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Showing papers on "Somatosensory system published in 2018"


Journal ArticleDOI
TL;DR: Functional magnetic resonance imaging study in 21 healthy subjects under three different conditions reveals mechanisms for enhancing motor function with somatosensory stimulation, and suggests that network function cannot be thoroughly understood when weak ties are disregarded.
Abstract: Motor performance is improved by stimulation of the agonist muscle during movement. However, related brain mechanisms remain unknown. In this work, we perform a functional magnetic resonance imaging (fMRI) study in 21 healthy subjects under three different conditions: (1) movement of right ankle alone; (2) movement and simultaneous stimulation of the agonist muscle; or (3) movement and simultaneous stimulation of a control area. We constructed weighted brain networks for each condition by using functional connectivity. Network features were analyzed using graph theoretical approaches. We found that: (1) the second condition evokes the strongest and most widespread brain activations (5147 vs. 4419 and 2320 activated voxels); and (2) this condition also induces a unique network layout and changes hubs and the modular structure of the brain motor network by activating the most "silent" links between primary somatosensory centers and the motor cortex, particularly weak links from the thalamus to the left primary motor cortex (M1). Significant statistical differences were found when the strength values of the right cerebellum (P < 0.001) or the left thalamus (P = 0.006) were compared among the three conditions. Over the years, studies reported a small number of projections from the thalamus to the motor cortex. This is the first work to present functions of these pathways. These findings reveal mechanisms for enhancing motor function with somatosensory stimulation, and suggest that network function cannot be thoroughly understood when weak ties are disregarded.

269 citations


Journal ArticleDOI
TL;DR: TFUS targeted at unilateral sensory thalamus inhibited the amplitude of the P14 SEP as compared to sham, and there is evidence of translation of this effect to time windows of the EEG commensurate with SI and SII activities.
Abstract: Transcranial focused ultrasound (tFUS) has proven capable of stimulating cortical tissue in humans. tFUS confers high spatial resolutions with deep focal lengths and as such, has the potential to noninvasively modulate neural targets deep to the cortex in humans. We test the ability of single-element tFUS to noninvasively modulate unilateral thalamus in humans. Participants (N = 40) underwent either tFUS or sham neuromodulation targeted at the unilateral sensory thalamus that contains the ventro-posterior lateral (VPL) nucleus of thalamus. Somatosensory evoked potentials (SEPs) were recorded from scalp electrodes contralateral to median nerve stimulation. Activity of the unilateral sensory thalamus was indexed by the P14 SEP generated in the VPL nucleus and cortical somatosensory activity by subsequent inflexions of the SEP and through time/frequency analysis. Participants also under went tactile behavioral assessment during either the tFUS or sham condition in a separate experiment. A detailed acoustic model using computed tomography (CT) and magnetic resonance imaging (MRI) is also presented to assess the effect of individual skull morphology for single-element deep brain neuromodulation in humans. tFUS targeted at unilateral sensory thalamus inhibited the amplitude of the P14 SEP as compared to sham. There is evidence of translation of this effect to time windows of the EEG commensurate with SI and SII activities. These results were accompanied by alpha and beta power attenuation as well as time-locked gamma power inhibition. Furthermore, participants performed significantly worse than chance on a discrimination task during tFUS stimulation.

187 citations


Journal ArticleDOI
10 Apr 2018-eLife
TL;DR: In a tetraplegic human with two microelectrode arrays implanted in S1, replicable elicitations of sensations in both the cutaneous and proprioceptive modalities localized to the contralateral arm are reported, dependent on both amplitude and frequency of stimulation.
Abstract: Nerves throughout the body send information about touch, temperature, body position and pain through the spinal cord to the brain. A part of the brain called the somatosensory cortex processes this information. Spinal cord injuries disrupt these messages. Even though the somatosensory cortex has not been damaged, sensation is lost for the affected body areas. No treatment exists to repair the spinal cord so the loss of sensation is permanent. Applying electricity to the somatosensory cortex can produce artificial sensations. Scientists are testing this approach to restore a sense of touch for people with spinal cord injury. Early experiments show that using different patterns of electrical stimulation generates unnatural sensations in different body parts. People receiving the stimulation describe it as tingling or shocks. Scientists wonder if they can improve the technique to mimic feelings like touch or body position to make it easier for people with a spinal injury to move or use prostheses. Now, Armenta Salas et al. generated more natural sensations in a person with a spinal cord injury. Instead of taking the usual approach of delivering large currents to the surface of cortex, they inserted small electrodes into the inside of the cortex to stimulate it with small currents. In the experiments, electrodes were implanted in the somatosensory cortex of a volunteer who had lost the use of his limbs and torso because of a spinal injury. Armenta Salas et al. applied different patterns of electrical stimuli and the volunteer reported what they felt like. The patient described sensations like a pinch or squeeze in the forearm or upper arm with certain patterns. In some cases, the patient reported the sensation of the arm moving with stronger electrical currents. The experiments show that electrical stimulation of the brain can recreate some natural sensations. These sensations could help patients using robotic or prosthetic arms become more dexterous. It might also help patients view artificial limbs as part of their bodies, which could improve their sense of wellbeing.

179 citations


Journal ArticleDOI
01 Sep 2018-Nature
TL;DR: Investigating whether sensory inflow through the spinal cord undergoes direct top-down control by the cortex reveals direct cortical modulation of normal and pathological tactile sensory processing in the spinal Cord and opens up opportunities for new treatments for neuropathic pain.
Abstract: Current models of somatosensory perception emphasize transmission from primary sensory neurons to the spinal cord and on to the brain1-4 Mental influence on perception is largely assumed to occur locally within the brain Here we investigate whether sensory inflow through the spinal cord undergoes direct top-down control by the cortex Although the corticospinal tract (CST) is traditionally viewed as a primary motor pathway5, a subset of corticospinal neurons (CSNs) originating in the primary and secondary somatosensory cortex directly innervate the spinal dorsal horn via CST axons Either reduction in somatosensory CSN activity or transection of the CST in mice selectively impairs behavioural responses to light touch without altering responses to noxious stimuli Moreover, such CSN manipulation greatly attenuates tactile allodynia in a model of peripheral neuropathic pain Tactile stimulation activates somatosensory CSNs, and their corticospinal projections facilitate light-touch-evoked activity of cholecystokinin interneurons in the deep dorsal horn This touch-driven feed-forward spinal-cortical-spinal sensitization loop is important for the recruitment of spinal nociceptive neurons under tactile allodynia These results reveal direct cortical modulation of normal and pathological tactile sensory processing in the spinal cord and open up opportunities for new treatments for neuropathic pain

154 citations


OtherDOI
TL;DR: This review examines briefly the receptors that mediate touch and proprioception, their associated nerve fibers, and pathways they follow to the cerebral cortex, and discusses how various features of objects are encoded in the various cortical fields and the susceptibility of these neural codes to attention and other forms of higher-order modulation.
Abstract: The sense of proprioception allows us to keep track of our limb posture and movements and the sense of touch provides us with information about objects with which we come into contact. In both senses, mechanoreceptors convert the deformation of tissues-skin, muscles, tendons, ligaments, or joints-into neural signals. Tactile and proprioceptive signals are then relayed by the peripheral nerves to the central nervous system, where they are processed to give rise to percepts of objects and of the state of our body. In this review, we first examine briefly the receptors that mediate touch and proprioception, their associated nerve fibers, and pathways they follow to the cerebral cortex. We then provide an overview of the different cortical areas that process tactile and proprioceptive information. Next, we discuss how various features of objects-their shape, motion, and texture, for example-are encoded in the various cortical fields, and the susceptibility of these neural codes to attention and other forms of higher-order modulation. Finally, we summarize recent efforts to restore the senses of touch and proprioception by electrically stimulating somatosensory cortex. © 2018 American Physiological Society. Compr Physiol 8:1575-1602, 2018.

139 citations


Journal ArticleDOI
16 Jan 2018-eLife
TL;DR: It is shown that optogenetic inhibition of keratinocytes decreases behavioral and cellular mechanosensitivity, and this lays a vital foundation for subsequent studies into the dysfunctional signaling that occurs in cutaneous pain and itch disorders, and ultimately, the development of novel topical therapeutics for these conditions.
Abstract: The skin is the largest sensory organ of the body, and the first point of contact with the outside world. Whether it is being pinched or caressed, the skin’s sense of touch informs organisms about their surroundings and allows them to react appropriately. Nerve cells present in the skin capture information about touch and transmit it to the brain where it is decoded. However, there are many other types of cells in the skin besides nerve cells. The role that these other skin cells play in perceiving non-painful and painful touch is still unclear. Moehring et al. now report how the skin cells that form 95% of the most outer layer of the skin are involved in detecting touch. In mutant mice whose cells can be ‘switched off’ by a certain light, artificially deactivating these cells makes the animals less able to respond to tactile stimuli. Further experiments show that when pressure is applied onto the skin, the surface skin cells release a chemical messenger, which then binds specifically to the nerve cells. When the messaging molecule is experimentally destroyed or prevented from attaching to the nerve cell, the mice react less to non-painful and painful touch. This means the cells at the surface of the skin detect tactile signals from the environment and then communicate this information to the nerve cells, where it is taken to the brain. Disrupted communication between the cells in the outer layer of the skin and the nerve cells is found in painful and itchy skin conditions such as eczema and psoriasis. Knowing how these two types of cells normally work together may help with finding new pain and itch treatments for these skin disorders.

125 citations


Journal ArticleDOI
03 Jan 2018-Neuron
TL;DR: Neuronal activity in medial prefrontal cortex and dorsal hippocampus appears to contribute directly to task performance, perhaps providing top-down control of learned, context-dependent transformation of sensory input into goal-directed motor output.

111 citations


Journal ArticleDOI
17 Sep 2018-Nature
TL;DR: The combined optogenetic and lesion approach suggests that manipulations of the sensory cortex may be only temporarily disruptive to other brain structures that are themselves capable of coordinating multiple, arbitrary movements with sensation, and that the somatosensory cortex might be dispensable for active detection of objects in the environment.
Abstract: For many of our senses, the role of the cerebral cortex in detecting stimuli is controversial1–17. Here we examine the effects of both acute and chronic inactivation of the primary somatosensory cortex in mice trained to move their large facial whiskers to detect an object by touch and respond with a lever to obtain a water reward. Using transgenic mice, we expressed inhibitory opsins in excitatory cortical neurons. Transient optogenetic inactivation of the primary somatosensory cortex, as well as permanent lesions, initially produced both movement and sensory deficits that impaired detection behaviour, demonstrating the link between sensory and motor systems during active sensing. Unexpectedly, lesioned mice had recovered full behavioural capabilities by the subsequent session. This rapid recovery was experience-dependent, and early re-exposure to the task after lesioning facilitated recovery. Furthermore, ablation of the primary somatosensory cortex before learning did not affect task acquisition. This combined optogenetic and lesion approach suggests that manipulations of the sensory cortex may be only temporarily disruptive to other brain structures that are themselves capable of coordinating multiple, arbitrary movements with sensation. Thus, the somatosensory cortex may be dispensable for active detection of objects in the environment. Mice can learn to detect objects with their whiskers and respond appropriately even in the absence of their primary somatosensory cortex.

106 citations


Journal ArticleDOI
TL;DR: A novel pattern of weak, delayed, thalamus-evoked inhibition in layer 2 suggests a longer integration window for incoming sensory information and may facilitate stimulus detection and plasticity in superficial pyramidal neurons.
Abstract: Higher-order thalamic nuclei, such as the posterior medial nucleus (POm) in the somatosensory system or the pulvinar in the visual system, densely innervate the cortex and can influence perception and plasticity. To systematically evaluate how higher-order thalamic nuclei can drive cortical circuits, we investigated cell-type selective responses to POm stimulation in mouse primary somatosensory (barrel) cortex, using genetically targeted whole-cell recordings in acute brain slices. We find that ChR2-evoked thalamic input selectively targets specific cell types in the neocortex, revealing layer-specific modules for the summation and processing of POm input. Evoked activity in pyramidal neurons from deep layers is fast and synchronized by rapid feedforward inhibition from GABAergic parvalbumin-expressing neurons, and activity in superficial layers is weaker and prolonged, facilitated by slow inhibition from GABAergic neurons expressing the 5HT3a receptor. Somatostatin-expressing GABAergic neurons do not receive direct input in either layer and their spontaneous activity is suppressed during POm stimulation. This novel pattern of weak, delayed, thalamus-evoked inhibition in layer 2 suggests a longer integration window for incoming sensory information and may facilitate stimulus detection and plasticity in superficial pyramidal neurons.

97 citations


Posted ContentDOI
04 Jun 2018-bioRxiv
TL;DR: The findings stress the need to include a peripheral multisensory control stimulation in the study design to enable a dissociation between truly transcranial and non-transcranial components of TEPs.
Abstract: Transcranial Magnetic Stimulation (TMS) excites populations of neurons in the stimulated cortex, and the resulting activation may spread to connected brain regions. The distributed cortical response can be recorded with electroencephalography (EEG). Since TMS also stimulates peripheral sensory and motor axons and generates a loud click sound, the TMS-evoked EEG potential (TEP) not only reflects neural activity induced by transcranial neuronal excitation but also neural activity reflecting somatosensory and auditory processing. In 17 healthy young individuals, we systematically assessed the contribution of multisensory peripheral stimulation to TEPs using a TMS-compatible EEG system. Real TMS was delivered with a figure-of-eight coil over the left para-median posterior parietal cortex or superior frontal gyrus with the coil being oriented perpendicularly or in parallel to the target gyrus. We also recorded the EEG responses evoked by sham stimulation over the posterior parietal and superior frontal cortex, mimicking the auditory and somatosensory sensations evoked by real TMS. We applied state-of-the-art procedures to attenuate somatosensory and auditory confounds during real TMS, including the placement of a foam layer underneath the coil and auditory noise masking. Despite these precautions, the temporal and spatial features of the cortical potentials evoked by real TMS at the prefrontal and parietal site closely resembled the cortical potentials evoked by realistic sham TMS, both for early and late TEP components. Our findings stress the need to include a peripheral multisensory control stimulation in the study design to enable a dissociation between truly transcranial and non-transcranial components of TEPs.

83 citations


Journal ArticleDOI
TL;DR: It is concluded that the process of mechanotransduction is not required for adaptation, and artificial touch naturally experiences adaptation-induced adjustments of the dynamic range of sensations, which confers to bionic hands enhanced sensitivity to changes in stimulation and thus a more natural sensory experience.
Abstract: Objective. Sensory systems adapt their sensitivity to ambient stimulation levels to improve their responsiveness to changes in stimulation. The sense of touch is also subject to adaptation, as evidenced by the desensitization produced by prolonged vibratory stimulation of the skin. Electrical stimulation of nerves elicits tactile sensations that can convey feedback for bionic limbs. In this study, we investigate whether artificial touch is also subject to adaptation, despite the fact that the peripheral mechanotransducers are bypassed. Approach. Using well-established psychophysical paradigms, we characterize the time course and magnitude of sensory adaptation caused by extended electrical stimulation of the residual somatosensory nerves in three human amputees implanted with cuff electrodes. Main results. We find that electrical stimulation of the nerve also induces perceptual adaptation that recovers after cessation of the stimulus. The time course and magnitude of electrically-induced adaptation are equivalent to their mechanically-induced counterparts. Significance. We conclude that, in natural touch, the process of mechanotransduction is not required for adaptation, and artificial touch naturally experiences adaptation-induced adjustments of the dynamic range of sensations. Further, as it does for native hands, adaptation confers to bionic hands enhanced sensitivity to changes in stimulation and thus a more natural sensory experience.

Journal ArticleDOI
TL;DR: It is found that SYNGAP1 haploinsufficiency in humans, which causes a sporadic neurodevelopmental disorder defined by cognitive impairment, autistic features, and epilepsy, also leads to deficits in tactile-related sensory processing, which may contribute to sensory phenotypes observed in patients.
Abstract: In addition to cognitive impairments, neurodevelopmental disorders often result in sensory processing deficits. However, the biological mechanisms that underlie impaired sensory processing associated with neurodevelopmental disorders are generally understudied and poorly understood. We found that SYNGAP1 haploinsufficiency in humans, which causes a sporadic neurodevelopmental disorder defined by cognitive impairment, autistic features, and epilepsy, also leads to deficits in tactile-related sensory processing. In vivo neurophysiological analysis in Syngap1 mouse models revealed that upper-lamina neurons in somatosensory cortex weakly encode information related to touch. This was caused by reduced synaptic connectivity and impaired intrinsic excitability within upper-lamina somatosensory cortex neurons. These results were unexpected, given that Syngap1 heterozygosity is known to cause circuit hyperexcitability in brain areas more directly linked to cognitive functions. Thus, Syngap1 heterozygosity causes a range of circuit-specific pathologies, including reduced activity within cortical neurons required for touch processing, which may contribute to sensory phenotypes observed in patients.

Journal ArticleDOI
TL;DR: It is indicated that electrical stimulation of somatosensory cortex through mini-ECoG grids has considerable potential for restoring useful sensation to patients with paralysis and amputation.
Abstract: Sensory feedback is a critical aspect of motor control rehabilitation following paralysis or amputation. Current human studies have demonstrated the ability to deliver some of this sensory information via brain-machine interfaces, although further testing is needed to understand the stimulation parameters effect on sensation. Here, we report a systematic evaluation of somatosensory restoration in humans, using cortical stimulation with subdural mini-electrocorticography (mini-ECoG) grids. Nine epilepsy patients undergoing implantation of cortical electrodes for seizure localization were also implanted with a subdural 64-channel mini-ECoG grid over the hand area of the primary somatosensory cortex (S1). We mapped the somatotopic location and size of receptive fields evoked by stimulation of individual channels of the mini-ECoG grid. We determined the effects on perception by varying stimulus parameters of pulse width, current amplitude, and frequency. Finally, a target localization task was used to demonstrate the use of artificial sensation in a behavioral task. We found a replicable somatotopic representation of the hand on the mini-ECoG grid across most subjects during electrical stimulation. The stimulus-evoked sensations were usually of artificial quality, but in some cases were more natural and of a cutaneous or proprioceptive nature. Increases in pulse width, current strength and frequency generally produced similar quality sensations at the same somatotopic location, but with a perception of increased intensity. The subjects produced near perfect performance when using the evoked sensory information in target acquisition tasks. These findings indicate that electrical stimulation of somatosensory cortex through mini-ECoG grids has considerable potential for restoring useful sensation to patients with paralysis and amputation.

Journal ArticleDOI
TL;DR: Functional responses induced by somatosensory stimulation of the wrists, ankles, and mouth had a distinct spatial organization as seen in the characteristic mature homunculus map, which may explain why acquired brain injury in this region during the preterm period cannot be compensated for by cortical reorganization and therefore can lead to long-lasting motor and sensory impairment.
Abstract: In the mature mammalian brain, the primary somatosensory and motor cortices are known to be spatially organized such that neural activity relating to specific body parts can be somatopically mapped onto an anatomical "homunculus". This organization creates an internal body representation which is fundamental for precise motor control, spatial awareness and social interaction. Although it is unknown when this organization develops in humans, animal studies suggest that it may emerge even before the time of normal birth. We therefore characterized the somatotopic organization of the primary sensorimotor cortices using functional MRI and a set of custom-made robotic tools in 35 healthy preterm infants aged from 31 + 6 to 36 + 3 weeks postmenstrual age. Functional responses induced by somatosensory stimulation of the wrists, ankles, and mouth had a distinct spatial organization as seen in the characteristic mature homunculus map. In comparison to the ankle, activation related to wrist stimulation was significantly larger and more commonly involved additional areas including the supplementary motor area and ipsilateral sensorimotor cortex. These results are in keeping with early intrinsic determination of a somatotopic map within the primary sensorimotor cortices. This may explain why acquired brain injury in this region during the preterm period cannot be compensated for by cortical reorganization and therefore can lead to long-lasting motor and sensory impairment.

Journal ArticleDOI
01 Mar 2018-Pain
TL;DR: The clinical entity of Burning mouth syndrome can be divided into 2 main subtypes compatible with either peripheral or central neuropathic pain, which may overlap in individual patients.
Abstract: Primary burning mouth syndrome (BMS) is defined as an "intraoral burning or dysaesthetic sensation, recurring daily… more than 3 months, without clinically evident causative lesions" (IHS 2013). In addition to pain, taste alterations are frequent (dysgeusia, xerostomia). Although lacking clinical signs of neuropathy, more accurate diagnostic methods have shown neuropathic involvement at various levels of the neuraxis in BMS: peripheral small fiber damage (thermal quantitative sensory testing, electrogustatometry, epithelial nerve fiber density), trigeminal system lesions in the periphery or the brainstem (brainstem reflex recordings, trigeminal neurography, evoked potentials), or signs of decreased inhibition within the central nervous system (deficient brainstem reflex habituation, positive signs in quantitative sensory testing, neurotransmitter-positron emission tomography findings indicative of deficient striatal dopamine function). Abnormalities in electrogustatometry indicate the involvement of the small Aδ taste afferents, in addition to somatosensory small fibers. According to these findings, the clinical entity of BMS can be divided into 2 main subtypes compatible with either peripheral or central neuropathic pain, which may overlap in individual patients. The central type does not respond to local treatments and associates often with psychiatric comorbidity (depression or anxiety), whereas the peripheral type responds to peripheral lidocaine blocks and topical clonazepam. Burning mouth syndrome is most prevalent in postmenopausal women, having led to a hypothesis that BMS is triggered as a consequence of nervous system damage caused by neurotoxic factors affecting especially vulnerable small fibers and basal ganglia in a setting of decrease in neuroprotective gonadal hormones and increase in stress hormone levels, typical for menopause.

Journal ArticleDOI
TL;DR: Long-range axonal projections of excitatory layer 2/3 neurons with cell bodies located in mouse primary somatosensory barrel cortex are studied to suggest extensive diversity in the axonal targets selected by individual nearby cortical long-range projection neurons with somata located in layer 1/3 of wS1.
Abstract: Excitatory projection neurons of the neocortex are thought to play important roles in perceptual and cognitive functions of the brain by directly connecting diverse cortical and subcortical areas. However, many aspects of the anatomical organization of these inter-areal connections are unknown. Here, we studied long-range axonal projections of excitatory layer 2/3 neurons with cell bodies located in mouse primary somatosensory barrel cortex (wS1). As a population, these neurons densely projected to secondary whisker somatosensory cortex (wS2) and primary/secondary whisker motor cortex (wM1/2), with additional axon in the dysgranular zone surrounding the barrel field, perirhinal temporal association cortex and striatum. In three-dimensional reconstructions of 6 individual wS2-projecting neurons and 9 individual wM1/2-projecting neurons, we found that both classes of neurons had extensive local axon in layers 2/3 and 5 of wS1. Neurons projecting to wS2 did not send axon to wM1/2, whereas a small subset of wM1/2-projecting neurons had relatively weak projections to wS2. A small fraction of projection neurons solely targeted wS2 or wM1/2. However, axon collaterals from wS2-projecting and wM1/2-projecting neurons were typically also found in subsets of various additional areas, including the dysgranular zone, perirhinal temporal association cortex and striatum. Our data suggest extensive diversity in the axonal targets selected by individual nearby cortical long-range projection neurons with somata located in layer 2/3 of wS1.

Journal ArticleDOI
21 Dec 2018-eLife
TL;DR: It is found that M1 initially establishes a sensory framework upon which its later-emerging role in motor control is built, and sensory responses originate in the deep thalamorecipient layers, not primary somatosensory cortex.
Abstract: Before primary motor cortex (M1) develops its motor functions, it functions like a somatosensory area. Here, by recording from neurons in the forelimb representation of M1 in postnatal day (P) 8-12 rats, we demonstrate a rapid shift in its sensory responses. At P8-10, M1 neurons respond overwhelmingly to feedback from sleep-related twitches of the forelimb, but the same neurons do not respond to wake-related movements. By P12, M1 neurons suddenly respond to wake movements, a transition that results from opening the sensory gate in the external cuneate nucleus. Also at P12, fewer M1 neurons respond to individual twitches, but the full complement of twitch-related feedback observed at P8 is unmasked through local disinhibition. Finally, through P12, M1 sensory responses originate in the deep thalamorecipient layers, not primary somatosensory cortex. These findings demonstrate that M1 initially establishes a sensory framework upon which its later-emerging role in motor control is built.

Journal ArticleDOI
TL;DR: This work identifies the mechanosensory architecture of oral tissues involved in feeding and finds that palatal Merkel cells reduce in number at key time-points that correlate with impaired oral abilities, such as swallowing and mastication in aged mice.
Abstract: Oral mechanoreception is implicated in fundamental functions including speech, food intake and swallowing; yet, the neuroanatomical substrates that encode mechanical stimuli are not well understood. Tactile perception is initiated by intricate mechanosensitive machinery involving dedicated cells and neurons. This signal transduction setup is coupled with the topology and mechanical properties of surrounding epithelium, thereby providing a sensitive and accurate system to detect stress fluctuations from the external environment. We mapped the distribution of anatomically distinct neuronal endings in mouse oral cavity using transgenic reporters, molecular markers and quantitative histomorphometry. We found that the tongue is equipped with an array of putative mechanoreceptors that express the principal mechanosensory channel Piezo2, including end bulbs of Krause innervating individual filiform papillae and a novel class of neuronal fibers innervating the epithelium surrounding taste buds. The hard palate and gums are densely populated with three classes of sensory afferents organized in discrete patterns including Merkel cell-neurite complexes, Meissner's corpuscles and glomerular corpuscles. In aged mice, we find that palatal Merkel cells reduce in number at key time-points that correlate with impaired oral abilities, such as swallowing and mastication. Collectively, this work identifies the mechanosensory architecture of oral tissues involved in feeding.

Journal ArticleDOI
TL;DR: The principles of information flow from the sensory periphery to the primary sensory cortex in a model sensory (whisker) system are introduced, and how the adaptive spike threshold gates the intracellular information transfer from the somatic post-synaptic potential to action potentials, controlling the information content of communication across somatosensory cortical neurons is discussed.

Journal ArticleDOI
TL;DR: The meta‐analysis showed significantly altered motor cortex, as well as cerebellar and parietal lobe changes, and qualitatively consistent reports of alterations in somatosensory brain structure, cortical reorganization, white matter diffusion and thalamic metabolites.

Journal ArticleDOI
TL;DR: Using cell type-specific and reversible optogenetic manipulations in the somatosensory cortex of both anesthetized and awake mice, it is demonstrated that L2/3 pyramidal neurons play a major role in amplifying sensory-evoked responses in L5 neurons.

Journal ArticleDOI
10 Apr 2018-eLife
TL;DR: Artificially activating neurons in the cortex can make a tetraplegic patient feel naturalistic sensations of skin pressure and arm movement as discussed by the authors, which can make them feel more relaxed.
Abstract: Artificially activating neurons in the cortex can make a tetraplegic patient feel naturalistic sensations of skin pressure and arm movement.

Journal ArticleDOI
TL;DR: It is demonstrated that hematopoietic cells present at the nerve injury site express the cytokine FL, the ligand of fms-like tyrosine kinase 3 receptor (FLT3), and a novel FLT3 inhibitor is identified that attenuates neuropathic pain in mice.
Abstract: Peripheral neuropathic pain (PNP) is a debilitating and intractable chronic disease, for which sensitization of somatosensory neurons present in dorsal root ganglia that project to the dorsal spinal cord is a key physiopathological process. Here, we show that hematopoietic cells present at the nerve injury site express the cytokine FL, the ligand of fms-like tyrosine kinase 3 receptor (FLT3). FLT3 activation by intra-sciatic nerve injection of FL is sufficient to produce pain hypersensitivity, activate PNP-associated gene expression and generate short-term and long-term sensitization of sensory neurons. Nerve injury-induced PNP symptoms and associated-molecular changes were strongly altered in Flt3-deficient mice or reversed after neuronal FLT3 downregulation in wild-type mice. A first-in-class FLT3 negative allosteric modulator, discovered by structure-based in silico screening, strongly reduced nerve injury-induced sensory hypersensitivity, but had no effect on nociception in non-injured animals. Collectively, our data suggest a new and specific therapeutic approach for PNP.

Journal ArticleDOI
TL;DR: This work aimed at studying resting‐state functional brain connectivity in patients with blepharospasm and its potential modulation by therapeutic botulinum toxin injections.
Abstract: Introduction Blepharospasm is characterized by involuntary eyelid spasms. It can be associated with perioral dystonia (Meige's syndrome or orofacial dystonia). We aimed at studying resting-state functional brain connectivity in these patients and its potential modulation by therapeutic botulinum toxin injections. Methods We performed resting-state functional MRI and a region of interest-based analysis of functional connectivity in 13 patients with blepharospasm/Meige's syndrome in comparison to 13 healthy controls. Patients were studied before and 4 weeks after botulinum toxin treatment. Simultaneous facial electromyography was applied to control for involuntary facial movements. Results Before botulinum toxin treatment, patients showed reduced functional connectivity between caudate and primary sensorimotor, somatosensory association and visual cortices as well as between putamen and parietal association cortex. Cerebellar areas displayed decreased functional connectivity to somatosensory and visual association cortices. On the cortical level, connectivity was reduced between the cingulate cortex and the primary sensorimotor/premotor and parietal association cortex, between premotor areas and the primary somatosensory cortices, and between the postcentral gyrus and temporoparietal, secondary somatosensory, cingular, and cerebellar regions. Botulinum toxin treatment modulated functional connectivity, especially between cerebellum and visual cortices. Conclusions Patients with blepharospasm/Meige's syndrome show altered functional connectivity at rest in widespread brain regions including basal ganglia, cerebellar, primary/secondary sensorimotor, and visual areas. Functionally, this may reflect a predisposition for defective movement inhibition and sensorimotor integration. Botulinum toxin treatment could modulate brain connectivity in blepharospasm by altering visual and sensory input.

Journal ArticleDOI
TL;DR: While HIV-infected participants had the capacity to efficiently gate somatosensory input, their overall oscillatory responses were weaker, spontaneous baseline activity was stronger, and their response to the second stimulation had an altered peak gamma frequency, it is proposed that this pattern of deficits suggests dysfunction in the somatosensor cortices, which is potentially secondary to accelerated aging.

Journal ArticleDOI
TL;DR: A non-canonical feedback circuit, originating in layer 4 of S2, rapidly modulates early tactile processing in mice, and is associated with whisker primary and secondary somatosensory cortices.

Journal ArticleDOI
TL;DR: These findings associate for the first time bilateral cortical functional reorganization in the S1 of HCP children with abnormalities in the structural integrity of the AST, and correlate these abnormalities with behaviorally-assessed sensory deficits.

Journal ArticleDOI
TL;DR: The results demonstrate that auditory frequency representations can be distributed over brain regions traditionally considered to be dedicated to somatosensation, and reveals a number of candidate brain areas that could support general temporal frequency processing and mediate the extensive and robust perceptual interactions between audition and touch.
Abstract: Recent studies have challenged the traditional notion of modality-dedicated cortical systems by showing that audition and touch evoke responses in the same sensory brain regions. While much of this work has focused on somatosensory responses in auditory regions, fewer studies have investigated sound responses and representations in somatosensory regions. In this functional magnetic resonance imaging (fMRI) study, we measured BOLD signal changes in participants performing an auditory frequency discrimination task and characterized activation patterns related to stimulus frequency using both univariate and multivariate analysis approaches. Outside of bilateral temporal lobe regions, we observed robust and frequency-specific responses to auditory stimulation in classically defined somatosensory areas. Moreover, using representational similarity analysis to define the relationships between multi-voxel activation patterns for all sound pairs, we found clear similarity patterns for auditory responses in the parietal lobe that correlated significantly with perceptual similarity judgments. Our results demonstrate that auditory frequency representations can be distributed over brain regions traditionally considered to be dedicated to somatosensation. The broad distribution of auditory and tactile responses over parietal and temporal regions reveals a number of candidate brain areas that could support general temporal frequency processing and mediate the extensive and robust perceptual interactions between audition and touch.

Journal ArticleDOI
TL;DR: The results confirm that optogenetic activation is a valid model for physiological neuronal input, and that differences in temporal behavior of only a few hundred milliseconds can be resolved in rodent fMRI.

Journal ArticleDOI
TL;DR: This review introduces the classification of DRG neurons based on single-cell RNA-sequencing and functional analyses, and talks about the technical approaches and studies on the molecular and cellular mechanisms underlying somatic sensations.
Abstract: Different physical and chemical stimuli are detected by the peripheral sensory receptors of dorsal root ganglion (DRG) neurons, and the generated inputs are transmitted via afferent fibers into the central nervous system. The gene expression profiles of DRG neurons contribute to the generation, transmission, and regulation of various somatosensory signals. Recently, the single-cell transcriptomes, cell types, and functional annotations of somatosensory neurons have been studied. In this review, we introduce our classification of DRG neurons based on single-cell RNA-sequencing and functional analyses, and discuss the technical approaches. Moreover, studies on the molecular and cellular mechanisms underlying somatic sensations are discussed.