle soreness and EMS, are represented differently in dreams compared to the dreams of amputees. The research suggests recent amputees, who might be more involved in psychological coping with the novel change in body configuration, dream more about their own body, pre- or post-amputation. Amputees’ dreams are less movement- and body-focused compared to the dreams of people with temporary body changes, likely reflecting adaptation to the new body schema over time. This study contributes to ongoing research into the relationship between the physical and dreamed body by further addressing the subjective dream experience of amputees.
... Of note, while we did not have imaging data before their injuries, we saw that the expected somatotopic organization is well preserved up to 35 years post-injury, joining growing evidence that substantial reorganization of the somatosensory cortex does not occur after injury in adults (Schone et al. 2023;Makin and Bensmaia 2017;Makin and Krakauer 2023;Ortiz-Catalan et al. 2020). ...
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.
... This interplay between somatosensory and motor areas may reflect the neural processing of sensory anticipation based on the planning and execution of motor outputs, where S1 starts to predict and anticipate expected feedback based on information provided by motor commands. It is worth noting that motor efferences and somatosensory afferents are spatially selectively distributed with ascending and descending pathways innervating the same body part, leading to the co-activation of motor and somatosensory representations at the cortical level during sensorimotor interactions (Makin & Bensmaia, 2017). Based on the abovementioned evidence, the relationship between the sensory and motor neural representations of body districts should be considered bidirectional, for which the functionality of somatosensory areas affects the motor cortex and vice versa (Conforto et al., 2002;Edwards et al., 2019;Hummel & Cohen, 2005). ...
Effective control of movement predominantly depends on the exchange and integration between sensory feedback received by our body and motor command. However, the precise mechanisms governing the adaptation of the motor system's response to altered somatosensory signals (i.e., discrepancies between an action performed and feedback received) following movement execution remain largely unclear. In order to address these questions, we developed a unique paradigm using virtual reality (VR) technology. This paradigm can induce spatial incongruence between the motor commands executed by a body district (i.e., moving the right hand) and the resulting somatosensory feedback received (i.e., feeling touch on the left ankle). We measured functional sensorimotor plasticity in 17 participants by assessing the effector's motor cortical excitability (right hand) before and after a 10‐min VR task. The results revealed a decrease in motor cortical excitability of the movement effector following exposure to a 10‐min conflict between the motor output and the somatosensory input, in comparison to the control condition where spatial congruence between the moved body part and the area of the body that received the feedback was maintained. This finding provides valuable insights into the functional plasticity resulting from spatial sensorimotor conflict arising from the discrepancy between the anticipated and received somatosensory feedback following movement execution. The cortical reorganization observed can be attributed to functional plasticity mechanisms within the sensorimotor cortex that are related to establishing a new connection between somatosensory input and motor output, guided by temporal binding and the Hebbian plasticity rule.
... This type of plasticity is sometimes accompanied by tactile sensations in the phantom hand when the face is touched (Halligan et al., 1993;Ramachandran, 1993). The stability of cortical representations, the cortical plasticity mechanisms, and their limits, as well as the multiple factors involved in such processes, have all been topics of intense debate (Makin and Bensmaia, 2017;Makin and Flor, 2020). ...
Background
Interactions between the somatosensory and motor cortices are of fundamental importance for motor control. Although physically distant, face and hand representations are side by side in the sensorimotor cortex and interact functionally. Traumatic brachial plexus injury (TBPI) interferes with upper limb sensorimotor function, causes bilateral cortical reorganization, and is associated with chronic pain. Thus, TBPI may affect sensorimotor interactions between face and hand representations.
Objective
The aim of this study was to investigate changes in hand–hand and face–hand sensorimotor integration in TBPI patients using an afferent inhibition (AI) paradigm.
Method
The experimental design consisted of electrical stimulation (ES) applied to the hand or face followed by transcranial magnetic stimulation (TMS) to the primary motor cortex to activate a hand muscle representation. In the AI paradigm, the motor evoked potential (MEP) in a target muscle is significantly reduced when preceded by an ES at short-latency (SAI) or long-latency (LAI) interstimulus intervals. We tested 18 healthy adults (control group, CG), evaluated on the dominant upper limb, and nine TBPI patients, evaluated on the injured or the uninjured limb. A detailed clinical evaluation complemented the physiological investigation.
Results
Although hand–hand SAI was present in both the CG and the TBPI groups, hand–hand LAI was present in the CG only. Moreover, less AI was observed in TBPI patients than the CG both for face–hand SAI and LAI.
Conclusion
Our results indicate that sensorimotor integration involving both hand and face sensorimotor representations is affected by TBPI.
... Our hypothesis that a degenerated myelin border relates to more functional overlap is therefore not confirmed by our data. The finding that cortical fields remain microstructurally distinct in healthy aging highlights limits to age-related plasticity within M1 (Sereno, 2005), providing a mechanistic explanation as to why maps are often maintained after deprivation (Makin and Bensmaia, 2017;Striem-Amit et al., 2018), and why body representations are often preserved in older age (Riemer et al., 2019). Moreover, since the low-myelin borders differ between individuals, they may explain the high inter-individual variability in neurodegenerative diseases involving topographic disease spread (Schreiber et al., 2021). ...
Topographic maps form a critical feature of cortical organization, yet are poorly described with respect to their microstructure in the living aging brain. We acquired quantitative structural and functional 7T-MRI data from younger and older adults to characterize layer-wise topographic maps of the primary motor cortex (M1). Using parcellation-inspired techniques, we show that quantitative T1 and Quantitative Susceptibility Maps values of the hand, face, and foot areas differ significantly, revealing microstructurally distinct cortical fields in M1. We show that these fields are distinct in older adults and that myelin borders between them do not degenerate. We further show that the output layer 5 of M1 shows a particular vulnerability to age-related increased iron, while layer 5 and the superficial layer show increased diamagnetic substance, likely reflecting calcifications. Taken together, we provide a novel 3D model of M1 microstructure, where body parts form distinct structural units, but layers show specific vulnerability toward increased iron and calcium in older adults. Our findings have implications for understanding sensorimotor organization and aging, in addition to topographic disease spread.
... Whilst a significant body of data shows that the degrees of cortical reorganization and pain are correlated (see Vittersø et al., 2022, for a review), this does not necessarily imply causation. Indeed, many subsequent studies have instead demonstrated preservation of the limb area in the cortex (see Makin and Bensmaia, 2017, for a discussion), while more advanced neuroimaging studies have not been able to repeat the purported invasion of the surrounding areas (see Muret and Makin, 2021). Speculation as to the exact neurophysiological mechanisms behind distorted body perceptions and neuropathic pain is largely beyond the scope of this review (for a recent review summarizing the evidence for the maladaptive cortical model, see Vittersø et al., 2022). ...
Chronic neuropathic pain is highly disabling and difficult to treat and manage. Patients with such conditions often report altered bodily perceptions that are thought to be associated with maladaptive structural and functional alterations in the somatosensory cortex. Manipulating these altered perceptions using body illusions in virtual reality is being investigated and may have positive clinical implications for the treatment of these conditions. Here, we have conducted a narrative review of the evidence for the types of bodily distortions associated with a variety of peripheral and central neuropathic pain conditions. In addition, we summarize the experimental and clinical studies that have explored embodiment and body transformation illusions in immersive virtual reality for neuropathic pain relief, which are thought to target these maladaptive changes, as well as suggesting directions for future research.
... Our results suggest that the perception changes observed during the trial were caused by the peripheral nerve reactions to the implanted electrodes more than a major effect of the neuroprosthetic use inducing a brain plasticity and remap [53]. This is in line with findings on the high stability of the cortical sensory map in adulthood and their impossibility to be modified, even with prolonged exposure [54]. ...
Bioelectronic medicine is a promising venue for treatment of disabilities using implantable neural interfaces. Peripheral neurostimulation of residual nerves recently enabled multiple functional benefits in amputees. Despite the preliminary promising impact on patients' life, the overtime stability of implants and the related nerve reactions are unclear. To unveil the mechanisms and inform the design of better nerve-electrode interfaces, we engaged a multifaceted approach, merging functional responses from patients, their histological data, and corresponding computational modelling. Neurostimulation evoked different selective sensation locations and qualities overtime , with respective perceptual thresholds, that showed different degree of time stabilities dependent from the stimulating active sites. The histological analysis after explant showed mild tissue reactions, while electromechanically active sites and substrates remained conserved. Computational models, based on patients' histology, revealed the direct influence of the simulated tissue reaction to change of thresholds and type of perceived sensations. Novel insights of electrode biocompatibility was observed compared to animals and the increase of thresholds could be predicted computationally. This multifaced framework suggest that future intraneural implants should have easier implantation and higher biocompatibility counteracting the sensations changes through AI-based stimulations and electrode coatings.
... This type of plasticity is sometimes accompanied by tactile sensations in the phantom hand when the face is touched (Halligan et al., 1993;Ramachandran, 1993). The stability of cortical representations, the cortical plasticity mechanisms, and their limits, as well as the multiple factors involved in such processes, have all been topics of intense debate (Makin and Bensmaia, 2017;Makin and Flor, 2020). ...
Background
Traumatic brachial plexus injury (TBPI) is a potentially debilitating event, that usually affects young men following car or motorbike accidents. TBPI interferes with hand sensorimotor function, is associated with chronic pain, and causes cortical reorganization. Interactions between the somatosensory and motor cortices are of fundamental importance for motor control. The hands and face stand out as regions of high functionality with a privileged interaction existing between them, as reflected by the proximity and extension of their representations. Face-hand sensorimotor interactions have been demonstrated in healthy subjects.
Objective
The aim of this study was to investigate changes in the sensorimotor interaction in the hand and between the face and the hand in TBPI patients in order to better understand the plasticity of face-hand sensorimotor circuits following TBPI.
Method
The experimental design consisted of activating the representation of a hand muscle using transcranial magnetic stimulation (TMS) preceded by an electrical stimulation (ES) applied to the hand or face, which allows the investigation of the cortical reorganization resulting from TBPI. In the paradigm called afferent inhibition (AI), the motor evoked potential (MEP) in a target muscle is significantly reduced by a previous peripheral ES. AI can be evoked in short-latency (SAI) or long-latency (LAI) interstimulus intervals. Nine TBPI patients participated: five had partial sensorimotor function in their hands and were evaluated on the injured side (TBPI-I group) and four had complete loss of sensorimotor function in their hands and were evaluated on the uninjured side (TBPI-UI group). A control group (CG) included 18 healthy adults. A detailed clinical evaluation complemented the analysis.
Results
The results showed preserved hand sensorimotor integration for TBPI patients at SAI intervals, but not at LAI intervals. For the face-to-hand sensorimotor integration, the results showed no inhibition at SAI intervals for the TBPI patients. For LAI intervals, a facilitation effect was observed for the TBPI patients, an effect we termed long afferent facilitation or LAF. LAF positively correlated with results in the Central Sensitization Inventory and in the Disabilities Arm, Shoulder, and Hand questionnaire.
Conclusion
These results point to the existence of an inhibitory regulation system between the representations of the face and the hand that seems to be suppressed in TBPI and correlates with pain. Moreover, brain changes arising from TBPI are not restricted to the hemisphere contralateral to the injured limb, but extend to both hemispheres.
... In human patients with unilateral upper extremity amputation, deafferented S1 responds to stimulation of the ipsilateral intact hand (Makin et al., 2015;Valyear et al., 2020) in addition to the contralateral phantom hand Osborn et al., 2020), rather than to the corticallyadjacent lower face (which would be predicted by the classical explanation). Atypical ipsilateral responses in deafferented S1 are well-documented despite some evidence for a persistent cortical representation of the absent hand, wherein acquired amputees show a cortical representation of their intact hand, with a functional relationship between this "absent hand representation" and phantom sensation (Reilly et al., 2006;Makin and Bensmaia, 2017;Wesselink et al., 2019). However, representational persistence and S1 reorganization are not mutually exclusive because S1 could reorganize in ways that do or do not disrupt a hand representation. ...
Former amputees who undergo allogeneic hand transplantation or autogenic hand replantation (jointly, “hand restoration”) present a unique opportunity to measure the range of post-deafferentation plastic changes in the nervous system, especially primary somatosensory cortex (S1). However, few such patients exist, and previous studies compared single cases to small groups of typical adults. Here, we studied 5 individuals ( n = 8 sessions: a transplant with 2 sessions, a transplant with 3 sessions, and three replants with 1 session each). We used functional magnetic resonance imaging (fMRI) to measure S1 responsiveness to controlled pneumatic tactile stimulation delivered to each patient's left and right fingertips and lower face. These data were compared with responses acquired from typical adults ( n = 29) and current unilateral amputees ( n = 19). During stimulation of the affected hand, patients' affected S1 (contralateral to affected hand) responded to stimulation in a manner similar both to amputees and to typical adults. The presence of contralateral responses indicated grossly typical S1 function, but responses were universally at the low end of the range of typical variability. Patients' affected S1 showed substantial individual variability in responses to stimulation of the intact hand: while all patients fell within the range of typical adults, some patient sessions (4/8) had substantial ipsilateral responses similar to those exhibited by current amputees. Unlike hand restoration patients, current amputees exhibited substantial S1 reorganization compared to typical adults, including bilateral S1 responses to stimulation of the intact hand. In all three participant groups, we assessed tactile localization by measuring individuals' ability to identify the location of touch on the palm and fingers. Curiously, while transplant patients improved their tactile sensory localization over time, this was uncorrelated with changes in S1 responses to tactile stimuli. Overall, our results provide the first description of cortical responses to well-controlled tactile stimulation after hand restoration. Our case studies indicate that hand restoration patients show S1 function within the range of both typical adults and amputees, but with low-amplitude and individual-specific responses that indicate a wide range of potential cortical neurological changes following de-afferentation and re-afferentation.
... Here again, the positive feedback loop between neuroscience and neuroengineering emerges as a source of powerful scientific development. , but also they seem to be effective in subjects suffering from long-standing loss of sensory inputs (Makin and Bensmaia, 2017). Percept intensity can be modulated using high or low frequencies, depending on the somatosensory cortex stimulation sites (Callier et al., 2019;Hughes et al., 2021a). ...
In the last decades, clinical neuroscience found a novel ally in neurotechnologies, devices able to record and stimulate electrical activity in the nervous system. These technologies improved the ability to diagnose and treat neural disorders. Neurotechnologies are concurrently enabling a deeper understanding of healthy and pathological dynamics of the nervous system through stimulation and recordings during brain implants. On the other hand, clinical neurosciences are not only driving neuroengineering toward the most relevant clinical issues, but are also shaping the neurotechnologies thanks to clinical advancements. For instance, understanding the etiology of a disease informs the location of a therapeutical stimulation, but also the way stimulation patterns should be designed to be more effective/naturalistic. Here we describe cases of fruitful integration like Deep Brain Stimulation and cortical interfaces, to highlight how this symbiosis between clinical neuroscience and neurotechnology is closer to a novel integrated framework than to a simple interdisciplinary interaction.
... Many studies have shown the importance of experience in shaping the prior (Adams et al., 2004;Chambers et al., 2017;Snyder et al., 2015), and recent findings also seem to point toward the importance of effectors in sensorimotor priors (Yin et al., 2019) and dynamical adjustment during a task (Prsa et al., 2015). In addition, priors for own-body perception could be shaped early during development (Bahrick and Watson, 1985;Bremner, 2016;Rochat, 1998) and influenced by genetic and anatomical factors related to the organization of cortical and subcortical maps and pathways (Makin and Bensmaia, 2017;Stein et al., 2014). ...
Many studies have investigated the contributions of vision, touch, and proprioception to body ownership, i.e., the multisensory perception of limbs and body parts as our own. However, the computational processes and principles that determine subjectively experienced body ownership remain unclear. To address this issue, we developed a detection-like psychophysics task based on the classic rubber hand illusion paradigm where participants were asked to report whether the rubber hand felt like their own (the illusion) or not. We manipulated the asynchrony of visual and tactile stimuli delivered to the rubber hand and the hidden real hand under different levels of visual noise. We found that (1) the probability of the emergence of the rubber hand illusion increased with visual noise and was well predicted by a causal inference model involving the observer computing the probability of the visual and tactile signals coming from a common source; (2) the causal inference model outperformed a non-Bayesian model involving the observer not taking into account sensory uncertainty; (3) by comparing body ownership and visuotactile synchrony detection, we found that the prior probability of inferring a common cause for the two types of multisensory percept was correlated but greater for ownership, which suggests that individual differences in rubber hand illusion can be explained at the computational level as differences in how priors are used in the multisensory integration process. These results imply that the same statistical principles determine the perception of the bodily self and the external world.
... It is worth noting that the participant's long-term tactile impairment could have resulted in representations of touch in S1 that are altered relative to healthy humans. This is unlikely to be a major effect on the findings of this study, because recent work has shown that topographic representations in S1 are highly preserved in tetraplegic people, even years post-injury [60], [61]. ...
The responsiveness of primary somatosensory cortex (S1) to physical tactile stimuli is well documented but the extent to which it is modulated by vision is unresolved. Additionally, recent literature has suggested that tactile events are represented in S1 in a more complex, generalized manner than its long-established topographic organization. To better characterize S1 function, neural activity was recorded from a tetraplegic patient implanted with microelectrode arrays in S1 during 1s stroking touches to the forearm (evoking numb sensation) or finger (naturalistic sensation). Touch conditions included visually observed first person physical touches, physical touches without vision, and visual touches without physical contact which occurred either to a third person, an inanimate object, or the patient's own body in virtual reality. Two major findings emerged from this dataset. The first was that vision strongly modulates S1 activity, but only if there is a physical element to the touch, suggesting that passive observation of touches is not sufficient to recruit S1 neurons. The second was that despite the location of the recording arrays in a putative arm area of S1, neural activity was able to represent both arm and finger touches in physical touch conditions. Arm touches were encoded more strongly and specifically, supporting the idea that S1 encodes tactile events primarily through its topographic organization, as well as in a more general manner encompassing larger areas of the body.
... Greater S1 stability does not appear to be related to unit sortability (Fig. S2), but rather may be an intrinsic property of region. This seems consistent with our current understanding of the relative functional roles of sensory and motor cortices: sensory processing favors stability and efficiency 47,48 , whereas motor control favors flexibility and redundancy, particularly in uncertain environments or while learning new skills 49 . ...
Understanding the cortical representations of movements and their stability can shed light on improved brain-machine interface (BMI) approaches to decode these representations without frequent recalibration. Here, we characterize the spatial organization (somatotopy) and stability of the bilateral sensorimotor map of forearm muscles in an incomplete-high spinal-cord injury study participant implanted bilaterally in the primary motor and sensory cortices with Utah microelectrode arrays (MEAs). We built representation maps by recording bilateral multiunit activity (MUA) and surface electromyography (EMG) as the participant executed voluntary contractions of the extensor carpi radialis (ECR), and attempted motions in the flexor carpi radialis (FCR), which was paralytic. To assess stability, we repeatedly mapped and compared left- and right-wrist-extensor-related activity throughout several sessions, comparing somatotopy of active electrodes, as well as neural signals both at the within-electrode (multiunit) and cross-electrode (network) levels. Wrist motions showed significant activation in motor and sensory cortical electrodes. Within electrodes, firing strength stability diminished as the time increased between consecutive measurements (hours within a session, or days across sessions), with higher stability observed in sensory cortex than in motor, and in the contralateral hemisphere than in the ipsilateral. However, we observed no differences at network level, and no evidence of decoding instabilities for wrist EMG, either across timespans of hours or days, or across recording area. While map stability differs between brain area and hemisphere at multiunit/electrode level, these differences are nullified at ensemble level.
... It is often accompanied by neuropathic and phantom limb pain, leading to poor prognosis and recovery. Substantial research shows that PNI and sensory deprivation prompt a complex sequence of changes in neural activity that lead to the remapping of cortical representations in humans [1,2], non-human primates [3], and rodent brains [4]. Evidence suggests that this plasticity dictates the degree of sensory complications [5,6]. ...
Peripheral nerve injury induces cortical remapping that can lead to sensory complications. There is evidence that inhibitory interneurons play a role in this process, but the exact mechanism remains unclear. Glutamate decarboxylase-1 (GAD1) is a protein expressed exclusively in inhibitory interneurons. Transgenic rats encoding GAD1–GCaMP were generated to visualize the activity in GAD1 neurons through genetically encoded calcium indicators (GCaMP6s) in the somatosensory cortex. Forepaw denervation was performed in adult rats, and fluorescent Ca2+ imaging on cortical slices was obtained. Local, intrahemispheric stimulation (cortical layers 2/3 and 5) induced a significantly higher fluorescence change of GAD1-expressing neurons, and a significantly higher number of neurons were responsive to stimulation in the denervated rats compared to control rats. However, remote, interhemispheric stimulation of the corpus callosum induced a significantly lower fluorescence change of GAD1-expressing neurons, and significantly fewer neurons were deemed responsive to stimulation within layer 5 in denervated rats compared to control rats. These results suggest that injury impacts interhemispheric communication, leading to an overall decrease in the activity of inhibitory interneurons in layer 5. Overall, our results provide direct evidence that inhibitory interneuron activity in the deprived S1 is altered after injury, a phenomenon likely to affect sensory processing.
... This age-related topographic stability suggests that there are limits to cortical plasticity and cortical spread within M1 in both younger and older adults [41]. This provides a mechanistic explanation as to why topographical organization is often maintained after learning or with deprivation, such as in amputees [42], [43], and as to why body representations are often preserved in older age [44]. However, as these borders also differ between individuals, our findings open up the investigation of these borders as a possible mechanism in neurodegenerative diseases that involve topographical disease spread [45]. ...
Age-related cortical plasticity reveals insights into the mechanisms underlying the stability and flexibility of neuronal circuits. Classical parcellation has long demonstrated the importance of microstructural features yet 3D approaches have rarely been applied to human brain organization in-vivo. We acquired functional and structural 7T-MRI and behavioral data of living younger and older adults to investigate human primary motor cortex (M1) aging, employing 3D parcellation techniques. We identify distinct cortical fields in M1 based on quantitative tissue contrast, which are, along with the myelin-poor borders between them, stable with age. We also show age-related iron accumulation, particularly in the output layer 5b and the lower limb field. Our data offers a new model of human M1 with distinct cortical fields, a mechanistic explanation for the stability of topographic organization in the context of aging and plasticity, and highlights the specific vulnerability of output signal flows to cortical plasticity.
... In our experiments, a reorganization of spatial readout mechanisms by downstream areas could still be at play. The extent of such reorganization during neuroprosthesis use has been debated (Makin and Bensmaia, 2017). Recent studies on participants using a sensorimotor bionic arm suggest that long-term perceptual alignment of the prosthesis and the missing limb requires that sensor location and the connected nerve sensation should roughly match (Cuberovic et al., 2019;Ortiz-Catalan et al., 2020;Schofield et al., 2020). ...
The topographic organization is a prominent feature of sensory cortices, but its functional role remains controversial. Particularly, it is not well determined how integration of activity within a cortical area depends on its topography during sensory-guided behavior. Here, we train mice expressing channelrhodopsin in excitatory neurons to track a photostimulation bar that rotated smoothly over the topographic whisker representation of the primary somatosensory cortex. Mice learn to discriminate angular positions of the light bar to obtain a reward. They fail not only when the spatiotemporal continuity of the photostimulation is disrupted in this area but also when cortical areas displaying map discontinuities, such as the trunk and legs, or areas without topographic map, such as the posterior parietal cortex, are photostimulated. In contrast, when cortical topographic continuity enables to predict future sensory activation, mice demonstrate anticipation of reward availability. These findings could be helpful for optimizing feedback while designing cortical neuroprostheses.
... The median nerve skin was consistently located in the cortical region responding to ulnar nerve inputs without cortical shifting to the original area after operation, even 2.9 years later [98]. In other words, topographies in the primary somatosensory cortex are relatively stable and their preservation does not depend on peripheral sensory inputs [99]. We should note that this sensory cortex organizational pattern is distinct from that in the motor cortex. ...
Peripheral nerve injury can lead to partial or complete loss of limb function, and nerve transfer is an effective surgical salvage for patients with these injuries. The inability of deprived cortical regions representing damaged nerves to overcome corresponding maladaptive plasticity after the reinnervation of muscle fibers and sensory receptors is thought to be correlated with lasting and unfavorable functional recovery. However, the concept of central nervous system plasticity is rarely elucidated in classical textbooks involving peripheral nerve injury, let alone peripheral nerve transfer. This article is aimed at providing a comprehensive understanding of central nervous system plasticity involving peripheral nerve injury by reviewing studies mainly in human or nonhuman primate and by highlighting the functional and structural modifications in the central nervous system after peripheral nerve transfer. Hopefully, it will help surgeons perform successful nerve transfer under the guidance of modern concepts in neuroplasticity.
... Stimulation of the peripheral nerves (Ulnar, Median and Radial) using implanted electrodes has been shown to, in most cases, produce referred sensations matching the innervation areas even 20 years post-amputation. The stability of innervation areas confirms that the original somatosensory pathways remain intact following amputation, despite the apparent reorganisation present as hand maps [46], [47]. Congenital amputees do not report phantom sensations as the required somatosensory pathways have never developed [48]. ...
The addition of sensory feedback to upper-limb prostheses has been shown to improve control, increase embodiment, and reduce phantom limb pain. However, most commercial prostheses do not incorporate sensory feedback due to several factors. This paper focuses on the major challenges of a lack of deep understanding of user needs, the unavailability of tailored, realistic outcome measures and the segregation between research on control and sensory feedback. The use of methods such as the Person-Based Approach and co-creation can improve the design and testing process. Stronger collaboration between researchers can integrate different prostheses research areas to accelerate the translation process.
... However, these previous studies were unable to determine whether such activity represents functional reorganization, supporting the sensorimotor hand. Therefore, some descriptions of face-hand remapping may be misleading [76]. For example, Curt et al. (2002) did not report the topographical reorganization of M1 but did observe increased activation during tongue movements [36]. ...
Spinal cord injuries (SCI) are disruptive neurological events that severly affect the body leading to the interruption of sensorimotor and autonomic pathways. Recent research highlighted SCI-related alterations extend beyond than the expected network, involving most of the central nervous system and goes far beyond primary sensorimotor cortices. The present perspective offers an alternative, useful way to interpret conflicting findings by focusing on the deafferented and deefferented body as the central object of interest. After an introduction to the main processes involved in reorganization according to SCI, we will focus separately on the body regions of the head, upper limbs, and lower limbs in complete, incomplete, and deafferent SCI participants. On one hand, the imprinting of the body’s spatial organization is entrenched in the brain such that its representation likely lasts for the entire lifetime of patients, independent of the severity of the SCI. However, neural activity is extremely adaptable, even over short time scales, and is modulated by changing conditions or different compensative strategies. Therefore, a better understanding of both aspects is an invaluable clinical resource for rehabilitation and the successful use of modern robotic technologies.
... Indeed, such pre-existing cortico-cortical connections between, for example, visual areas and other (preserved) modality areas, which are suppressed under normal circumstances, could facilitate information transfer to the visual cortex (Schroeder et al. 2003;Ptito & Kupers, 2005;Masuda, Dumoulin, Nakadomari, & Wandell, 2008;Cappe, Rouiller, & Barone, 2009;Masuda et al., 2010). Given the compelling results from both animal and human studies (Convento, Vallar, Galantini, & Bolognini, 2013;Humanes-Valera, Aguilar, & Foffani, 2013;Makin & Bensmaia, 2017), the "unmasking" hypothesis is thought to explain at least some of the general processes observed in the reorganization of the adult cortex (see Singh et al., 2018). Although the specific mechanism underlying the rerouting of non-visual information to the visual cortex has not been fully understood, sensory deprivation studies remain an attractive method of exploring one of the most fascinating properties of the human brain, namely, plasticity. ...
In the present study, we investigated the effect of short-term visual deprivation on discriminative touch, cardiac interoception, and thermosensation by asking 64 healthy volunteers to perform four behavioral tasks. The experimental group contained 32 subjects who were blindfolded and kept in complete darkness for 110 minutes, while the control group consisted of 32 volunteers who were not blindfolded but were otherwise kept under identical experimental conditions. Both groups performed the required tasks three times: before and directly after deprivation (or control) and after an additional washout period of 40 minutes, in which all participants were exposed to normal light conditions. Our results showed that short-term visual deprivation had no effect on any of the senses tested. This finding suggests that short-term visual deprivation does not modulate basic bodily senses and extends this principle beyond tactile processing to the interoceptive modalities of cardiac and thermal sensations.
... Therefore, vibrotactile stimulation at varying frequencies can be used to disentangle the central processing of different mechanoreceptor inputs (Avanzino et al., 2014). Although the proprioceptive input axis has rarely been studied in the context of LBP, the primary somatosensory cortex (S1), which is the major cortical target of proprioceptive information (Riemann and Lephart, 2002;Kim et al., 2015), is likely to play a key part given its crucial role in sensorimotor integration and in the persistence of pain (Bingel et al., 2004;Lee et al., 2013;Massé-Alarie and Schneider, 2016;Makin and Bensmaia, 2017;Meier et al., 2018;Jenkins et al., 2021). ...
Topographic organization is a hallmark of vertebrate cortex architecture, characterized by ordered projections of the body’s sensory surfaces onto brain systems. High-resolution functional magnetic resonance imaging (fMRI) has proven itself as a valuable tool to investigate the cortical landscape and its (mal-)adaptive plasticity with respect to various body part representations, in particular extremities such as the hand and fingers. Less is known, however, about the cortical representation of the human back. We therefore validated a novel, MRI-compatible method of mapping cortical representations of sensory afferents of the back, using vibrotactile stimulation at varying frequencies and paraspinal locations, in conjunction with fMRI. We expected high-frequency stimulation to be associated with differential neuronal activity in the primary somatosensory cortex (S1) compared to low-frequency stimulation and that somatosensory representations would differ across the thoracolumbar axis. We found significant differences between neural representations of high- and low-frequency stimulation and between representations of thoracic and lumbar paraspinal locations, in several bilateral S1 sub-regions, and in regions of the primary motor cortex (M1). High-frequency stimulation preferentially activated Brodmann Area (BA) regions BA3a and BA4p, while low-frequency stimulation was more encoded in BA3b and BA4a. Moreover, we found clear topographic differences in S1 for representations of the upper and lower back during high-frequency stimulation. We present the first neurobiological validation of a method for establishing detailed cortical maps of the human back, which might serve as a novel tool to evaluate the pathological significance of neuroplastic changes in clinical conditions such as chronic low back pain.
Key points
Detailed investigations of cortical representations of somatosensory paraspinal afferents along the thoracolumbar axis are lacking.
Using fMRI combined with a novel vibrotactile stimulation device (“pneuVID”) we investigated different sensorimotor cortical representations of the back and explored topographic differences between the upper and lower back.
We found differential sub-regional sensorimotor neural representations of high- and low-frequency stimulation, as well as revealing initial evidence of the somatotopy of upper and lower paraspinal representations.
The current approach might serve as a promising tool to elucidate the role of cortical reorganisation in the pathophysiology of clinical conditions such as chronic low back pain.
... Toutefois, les structures sensori-motrices du cortex cérébral sont toujours présentes. Il est vrai que la plasticité corticale et les dérèglements périphériques induisent une réorganisation(Reilly et Sirigu, 2008;Flor, 2002;Van den Heiligenberg et al., 2018;Makin et Bensmaia, 2017), mais le cerveau n'est pas directement touché comme dans le cas d'un accident vasculaire cérébral. Au même titre que la substitution sensorielle fonctionne pour les déficients visuels, on peut émettre l'hypothèse que des stimulations vibrotactiles sur le moignon donnant des informations sur la configuration de la main ou du bras iront projeter sur des zones cérébrales dédiées à la sensorialité de la main ou du bras. ...
La perte d'autonomie engendrée par l'amputation du membre supérieur touche, en France, une population jeune et active. Les répercussions sur le plan physique et psychologique en font une problématique à la fois clinique, technique et scientifique. La faible prévalence de l'amputation du membre supérieur fait qu'elle est considérée comme une pathologie orpheline. L'appareillage proposé aux patients reste très limité dans ses commandes malgré les progrès technologiques et les multiples fonctionnalités apportées par les prothèses de dernière génération. Le contrôle de ces outils reste complexe et non intuitif, ce qui a pour conséquence un taux d'abandon élevé. Les travaux sur les prothèses myoélectriques ont mis en avant que pour être pleinement fonctionnelle et utilisée par les patients, la prothèse devrait pouvoir (i) générer des réponses réflexes, et (ii) redonner une sensorialité perdue. Durant cette thèse, nous avons exploré ces deux aspects que sont les comportements réflexes et la substitution sensorielle. La première partie étudie la régulation de la commande motrice par les boucles sensorimotrices de bas niveau. Nous avons testé un réseau simplifié connecté à un modèle musculo-squelettique de bras dans l'objectif de produire des mouvements d'amplitudes et de durées déterminées. Les capacités du réseau à produire ces comportements ont été évaluées par trois algorithmes d'optimisation. Cette étude nous a permis d’explorer l’espace des comportements possibles du système neuro-mécanique. Bien que très simplifié, le système était capable de produire des mouvements biologiquement plausibles en présence de gravité. Ce réseau simplifié montre une grande richesse d’expressions comportementales où un même mouvement peut être produit par plusieurs combinaisons de paramètres. Ce type de réseau est un candidat potentiel pour faire le lien entre les commandes descendantes basiques telles que les enregistrements d'activité musculaire (EMG) et les mouvements produits par les moteurs de la prothèse. De plus, cette structure a le potentiel de produire des réponses réflexes. Concernant l'étude de la substitution sensorielle, nous avons mis au point un dispositif produisant des stimulations vibrotactiles permettant de donner au sujet les informations de position angulaire de leur coude. Nous l'avons utilisé dans plusieurs expérimentations et mis en évidence les bonnes capacités de discrimination spatiale chez des patients amputés et des sujets sains. Nous l'avons ensuite utilisé dans un contrôle en ligne d'un bras virtuel où les vibrations permettaient de donner des repères spatiaux dans une tâche d'atteinte de cibles. Cette expérience a révélé que le feedback proprioceptif permettait d'améliorer la performance par rapport à une condition sans feedback. En revanche, si l'ajout du feedback proprioceptif à la vision n'a pas amélioré la performance, il ne l'a pas dégradé non plus. De plus, le contrôle en présence des deux feedback a été le plus apprécié des sujets. Ce travail nous a permis d'enrichir les connaissances autour de la commande des prothèses myoélectriques avec pour objectif de se rapprocher du contrôle le plus naturel possible.
... As suggested by Jacobs and Donoghue (1991), one possible mechanism of cortical reorganization is the unmasking of pre-existing lateral intracortical excitatory connections via the reduction of activity in intracortical inhibitory circuits. The inhibitory sensorimotor interactions observed here might contribute to maintaining functional boundaries between face and hand cortical territories and might be one of the potential physiological substrates upon which a multitude of remotely represented body parts may enter a (missing) hand territory based upon the frequency of usage of these body parts (Hahamy et al., 2017;Makin et al., 2013;Makin & Bensmaia, 2017). ...
Reorganization of the sensorimotor cortex following permanent (e.g., amputation) or temporary (e.g., local anaesthesia) deafferentation of the hand has revealed large‐scale plastic changes between the hand and face representations that are accompanied by perceptual correlates. The physiological mechanisms underlying this reorganization remain poorly understood. The aim of this study was to investigate sensorimotor interactions between the face and hand using an afferent inhibition transcranial magnetic stimulation protocol in which the motor evoked potential elicited by the magnetic pulse is inhibited when it is preceded by an afferent stimulus. We hypothesized that if face and hand representations in the sensorimotor cortex are functionally coupled, then electrocutaneous stimulation of the face would inhibit hand muscle motor responses. In two separate experiments, we delivered an electrocutaneous stimulus to either the skin over the right upper lip (Experiment 1) or right cheek (Experiment 2) and recorded muscular activity from the right first dorsal interosseous. Both lip and cheek stimulation inhibited right first dorsal interosseous motor evoked potentials. To investigate the specificity of this effect, we conducted two additional experiments in which electrocutaneous stimulation was applied to either the right forearm (Experiment 3) or right upper arm (Experiment 4). Forearm and upper arm stimulation also significantly inhibited the right first dorsal interosseous motor evoked potentials, but this inhibition was less robust than the inhibition associated with face stimulation. These findings provide the first evidence for face‐to‐hand afferent inhibition.
... Here, the cortical hand territory in the primary somatosensory cortex (hereafter S1), suffers an extreme loss of sensory input in tandem with dramatic alterations of motor behaviour 1,2 . The functional and perceptual correlates of amputation-related plasticity are currently debated 3,4 . In particular, it is not clear whether functional cortical reorganisation is restricted to early life development or can also occur in adults. ...
Cortical remapping after hand loss in the primary somatosensory cortex (S1) is thought to be predominantly dictated by cortical proximity, with adjacent body parts remapping into the deprived area. Traditionally, this remapping has been characterised by changes in the lip representation, which is assumed to be the immediate neighbour of the hand based on electrophysiological research in non-human primates. However, the orientation of facial somatotopy in humans is debated, with contrasting work reporting both an inverted and upright topography. We aimed to fill this gap in the S1 homunculus by investigating the topographic organisation of the face. Using both univariate and multivariate approaches we examined the extent of face-to-hand remapping in individuals with a congenital and acquired missing hand (hereafter one-handers and amputees, respectively), relative to two-handed controls. Participants were asked to move different facial parts (forehead, nose, lips, tongue) during fMRI scanning. We first report evidence for an upright facial organisation in all three groups, with the upper face and not the lips bordering the hand area. We further found little evidence for remapping of all tested facial parts in amputees, with no significant relationship to the chronicity of their PLP. In contrast, we found converging evidence for a complex pattern of face remapping in congenital one-handers across all facial parts, where the location of the cortical neighbour, the forehead, is shown to shift away from the deprived hand area, which is subsequently activated by the lips and the tongue. Together, our findings demonstrate that the face representation in humans is highly plastic, but that this plasticity is restricted by the developmental stage of input deprivation, rather than cortical proximity.
Pioneering investigations in the mid-19th century revealed that the perception of tactile cues presented to the surface of the skin improves with training, which is referred to as tactile learning. Surprisingly, tactile learning also occurs for body parts and skin locations that are not physically involved in the training. For example, after training of a finger, tactile learning transfers to adjacent untrained fingers. This suggests that the transfer of tactile learning follows a somatotopic pattern and involves brain regions such as the primary somatosensory cortex (S1), in which the trained and untrained body parts and skin locations are represented close to each other. However, other results showed that transfer occurs between body parts that are not represented close to each other in S1—for example, between the hand and the foot. These and similar findings have led to the suggestion of additional cortical mechanisms to explain the transfer of tactile learning. Here, different mechanisms are reviewed, and the extent to which they can explain the transfer of tactile learning is discussed. What all of these mechanisms have in common is that they assume a representational or functional relationship between the trained and untrained body parts and skin locations. However, none of these mechanisms alone can explain the complex pattern of transfer results, and it is likely that different mechanisms interact to enable transfer, perhaps in concert with higher somatosensory and decision-making areas.
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.
The human body is represented in a topographic pattern in the primary somatosensory cortex (S1), and genital representation is displaced below the toe representation. However, the relationship between the representation of the genitals and toe in S1 remains unclear. In this study, tactile stimulation was applied to the big toe in healthy subjects to observe changes in tactile acuity in the unstimulated genital area, abdomen, and metacarpal dorsal. Then tactile stimulation was applied to the right abdomen and metacarpal dorsal to observe changes in tactile acuity in bilateral genitals. The results revealed that tactile stimulation of the big toe led to a reduction in the 2-point discrimination threshold (2PDT) not only in the stimulated big toe but also in the bilateral unstimulated genitals, whereas the bilateral abdomen and metacarpal dorsal threshold remained unchanged. On the other hand, tactile stimulation of the abdomen and metacarpal dorsal did not elicit 2-point discrimination threshold changes in the bilateral genitals. Cortical and subcortical mechanisms have been proposed to account for the findings. One explanation involves the intracortical interaction between 2 adjacent representations. Another possible explanation is that the information content of a specific body part is broadly distributed across the S1. Moreover, exploring the links between human behaviors and changes in the cerebral cortex is of significant importance.
Despite the increasing incidence and prevalence of amputation across the globe, individuals with acquired limb loss continue to struggle with functional recovery and chronic pain. A more complete understanding of the motor and sensory remodeling of the peripheral and central nervous system that occurs postamputation may help advance clinical interventions to improve the quality of life for individuals with acquired limb loss. The purpose of this article is to first provide background clinical context on individuals with acquired limb loss and then to provide a comprehensive review of the known motor and sensory neural adaptations from both animal models and human clinical trials. Finally, the article bridges the gap between basic science researchers and clinicians that treat individuals with limb loss by explaining how current clinical treatments may restore function and modulate phantom limb pain using the underlying neural adaptations described above. This review should encourage the further development of novel treatments with known neurological targets to improve the recovery of individuals postamputation.
Significance Statement In the United States, 1.6 million people live with limb loss; this number is expected to more than double by 2050. Improved surgical procedures enhance recovery, and new prosthetics and neural interfaces can replace missing limbs with those that communicate bidirectionally with the brain. These advances have been fairly successful, but still most patients experience persistent problems like phantom limb pain, and others discontinue prostheses instead of learning to use them daily. These problematic patient outcomes may be due in part to the lack of consensus among basic and clinical researchers regarding the plasticity mechanisms that occur in the brain after amputation injuries. Here we review results from clinical and animal model studies to bridge this clinical–basic science gap.
Neurological insults, such as congenital blindness, deafness, amputation, and stroke, often result in surprising and impressive behavioural changes. Cortical reorganisation, which refers to preserved brain tissue taking on a new functional role, is often invoked to account for these behavioural changes. Here, we revisit many of the classical animal and patient cortical remapping studies that spawned this notion of reorganisation. We highlight empirical, methodological, and conceptual problems that call this notion into doubt. We argue that appeal to the idea of reorganisation is attributable in part to the way that cortical maps are empirically derived. Specifically, cortical maps are often defined based on oversimplified assumptions of ‘winner-takes-all’, which in turn leads to an erroneous interpretation of what it means when these maps appear to change. Conceptually, remapping is interpreted as a circuit receiving novel input and processing it in a way unrelated to its original function. This implies that neurons are either pluripotent enough to change what they are tuned to or that a circuit can change what it computes. Instead of reorganisation, we argue that remapping is more likely to occur due to potentiation of pre-existing architecture that already has the requisite representational and computational capacity pre-injury. This architecture can be facilitated via Hebbian and homeostatic plasticity mechanisms. Crucially, our revised framework proposes that opportunities for functional change are constrained throughout the lifespan by the underlying structural ‘blueprint’. At no period, including early in development, does the cortex offer structural opportunities for functional pluripotency. We conclude that reorganisation as a distinct form of cortical plasticity, ubiquitously evoked with words such as ‘take-over’’ and ‘rewiring’, does not exist.
Some amputees have been famously reported to perceive facial touch as arising from their phantom hand. These referred sensations have since been replicated across multiple neurological disorders and were classically interpreted as a perceptual correlate of cortical plasticity. Common to all these and related studies is that participants might have been influenced in their self-reports by the experimental design or related contextual biases. Here, we investigated whether referred sensations reports might be confounded by demand characteristics (e.g., compliance, expectation, suggestion). Unilateral upper-limb amputees (N = 18), congenital one-handers (N = 19), and two-handers (N = 22) were repeatedly stimulated with computer-controlled vibrations on 10 body-parts and asked to report the occurrence of any concurrent sensations on their hand(s). To further manipulate expectations, we gave participants the suggestion that some of these vibrations had a higher probability to evoke referred sensations. We also assessed similarity between (phantom) hand and face representation in primary somatosensory cortex (S1), using functional Magnetic Resonance Imaging (fMRI) multivariate representational similarity analysis. We replicated robust reports of referred sensations in amputees towards their phantom hand; however, the frequency and distribution of reported referred sensations were similar across groups. Moreover, referred sensations were evoked by stimulation of multiple body-parts and similarly reported on both the intact and phantom hand in amputees. Face-to-phantom-hand representational similarity was not different in amputees' missing hand region, compared with controls. These findings weaken the interpretation of referred sensations as a perceptual correlate of S1 plasticity and reveal the need to account for contextual biases when evaluating anomalous perceptual phenomena.
Recent literature suggests that tactile events are represented in the primary somatosensory cortex (S1) beyond its long-established topography; in addition, the extent to which S1 is modulated by vision remains unclear. To better characterize S1, human electrophysiological data were recorded during touches to the forearm or finger. Conditions included visually observed physical touches, physical touches without vision, and visual touches without physical contact. Two major findings emerge from this dataset. First, vision strongly modulates S1 area 1, but only if there is a physical element to the touch, suggesting that passive touch observation is insufficient to elicit neural responses. Second, despite recording in a putative arm area of S1, neural activity represents both arm and finger stimuli during physical touches. Arm touches are encoded more strongly and specifically, supporting the idea that S1 encodes tactile events primarily through its topographic organization but also more generally, encompassing other areas of the body.
Cortical remapping after hand loss in the primary somatosensory cortex (S1) is thought to be predominantly dictated by cortical proximity, with adjacent body parts remapping into the deprived area. Traditionally, this remapping has been characterised by changes in the lip representation, which is assumed to be the immediate neighbour of the hand based on electrophysiological research in non-human primates. However, the orientation of facial somatotopy in humans is debated, with contrasting work reporting both an inverted and upright topography. We aimed to fill this gap in the S1 homunculus by investigating the topographic organisation of the face. Using both univariate and multivariate approaches we examined the extent of face-to-hand remapping in individuals with a congenital and acquired missing hand (hereafter one-handers and amputees, respectively), relative to two-handed controls. Participants were asked to move different facial parts (forehead, nose, lips, tongue) during fMRI scanning. We first confirmed an upright face organisation in all three groups, with the upper-face and not the lips bordering the hand area. We further found little evidence for remapping of both forehead and lips in amputees, with no significant relationship to the chronicity of their PLP. In contrast, we found converging evidence for a complex pattern of face remapping in congenital one-handers across multiple facial parts, where relative to controls, the location of the cortical neighbour - the forehead - is shown to shift away from the deprived hand area, which is subsequently more activated by the lips and the tongue. Together, our findings demonstrate that the face representation in humans is highly plastic, but that this plasticity is restricted by the developmental stage of input deprivation, rather than cortical proximity.
A rich literature has documented changes in cortical representations of the body in somatosensory and motor cortex. Recent clinical studies of brain–machine interfaces designed to assist paralyzed patients have afforded the opportunity to record from and stimulate human somatosensory, motor, and action-related areas of the posterior parietal cortex. These studies show considerable preserved structure in the cortical somato-motor system. Motor cortex can immediately control assistive devices, stimulation of somatosensory cortex produces sensations in an orderly somatotopic map, and the posterior parietal cortex shows a high-dimensional representation of cognitive action variables. These results are strikingly similar to what would be expected in a healthy subject, demonstrating considerable stability of adult cortex even after severe injury and despite potential plasticity-induced new activations within the same region of cortex. Clinically, these results emphasize the importance of targeting cortical areas for BMI control signals that are consistent with their normal functional role.
Introduction:
Most patients with amputation (up to 80 %) suffer from phantom limb pain postsurgery. These are often multimorbid patients who also have multiple risk factors for the development of chronic pain from a pain medicine perspective. Surgical removal of the body part and sectioning of peripheral nerves result in a lack of afferent feedback, followed by neuroplastic changes in the sensorimotor cortex. The experience of severe pain, peripheral, spinal, and cortical sensitization mechanisms, and changes in the body scheme contribute to chronic phantom limb pain. Psychosocial factors may also affect the course and the severity of the pain. Modern amputation medicine is an interdisciplinary responsibility.
Methods:
This review aims to provide an interdisciplinary overview of recent evidence-based and clinical knowledge.
Results:
The scientific evidence for best practice is weak and contrasted by various clinical reports describing the polypragmatic use of drugs and interventional techniques. Approaches to restore the body scheme and integration of sensorimotor input are of importance. Modern techniques, including apps and virtual reality, offer an exciting supplement to already established approaches based on mirror therapy. Targeted prosthesis care helps to obtain or restore limb function and at the same time plays an important role reshaping the body scheme.
Discussion:
Consequent prevention and treatment of severe postoperative pain and early integration of pharmacological and nonpharmacological interventions are required to reduce severe phantom limb pain. To obtain or restore body function, foresighted surgical planning and technique as well as an appropriate interdisciplinary management is needed.
Background
The evidences for demonstrating the contributions of the cerebral cortex in human postural control is increasing. However, there remain little insights about the cortical correlates of balance control in lower-limb amputees. The present study aimed to investigate the cortical activity and balance performance of transfemoral amputees in comparison to healthy individuals during a continuous balance task (CBT).
Methods
The postural stability of the participants was defined with limit of stability parameter. Electroencephalography (EEG) data were recorded in synchronization with the center of pressure (CoP) data from eighteen individuals (including eight unilateral transfemoral amputees). We anticipated that, due to the limb loss, the postural demand of transfemoral amputees increases which significantly modulates the spectral power of intrinsic cortical oscillations.
Findings
Using the independent components from the sensorimotor areas and supplementary motor area (SMA), our results present a well-pronounced drop of alpha spectral power at sensorimotor area contralateral to sound limb of amputees in comparison to SMA and the sensorimotor area contralateral to prosthetic limb. Following this, we found significantly higher (p < 0.05) limit of stability (LOS) at their sound limb than at the prosthetic limb. Healthy individuals have similar contribution from both the limbs and the EEG alpha spectral power was similar across the three regions of the cortex during the balance control task as expected. Overall, a decent correlation was found between the LOS and alpha spectral power in both amputee and healthy individuals (Pearson’s correlation coefficient > 0.5).
Interpretation
By externally stimulating the highlighted cortical regions, neuroplasticity might be promoted which helps to reduce the training time for the efficient rehabilitation of amputees. Additionally, this new knowledge might benefit in the designing and development of innovative interventions to prevent falls due to lower limb amputation.
Touch plays a fundamental role in our daily activities. It has long been known that, thanks to brain plasticity, tactile acuity can be improved following training. Another form of tactile improvement, independent from training, can be achieved through a simple mechanical stimulation of a small region of the skin, called repetitive somatosensory stimulation (RSS). RSS of a finger was well known to improve tactile acuity locally (on the stimulated finger) and also remotely (on the face). However, topography of tactile improvement, especially on other unstimulated fingers, was unknown. In addition, the hypothesis of applying the RSS to another body region (notably the face) and investigate the possible effects, both in face and fingers, was not explored. The aim of this work of thesis was therefore investigating the topography of the RSS-induced tactile improvement within and between body regions. One first study revealed that RSS of a finger induces tactile improvement both locally and remotely in fingers. The second study showed that, when applied on the face, RSS is able to induce tactile improvement both locally, on the face, and remotely, in the hand, demonstrating that the tactile improvement between the hand and the face is bidirectional. Overall, the experimental data I provide constitute a significant contribution to the study of the topography of RSS-induced tactile changes
Tactile and proprioceptive feedback is critical for sensorimotor integration when we use our hand to perform daily tasks. Here, we evaluated how externally evoked tactile and proprioceptive feedback and myoelectric control strategies affected the recognition of object properties when participants controlled a prosthetic hand. Fingertip tactile sensation was elicited using a transcutaneous nerve stimulation grid to encode the prosthetics fingertip forces. An array of tactors elicited patterned vibratory stimuli to encode proprioceptive kinematic information of the prosthetic finger joint. Myoelectric signals of the finger flexor and extensor were used to control the position or velocity of joint angles of the prosthesis. Participants were asked to perform object property (stiffness and size) recognition, by controlling the prosthetic hand with concurrent tactile and proprioceptive feedback. With the evoked feedback, intact and amputee participants recognized the object stiffness and size at success rates ranging from 50% to 100% in both position and velocity control with no significant difference across control schemes. Our findings show that evoked somatosensory feedback in a non-invasive manner can facilitate closed-loop control of the prosthetic hand and allowed for recognition of different object properties. The outcomes can facilitate our understanding on the role of sensory feedback during bidirectional human-machine interactions, which can potentially promote user experience in object interactions using prosthetic hands.
The emergence of robotic body augmentation provides exciting innovations that will revolutionize the fields of robotics, human–machine interaction and wearable electronics. Although augmentative devices such as extra robotic arms and fingers are informed by restorative technologies in many ways, they also introduce unique challenges for bidirectional human–machine collaboration. Can humans adapt and learn to operate a new robotic limb collaboratively with their biological limbs, without restricting other physical abilities? To successfully achieve robotic body augmentation, we need to ensure that, by giving a user an additional (artificial) limb, we are not trading off the functionalities of an existing (biological) one. Here, we introduce the ‘neural resource allocation problem’ and discuss how to allow the effective voluntary control of augmentative devices without compromising control of the biological body. In reviewing the relevant literature on extra robotic fingers and arms, we critically assess the range of potential solutions available for this neural resource allocation problem. For this purpose, we combine multiple perspectives from engineering and neuroscience with considerations including human–machine interaction, sensory–motor integration, ethics and law. In summary, we aim to define common foundations and operating principles for the successful implementation of robotic body augmentation.
Advances in our understanding of brain function, along with the development of neural interfaces that allow for the monitoring and activation of neurons, have paved the way for brain machine interfaces (BMI), which harness neural signals to reanimate the limbs via electrical activation of the muscles, or to control extra-corporeal devices, thereby bypassing the muscles and senses altogether. BMIs consist of reading out motor intent from the neuronal responses monitored in motor regions of the brain and executing intended movements using bionic limbs, reanimated limbs, or exoskeletons. BMIs also allow for the restoration of the sense of touch by electrically activating neurons in somatosensory regions of the brain, thereby evoking vivid tactile sensations and conveying feedback about object interactions. In this review, we discuss the neural mechanisms of motor control and somatosensation in able-bodied individuals and describe approaches to use neuronal responses as control signals for movement restoration and to activate residual sensory pathways to restore touch. While the focus of the review is on intracortical approaches, we also describe alternative signal sources for control and non-invasive strategies for sensory restoration.
Microstimulation in the somatosensory cortex can evoke artificial tactile percepts and can be incorporated into bidirectional brain-computer interfaces (BCIs) to restore function after injury or disease. However, little is known about how stimulation parameters themselves affect perception. Here, we stimulated through microelectrode arrays implanted in the somatosensory cortex of two human participants with cervical spinal cord injury and varied the stimulus amplitude, frequency and train duration. Increasing the amplitude and train duration increased the perceived intensity on all tested electrodes. Surprisingly, we found that increasing the frequency evoked more intense percepts on some electrodes but evoked less intense percepts on other electrodes. These different frequency-intensity relationships were divided into three groups which also evoked distinct percept qualities at different stimulus frequencies. Neighboring electrode sites were more likely to belong to the same group. These results support the idea that stimulation frequency directly controls tactile perception and that these different percepts may be related to the organization of somatosensory cortex, which will facilitate principled development of stimulation strategies for bidirectional BCIs.
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.
Even decades following amputation individuals report a continuous, oftentimes painful sensation of the missing limb. Phantom limb pain (PLP) is notorious for being difficult to treat, probably due to our insufficient understanding of its underlying causes. Currently, PLP is thought to result from maladaptive brain reorganisation, where the lost input from the missing hand triggers invasion of neighbouring brain representations into the missing hand brain territory. The maladaptive reorganisation theory has influenced not only neuroscientists, but also philosophers and clinicians. Beyond insights into the malleability of body representation in the brain, this theory provides opportunities for treating PLP. Although the theory is supported by multiple studies, the main assumption that input loss from the hand triggers maladaptive domino effects in the brain has been recently challenged. Further, treatments designed to alleviate PLP by reversing maladaptive reorganisation do not work consistently. In this book chapter we describe the experience of phantom sensations and review classical and contemporary studies of the neural basis of this curious phenomenon. We highlight evidence of PLP being driven by false input from the injured arm nerve and new research suggesting that brain plasticity following amputation is assistive, rather than harmful.
Brains of adult monkeys with chronic lesions of dorsal columns of spinal cord at cervical levels undergo large-scale reorganization. Reorganization results in expansion of intact chin inputs, which reactivate neurons in the deafferented hand representation in the primary somatosensory cortex (area 3b), ventroposterior nucleus of the thalamus and cuneate nucleus of the brainstem. A likely contributing mechanism for this large-scale plasticity is sprouting of axons across the hand–face border. Here we determined whether such sprouting takes place in area 3b. We first determined the extent of intrinsic corticocortical connectivity between the hand and the face representations in normal area 3b. Small amounts of neuroanatomical tracers were injected in these representations close to the electrophysiologically determined hand–face border. Locations of the labeled neurons were mapped with respect to the detailed electrophysiological somatotopic maps and histologically determined hand–face border revealed in sections of the flattened cortex stained for myelin. Results show that intracortical projections across the hand–face border are few. In monkeys with chronic unilateral lesions of the dorsal columns and expanded chin representation, connections across the hand–face border were not different compared with normal monkeys. Thalamocortical connections from the hand and face representations in the ventroposterior nucleus to area 3b also remained unaltered after injury. The results show that sprouting of intrinsic connections in area 3b or the thalamocortical inputs does not contribute to large-scale cortical plasticity.
The first decade and a half of the twenty-first century brought about two major innovations in neuroprosthetics: the development of anthropomorphic robotic limbs that replicate much of the function of a native human arm and the refinement of algorithms that decode intended movements from brain activity. However, skilled manipulation of objects requires somatosensory feedback, for which vision is a poor substitute. For upper-limb neuroprostheses to be clinically viable, they must therefore provide for the restoration of touch and proprioception. In this review, I discuss efforts to elicit meaningful tactile sensations through stimulation of neurons in somatosensory cortex. I focus on biomimetic approaches to sensory restoration, which leverage our current understanding about how information about grasped objects is encoded in the brain of intact individuals. I argue that not only can sensory neuroscience inform the development of sensory neuroprostheses, but also that the converse is true: stimulating the brain offers an exceptional opportunity to causally interrogate neural circuits and test hypotheses about natural neural coding.
The role of cortical activity in generating and abolishing chronic pain is increasingly emphasized in the clinical community. Perhaps the most striking example of this is the maladaptive plasticity theory, according to which phantom pain arises from remapping of cortically neighbouring representations (lower face) into the territory of the missing hand following amputation. This theory has been extended to a wide range of chronic pain conditions, such as complex regional pain syndrome. Yet, despite its growing popularity, the evidence to support the maladaptive plasticity theory is largely based on correlations between pain ratings and oftentimes crude measurements of cortical reorganization, with little consideration of potential contributions of other clinical factors, such as adaptive behaviour, in driving the identified brain plasticity. Here, we used a physiologically meaningful measurement of cortical reorganization to reassess its relationship to phantom pain in upper limb amputees. We identified small yet consistent shifts in lip representation contralateral to the missing hand towards, but not invading, the hand area. However, we were unable to identify any statistical relationship between cortical reorganization and phantom sensations or pain either with this measurement or with the traditional Eucledian distance measurement. Instead, we demonstrate that other factors may contribute to the observed remapping. Further research that reassesses more broadly the relationship between cortical reorganization and chronic pain is warranted.
© The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.
There is an ongoing debate about whether adult human primary visual cortex (V1) is capable of large-scale cortical reorganization in response to bilateral retinal lesions. Animal models suggest that the visual neural circuitry maintains some plasticity through adulthood, and there are also a few human imaging studies in support this notion. However, the interpretation of these data has been brought into question, because there are factors besides cortical reorganization, such as the presence of sampling bias and/or the unmasking of task-dependent feedback signals from higher level visual areas, that could also explain the results. How reasonable would it be to accept that adult human V1 does not reorganize itself in the face of disease? Here, we discuss new evidence for the hypothesis that adult human V1 is not as capable of reorganization as in animals and juveniles, because in adult humans, cortical reorganization would come with costs that outweigh its benefits. These costs are likely functional and visible in recent experiments on adaptation — a rapid, short-term form of neural plasticity — where they prevent reorganization from being sustained over the long term.
Touch perception on the fingers and hand is essential for fine motor control, contributes to our sense of self, allows for effective communication, and aids in our fundamental perception of the world. Despite increasingly sophisticated mechatronics, prosthetic devices still do not directly convey sensation back to their wearers. We show that implanted peripheral nerve interfaces in two human subjects with upper limb amputation provided stable, natural touch sensation in their hands for more than 1 year. Electrical stimulation using implanted peripheral nerve cuff electrodes that did not penetrate the nerve produced touch perceptions at many locations on the phantom hand with repeatable, stable responses in the two subjects for 16 and 24 months. Patterned stimulation intensity produced a sensation that the subjects described as natural and without "tingling," or paresthesia. Different patterns produced different types of sensory perception at the same location on the phantom hand. The two subjects reported tactile perceptions they described as natural tapping, constant pressure, light moving touch, and vibration. Changing average stimulation intensity controlled the size of the percept area; changing stimulation frequency controlled sensation strength. Artificial touch sensation improved the subjects' ability to control grasping strength of the prosthesis and enabled them to better manipulate delicate objects. Thus, electrical stimulation through peripheral nerve electrodes produced long-term sensory restoration after limb loss.
Nearly all amputees continue to feel their missing limb as if it still existed, and many experience chronic phantom limb pain (PLP). There is currently a broad consensus among investigators that the origin of these sensations is a top-down phenomenon, triggered by loss of sensory input and caused by maladaptive cortical plasticity. We tested the alternative hypothesis that PLP is primarily a bottom-up process, one due not to the loss of input but rather to exaggerated input, generated ectopically in axotomized primary afferent neurons in the dorsal root ganglia (DRG) that used to innervate the limb. In 31 amputees, the local anesthetic lidocaine was applied intrathecally and/or to the DRG surface (intraforaminal epidural block). This rapidly and reversibly extinguished PLP and also nonpainful phantom limb sensation. Control injections were ineffective. For intraforaminal block, the effect was topographically appropriate. This could also be demonstrated using dilute lidocaine concentrations that are sufficient to suppress DRG ectopia but not to block the propagation of impulses generated further distally in the nerve. PLP is driven primarily by activity generated within DRG. We recommend the DRG as a target for treatment of PLP and perhaps also other types of regional neuropathic pain.
Keywords
DRG; Ectopic firing; Electrogenesis; Intraforaminal; Neuropathic pain; Phantom limb pain
Corresponding author contact information
Corresponding author. Address: Department of Cell & Developmental Biology, Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel. Tel.: +972 2 6585085; fax: +972 2 6586027.
Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
Adult mammalian brains undergo reorganization following deafferentations due to peripheral nerve, cortical or spinal cord injuries. The largest extent of cortical reorganization is seen in area 3b of the somatosensory cortex of monkeys with chronic transection of the dorsal roots or dorsal columns of the spinal cord. These injuries cause expansion of intact face inputs into the deafferented hand cortex, resulting in a change of representational boundaries by more than 7 mm. Here we show that large-scale reorganization in area 3b following spinal cord injuries is due to changes at the level of the brainstem nuclei and not due to cortical mechanisms. Selective inactivation of the reorganized cuneate nucleus of the brainstem eliminates observed face expansion in area 3b. Thus, the substrate for the observed expanded face representation in area 3b lies in the cuneate nucleus.
Amputation of the dominant hand forces patients to use the nondominant hand exclusively, including for tasks (e.g., writing and drawing) that were formerly the sole domain of the dominant hand. The behavioral and neurological effects of this chronic forced use of the nondominant hand remain largely unknown. Yet, these effects may shed light on the potential to compensate for degradation or loss of dominant hand function, as well as the mechanisms that support motor learning under conditions of very long-term training. We used a novel precision drawing task and fMRI to investigate 8 adult human amputees with chronic (mean 33 years) unilateral dominant (right) hand absence, and right-handed matched controls (8 for fMRI, 19 for behavior). Amputees' precision drawing performances with their left hands reached levels of smoothness (associated with left hemisphere control), acceleration time (associated with right hemisphere control), and speed equivalent to controls' right hands, whereas accuracy maintained a level comparable with controls' left hands. This compensation is supported by an experience-dependent shift from heavy reliance on the dorsodorsal parietofrontal pathway (feedback control) to the ventrodorsal pathway and prefrontal regions involved in the cognitive control of goal-directed actions. Relative to controls, amputees also showed increased activity within the former cortical sensorimotor hand territory in the left (ipsilateral) hemisphere. These data demonstrate that, with chronic and exclusive forced use, the speed and quality of nondominant hand precision endpoint control in drawing can achieve levels nearly comparable with the dominant hand.
Phantom pain after arm amputation is widely believed to arise from maladaptive cortical reorganization, triggered by loss of sensory input. We instead propose that chronic phantom pain experience drives plasticity by maintaining local cortical representations and disrupting inter-regional connectivity. Here we show that, while loss of sensory input is generally characterized by structural and functional degeneration in the deprived sensorimotor cortex, the experience of persistent pain is associated with preserved structure and functional organization in the former hand area. Furthermore, consistent with the isolated nature of phantom experience, phantom pain is associated with reduced inter-regional functional connectivity in the primary sensorimotor cortex. We therefore propose that contrary to the maladaptive model, cortical plasticity associated with phantom pain is driven by powerful and long-lasting subjective sensory experience, such as triggered by nociceptive or top-down inputs. Our results prompt a revisiting of the link between phantom pain and brain organization.
Amputees can move their phantom limb at will. These 'movements without movements' have generally been considered as motor imagery rather than motor execution, but amputees can in fact perform both executed and imagined movements with their phantom and they report distinct perceptions during each task. Behavioural evidence for this dual ability comes from the fact that executed movements are associated with stump muscle contractions whereas imagined movements are not, and that phantom executed movements are slower than intact hand executed movements whereas the speed of imagined movements is identical for both hands. Since neither execution nor imagination produces any visible movement, we hypothesized that the perceptual difference between these two motor tasks relies on the activation of distinct cerebral networks. Using functional magnetic resonance imaging and changes in functional connectivity (dynamic causal modelling), we examined the activity associated with imagined and executed movements of the intact and phantom hands of 14 upper-limb amputees. Distinct but partially overlapping cerebral networks were active during both executed and imagined phantom limb movements (both performed at the same speed). A region of interest analysis revealed a 'switch' between execution and imagination; during execution there was more activity in the primary somatosensory cortex, the primary motor cortex and the anterior lobe of the cerebellum, while during imagination there was more activity in the parietal and occipital lobes, and the posterior lobe of the cerebellum. In overlapping areas, task-related differences were detected in the location of activation peaks. The dynamic causal modelling analysis further confirmed the presence of a clear neurophysiological distinction between imagination and execution, as motor imagery and motor execution had opposite effects on the supplementary motor area-primary motor cortex network. This is the first imaging evidence that the neurophysiological network activated during phantom limb movements is similar to that of executed movements of intact limbs and differs from the phantom limb imagination network. The dual ability of amputees to execute and imagine movements of their phantom limb and the fact that these two tasks activate distinct cortical networks are important factors to consider when designing rehabilitation programmes for the treatment of phantom limb pain.
Information processing in the cerebral cortex involves interactions among distributed areas. Anatomical connectivity suggests that certain areas form local hierarchical relations such as within the visual system. Other connectivity patterns, particularly among association areas, suggest the presence of large-scale circuits without clear hierarchical relations. In this study the organization of networks in the human cerebrum was explored using resting-state functional connectivity MRI. Data from 1,000 subjects were registered using surface-based alignment. A clustering approach was employed to identify and replicate networks of functionally coupled regions across the cerebral cortex. The results revealed local networks confined to sensory and motor cortices as well as distributed networks of association regions. Within the sensory and motor cortices, functional connectivity followed topographic representations across adjacent areas. In association cortex, the connectivity patterns often showed abrupt transitions between network boundaries. Focused analyses were performed to better understand properties of network connectivity. A canonical sensory-motor pathway involving primary visual area, putative middle temporal area complex (MT+), lateral intraparietal area, and frontal eye field was analyzed to explore how interactions might arise within and between networks. Results showed that adjacent regions of the MT+ complex demonstrate differential connectivity consistent with a hierarchical pathway that spans networks. The functional connectivity of parietal and prefrontal association cortices was next explored. Distinct connectivity profiles of neighboring regions suggest they participate in distributed networks that, while showing evidence for interactions, are embedded within largely parallel, interdigitated circuits. We conclude by discussing the organization of these large-scale cerebral networks in relation to monkey anatomy and their potential evolutionary expansion in humans to support cognition.
The occipital lobe contains retinotopic representations of the visual field. The representation of the central retina in early visual areas (V1-3) is found at the occipital pole. When the central retina is lesioned in both eyes by macular degeneration, this region of visual cortex at the occipital pole is accordingly deprived of input. However, even when such lesions occur in adulthood, some visually driven activity in and around the occipital pole can be observed. It has been suggested that this activity is a result of remapping of this area so that it now responds to inputs from intact, peripheral retina. We evaluated whether or not remapping of visual cortex underlies this activity. Our functional magnetic resonance imaging results provide no evidence of remapping, questioning the contemporary view that early visual areas of the adult human brain have the capacity to reorganize extensively.
There is growing evidence that sensory deprivation is associated with crossmodal neuroplastic changes in the brain. After visual or auditory deprivation, brain areas that are normally associated with the lost sense are recruited by spared sensory modalities. These changes underlie adaptive and compensatory behaviours in blind and deaf individuals. Although there are differences between these populations owing to the nature of the deprived sensory modality, there seem to be common principles regarding how the brain copes with sensory loss and the factors that influence neuroplastic changes. Here, we discuss crossmodal neuroplasticity with regards to behavioural adaptation after sensory deprivation and highlight the possibility of maladaptive consequences within the context of rehabilitation.
Human motor development is thought to result from a complex interaction between genes and experience. The well-known somatotopic organization of the primate primary motor cortex (M1) emerges postnatally. Although adaptive changes in response to learning and use occur throughout life, somatotopy is maintained as reorganization is restricted to modifications within major body part representations. We report of a unique opportunity to evaluate the influence of experience on the genetically determined somatotopic organization of motor cortex in humans. We examined the motor "foot" representation in subjects with congenitally compromised hand function and compensatory skillful foot use. Functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) of M1 revealed that the foot was represented in the classical medial foot area of M1 and was several centimetres away in nonadjacent cortex in the vicinity of the lateral "hand" area. Both areas had direct output to the spinal motor neurons innervating foot muscles and were behaviorally relevant because experimental disruption of either area by TMS altered reaction times. We demonstrate a unique, nonsomatotopically organized M1 in humans, which emerged as a function of grossly altered motor behavior from the earliest stages of development. Our results imply that during early motor development experience may play a more critical role in the shaping of genetically determined neural networks than previously assumed.
We describe how upper limb amputees can be made to experience a rubber hand as part of their own body. This was accomplished by applying synchronous touches to the stump, which was out of view, and to the index finger of a rubber hand, placed in full view (26 cm medial to the stump). This elicited an illusion of sensing touch on the artificial hand, rather than on the stump and a feeling of ownership of the rubber hand developed. This effect was supported by quantitative subjective reports in the form of questionnaires, behavioural data in the form of misreaching in a pointing task when asked to localize the position of the touch, and physiological evidence obtained by skin conductance responses when threatening the hand prosthesis. Our findings outline a simple method for transferring tactile sensations from the stump to a prosthetic limb by tricking the brain, thereby making an important contribution to the field of neuroprosthetics where a major goal is to develop artificial limbs that feel like a real parts of the body.
Adult brains undergo large-scale plastic changes after peripheral and central injuries. Although it has been shown that both the cortical and thalamic representations can reorganize, uncertainties exist regarding the extent, nature, and time course of changes at each level. We have determined how cortical representations in the somatosensory area 3b and the ventroposterior (VP) nucleus of thalamus are affected by long standing unilateral dorsal column lesions at cervical levels in macaque monkeys. In monkeys with recovery periods of 22-23 months, the intact face inputs expanded into the deafferented hand region of area 3b after complete or partial lesions of the dorsal columns. The expansion of the face region could extend all the way medially into the leg and foot representations. In the same monkeys, similar expansions of the face representation take place in the VP nucleus of the thalamus, indicating that both these processing levels undergo similar reorganizations. The receptive fields of the expanded representations were similar in somatosensory cortex and thalamus. In two monkeys, we determined the extent of the brain reorganization immediately after dorsal column lesions. In these monkeys, the deafferented regions of area 3b and the VP nucleus became unresponsive to the peripheral touch immediately after the lesion. No reorganization was seen in the cortex or the VP nucleus. A comparison of the extents of deafferentation across the monkeys shows that even if the dorsal column lesion is partial, preserving most of the hand representation, it is sufficient to induce an expansion of the face representation.
After limited sensory deafferentations in adult primates, somatosensory cortical maps reorganize over a distance of 1 to 2
millimeters mediolaterally, that is, in the dimension along which different body parts are represented. This amount of reorganization
was considered to be an upper limit imposed by the size of the projection zones of individual thalamocortical axons, which
typically also extend a mediolateral distance of 1 to 2 millimeters. However, after extensive long-term deafferentations in
adult primates, changes in cortical maps were found to be an order of magnitude greater than those previously described. These
results show the need for a reevaluation of both the upper limit of cortical reorganization in adult primates and the mechanisms
responsible for it.
Previous studies have shown that the primary somatosensory cortex of adult mammals undergoes somatotopic reorganization in response to peripheral nerve transection. The present study assesses how cortical organization is affected when a transected nerve subsequently regenerates. The median nerve to one hand of adult owl monkeys was transected and repaired. Following nerve regeneration, the representations of the hand in cortical areas 3b and 1 were studied with neurophysiological mapping methods. The major results were as follows: Peripherally, median nerve transection, repair, and regeneration resulted in reinnervation of the median nerve skin territory. Centrally, both the initial loss and subsequent regeneration of median nerve inputs caused reorganizational changes in cortex. Reorganizational changes were specifically restricted to regions of the hand cortex where inputs from the median nerve were normally represented. The functional features of cortical regions that recovered tactile responsiveness from reinnervated skin regions were abnormal in several respects. Most notably, these regions contained recording sites with abnormally located or multiple cutaneous receptive fields, and contained major topographical changes, such as reestablishment of palmar pad or digit representations in small, discontinuous patches of cortex. Normal organizational features were reestablished to a more limited extent. These features included recovery of delimited, discrete receptive fields and reestablishment of topographic representations for localized skin areas. Different transformations in topographical organization were seen in areas 3b and 1 of the same monkey. These results suggest that nerve regeneration reestablishes the cortical capacity to process tactile information from reinnervated skin via a prolonged reorganizational process that appears dependent on peripheral and central factors. Cortical recovery mechanisms clearly appear to have limitations, since preinjury patterns of cortical organization are not widely recovered even almost 1 year after repair. We suggest possible relationships between cortical reorganizational changes in these primates, and postrepair sensory changes in humans.
Although phantom-limb pain is a frequent consequence of the amputation of an extremity, little is known about its origin. On the basis of the demonstration of substantial plasticity of the somatosensory cortex after amputation or somatosensory deafferentation in adult monkeys, it has been suggested that cortical reorganization could account for some non-painful phantom-limb phenomena in amputees and that cortical reorganization has an adaptive (that is, pain-preventing) function. Theoretical and empirical work on chronic back pain has revealed a positive relationship between the amount of cortical alteration and the magnitude of pain, so we predicted that cortical reorganization and phantom-limb pain should be positively related. Using non-invasive neuromagnetic imaging techniques to determine cortical reorganization in humans, we report a very strong direct relationship (r = 0.93) between the amount of cortical reorganization and the magnitude of phantom limb pain (but not non-painful phantom phenomena) experienced after arm amputation. These data indicate that phantom-limb pain is related to, and may be a consequence of, plastic changes in primary somatosensory cortex.
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.
Understanding the amazingly complex human cerebral cortex requires a map (or parcellation) of its major subdivisions, known as cortical areas. Making an accurate areal map has been a century-old objective in neuroscience. Using multi-modal magnetic resonance images from the Human Connectome Project (HCP) and an objective semi-automated neuroanatomical approach, we delineated 180 areas per hemisphere bounded by sharp changes in cortical architecture, function, connectivity, and/or topography in a precisely aligned group average of 210 healthy young adults. We characterized 97 new areas and 83 areas previously reported using post-mortem microscopy or other specialized study-specific approaches. To enable automated delineation and identification of these areas in new HCP subjects and in future studies, we trained a machine-learning classifier to recognize the multi-modal 'fingerprint' of each cortical area. This classifier detected the presence of 96.6% of the cortical areas in new subjects, replicated the group parcellation, and could correctly locate areas in individuals with atypical parcellations. The freely available parcellation and classifier will enable substantially improved neuroanatomical precision for studies of the structural and functional organization of human cerebral cortex and its variation across individuals and in development, aging, and disease.
A substantial body of evidence documents massive reorganization of primary sensory and motor cortices following hand amputation, the extent of which is correlated with phantom limb pain. Many therapies for phantom limb pain are based upon the idea that plastic changes after amputation are maladaptive and attempt to normalize representations of cortical areas adjacent to the hand area. Recent data suggest, however, that higher levels of phantom pain are associated with stronger local activity and more structural integrity in the missing hand area rather than with reorganization of neighbouring body parts. While these models appear to be mutually exclusive they could co-exist, and one reason for the apparent discrepancy between them might be that no single study has examined the organisation of lip, elbow, and hand movements in the same participants. In this study we thoroughly examined the 3D anatomy of the central sulcus and BOLD responses during movements of the hand, elbow, and lips using MRI techniques in 11 upper-limb amputees and 17 healthy control subjects. We observed different reorganizational patterns for all three body parts as the former hand area showed few signs of reorganization, but the lip and elbow representations reorganized and shifted towards the hand area. We also found that poorer voluntary control and higher levels of pain in the phantom limb were powerful drivers of the lip and elbow topological changes. In addition to providing further support for the maladaptative plasticity model, we demonstrate for the first time that motor capacities of the phantom limb correlate with post-amputation reorganization, and that this reorganization is not limited to the face and hand representations but also includes the proximal upper-limb.
The neural mechanisms that permit perception of phantom limbs have been investigated over many years (Melzack, 1989a; Sherman, 1989a, 1989b; Sherman, Arena et al., 1990). A basic explanation of the underlying concepts is included in the attached amputee guide (Appendix II). A huge body of research has demonstrated that sensations reaching the brain are identified as to location on the skin by the homunculi in the sensory parts of the brain, including the somatosensory cortex, which contains several representations of the entire body surface. Thus, a pinch of the left index finger tip stimulates neurons in a location on the homunculi representing the left index finger tip. If the finger has been amputated, and the same signal is started by stimuli anywhere along the remaining nerve paths between the finger’s stump and the homunculi, the resulting sensation seems to emanate from the finger tip. The real question is how these misleading impulses form and why the resulting sensation is frequently, but not always, painful. The relationships among phantom pain, phantom sensations, and possible changes in the homunculi are discussed in this and subsequent chapters.
A complete unilateral lesion of the dorsal column somatosensory pathway in the upper cervical spinal cord deactivates neurons in the hand region in contralateral somatosensory cortex (areas 3b and 1). Over weeks to months of recovery, parts of the hand region become reactivated by touch on the hand or face. In order to determine if changes in cortical connections potentially contribute to this reactivation, we injected tracers into electrophysiologically identified locations in cortex of area 3b representing the reactivated hand and normally activated face in adult squirrel monkeys. Our results indicated that most of the expected connections of area 3b remained for partially reactivated area 3b, including the majority of intrinsic connections within area 3b; feedback connections from area 1, secondary somatosensory cortex (S2), parietal ventral area (PV) and other cortical areas; and thalamic inputs from the ventroposterior lateral nucleus (VPL). In addition, tracer injections in the reactivated hand region of area 3b labeled more neurons in the face and shoulder regions of area 3b than in normal monkeys, and injections in the face region of area 3b labeled more neurons in the hand region. Unexpectedly, the intrinsic connections within area 3b hand cortex were more widespread after incomplete dorsal column lesions (DCLs) than after a complete DCL. Although these additional connections were limited, these changes in connections may contribute to the reactivation process after injuries. This article is protected by copyright. All rights reserved.
The topography of the somatosensory maps of our body [1] can be largely shaped by alterations of peripheral sensory inputs [2, 3]. Following hand amputation, the hand cortical territory becomes responsive to facial cutaneous stimulation [4–7]. Amputation-induced remapping, however, reverses after transplantation, as the grafted hand (re)gains its sensorimotor representation [8]. Here, we investigate hand tactile perception in a former amputee by touching either grafted hand singly or in combination with another body part. The results showed that tactile sensitivity recovered rapidly, being remarkably good 5 months after transplant. In the right grafted hand, however, the newly acquired somatosensory awareness was strikingly hampered when the ipsilateral face was touched simultaneously, i.e., right face perception extinguished right hand perception. Ipsilateral face-hand extinction was present in the formerly dominant right hand 5 months after transplant and eventually disappeared 6 months afterwards. Control conditions' results showed that right hand tactile awareness was not extinguished either by contralateral left face and left hand stimulation or ipsilateral stimulation of the arm, which is bodily close to, but cortically far from, the hand. We suggest that ipsilateral face-hand extinction is a perceptual counterpart of the remapping that occurs after allograft and eyewitnesses the inherently competitive nature of sensory representations.
The cerebral cortex communicates with the cerebellum via polysynaptic circuits. Separate regions of the cerebellum are connected to distinct cerebral areas, forming a complex topography. In this study we explored the organization of cerebrocerebellar circuits in the human using resting-state functional connectivity MRI (fcMRI). Data from 1,000 subjects were registered using nonlinear deformation of the cerebellum in combination with surface-based alignment of the cerebral cortex. The foot, hand, and tongue representations were localized in subjects performing movements. fcMRI maps derived from seed regions placed in different parts of the motor body representation yielded the expected inverted map of somatomotor topography in the anterior lobe and the upright map in the posterior lobe. Next, we mapped the complete topography of the cerebellum by estimating the principal cerebral target for each point in the cerebellum in a discovery sample of 500 subjects and replicated the topography in 500 independent subjects. The majority of the human cerebellum maps to association areas. Quantitative analysis of 17 distinct cerebral networks revealed that the extent of the cerebellum dedicated to each network is proportional to the network's extent in the cerebrum with a few exceptions, including primary visual cortex, which is not represented in the cerebellum. Like somatomotor representations, cerebellar regions linked to association cortex have separate anterior and posterior representations that are oriented as mirror images of one another. The orderly topography of the representations suggests that the cerebellum possesses at least two large, homotopic maps of the full cerebrum and possibly a smaller third map.
Evolutionary concepts such as adaptation and maladaptation have been used by neuroscientists to explain brain properties and mechanisms. In particular, one of the most compelling characteristics of the brain, known as neuroplasticity, denotes the ability of the brain to continuously adapt its functional and structural organization to changing requirements. Although brain plasticity has evolved to favor adaptation, there are cases in which the same mechanisms underlying adaptive plasticity can turn into maladaptive changes. Here, we will consider brain plasticity and its functional and structural consequences from an evolutionary perspective, discussing cases of adaptive and maladaptive plasticity and using examples from typical and atypical development.
Reduced somatosensation is a common impairment after stroke. This somatosensory deficit is known to be a reliable predictor of poor rehabilitation outcome. Several methods of physical therapy have addressed this problem, but with only moderate success. Here, we used a new neural plasticity-based approach, ie, a simple, inexpensive, pharmacologically induced temporary functional deafferentation (TFD) of the forearm to investigate whether TFD might result in beneficial effects on the somatosensory sensibility and motor capacity of the stroke-affected hand.
Examination was performed over 2 consecutive days of an efficient rehabilitation program for stroke patients referred to as constraint-induced movement therapy. Patients were deafferented on one of these days but not on the other (placebo session). The order of deafferentation and nondeafferentation was counterbalanced across patients. TFD of the stroke-affected forearm was realized using an anesthetic cream. Somatosensory abilities were assessed by a Grating orienting task, and a shape-sorter drum task was used to test motor performance. Both tests were performed each day before and after the constraint-induced movement therapy training session.
We found significantly better outcomes for Grating orienting task and shape-sorter drum task after TFD on the forearm as compared to placebo, indicating increased somatosensory abilities and motor performance in stroke patients using the simple TFD procedure.
The improvement was achieved during the course of one of the best established poststroke rehabilitation programs, suggesting that TFD on the more affected forearm might become an efficient additional tool in stroke rehabilitation.
Various forms of category-specificity have been described at both the cognitive and neural levels, inviting the inference that different semantic domains are processed by distinct, dedicated mechanisms. In this paper, we argue for an extension of a domain-specific interpretation to these phenomena that is based on network-level analyses of functional coupling among brain regions. On this view, domain-specificity in one region of the brain emerges because of innate connectivity with a network of regions that also process information about that domain. Recent findings are reviewed that converge with this framework, and a new direction is outlined for understanding the neural principles that shape the organization of conceptual knowledge.
Phantom limb syndrome (PLS) is common after limb amputations, involving up to 90% of amputees. Although many different therapies have been evaluated, none has been found to be highly effective. Therefore, we evaluated the efficacy of a prolonged perineural infusion of a high concentration of local anesthetic solution in preventing PLS.
A perineural catheter was placed immediately before or during surgery in 71 patients undergoing lower extremity amputation. A continuous infusion of 0.5% ropivacaine was started intraoperatively at 5 mL/h using an elastomeric (nonelectronic) pump, and continued for 4 to 83 days after surgery. PLS was evaluated on the first postoperative day and then 1, 2, 3, and 4 weeks, and 3, 6, 9, and 12 months after surgery. To evaluate the presence and severity of PLS while the patient was receiving the ropivacaine infusion, it was discontinued for 6 to 12 hours before each assessment period (i.e., until the sensation in the extremity returned). The severity of phantom limb and stump pain was assessed using a 5-point verbal rating scale (VRS), with 0 = no pain to 4 = intolerable pain, and "phantom" sensations were recorded as present or absent. If the VRS score was >1 or significant phantom sensations were present, the ropivacaine infusion was immediately restarted at 5 mL/h. If the VRS score remained at 0 to 1 and the patient had not experienced phantom sensations for 48 hours, the infusion was permanently discontinued and the catheter was removed.
Median duration of the local anesthetic infusion was 30 days (95% confidence interval, 25-30 days). On postoperative day 1, 73% of the patients complained of severe-to-intolerable pain (visual analog scale >2). However, the incidence of severe-to-intolerable phantom limb pain was only 3% at the end of the 12-month evaluation period. At the end of the 12-month period, the percentage of patients with VRS pain scores were 0 = 84%, 1 = 10%, 2 = 3%, 3 = 3%, and 4 = none. However, phantom limb sensations were present in 39% of patients at the end of the 12-month evaluation period. All patients were able to manage the elastomeric catheter infusion system at home.
Use of a prolonged postoperative perineural infusion of ropivacaine 0.5% seems to be an effective therapy for the treatment of phantom limb pain and sensations after lower extremity amputation.
This article reviews the potential use of visual feedback, focusing on mirror visual feedback, introduced over 15 years ago, for the treatment of many chronic neurological disorders that have long been regarded as intractable such as phantom pain, hemiparesis from stroke and complex regional pain syndrome. Apart from its clinical importance, mirror visual feedback paves the way for a paradigm shift in the way we approach neurological disorders. Instead of resulting entirely from irreversible damage to specialized brain modules, some of them may arise from short-term functional shifts that are potentially reversible. If so, relatively simple therapies can be devised--of which mirror visual feedback is an example--to restore function.
Amputation induces substantial reorganization of the body part somatotopy in primary sensory cortex (S1 complex, hereafter S1) [1, 2], and these effects of deafferentiation increase with time [3]. Determining whether these changes are reversible is critical for understanding the potential to recover from deafferenting injuries. Earlier BOLD fMRI data demonstrate increased S1 activity in response to stimulation of an allogenically transplanted hand [4]. Here, we report the first evidence that the representation of a transplanted hand can actually recapture the pre-amputation S1 hand territory. A 54-year-old male received a unilateral hand transplant 35 years after traumatic amputation of his right hand. Despite limited sensation, palmar tactile stimulation delivered 4 months post-transplant evoked contralateral S1 responses that were indistinguishable in location and amplitude from those detected in healthy matched controls. We find no evidence for persistent intrusion of representations of the face within the representation of the transplanted hand, although such intrusions are commonly reported in amputees [5, 6]. Our results suggest that even decades after complete deafferentiation, restoring afferent input to S1 leads to re-establishment of the gross hand representation within its original territory. Unexpectedly, large ipsilateral S1 responses accompanied sensory stimulation of the patient's intact hand. These may reflect a change in interhemispheric inhibition that could contribute to maintaining latent hand representations during the period of amputation.
Anterograde and retrograde transport methods were used to study the corticocortical connectivity of areas 3a, 3b, 1, 2, 5, 4 and 6 of the monkey cerebral cortex. Fields were identified by cytoarchitectonic features and by thalamic connectivity in the same brains. Area 3a was identified by first recording a short latency group I afferent evoked potential. Attempts were made to analyze the data in terms of: (1) routes whereby somatic sensory input might influence the performance of motor cortex neurons; (2) possible multiple representations of the body surface in the component fields of the first somatic sensory area (SI).
Apart from vertical interlaminar connections, two types of intracortical connectivity are recognized. The first, regarded as “non‐specific,” consists of axons spreading out in layers I, III and V‐VI from all sides of an injection of isotope; these cross architectonic borders indiscrimininately. They are not unique to the regions studied. The second is formed by axons entering the white matter and re‐entering other fields. In these, they terminate in layers I‐IV in one or more mediolaterally oriented strips of fairly constant width (0.5–;1 mm) and separated by gaps of comparable size. Though there is a broadly systematic topography in these projections, the strips are probably best regarded as representing some feature other than receptive field position. Separate representations are nevertheless implied in area 3b, in areas 1 and 2 (together), in areas 3a and 4 (together) and in area 5; with, in each case, the representations of the digits pointed at the central sulcus.
Area 3b is not connected with areas 3a or 4, but projects to a combined areas 1 and 2. Area 1 is reciprocally connected with area 3a and area 2 reciprocally with area 4. The connectivity of area 3a, as conventionally identified, is such that it is probably best regarded not as an entity, but as a part of area 4. Areas identified by others as area 3a should probably be regraded as parts of area 3b. Parts of area 5 that should be more properly considered as area 2, and other parts that receive thalamic input not from the ventrobasal complex but from the lateral nuclear complex and anterior pulvinar, are also interconnected with area 4. More posterior parts of area 5 are connected with laterally placed parts of area 6. A more medial part of area 6, the supplementary motor area, occupies a pivotal position in the sensory‐motor cortex, for it receives fibers from areas 3a, 4, 1, 2 and 5 (all parts), and projects back to areas 3a, 4 and 5.
Microelectrode mapping experiments indicate that the classical primary somatosensory cortex of monkeys consists of as many as four separate body representations rather than just one. Two complete body surface representations occupy cortical fields 3b and 1. In addition, area 2 contains an orderly representation of predominantly "deep" body tissues. Area 3a may constitute a fourth representation.
The necessity for a sensory feedback system that would enhance patient acceptability of motorized hand prostheses is now generally acknowledged. Afferent electrical stimulation of the nerves in the amputation stump can convey sensory feedback from prostheses with the advantage of eliciting sensations in the phantom image of the lost hand. Experiments with percutaneous nerve stimulation of the amputation stump in below-elbow amputees showed that with stable electrode conditions, amplitude modulated stimulation was better than frequency modulated stimulation in terms of accuracy, delay, and transinformation both with intermittent and uninterrupted stimulation. With unstable electrode conditions, different results were noticed, since amplitude modulated stimulation is very sensitive even to minor changes in electrode position. It is concluded that afferent electrical nerve stimulation with adequate training and stable electrodes had characteristics of accuracy, transinformation and delay which are good enough to make it a suitable method of conveying information in a prosthesis feedback system.
Following long-term deafferentation of one upper limb in adult primates, the cortical areas corresponding to that limb become responsive to stimuli applied to the face. To explore this phenomenon, we studied some patients after upper limb amputation. In patient VQ, stimuli applied to the lower face or 7 cm above the stump evoked precisely localized referred sensations in individual digits which were often modality specific. Similarly, in another patient, WK several complete somatotopic representations of the phantom limb were found, on the face, chest and axilla, indicating the emergence of such maps in regions remote from the stump. These effects may be a direct perceptual correlate of the physiological observations of Merzenick et al (1984), Wall (1977) and Pons et al (1991).
e of amputation. Furthermore, there was precise one-to-one correspondence between these points and those on the phantom limb. (3). (ii) Sensations were referred most often to the hand, especially to the digits with an overrepresentation of the thumb and "pinky." This may reflect the high cortical magnification of these areas. (iii) The referred sensations were modality-specific; for example, a drop of warm water trickling down the face was felt as "warm water trickling down"in the phantom hand. (iv) Reference fields were somatotopically organized. we suggest that this is a direct consequence of the remapping observed by physiologists (1). (v) There was a vivid persistence of short-term "memory" of complex sensations; when we gripped and released the finger adjacent to the amputated finger the patient felt the phantom finger being "gripped," and this sensation persisted for 7 or 8 seconds in the phantom. (v1) Reorganization was relatively rapid. In one patient, our study was carried out
BEFORE A KITTEN OPENS ITS EYES, and long before the eyes are used in visual exploration, single cells of the primary visual cortex respond to natural stimulation with the same specificity as is found in the adult (5). This sug- gests that the anatomical connections between retina and striate cortex are for the most part innate. During the first 3 months of life the connections are highly susceptible to the effects of visual deprivation, to the extent that ex- clusion of all form and some light from one eye leads to a severe decline in the ability of that eye to influence cortical cells. Anatomical and physio- logical evidence suggests that the defect is chiefly, though not entirely, a cortical one (7-9). The object of the present study was to influence cortical connections by some means less drastic than covering one or both eyes. We wished if possi- ble to alter the input in such a way that there would be no question of effects on the visual pathway below the level of the striate cortex. A method was suggested by the well-known clinical observation that a child with a squint (strabismus or nonparallel visual axes) may suffer a deterioration of vision in one eye (amblyopia ex anopsia). Since the visual pathways from the two eyes are for practical purposes separate up to the level of the striate cortex, it is unlikely that in these children the defect is in the retina or geniculate. An artificial squint therefore seemed to provide a possible means of obtaining a cortical defect while sparing the retina and lateral geniculate body. Accord- ingly, we produced a divergent strabismus by cutting one of the extraocular muscles in each of four newborn kittens, with the plan of testing vision and recording from single cortical cells after several months to a year. When at length each eye was tested in these kittens by observing the ani- mal's behavior with the other eye covered the results were disappointing: there was not the slightest suggestion of any defect in vision in either eye. This was not entirely unexpected, since with both eyes uncovered the ani- mals had appeared to fix at times with one eye and at times with the other. At this stage there seemed to be little point in proceeding further, for there - .--
The cortical representations of the hand in area 3b in adult owl monkeys were defined with use of microelectrode mapping techniques 2–8 months after surgical amputation of digit 3, or of both digits 2 and 3. Digital nerves were tied to prevent their regeneration within the amputation stump. Successive maps were derived in several monkeys to determine the nature of changes in map organization in the same individuals over time.
In all monkeys studied, the representations of adjacent digits and palmar surfaces expanded topographically to occupy most or all of the cortical territories formerly representing the amputated digit(s). With the expansion of the representations of these surrounding skin surfaces (1) there were severalfold increases in their magnification and (2) roughly corresponding decreases in receptive field areas. Thus, with increases in magnification, surrounding skin surfaces were represented in correspondingly finer grain, implying that the rule relating receptive field overlap to separation in distance across the cortex (see Sur et al., '80) was dynamically maintained as receptive fields progressively decreased in size.
These studies also revealed that: (1) the discontinuities between the representations of the digits underwent significant translocations (usually by hundreds of microns) after amputation, and sharp new discontinuous boundaries formed where usually separated, expanded digital representations (e.g., of digits 1 and 4) approached each other in the reorganizing map, implying that these map discontinuities are normally dynamically maintained. (2) Changes in receptive field sizes with expansion of representations of surrounding skin surfaces into the deprived cortical zone had a spatial distribution and time course similar to changes in sensory acuity on the stumps of human amputees. This suggests that experience-dependent map changes result in changes in sensory capabilities. (3) The major topographic changes were limited to a cortical zone 500–700 μm on either side of the initial boundaries of the representation of the amputated digits. More distant regions did not appear to reorganize (i.e., were not occupied by inputs from surrounding skin surfaces) even many months after amputation. (4) The representations of some skin surfaces moved in entirety to locations within the former territories of representation of amputated digits in every monkey studied. In man, no mislocation errors or perceptual distortions result from stimulation of surfaces surrounding a digital amputation. This constitutes further evidence that any given skin surface can be represented by many alternative functional maps at different times of life in these cortical fields (Merzenich et al., '83b).
These studies further demonstrate that basic features of somatosensory cortical maps (receptive field sizes, cortical sites of representation of given skin surfaces, representational discontinuities, and probably submodality column boundaries) are dynamically maintained. They suggest that cortical skin surface maps are alterable by experience in adults, and that experience-dependent map changes reflect and possibly account for concomitant changes in tactual abilities. Finally, these results bear implications for mechanisms underlying these cortical map dynamics.
Findings of intraoperative rolandic cortex mapping during awake craniotomy for a tumor in a patient with a contralateral upper-extremity amputation are presented. This patient sustained a traumatic amputation at the mid-humerus 24 years previously. Initially he had experienced rare painless phantom limb sensations but none in the past 10 years. Functional mapping during an awake craniotomy was performed to maximize safe tumor resection. Typical temporal and frontal speech areas were identified; motor representation of face and jaw extended more superiorly than sensory representation. Shoulder movements were evoked more laterally than usual at the superior aspect of the craniotomy. A small region of precentral gyrus, between the jaw and shoulder representations, elicited no detectable effect when stimulated. Somatosensory mapping showed a similar topographical distribution of face and mouth cortex; however, posterior and inferior to the shoulder motor cortex, right arm and hand (phantom) sensations were evoked. Evidence suggests that significant motor reorganization occurs following an amputation, with expansion of neighboring homuncular representations without loss of somatosensory representation, despite a long period of time without any sensation referable to the amputated limb. Contrary to models of sensory cortex plasticity, the plasticity of the adult cortex may be system specific, with reorganization present in motor, but not in sensory, cortical systems.
We report a follow-up study of a patient who initially suffered from carpal tunnel syndrome in the right hand, that was alleviated by surgery. Subsequently, the patient's right arm was amputated, and a phantom limb was experienced. Originally, stimuli applied to different areas on the right side of the face evoked sensations that were referred to the phantom by precise topographic mapping. On follow-up, one year after our initial studies, the topography of referred mapping had become extremely disorganized. Furthermore, a new, equally disorganized, pattern of referred sensations was now found upon stimulation of the left side of the face.
Recent behavioral and physiological evidence suggests that even brief sensory deprivation can lead to the rapid emergence of new and functionally effective neural connections in the adult human brain.