Chapter 5 - Sensory feedback for upper limb prostheses

Somatosensory evoked potentials (SEPs) recorded with electroencephalography offer insights into cortical responses to tactile stimulation, typically elicited through temporally precise electrical stimulation. Although vibrotactile stimulation is more ecologically valid but less common, studies directly comparing EEG responses to both electrical and vibrotactile finger stimulation are limited. This study examines and compares (a) cortical responses, (b) connectivity patterns, and (c) somatotopic accuracy of these stimulation types on the fingers. In two experiments, SEPs were recorded from healthy participants' right-hand finger stimulation, using either electrical (experiment 1, n = 22) or vibrotactile (experiment 2, n = 22) stimulation. Vibrotactile stimuli were delivered at 10, 50, and 250 Hz, targeting different ranges of tactile mechanoreceptors activations. Electrical stimulation reliability was assessed across two days, showing consistent SEP amplitudes and latencies. Both stimulation types generated three early components (P1, N1, P2), but all vibrotactile components were increasingly delayed compared to electrical stimulation. Vibrotactile stimulation exhibited stronger localized connectivity in early components (P1, N1) in the left hemisphere, while electrical stimulation showed broader connectivity at P2. Electrical stimulation provided a clearer somatotopic organization in the postcentral gyrus than vibrotactile stimulation. These findings suggest distinct processing for electrical versus vibrotactile finger stimulation. These two stimulation methods are not interchangeable in somatosensory studies: the temporal shift in vibrotactile responses reflects selective activation of Pacinian corpuscles, whereas electrical stimulation yields stronger generalized cortical processing. Electrical stimulation may engage a serial processing pathway starting in the primary somatosensory cortex, while vibrotactile stimulation could involve parallel processing in both primary and secondary somatosensory cortices.

The mammalian cortex is comprised of a multitude of cell types, wired together in intricate circuit motifs, which are recruited during different behavioral scenarios. Broadly speaking, neocortical neurons can either be defined as excitatory or inhibitory neurons, depending on the neurotransmitter they release when an action potential is conducted to the synaptic bouton. Glutamate-releasing excitatory neurons, and GABA (amino butyric acid)-releasing inhibitory neurons are present all through the cortex and form intricate connectivity motifs amongst each other to maintain the complex network activity of the cortex. One such motif is the inhibition of somatostatin (SST)-expressing neurons by vasoactive intestinal polypeptide (VIP)-expressing neurons. SST neurons are some of the most diverse inhibitory neurons in the cortex, and they can be morphologically classified into two cell types: Martinotti cells (MCs) and non-Martinotti cells (nMCs). MCs are defined by their typical axonal arbor that reaches into layer (L) 1, where it densely ramifies. On the other hand, nMCs have a locally restricted axonal arbor, ramifying intensely in the home layer. In the primary somatosensory cortex (S1), MCs are almost exclusively the type of SST neuron found in L2/3, L5b and L6, while nMCs are found exclusively in L4 and L5a. In sharp contrast, in the primary visual cortex (V1), studies have reported that the vast majority of L4 SST neurons are MCs. VIP neurons have been shown to preferentially target SST neurons, thereby lifting the inhibition of SSTs onto excitatory neurons. This ‘inhibition of inhibition’ is widely referred to as ‘disinhibition’, and the VIP-to-SST disinhibitory motif is one of the most well studied disinhibitory motifs across L2/3 of sensory and association areas of the mouse cortex. However, due to the heavy occurrence of MCs in L2/3, these studies have described the VIP-to-MC motif quite well, but the VIP-to-nMC motif is yet to be described. Furthermore, while several studies have focused on identifying the intralaminar impact of VIP neurons (i.e, within L2/3), not many have tried to shed light on the translaminar inhibition effected by VIP neurons. Most VIP somas are localized in L2/3 (~60%), however, they extend their axon vertically, in a narrow columnar projection through all the layers of the cortex, thereby being well-placed to extend inhibition onto the entire cortical column. Keeping in mind the different morphological subtypes of SST neurons present in L4 of S1 and V1 cortices, we wanted to study not just the translaminar effect of L2/3 VIP neurons, but also identify the VIP-to-nMC and VIP-to MC motifs in two different cortical sensory areas. Firstly, we studied the morphological and electrophysiological properties of L4 SST neurons in S1 and V1 cortices by means of whole-cell patch clamp electrophysiology followed by morphological reconstructions. In line with previous reports, we identified that the majority of SST neurons in L4 of S1 were nMCs, while L4 of V1 was populated by MCs. However, the electrophysiological properties of both SST subtypes were invariant across cortices. Secondly, we used paired whole-cell patch clamp electrophysiology to study the connectivity properties of L2/3 VIP neurons into L4 SST neurons in S1 and V1. Around 40-45% of tested SST cells were inhibited by VIP neurons in both cortices. Unitary synaptic properties of the VIP-to-nMC and VIP-to MC motifs were similar. We also studied the frequency-mediated differences in VIP inhibition onto nMCs and MCs. Here, we found strong differences in VIP-evoked responses onto SST neurons in both cortices. While we identified a subset of neurons in both cortices that responded to stimulation of VIP neurons at 50 Hz with short-term facilitation, we also found some SST neurons showing no appreciable form of short-term plasticity at any tested frequency. Crucially, in S1 but not in V1, we found a strong subset of SST neurons that responded to VIP stimulation at all frequencies, but especially at high frequency with strong short-term depression. We hypothesize that the differences in the functional embedding of the two motifs might be related to the reported differences in top-down inputs received by L4 neurons in both sensory areas. To summarize, we identify that the VIP-to-SST motif is present and hard-wired across two sensory areas of the mouse cortex. However, the recruitment of nMCs and MCs by temporally mediated activity of VIP neurons is starkly different, leading to the establishment of cortical area-specific and cell type-specific feedback disinhibitory motifs.

Induction of long-lasting potentiation in the secondary somatosensory cortex by thalamic stimulation requires cortico-cortical pathways from the primary somatosensory cortex.

The vestibular cortex is a distributed network of multisensory areas that plays a crucial role in balance, posture, and spatial orientation. The core region of the vestibular cortex is the parietoinsular vestibular cortex (PIVC), which is located at the junction between the posterior insula, parietal operculum, and retroinsular region. The PIVC is connected to other vestibular areas, the primary and secondary somatosensory cortices, and the premotor and posterior parietal cortices. It also sends projections to the vestibular nuclei in the brainstem. The PIVC is a multisensory region that integrates vestibular, visual, and somatosensory information to create a representation of head-in-space motion, which is used to control eye movements, posture, and balance. Other regions of the vestibular cortex include the primary somatosensory, posterior parietal, and frontal cortices. The primary somatosensory cortex is involved in processing information about touch and body position. The posterior parietal cortex is involved in integrating vestibular, visual, and somatosensory information to create a representation of spatial orientation. The frontal cortex is involved in controlling posture, and eye movements. The various methods used to stimulate the vestibular receptors in neuroimaging studies include caloric vestibular stimulation (CVS), galvanic vestibular stimulation (GVS), and auditory vestibular stimulation (AVS). CVS uses warm or cold water or air to stimulate the semicircular canals, GVS uses a weak electrical current to stimulate the vestibular nerve, and AVS uses high-intensity clicks or short tone bursts to stimulate the otolithic receptors.

During development, the neural circuits in the central auditory pathway are laid down and fine tuned; however, once adulthood is reached, it has generally been assumed that the neural circuits remain stable throughout the life span. Recent studies in the somatosensory and visual system have challenged this hard wired view of the nervous system since extensive remodeling and reorganization occur in both somatosensory and visual pathways when their peripheral inputs are either temporarily or permanently eliminated (Eysel et al., 1980, 1981; Merzenich and Kaas, 1982; Kaas et al., 1990). Because of the relative ease of deafferenting a specific segment of the peripheral receptor surface, the somatosensory system has been one of the most popular systems for studying the reorganization of the central nervous system. A striking example of the rapid reorganization that can occur in the somatosensory cortex is illustrated by studies in which the peripheral inputs from a specific digit or peripheral nerve is temporarily or permanently eliminated by chemical or surgical means (Dostrovsky et al., 1976; Devor and Wall, 1981; Calford and Tweedale, 1988). For example, some neurons in the somatosensory cortex have excitatory receptive fields that are only activated by mechanical stimulation delivered to a specific digit. If the peripheral inputs that activate the neuron are eliminated by amputating or anesthetizing the digit, the neuron does not become “silent” or inactive, but instead, rapidly shifts it excitatory receptive field to an adjacent region of the body surface to which it was originally unresponsive (Calford and Tweedale, 1988). This rapid reorganization is presumably due to the unmasking of the system’s intrinsic neural networks which were originally “covered over” by powerful inhibitory circuits. Functional reorganization is not unique to the somatosensory cortex. Indeed, it has been observed at the level of the brainstem and spinal cord following peripheral damage (Dostrovsky et al., 1976; Devor and Wall, 1981).

F191. Electrophysiological brain activity during motor imagery enhanced by brain–computer interface in healthy volunteers and post-stroke patients

Electrotactile stimulation has been suggested as a modality for providing sensory feedback in upper limb prostheses. This study investigates the multiday variability of subdermal and surface stimulation. Electrical stimulation was delivered using either surface or fine wire electrodes placed right under the skin in eight amputees for seven consecutive days. The variability of psychophysical measurements, including detection threshold (DT), pain threshold (PT), dynamic range (DR), just noticeable difference (JND), Weber fraction (WF) and quality of evoked sensations, was evaluated using the coefficient of variation (CoV). In addition, the systematic change in the mean of the parameters across days was assessed in both stimulation modalities. In the case of DT, PT, DR, and perceived intensity at 100 Hz, the CoV of surface stimulation was significantly smaller than that of subdermal stimulation. Only PT showed a significant systematic change in the mean value across days for both modalities. The outcome of this study has implications for the choice of modality in delivering sensory feedback, though the significance of the quantified variability needs to be evaluated using usability tests with user feedback.

Recent data and motor control theory argues that movement planning involves preparing the neural state of primary motor cortex (M1) for forthcoming action execution. Theories related to internal models, feedback control, and predictive coding also emphasize the importance of sensory prediction (and processing) before (and during) the movement itself, explaining why motor-related deficits can arise from damage to primary somatosensory cortex (S1). Motivated by this work, here we examined whether motor planning, in addition to changing the neural state of M1, changes the neural state of S1, preparing it for the sensory feedback that arises during action. We tested this idea in two human functional MRI studies (N = 31, 16 females) involving delayed object manipulation tasks, focusing our analysis on premovement activity patterns in M1 and S1. We found that the motor effector to be used in the upcoming action could be decoded, well before movement, from neural activity in M1 in both studies. Critically, we found that this effector information was also present, well before movement, in S1. In particular, we found that the encoding of effector information in area 3b (S1 proper) was linked to the contralateral hand, similarly to that found in M1, whereas in areas 1 and 2 this encoding was present in both the contralateral and ipsilateral hemispheres. Together, these findings suggest that motor planning not only prepares the motor system for movement but also changes the neural state of the somatosensory system, presumably allowing it to anticipate the sensory information received during movement.SIGNIFICANCE STATEMENT Whereas recent work on motor cortex has emphasized the critical role of movement planning in preparing neural activity for movement generation, it has not investigated the extent to which planning also modulates the activity in the adjacent primary somatosensory cortex. This reflects a key gap in knowledge, given that recent motor control theories emphasize the importance of sensory feedback processing in effective movement generation. Here, we find through a convergence of experiments and analyses, that the planning of object manipulation tasks, in addition to modulating the activity in the motor cortex, changes the state of neural activity in different subfields of the human S1. We suggest that this modulation prepares the S1 for the sensory information it will receive during action execution.

ABSTRACTAccording to current textbook knowledge, the primary somatosensory cortex (SI) supports unilateral tactile representations, whereas structures beyond SI, in particular the secondary somatosensory cortex (SII), support bilateral tactile representations. However, dexterous and well-coordinated bimanual motor tasks require early integration of bilateral tactile information. Sequential processing, first of unilateral and subsequently of bilateral sensory information, might not be sufficient to accomplish these tasks. This view of sequential processing in the somatosensory system might therefore be questioned, at least for demanding bimanual tasks. Evidence from the last 15 years is forcing a revision of this textbook notion. Studies in animals and humans indicate that SI is more than a simple relay for unilateral sensory information and, together with SII, contributes to the integration of somatosensory inputs from both sides of the body. Here, we review a series of recent works from our own and other laboratories in favour of interactions between tactile stimuli on the two sides of the body at early stages of processing. We focus on tactile processing, although a similar logic may also apply to other aspects of somatosensation. We begin by describing the basic anatomy and physiology of interhemispheric transfer, drawing on neurophysiological studies in animals and behavioural studies in humans that showed tactile interactions between body sides, both in healthy and in brain-damaged individuals. Then we describe the neural substrates of bilateral interactions in somatosensation as revealed by neurophysiological work in animals and neuroimaging studies in humans (i.e., functional magnetic resonance imaging, magnetoencephalography, and transcranial magnetic stimulation). Finally, we conclude with considerations on the dilemma of how efficiently integrating bilateral sensory information at early processing stages can coexist with more lateralized representations of somatosensory input, in the context of motor control.

Primary somatosensory cortex is actively involved in pain processing in human

We perceive the space in which we live by the use of all of our senses. Vision is the pre-eminent sense in primates, but we can also use audition, somatic sensation, and even olfaction. Our perception of space is calibrated by the accuracy of our movements through it. This calibration requires an intermodality equivalence, such that stimuli of disparate modalities ultimately evoke equivalent responses at some place in the nervous system. Clinical and experimental evidence has long implicated the posterior parietal cortex in the process by which the brain constructs an image of space (Critchley 1953). The posterior parietal cortex lies at the junction of visual and somatosensory cortices, and although historically it was thought to be a somatosensory association cortex, recent work has emphasized its visual nature (Hyvarinen and Poranen 1974; Lynch et al. 1977; Robinson et al. 1978). Such studies also demonstrated some convergence between vision and somatic sensation in the posterior parietal cortex of the monkey (Robinson et al. 1978; Leinonen et al. 1979).

Spatially selective firing of place cells, grid cells, boundary vector/border cells and head direction cells constitutes the basic building blocks of a canonical spatial navigation system centered on the hippocampal-entorhinal complex. While head direction cells can be found throughout the brain, spatial tuning outside the hippocampal formation is often non-specific or conjunctive to other representations such as a reward. Although the precise mechanism of spatially selective firing activity is not understood, various studies show sensory inputs, particularly vision, heavily modulate spatial representation in the hippocampal-entorhinal circuit. To better understand the contribution of other sensory inputs in shaping spatial representation in the brain, we performed recording from the primary somatosensory cortex in foraging rats. To our surprise, we were able to detect the full complement of spatially selective firing patterns similar to that reported in the hippocampal-entorhinal network, namely, place cells, head direction cells, boundary vector/border cells, grid cells and conjunctive cells, in the somatosensory cortex. These newly identified somatosensory spatial cells form a spatial map outside the hippocampal formation and support the hypothesis that location information modulates body representation in the somatosensory cortex. Our findings provide transformative insights into our understanding of how spatial information is processed and integrated in the brain, as well as functional operations of the somatosensory cortex in the context of rehabilitation with brain-machine interfaces.

Self-generated sensory stimulation can be distinguished from externally generated stimulation that is otherwise identical. To determine how the brain differentiates external from self-generated noxious stimulation and which structures of the lateral pain system use neural signals to predict the sensory consequences of self-generated painful stimulation, we used functional magnetic resonance imaging to examine healthy human subjects who received thermal-contact stimuli with noxious and non-noxious temperatures on the resting right hand in random order. These stimuli were internally (self-generated) or externally generated. Two additional conditions served as control conditions: to account for stimulus onset uncertainty, acoustic stimuli preceding the same thermal stimuli were used with variable or fixed delays but without any stimulus-eliciting movements. Whereas graded pain-related activity in the insula and secondary somatosensory cortex (SII) was independent of how the stimulus was generated, it was attenuated in the primary somatosensory cortex (SI) during self-generated stimulation. These data agree with recent concepts of the parallel processing of nociceptive signals to the primary and secondary somatosensory cortices. They also suggest that brain areas that encode pain intensity do not distinguish between internally or externally applied noxious stimuli, i.e., this adaptive biological mechanism prevents harm to the individual. The attenuated activation of SI during self-generated painful stimulation might be a result of the predictability of the sensory consequences of the pain-related action.

OPINION article Front. Hum. Neurosci., 09 December 2011Sec. Cognitive Neuroscience volume 5 - 2011 | https://doi.org/10.3389/fnhum.2011.00162

The pain matrix, which includes several brain regions that respond to pain sensation, contribute to the development of chronic pain. Thus, it is essential to understand the mechanism of causing chronic pain in the pain matrix such as anterior cingulate (ACC), or primary somatosensory (S1) cortex. Recently, combined experiment with the behavior tests and in vivo calcium imaging using fiber photometry revealed the interaction between the neuronal function in deep brain regions of the pain matrix including ACC and the phenotype of chronic pain. However, it remains unclear whether this combined experiment can identify the interaction between neuronal activity in S1, which receive pain sensation, and pain behaviors such as hyperalgesia or allodynia. In this study, to examine whether the interaction between change of neuronal activity in S1 and hyperalgesia in hind paw before and after causing inflammatory pain was detected from same animal, the combined experiment of in vivo fiber photometry system and von Frey hairs test was applied. This combined experiment detected that amplitude of calcium responses in S1 neurons increased and the mechanical threshold of hind paw decreased from same animals which have an inflammatory pain. Moreover, we found that the values between amplitude of calcium responses and mechanical thresholds were shifted to negative correlation after causing inflammatory pain. Thus, the combined experiment with fiber photometry and the behavior tests has a possibility that can simultaneously consider the interaction between neuronal activity in pain matrix and pain induced behaviors and the effects of analgesics or pain treatments.