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Introduction/Aims: While amyotrophic lateral sclerosis (ALS) is primarily characterized as a motor system disorder, there is a growing body of evidence indicating sensory involvement. This study aimed to examine the hypothesis that somatosensory processing is impaired in ALS. Methods: Study participants were ALS patients followed at the Neuromuscular Outpatient Unit, as well as healthy volunteers, from March 2021 to July 2023. The Medical Research Council (MRC) sum score was calculated for nine muscle groups bilaterally. The clinical status of patients was evaluated with the ALS Functional Rating Scale‐Revised (ALSFRS‐R) and the Penn Upper Motor Neuron core. Somatosensory temporal discrimination thresholds (STDTs) were recorded on the medial and lateral parts of both hands. Somatosensory cortex excitability was investigated with the paired somatosensory evoked potentials (SEP) paradigm in a subgroup. Results: Increased STD values were detected in ALS patients compared to controls in both medial (107.66 ± 35 ms vs. 82.7 ± 32.5 ms, p =.001) and lateral (106.5 ± 34.5 ms vs. 82.9 ± 31.3 ms, p =.002) hands. There were no significant differences in STDTs among ALS patients across four regions (medial and lateral parts of the right and left hands). Amplitude ratios obtained from the paired‐pulse SEP paradigm were approximately 1 for all interstimulus intervals (ISIs). STDTs did not show any correlations with motor findings or scales. Discussion: Somatosensory processing appears to be compromised among ALS patients. The lack of correlation between impaired STDT and motor findings implies that it is a purely sensory deficit in ALS. [ABSTRACT FROM AUTHOR]

Micro-electrocorticography (µECoG) electrodes have emerged to balance the trade-off between invasiveness and signal quality in brain recordings. However, its large-scale applicability is still hindered by a lack of comparative studies assessing the relationship between ECoG and traditional recording methods such as penetrating electrodes. This study aimed to compare somatosensory evoked potentials (SEPs) through the lenses of a µECoG and an intracortical microelectrode array (MEA). The electrodes were implanted in the pig's primary somatosensory cortex, while SEPs were generated by applying electrical stimulation to the ulnar nerve. The SEP amplitude, signal-to-noise ratio (SNR), power spectral density (PSD), and correlation structure were analysed. Overall, SEPs resulting from MEA recordings had higher amplitudes and contained significantly more spectral power, especially at higher frequencies. However, the SNRs were similar between the interfaces. These results demonstrate the feasibility of using µECoG to decode SEPs with wide-range applications in physiology monitoring and brain–computer interfaces. [ABSTRACT FROM AUTHOR]

Abstract Background To gain a comprehensive understanding of the altered sensory processing in patients with migraine, in this study, we developed an electroencephalography (EEG) protocol for examining brainstem and cortical responses to sensory stimulation. Furthermore, machine learning techniques were employed to identify neural signatures from evoked brainstem–cortex activation and their interactions, facilitating the identification of the presence and subtype of migraine. Methods This study analysed 1,000-epoch-averaged somatosensory evoked responses from 342 participants, comprising 113 healthy controls (HCs), 106 patients with chronic migraine (CM), and 123 patients with episodic migraine (EM). Activation amplitude and effective connectivity were obtained using weighted minimum norm estimates with spectral Granger causality analysis. This study used support vector machine algorithms to develop classification models; multimodal data (amplitude, connectivity, and scores of psychometric assessments) were applied to assess the reliability and generalisability of the identification results from the classification models. Results The findings revealed that patients with migraine exhibited reduced amplitudes for responses in both the brainstem and cortical regions and increased effective connectivity between these regions in the gamma and high-gamma frequency bands. The classification model with characteristic features performed well in distinguishing patients with CM from HCs, achieving an accuracy of 81.8% and an area under the curve (AUC) of 0.86 during training and an accuracy of 76.2% and an AUC of 0.89 during independent testing. Similarly, the model effectively identified patients with EM, with an accuracy of 77.5% and an AUC of 0.84 during training and an accuracy of 87% and an AUC of 0.88 during independent testing. Additionally, the model successfully differentiated patients with CM from patients with EM, with an accuracy of 70.5% and an AUC of 0.73 during training and an accuracy of 72.7% and an AUC of 0.74 during independent testing. Conclusion Altered brainstem-cortex activation and interaction are characteristic of the abnormal sensory processing in migraine. Combining evoked activity analysis with machine learning offers a reliable and generalisable tool for identifying patients with migraine and for assessing the severity of their condition. Thus, this approach is an effective and rapid diagnostic tool for clinicians.

Rhythmic movement is the fundamental motion dynamics characterized by repetitive patterns. Precisely defining onsets in rhythmic movement is essential for a comprehensive analysis of motor functions. Our study introduces an automated method for detecting rat's forelimb foot-strike onsets using deep learning tools. This method demonstrates high accuracy of onset detection by combining two techniques using joint coordinates and behavioral confidence scale. The analysis extends to neural oscillatory responses in the rat's somatosensory cortex, validating the effectiveness of our combined approach. Our technique streamlines experimentation, demanding only a camera and GPU-accelerated computer. This approach is applicable across various contexts and promotes our understanding of brain functions during rhythmic movements.

Abstract Integrating artificial limbs as part of one's body involves complex neuroplastic changes resulting from various sensory inputs. While somatosensory feedback is crucial, plastic processes that enable embodiment remain unknown. We investigated this using somatosensory evoked fields (SEFs) in the primary somatosensory cortex (S1) following the Rubber Hand Illusion (RHI), known to quickly induce artificial limb embodiment. During electrical stimulation of the little finger and thumb, 19 adults underwent neuromagnetic recordings before and after the RHI. We found early SEF displacement, including an illusion-brain correlation between extent of embodiment and specific changes to the first cortical response at 20 ms in Area 3b, within S1. Furthermore, we observed a posteriorly directed displacement at 35 ms towards Area 1, known to be important for visual integration during touch perception. That this second displacement was unrelated to extent of embodiment implies a functional distinction between neuroplastic changes of these components and areas. The earlier shift in Area 3b may shape extent of limb ownership, while subsequent displacement into Area 1 may relate to early visual-tactile integration that initiates embodiment. Here we provide evidence for multiple neuroplastic processes in S1—lasting beyond the illusion—supporting integration of artificial limbs like prostheses within the body representation.

Background: To gain a comprehensive understanding of the altered sensory processing in patients with migraine, in this study, we developed an electroencephalography (EEG) protocol for examining brainstem and cortical responses to sensory stimulation. Furthermore, machine learning techniques were employed to identify neural signatures from evoked brainstem–cortex activation and their interactions, facilitating the identification of the presence and subtype of migraine. Methods: This study analysed 1,000-epoch-averaged somatosensory evoked responses from 342 participants, comprising 113 healthy controls (HCs), 106 patients with chronic migraine (CM), and 123 patients with episodic migraine (EM). Activation amplitude and effective connectivity were obtained using weighted minimum norm estimates with spectral Granger causality analysis. This study used support vector machine algorithms to develop classification models; multimodal data (amplitude, connectivity, and scores of psychometric assessments) were applied to assess the reliability and generalisability of the identification results from the classification models. Results: The findings revealed that patients with migraine exhibited reduced amplitudes for responses in both the brainstem and cortical regions and increased effective connectivity between these regions in the gamma and high-gamma frequency bands. The classification model with characteristic features performed well in distinguishing patients with CM from HCs, achieving an accuracy of 81.8% and an area under the curve (AUC) of 0.86 during training and an accuracy of 76.2% and an AUC of 0.89 during independent testing. Similarly, the model effectively identified patients with EM, with an accuracy of 77.5% and an AUC of 0.84 during training and an accuracy of 87% and an AUC of 0.88 during independent testing. Additionally, the model successfully differentiated patients with CM from patients with EM, with an accuracy of 70.5% and an AUC of 0.73 during training and an accuracy of 72.7% and an AUC of 0.74 during independent testing. Conclusion: Altered brainstem-cortex activation and interaction are characteristic of the abnormal sensory processing in migraine. Combining evoked activity analysis with machine learning offers a reliable and generalisable tool for identifying patients with migraine and for assessing the severity of their condition. Thus, this approach is an effective and rapid diagnostic tool for clinicians. [ABSTRACT FROM AUTHOR]

Rhythmic movement is the fundamental motion dynamics characterized by repetitive patterns. Precisely defining onsets in rhythmic movement is essential for a comprehensive analysis of motor functions. Our study introduces an automated method for detecting rat's forelimb foot-strike onsets using deep learning tools. This method demonstrates high accuracy of onset detection by combining two techniques using joint coordinates and behavioral confidence scale. The analysis extends to neural oscillatory responses in the rat's somatosensory cortex, validating the effectiveness of our combined approach. Our technique streamlines experimentation, demanding only a camera and GPU-accelerated computer. This approach is applicable across various contexts and promotes our understanding of brain functions during rhythmic movements. • Defining onsets in rhythmic motion is crucial for an analysis of motor functions. • We introduced automated detection of foot-strike onsets using deep learning tools. • This detection method combines two deep learning techniques. • This method enables accurate detection of onsets across many animal subjects. • This method promotes understanding of brain functions during rhythmic movements. [ABSTRACT FROM AUTHOR]

• The interhemispheric connection between primary somatosensory areas can be probed by using bilateral median nerve stimulation. • N20 potentials and the late component of the high-frequency oscillations vary significantly across interstimulus intervals. • Findings suggest interhemispheric interaction between the primary somatosensory cortices, through corpus callosum. This study aimed at investigating the effect of median nerve stimulation on ipsilateral cortical potentials evoked by contralateral median nerve electrical stimulation. We recorded somatosensory-evoked potentials (SEPs) from the left parietal cortex in 15 right-handed, healthy subjects. We administered bilateral median nerve stimulation, with the ipsilateral stimulation preceding the stimulation on the contralateral by intervals of 5, 10, 20, or 40 ms. We adjusted these intervals based on each individual's N20 latency. As a measure of S1 excitability, the amplitude of the N20 and the area of the High Frequency Oscillation (HFO) burst were analyzed for each condition. The results revealed significant inhibition of N20 amplitude by ipsilateral median nerve stimulation at interstimulus intervals (ISIs) between 5 and 40 ms. Late HFO burst was suppressed at short ISIs of 5 and 10 ms, pointing to a transcallosal inhibitory effect on S1 intracortical circuits. Findings suggest interhemispheric interaction between the primary somatosensory areas, supporting the existence of transcallosal transfer of tactile information. This study provides valuable insights into the interhemispheric connections between primary sensory areas and underscore the potential role of interhemispheric interactions in somatosensory processing. [ABSTRACT FROM AUTHOR]

Objective: To identify the most common locations of cluster headache pain from an international, non–clinic‐based survey of participants with cluster headache, and to compare these locations to other cluster headache features as well as to somatotopic maps of peripheral, brainstem, thalamic, and cortical areas. Background: Official criteria for cluster headache state pain in the orbital, supraorbital, and/or temporal areas, yet studies have noted pain extending beyond these locations, and the occipital nerve appears relevant, given the effectiveness of suboccipital corticosteroid injections and occipital nerve stimulation. Furthermore, cranial autonomic features vary between patients, and it is not clear if the trigeminovascular reflex is dermatome specific (e.g., do patients with maxillary or V2 division pain have more rhinorrhea?). Finally, functional imaging studies show early activation of the posterior hypothalamus in a cluster headache attack. However, the first somatosensory area to be sensitized is unclear; the first area can be hypothesized based on the complete map of pain locations. Methods: The International Cluster Headache Questionnaire was an internet‐based cross‐sectional survey that included a clickable pain map of the face. These data were compared to several other datasets: (1) a meta‐analysis of 22 previous publications of pain location in cluster headache (consisting of 6074 patients); (2) four cephalic dermatome maps; (3) participants' survey responses for demographics, autonomic features, and effective medications; and (4) previously published somatotopic maps of the brainstem, thalamus, primary somatosensory cortex, and higher order somatosensory cortex. Results: One thousand five hundred eighty‐nine participants completed the pain map portion of the survey, and the primary locations of pain across all respondents was the orbital, periorbital, and temporal areas with a secondary location in the lower occiput; these primary and secondary locations were consistent with our meta‐analysis of 22 previous publications. Of the four cephalic dermatomes (V1, V2, V3, and a combination of C2‐3), our study found that most respondents had pain in two or more dermatomes (range 85.7% to 88.7%, or 1361–1410 of 1589 respondents, across the four dermatome maps). Dermatomes did not correlate with their respective autonomic features or with medication effectiveness. The first area to be sensitized in the canonical somatosensory pathway is either a subcortical (brainstem or thalamus) or higher order somatosensory area (parietal ventral or secondary somatosensory cortices) because the primary somatosensory cortex (area 3b) and somatosensory area 1 have discontinuous face and occipital regions. Conclusions: The primary pain locations in cluster headache are the orbital, supraorbital, and temporal areas, consistent with the official International Classification of Headache Disorders criteria. However, activation of the occiput in many participants suggests a role for the occipital nerve, and the pain locations suggest that somatosensory sensitization does not start in the primary somatosensory cortex. Plain Language Summary: Cluster headache (CH) pain is often thought to be located in or around the eye; however, multiple studies have documented pain elsewhere, and procedures that target nerves in the back of the head can help CH. In this large survey (1604 respondents) with a clickable pain map of the face, we found that (1) most respondents had pain extending beyond the area of the eye, and (2) the pain location did not correlate with autonomic symptoms, medication effectiveness, or other CH features. Cluster headache pain beyond the eye is common, and based on the pattern of areas activated, we hypothesized which parts of the brain's somatosensory system may be activated first in cluster attacks. [ABSTRACT FROM AUTHOR]

Background: Grating orientation discrimination (GOD) is commonly used to assess somatosensory spatial processing. It allows discrimination between parallel and orthogonal orientations of tactile stimuli applied to the fingertip. Despite its widespread application, the underlying mechanisms of GOD, particularly the role of cortico-cortical interactions and local brain activity in this process, remain elusive. Therefore, we aimed to investigate how a specific cortico-cortical network and inhibitory circuits within the primary somatosensory cortex (S1) and secondary somatosensory cortex (S2) contribute to GOD. Methods: In total, 51 healthy young adults were included in our study. We recorded resting-state magnetoencephalography (MEG) and somatosensory-evoked magnetic field (SEF) in participants with open eyes. We converted the data into a source space based on individual structural magnetic resonance imaging. Next, we estimated S1- and S2-seed resting-state functional connectivity (rs-FC) at the alpha and beta bands through resting-state MEG using the amplitude envelope correlation method across the entire brain (i.e., S1/S2-seeds × 15,000 vertices × two frequencies). We assessed the inhibitory response in the S1 and S2 from SEFs using a paired-pulse paradigm. We automatically measured the GOD task in parallel and orthogonal orientations to the index finger, applying various groove widths with a custom-made device. Results: We observed a specific association between the GOD threshold (all P < 0.048) and the alpha rs-FC in the S1–superior parietal lobule and S1–adjacent to the parieto-occipital sulcus (i.e., lower rs-FC values corresponded to higher performance). In contrast, no association was observed between the local responses and the threshold. Discussion: The results of this study underpin the significance of specific cortico-cortical networks in recognizing variations in tactile stimuli.

Background: Chronic ankle instability (CAI) has been considered a neurophysiological disease, having as symptoms dysfunction in somatosensory and motor system excitability. Rehabilitation has been considered an effective treatment for CAI. However, few studies have explored the effects of rehabilitation on neuroplasticity in the CAI population. Objective: The purpose of this study was to investigate the effects of rehabilitation on cortical activities for postural control in CAI patients and to find the correlation between the change in cortical activities and patient-reported outcomes (PROs). Methods: Thirteen participants with CAI (6 female, 7 male, age = 33.8 ± 7.7 years, BMI = 24.7 ± 4.9 kg/m2) received a home exercise program for about 40 min per day, four days per week and six weeks, including ankle range-of-motion exercise, muscle strengthening, and balance activities. Cortical activation, PROs and Y-balance test outcomes were assessed and compared before and after rehabilitation. Cortical activation was detected via Functional near-infrared spectroscopy (fNIRS) while the participants performed single-leg stance tasks. Results: The participants had better PROs and Y balance test outcomes after rehabilitation. Greater cortical activation was observed in the primary somatosensory cortex (S1, d = 0.66, p = 0.035), the superior temporal gyrus (STG, d = 1.06, p = 0.002) and the middle temporal gyrus (MTG, d = 0.66, p = 0.035) in CAI patients after rehabilitation. Moreover, significant positive correlations were observed between the recovery of ankle symptoms and the change of cortical activation in S1 (r = 0.74, p = 0.005) and STG (r = 0.72, p = 0.007) respectively. Conclusion: The current study reveals that six weeks of rehabilitation can cause greater cortical activation in S1, STG and MTG. This increase in cortical activation suggested a better ability to perceive somatosensory stimuli and may have a compensatory role in function improvement.

Background: Transcranial direct current stimulation (tDCS) is a frequently used brain stimulation method; however, studies on tactile perception using tDCS are inconsistent, which might be explained by the variations in endogenous and exogenous parameters that influence tDCS. Objectives: We aimed to investigate the effect of one of these endogenous parameters—the tDCS amplitude—on tactile perception. Methods: We conducted this experiment on 28 undergraduates/graduates aged 18–36 years. In separate sessions, participants received 20 min of 1 mA or 1.5 mA current tDCS in a counterbalanced order. Half of the participants received anodal tDCS of the left SI coupled with cathodal tDCS of the right SI, and this montage was reversed for the other half. Pre- and post-tDCS tactile discrimination performance was assessed using the Grating Orientation Task (GOT). In this task, plastic domes with gratings of different widths cut into their surfaces are placed on the fingertip, and participants have to rate the orientation of the gratings. Results: Linear modeling with amplitude, dome, and session as within factors and montage as between factors revealed the following: significant main effects of grating width, montage, and session and a marginally significant interaction effect of session and amplitude. Posthoc t-tests indicated that performance in GOT improved after 1 mA but not 1.5 mA tDCS independent of the montage pattern of the electrodes. Conclusion: Increasing the stimulation amplitude from 1 mA to 1.5 mA does not facilitate the tDCS effect on GOT performance. On the contrary, the effect seemed more robust for the lower-current amplitude.

Micro-electrocorticography (µECoG) electrodes have emerged to balance the trade-off between invasiveness and signal quality in brain recordings. However, its large-scale applicability is still hindered by a lack of comparative studies assessing the relationship between ECoG and traditional recording methods such as penetrating electrodes. This study aimed to compare somatosensory evoked potentials (SEPs) through the lenses of a µECoG and an intracortical microelectrode array (MEA). The electrodes were implanted in the pig’s primary somatosensory cortex, while SEPs were generated by applying electrical stimulation to the ulnar nerve. The SEP amplitude, signal-to-noise ratio (SNR), power spectral density (PSD), and correlation structure were analysed. Overall, SEPs resulting from MEA recordings had higher amplitudes and contained significantly more spectral power, especially at higher frequencies. However, the SNRs were similar between the interfaces. These results demonstrate the feasibility of using µECoG to decode SEPs with wide-range applications in physiology monitoring and brain–computer interfaces.

What happens once a cortical territory becomes functionally redundant? We studied changes in brain function and behavior for the remaining hand in humans (male and female) with either a missing hand from birth (one-handers) or due to amputation. Previous studies reported that amputees, but not one-handers, show increased ipsilateral activity in the somatosensory territory of the missing hand (i.e., remapping). We used a complex finger task to explore whether this observed remapping in amputees involves recruiting more neural resources to support the intact hand to meet greater motor control demands. Using basic fMRI analysis, we found that only amputees had more ipsilateral activity when motor demand increased; however, this did not match any noticeable improvement in their behavioral task performance. More advanced multivariate fMRI analyses showed that amputees had stronger and more typical representation--relative to controls' contralateral hand representation--compared with one-handers. This suggests that in amputees, both hand areas work together more collaboratively, potentially reflecting the intact hand's efference copy. One-handers struggled to learn difficult finger configurations, but this did not translate to differences in univariate or multivariate activity relative to controls. Additional white matter analysis provided conclusive evidence that the structural connectivity between the two hand areas did not vary across groups. Together, our results suggest that enhanced activity in the missing hand territory may not reflect intact hand function. Instead, we suggest that plasticity is more restricted than generally assumed and may depend on the availability of homologous pathways acquired early in life. [ABSTRACT FROM AUTHOR]

Background: Interoception, the processing and integration of bodily signals, is crucial for emotional experiences and overall well-being. The interoceptive network, including the somatosensory cortices, has been recognized for its role in interoceptive and emotional processing. High-definition transcranial, direct-current stimulation (HD-tDCS) has been demonstrated to modulate brain activity in the primary somatosensory cortex (S1). Based on those findings, we hypothesized that anodal HD-tDCS over the right S1 would enhance interoceptive abilities and heighten emotional perception. Methods: Thirty-six healthy adults participated in two sessions separated by at least one week. A 20-min HD-tDCS stimulation (2 mA), and a sham stimulation, were applied in randomized order. Both conditions involved pre-tDCS physical activation by ergometer cycling. Interoceptive abilities were assessed before and after both sessions using a heartbeat-perception and respiratory-load task. Emotional perception was measured using four matched international affective picture system (IAPS) picture sets presented randomly. Results: Active HD-tDCS did not significantly improve interoceptive accuracy, interoceptive emotion evaluation, or interoceptive sensibility. However, a notable increase in cardiac interoceptive awareness was observed after active HD-tDCS. The expected enhancement of emotional processing was not observed. Conclusions: This study represents the first attempt to modulate interoceptive and emotional processing using HD-tDCS over S1. Although consistent enhancement was not observed, our findings provide insights into the modulation of interoceptive and emotional processes with HD-tDCS, suggesting avenues for further research. Further studies should consider the nuanced effects of stimulation techniques and the complex interplay between interoception and emotion. [ABSTRACT FROM AUTHOR]

Background: Transcutaneous auricular vagus nerve stimulation (taVNS) emerges as a promising neuromodulatory technique. However, taVNS uses left ear stimulation in stroke survivors with either left or right hemiparesis. Understanding its influence on the cortical responses is pivotal for optimizing post-stroke rehabilitation protocols. Objective: The primary objective of this study was to elucidate the influence of taVNS on cortical responses in stroke patients presenting with either left or right hemiparesis and to discern its potential ramifications for upper limb rehabilitative processes. Methods: We employed functional near-infrared spectroscopy (fNIRS) to ascertain patterns of cerebral activation in stroke patients as they engaged in a “block transfer” task. Additionally, the Lateralization Index (LI) was utilized to quantify the lateralization dynamics of cerebral functions. Results: In patients exhibiting left-side hemiplegia, there was a notable increase in activation within the pre-motor and supplementary motor cortex (PMC-SMC) of the unaffected hemisphere as well as in the left Broca area. Conversely, those with right-side hemiplegia displayed heightened activation in the affected primary somatosensory cortex (PSC) region following treatment. Significantly, taVNS markedly amplified cerebral activation, with a pronounced impact on the left motor cortical network across both cohorts. Intriguingly, the LI showcased consistency, suggesting a harmonized enhancement across both compromised and uncompromised cerebral regions. Conclusion: TaVNS can significantly bolster the activation within compromised cerebral territories, particularly within the left motor cortical domain, without destabilizing cerebral lateralization. TaVNS could play a pivotal role in enhancing upper limb functional restoration post-stroke through precise neuromodulatory and neuroplastic interventions. [ABSTRACT FROM AUTHOR]

Objective: In this randomized, double‐blind, sham‐controlled trial, we explored the effect of 20 Hz transcutaneous auricular vagus nerve stimulation (taVNS) on gait impairments in Parkinson's disease (PD) patients and investigated the underlying neural mechanism. Methods: In total, 22 PD patients and 14 healthy controls were enrolled. PD patients were randomized (1:1) to receive active or sham taVNS (same position as active taVNS group but without releasing current) twice a day for 1 week. Meanwhile, all subjects were measured activation in the bilateral frontal and sensorimotor cortex during usual walking by functional near‐infrared spectroscopy. Results: PD patients showed instable gait with insufficient range of motion during usual walking. Active taVNS improved gait characteristics including step length, stride velocity, stride length, and step length variability compared with sham taVNS after completion of the 7‐day therapy. No difference was found in the Unified Parkinson's Disease Rating Scale III, Timed Up and Go, Tinetti Balance, and Gait scores. Moreover, PD patients had higher relative change of oxyhemoglobin in the left dorsolateral prefrontal cortex, pre‐motor area, supplementary motor area, primary motor cortex, and primary somatosensory cortex than HCs group during usual walking. Hemodynamic responses in the left primary somatosensory cortex were significantly decreased after taVNS therapy. Conclusion: taVNS can relieve gait impairments and remodel sensorimotor integration in PD patients. [ABSTRACT FROM AUTHOR]

Chronic ankle instability (CAI) has been considered a neurophysiological condition, with dysfunctional somatosensory and motor system excitability. However, few researchers have explored the changes in cortical activation during balance tasks of patients with CAI. To compare the cortical activity during single-legged stance among CAI, copers, and uninjured control participants and to compare dynamic balance across groups. Cross-sectional study. Biomechanics laboratory. A total of 22 participants with CAI (median [interquartile range]; age = 34.5 [11.0] years, height = 170.0 [15.8] cm, mass = 67.0 [16.2] kg), 17 copers (age = 27.0 [14.0] years, height = 170.0 [9.5] cm, mass = 66.5 [16.5] kg), and 21 uninjured control participants (age = 25.0 [10.5] years, height = 170.0 [11.0] cm, mass = 64.0 [16.5] kg). Participants performed single-legged stance while cortical activation was tested with functional near-infrared spectroscopy. The peak oxyhemoglobin response of the activated cortex was calculated and compared across groups. The Y-Balance test outcomes and patient-reported outcomes were assessed and compared across groups. The CAI group had worse Y-balance test and patient-reported outcomes than the coper and uninjured control groups. Differences in the peak oxyhemoglobin response were observed for the primary somatosensory cortex (S1; F2,57 = 4.347, P =.017, ηp2 = 0.132) and superior temporal gyrus (STG; F2,57 = 4.548, P =.015, ηp2 = 0.138). Specifically, copers demonstrated greater activation in S1 and STG than the CAI (d = 0.73, P =.034, and d = 0.69, P =.043, respectively) and uninjured control (d = 0.77, P =.036, and d = 0.88, P =.022, respectively) groups. No differences were found in the cortical activation between CAI and uninjured control participants. Copers displayed greater cortical activation in S1 and STG than CAI and uninjured control participants. Greater activation in S1 and STG suggested a better ability to perceive somatosensory stimuli and may represent a compensatory mechanism that allows copers to maintain good functional ability after the initial severe ankle sprain. [ABSTRACT FROM AUTHOR]

Aims: Neuropathic pain after spinal cord injury (SCI) remains a common and thorny problem, influencing the life quality severely. This study aimed to elucidate the reorganization of the primary sensory cortex (S1) and the regulatory mechanism of the lateral parabrachial nucleus (lPBN) in the presence of allodynia or hyperalgesia after left spinal cord hemisection injury (LHS). Methods: Through behavioral tests, we first identified mechanical allodynia and thermal hyperalgesia following LHS. We then applied two‐photon microscopy to observe calcium activity in S1 during mechanical or thermal stimulation and long‐term spontaneous calcium activity after LHS. By slice patch clamp recording, the electrophysiological characteristics of neurons in lPBN were explored. Finally, exploiting chemogenetic activation or inhibition of the neurons in lPBN, allodynia or hyperalgesia was regulated. Results: The calcium activity in left S1 was increased during mechanical stimulation of right hind limb and thermal stimulation of tail, whereas in right S1 it was increased only with thermal stimulation of tail. The spontaneous calcium activity in right S1 changed more dramatically than that in left S1 after LHS. The lPBN was also activated after LHS, and exploiting chemogenetic activation or inhibition of the neurons in lPBN could induce or alleviate allodynia and hyperalgesia in central neuropathic pain. Conclusion: The neuronal activity changes in S1 are closely related to limb pain, which has accurate anatomical correspondence. After LHS, the spontaneously increased functional connectivity of calcium transient in left S1 is likely causing the mechanical allodynia in right hind limb and increased neuronal activity in bilateral S1 may induce thermal hyperalgesia in tail. This state of allodynia and hyperalgesia can be regulated by lPBN. [ABSTRACT FROM AUTHOR]

Functional magnetic resonance imaging can provide detailed maps of how sensory space is mapped in the human brain. Here, we use a novel 16 stimulator setup (a 4 × 4 grid) to measure two-dimensional sensory maps of between and within-digit (D2–D4) space using high spatial-resolution (1.25 mm isotropic) imaging at 7 Tesla together with population receptive field (pRF) mapping in 10 participants. Using a 2D Gaussian pRF model, we capture maps of the coverage of digits D2–D5 across Brodmann areas and estimate pRF size and shape. In addition, we compare results to previous studies that used fewer stimulators by constraining pRF models to a 1D Gaussian Between Digit or 1D Gaussian Within Digit model. We show that pRFs across somatosensory areas tend to have a strong preference to cover the within-digit axis. We show an increase in pRF size moving from D2–D5. We quantify pRF shapes in Brodmann area (BA) 3b, 3a, 1, 2 and show differences in pRF size in Brodmann areas 3a-2, with larger estimates for BA2. Generally, the 2D Gaussian pRF model better represents pRF coverage maps generated by our data, which itself is produced from a 2D stimulation grid. [ABSTRACT FROM AUTHOR]

Spinal cord injury is a devastating condition that haunts human lives. Typically, patients experience referred phantom sensations on the hand when they are touched on the face. In adult monkeys, massive deafferentations such as chronic dorsal column lesions at higher cervical levels result in the large-scale expansion of face inputs into the deafferented hand cortex of area 3b. However, adult rats with thoracic dorsal column lesions do not demonstrate such large-scale reorganization. The large-scale face expansion in area 3b of monkeys is driven by the reorganization of the cuneate nucleus in the medulla. The sprouting of afferents from the trigeminal nucleus to the adjacent deafferented cuneate nucleus is facilitated by close proximity and compactness of the medulla in primates. Previously, in adult rats with thoracic lesions, the cuneate nucleus was not deafferented and its functional organization was not explored. The extent of the deafferentation and the duration of the recovery period are two major factors that determine the extent of reorganization. Hence, higher cervical (C3-C4) dorsal column lesions were performed, which cause massive deafferentations, and physiological maps were obtained after prolonged recovery periods (3 weeks −18 months). In spite of the above, the expansion of the intact face inputs was not observed in the deafferented zones of the primary somatosensory cortex (SI) and medulla of adult rats. The deafferented forelimb and hindlimb representations in SI were unresponsive to cutaneous stimulation of any part of the body. The cuneate and gracile nuclei in rats with complete dorsal column lesions remained mostly inactive except for a few sites which responded to stimulation of the spared upper arm. Hence, dorsal column lesions have different effects on the adult primate and rodent somatosensory systems. Appreciating this inter-species difference can aid in identifying the underlying neural substrates and restrict maladaptive reorganizations to cure phantom sensations.

Background: Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, is widely used as a general anaesthetic. However, the mechanisms of analgesic/anaesthetic effects induced by ketamine are only partially understood. Previously, studies have demonstrated that various general anaesthetics affect the primary somatosensory cortex (S1), a potential target of general anaesthetics in the central nervous system. However, it is unknown if astrocyte activities affect ketamine's effects on information transmission in S1 pyramidal neurons. Methods: The whole-cell patch-clamp technique was employed to study the role of astrocytes in ketamine-induced anaesthetic actions. The whole-cell patch-clamp method was used to record the spontaneous postsynaptic currents (SPSCs) of rat S1 pyramidal neurons. We used the glia-selective inhibitor of the aconitase enzyme fluorocitrate (FC), to test if astrocyte activities alter the effects of ketamine on S1 pyramidal neurons. Results: Ketamine lowered the SPSCs of rat S1 pyramidal neurons in a concentration-dependent manner at clinically relevant doses. The concentration-effect curve revealed that ketamine had an EC50 value of 462.1 M for suppressing SPSCs. In rat S1 pyramidal neurons, the glia-selective metabolic inhibitor fluorocitrate (FC), which inhibits the aconitase enzyme, lowered the amplitude and frequency of SPSCs. The inhibitory impact of ketamine on the amplitude and frequency of SPSCs was significantly amplified in the presence of FC. Conclusions: Astrocytes impact the effects of ketamine on pre- and postsynaptic components and play a role in synaptic transmission. [ABSTRACT FROM AUTHOR]

Abstract Toxoplasma gondii is able to manipulate the host immune system to establish a persistent and efficient infection, contributing to the development of brain abnormalities with behavioral repercussions. In this context, this work aimed to evaluate the effects of T. gondii infection on the systemic inflammatory response and structure of the primary somatosensory cortex (PSC). C57BL/6 and BALB/c mice were infected with T. gondii ME49 strain tissue cysts and accompanied for 30 days. After this period, levels of cytokines IFN-γ, IL-12, TNF-α and TGF-β were measured. After blood collection, mice were perfused and the brains were submitted to immunohistochemistry for perineuronal net (PNN) evaluation and cyst quantification. The results showed that C57BL/6 mice presented higher levels of TNF-α and IL-12, while the levels of TGF-β were similar between the two mouse lineages, associated with the elevated number of tissue cysts, with a higher occurrence of cysts in the posterior area of the PSC when compared to BALB/c mice, which presented a more homogeneous cyst distribution. Immunohistochemistry analysis revealed a greater loss of PNN labeling in C57BL/6 animals compared to BALB/c. These data raised a discussion about the ability of T. gondii to stimulate a systemic inflammatory response capable of indirectly interfering in the brain structure and function. Graphical Abstract

Chronic exposure to stressful experiences impairs synaptic plasticity. Previous studies have shown that the spine densities of pyramidal neurons, the turnover of mushroom-type spines, and the excitatory–inhibitory balance in the primary somatosensory cortex (S1) are modulated by stress. Trans-synaptic cell adhesion molecules (CAMs) are implicated in stress-induced synaptic deficits. However, it remains unknown whether stress dysregulates CAMs in S1 and thereby impairs synaptic plasticity. In this study, we applied the early-life stress (ELS), chronic social defeat stress (CSDS), and chronic restraint stress paradigms and measured the mRNA levels of nectin1 in S1 of wild-type and conditional forebrain corticotropin-releasing hormone receptor 1 type (CRHR1) conditional knockout mice. We found that ELS increased nectin1 mRNA levels in S1 in adult but not adolescent mice. Moreover, CSDS increased the nectin1 mRNA levels in S1 in adult mice via the CRH-CRHR1 system. Our findings suggest that S1 is vulnerable to repeated stress exposures at some life stages, and dysregulated nectin1 expression may underlie stress-induced structural and functional abnormalities in S1.

Cytoplasmic dynein is an important intracellular motor protein that plays an important role in neuronal growth, axonal polarity formation, dendritic differentiation, and dendritic spine development among others. The intermediate chain of dynein, encoded by Dync1i1, plays a vital role in the dynein complex. Therefore, we assessed the behavioral and related neuronal activities in mice with dync1i1 gene knockout. Neuronal activities in primary somatosensory cortex were recorded by in vivo electrophysiology and manipulated by optogenetic and chemogenetics. Nociception of mechanical, thermal, and cold pain in Dync1i1−/− mice were impaired. The activities of parvalbumin (PV) interneurons and gamma oscillation in primary somatosensory were also impaired when exposed to mechanical nociceptive stimulation. This neuronal dysfunction was rescued by optogenetic activation of PV neurons in Dync1i1−/− mice, and mimicked by suppressing PV neurons using chemogenetics in WT mice. Impaired pain sensations in Dync1i1−/− mice were correlated with impaired gamma oscillations due to a loss of interneurons, especially the PV type. This genotype-driven approach revealed an association between impaired pain sensation and cytoplasmic dynein complex.

Musician's dystonia presents with a persistent deterioration of motor control during musical performance. A predominant hypothesis has been that this is underpinned by maladaptive neural changes to the somatotopic organization of finger representations within primary somatosensory cortex. Here, we tested this hypothesis by investigating the finger-specific activity patterns in the primary somatosensory and motor cortex using functional MRI and multivariate pattern analysis in nine musicians with dystonia and nine healthy musicians. A purpose-built keyboard device allowed characterization of activity patterns elicited during passive extension and active finger presses of individual fingers. We analysed the data using both traditional spatial analysis and state-of-the art multivariate analyses. Our analysis reveals that digit representations in musicians were poorly captured by spatial analyses. An optimized spatial metric found clear somatotopy but no difference in the spatial geometry between fingers with dystonia. Representational similarity analysis was confirmed as a more reliable technique than all spatial metrics evaluated. Significantly, the dissimilarity architecture was equivalent for musicians with and without dystonia. No expansion or spatial shift of digit representation maps were found in the symptomatic group. Our results therefore indicate that the neural representation of generic finger maps in primary sensorimotor cortex is intact in musician's dystonia. These results speak against the idea that task-specific dystonia is associated with a distorted hand somatotopy and lend weight to an alternative hypothesis that task-specific dystonia is due to a higher-order disruption of skill encoding. Such a formulation can better explain the task-specific deficit and offers alternative inroads for therapeutic interventions. [ABSTRACT FROM AUTHOR]

Motor impairments and sensory processing abnormalities are prevalent in autism spectrum disorder (ASD), closely related to the core functions of the primary motor cortex (M1) and the primary somatosensory cortex (S1). Currently, there is limited knowledge about potential therapeutic targets in the subregions of M1 and S1 in ASD patients. This study aims to map clinically significant functional subregions of M1 and S1. Resting-state functional magnetic resonance imaging data (NTD = 266) from Autism Brain Imaging Data Exchange (ABIDE) were used for subregion modeling. We proposed a distance-weighted sparse representation algorithm to construct brain functional networks. Functional subregions of M1 and S1 were identified through consensus clustering at the group level. Differences in the characteristics of functional subregions were analyzed, along with their correlation with clinical scores. We observed symmetrical and continuous subregion organization from dorsal to ventral aspects in M1 and S1, with M1 subregions conforming to the functional pattern of the motor homunculus. Significant intergroup differences and clinical correlations were found in the dorsal and ventral aspects of M1 (p < 0.05/3, Bonferroni correction) and the ventromedial BA3 of S1 (p < 0.05/5). These functional characteristics were positively correlated with autism severity. All subregions showed significant results in the ROI-to-ROI intergroup differential analysis (p < 0.05/80). The generalizability of the segmentation model requires further evaluation. This study highlights the significance of M1 and S1 in ASD treatment and may provide new insights into brain parcellation and the identification of therapeutic targets for ASD. • Distance-weighted sparse learning aids in constructing robust brain functional networks. • The primary motor cortex is a targeted brain region for potential autism spectrum disorder patients. • The primary somatosensory cortex is a targeted brain region for potential autism spectrum disorder patients. [ABSTRACT FROM AUTHOR]

Background: Interoception, the processing and integration of bodily signals, is crucial for emotional experiences and overall well-being. The interoceptive network, including the somatosensory cortices, has been recognized for its role in interoceptive and emotional processing. High-definition transcranial, direct-current stimulation (HD-tDCS) has been demonstrated to modulate brain activity in the primary somatosensory cortex (S1). Based on those findings, we hypothesized that anodal HD-tDCS over the right S1 would enhance interoceptive abilities and heighten emotional perception. Methods: Thirty-six healthy adults participated in two sessions separated by at least one week. A 20-min HD-tDCS stimulation (2 mA), and a sham stimulation, were applied in randomized order. Both conditions involved pre-tDCS physical activation by ergometer cycling. Interoceptive abilities were assessed before and after both sessions using a heartbeat-perception and respiratory-load task. Emotional perception was measured using four matched international affective picture system (IAPS) picture sets presented randomly. Results: Active HD-tDCS did not significantly improve interoceptive accuracy, interoceptive emotion evaluation, or interoceptive sensibility. However, a notable increase in cardiac interoceptive awareness was observed after active HD-tDCS. The expected enhancement of emotional processing was not observed. Conclusions: This study represents the first attempt to modulate interoceptive and emotional processing using HD-tDCS over S1. Although consistent enhancement was not observed, our findings provide insights into the modulation of interoceptive and emotional processes with HD-tDCS, suggesting avenues for further research. Further studies should consider the nuanced effects of stimulation techniques and the complex interplay between interoception and emotion.

In non-human primate (NHP) optogenetics, infecting large cortical areas with viral vectors is often a difficult and time-consuming task. Here, we demonstrate the use of magnetic resonance (MR)-guided convection enhanced delivery (CED) of optogenetic viral vectors into primary somatosensory (S1) and motor (M1) cortices of macaques to obtain efficient, widespread cortical expression of light-sensitive ion channels. Adeno-associated viral (AAV) vectors encoding the red-shifted opsin C1V1 fused to yellow fluorescent protein (EYFP) were injected into the cortex of rhesus macaques under MR-guided CED. Three months post-infusion, epifluorescent imaging confirmed large regions of optogenetic expression (>130 mm2) in M1 and S1 in two macaques. Furthermore, we were able to record reliable light-evoked electrophysiology responses from the expressing areas using micro-electrocorticographic arrays. Later histological analysis and immunostaining against the reporter revealed widespread and dense optogenetic expression in M1 and S1 corresponding to the distribution indicated by epifluorescent imaging. This technique enables us to obtain expression across large areas of the cortex within a shorter period of time with minimal damage compared to the traditional techniques and can be an optimal approach for optogenetic viral delivery in large animals such as NHPs. This approach demonstrates great potential for network-level manipulation of neural circuits with cell-type specificity in animal models evolutionarily close to humans.

Childhood absence epilepsy seizures arise in the cortico-thalamocortical network due to multiple cellular and molecular mechanisms, which are still under investigation. Understanding the precise mechanisms is imperative given that treatment fails in ~30% of patients while adverse neurological sequelae remain common. Impaired GABAergic neurotransmission is commonly reported in research models investigating these mechanisms. Recently, we reported a region-specific reduction in the whole-tissue and synaptic GABAA receptor (GABAAR) α1 subunit and an increase in whole-tissue GAD65 in the primary somatosensory cortex (SoCx) of the adult epileptic stargazer mouse compared with its non-epileptic (NE) littermate. The current study investigated whether these changes occurred prior to the onset of seizures on postnatal days (PN) 17–18, suggesting a causative role. Synaptic and cytosolic fractions were biochemically isolated from primary SoCx lysates followed by semiquantitative Western blot analyses for GABAAR α1 and GAD65. We found no significant changes in synaptic GABAAR α1 and cytosolic GAD65 in the primary SoCx of the stargazer mice at the critical developmental stages of PN 7–9, 13–15, and 17–18. This indicates that altered levels of GABAAR α1 and GAD65 in adult mice do not directly contribute to the initial onset of absence seizures but are a later consequence of seizure activity. [ABSTRACT FROM AUTHOR]

Toxoplasma gondii is able to manipulate the host immune system to establish a persistent and efficient infection, contributing to the development of brain abnormalities with behavioral repercussions. In this context, this work aimed to evaluate the effects of T. gondii infection on the systemic inflammatory response and structure of the primary somatosensory cortex (PSC). C57BL/6 and BALB/c mice were infected with T. gondii ME49 strain tissue cysts and accompanied for 30 days. After this period, levels of cytokines IFN-γ, IL-12, TNF-α and TGF-β were measured. After blood collection, mice were perfused and the brains were submitted to immunohistochemistry for perineuronal net (PNN) evaluation and cyst quantification. The results showed that C57BL/6 mice presented higher levels of TNF-α and IL-12, while the levels of TGF-β were similar between the two mouse lineages, associated with the elevated number of tissue cysts, with a higher occurrence of cysts in the posterior area of the PSC when compared to BALB/c mice, which presented a more homogeneous cyst distribution. Immunohistochemistry analysis revealed a greater loss of PNN labeling in C57BL/6 animals compared to BALB/c. These data raised a discussion about the ability of T. gondii to stimulate a systemic inflammatory response capable of indirectly interfering in the brain structure and function. [ABSTRACT FROM AUTHOR]

Absence seizures are hyperexcitations within the cortico-thalamocortical (CTC) network, however the underlying causative mechanisms at the cellular and molecular level are still being elucidated and appear to be multifactorial. Dysfunctional feed-forward inhibition (FFI) is implicated as one cause of absence seizures. Previously, we reported altered excitation onto parvalbumin-positive (PV+) interneurons in the CTC network of the stargazer mouse model of absence epilepsy. In addition, downstream changes in GABAergic neurotransmission have also been identified in this model. Our current study assessed whether dysfunctional FFI affects GABAA receptor (GABAAR) subunit expression in the stargazer primary somatosensory cortex (SoCx). Global tissue expression of GABAAR subunits α1, α3, α4, α5, β2, β3, γ2 and δ were assessed using Western blotting (WB), while biochemically isolated subcellular fractions were assessed for the α and δ subunits. We found significant reductions in tissue and synaptic expression of GABAAR α1, 18% and 12.2%, respectively. However, immunogold-cytochemistry electron microscopy (ICC-EM), conducted to assess GABAAR α1 specifically at synapses between PV+ interneurons and their targets, showed no significant difference. These data demonstrate a loss of phasic GABAAR α1, indicating altered GABAergic inhibition which, coupled with dysfunctional FFI, could be one mechanism contributing to the generation or maintenance of absence seizures. [ABSTRACT FROM AUTHOR]

General anesthesia has been shown to induce significant changes in the functional connectivity of the cerebral cortex. However, traditional methods such as electroencephalography (EEG) or functional magnetic resonance imaging (fMRI) lack the spatial resolution to study the effects of general anesthesia on individual cortical neurons. This study aimed to use high-resolution two-photon imaging, which can provide single-neuron resolution, to investigate the characteristics of consciousness under general anesthesia. We used C57BL/6J and Thy1-GCamp6s mice and found that at similar levels of sedation, as measured by EEG, dexmedetomidine did not significantly inhibit the spontaneous activity of neuronal somata in the S1 cortex, but preserved the frequency of calcium events in neuronal spines. In contrast, propofol and ketamine dramatically inhibited the spontaneous activity of both neuronal somata and spines. The S1 cortex still responded to whisker stimulation under dexmedetomidine anesthesia, but not under propofol or ketamine anesthesia. Our results suggest that dexmedetomidine anesthesia has unique neuronal properties associated with its ability to facilitate easy awakening in the clinic. These findings provide insights into the development of more effective strategies for monitoring consciousness during general anesthesia. [ABSTRACT FROM AUTHOR]

This study implements the use of Danish Landrace pigs as subjects for the long-term potentiation (LTP)-like pain model. This is accomplished by analyzing changes in the primary somatosensory cortex (S1) in response to electrical stimulation on the ulnar nerve after applying high-frequency electrical stimulation (HFS) on the ulnar nerve. In this study, eight Danish Landrace pigs were electrically stimulated, through the ulnar nerve, to record the cortically evoked response in S1 by a 16-channel microelectrode array (MEA). Six of these pigs were subjected to HFS (four consecutive, 15 mA, 100 Hz, 1000 µs pulse duration) 45 min after the start of the experiment. Two pigs were used as control subjects to compare the cortical response to peripheral electrical stimulation without applying HFS. Low-frequency components of the intracortical signals (0.3–300 Hz) were analyzed using event-related potential (ERP) analysis, where the minimum peak during the first 30–50 ms (N1 component) in each channel was detected. The change in N1 was compared over time across the intervention and control groups. Spectral analysis was used to demonstrate the effect of the intervention on the evoked cortical oscillations computed between 75 ms and 200 ms after stimulus. ERP analysis showed an immediate increase in N1 amplitude that became statistically significant 45 mins after HFS (p

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 functional MRI (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 phantom limb pain (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.

Alterations of empathy for others’ pain among patients with chronic pain remained inconsistent. Here, applying a capsaicin-based ongoing pain model on healthy participants, this study investigated how ongoing first-hand pain influences empathic reactions to vicarious pain stimuli. Healthy participants were randomly treated with topical capsaicin cream (capsaicin group) or hand cream (control group) on the left forearm. Video clips showing limbs in painful and non-painful situations were used to induce empathic responses. The capsaicin group showed greater empathic neural responses in the right primary somatosensory cortex (S1) than the control group but smaller responses in the left anterior insula (AI) accompanied with smaller empathic pain-intensity ratings. Notably, the intensity of ongoing pain negatively correlated with empathy-related neural responses in the left AI. Inter-subject phase synchronization analysis was used to assess stimulus-dependent dynamic functional connectivity within or between brain regions engaged in pain empathy. The capsaicin group showed greater empathy-related neural synchronization within S1 and between S1 and AI, but less synchronization within AI and between AI and MCC. Behaviorally, the differential inter-subject pain-intensity rating alignment between painful and non-painful videos was more positive for the capsaicin group than for the control group, and this effect was partially mediated by the inter-subject neural synchronization between S1 and AI. These results suggest that ongoing first-hand pain facilitates neural activation and synchronization within brain regions associated with empathy-related somatosensory resonance at the cost of inhibiting activation and synchronization within brain regions engaged in empathy-related affective sharing.

Background: Multichannel tactile stimulation devices is need to investigate human finger population receptive field (pRF) characteristics in the primary somatosensory cortex during functional magnetic resonance imaging (fMRI). Purpose: To accurately characterize right‐hand somatosensory representation based on the Bayesian pRF model. Study Type: Prospective. Population: A water phantom and six healthy participants (four males, mean 23.8 years old). Field Strength/Sequence: T1‐weighted magnetization‐prepared rapid gradient‐echo, T2*‐weighted echo planar imaging at 3 T. Assessment: The piezoelectric actuated tactile stimulation device consisted of execution unit and control unit. The output performance of the device was measured by a laser displacement sensor. The effect of the device on images' signal‐to‐noise ratio (SNR) was measured by phantom experiments. The activation representation arrangement order, relative volumes, and receptive field size of the right hand were assessed during the along‐digits and cross‐digits paradigms. Statistical Tests: The normality of the data was tested by the Shapiro–Wilk method. A paired‐sample t test was performed to test pRF characteristics for all digit pairings. The significance level was set to P = 0.05 (false discovery rate [FDR] correct). Results: Percussive stimulation provided by the piezoelectric actuated tactile stimulator had a stable displacement (2.64 mm) over a wide range of vibration frequencies (0–30 Hz). The output delay of the device was 1 millisecond. The device did not affect the image's SNR (without the device: SNR = 138.24 ± 7.87, temporal SNR [TSNR] = 440.03 ± 52.08. With the device: SNR = 138.06 ± 8.44, TSNR = 438.52 ± 56.38. PSNR = 0.88, PTSNR = 0.46). Representations of right‐hand fingers showed the same arrangement order in both experiments (D1–D5 arranged along the central sulcus). However, the relative volumes of D3 showed significant differences in S1 (P = 0.003). Among four subareas, the relative volumes of D3 were significantly different in area 1 (P = 0.047). Data Conclusion: This developed stimulator, through experimental verification, could play a role in pRF mapping exploration. Level of Evidence: 2 Technical Efficacy Stage: 1 [ABSTRACT FROM AUTHOR]

Introduction: It is widely known that motor learning changes the excitability of the primary motor cortex. More recently, it has been shown that the primary somatosensory cortex (S1) also plays an important role in motor learning, but the details have not been fully examined. Therefore, we investigated how motor skill training affects somatosensory evoked potential (SEP) in 30 neurologically healthy subjects. Methods: SEP N20/P25_component and N20/P25 SEP paired-pulse depression (SEP-PPD) were assessed before and immediately after complex or simple visuomotor tasks. Results: Motor learning was induced more efficiently by the complex visuomotor task than by the simple visuomotor task. Both the N20/P25 SEP amplitude and N20/P25 SEP-PPD increased significantly immediately after the complex visuomotor task, but not after the simple visuomotor task. Furthermore, the altered N20/P25 SEP amplitude was associated with an increase in motor learning efficiency. Conclusion: These results suggest that motor learning modulated primary somatosensory cortex excitability. [ABSTRACT FROM AUTHOR]

Optimal limb coordination requires efficient transmission of somatosensory information to the sensorimotor cortex. The primary somatosensory cortex (S1) is frequently damaged by stroke, resulting in both somatosensory and motor impairments. Noninvasive brain stimulation (NIBS) to the primary motor cortex is thought to induce neural plasticity that facilitates neurorehabilitation. Several studies have also examined if NIBS to the S1 can enhance somatosensory processing as assessed by somatosensory‐evoked potentials (SEPs) and improve behavioural task performance, but it remains uncertain if NIBS can reliably modulate S1 plasticity or even whether SEPs can reflect this plasticity. This systematic review revealed that NIBS has relatively minor effects on SEPs or somatosensory task performance, but larger early SEP changes after NIBS can still predict improved performance. Similarly, decreased paired‐pulse inhibition in S1 post‐NIBS is associated with improved somatosensory performance. However, several studies still debate the role of inhibitory function in somatosensory performance after NIBS in terms of the direction of the change (i.e., disinhibition or inhibition). Altogether, early SEP and paired‐pulse inhibition (particularly inter‐stimulus intervals of 30–100 ms) may become useful biomarkers for somatosensory deficits, but improved NIBS protocols are required for therapeutic applications. [ABSTRACT FROM AUTHOR]

A pioneering study by Volkmann (1858) revealed that training on a tactile discrimination task improved task performance, indicative of tactile learning, and that such tactile learning transferred from trained to untrained body parts. However, the neural mechanisms underlying tactile learning and transfer of tactile learning have remained unclear. We trained groups of human subjects (female and male) in daily sessions on a tactile discrimination task either by stimulating the palm of the right hand or the sole of the right foot. Task performance before training was similar between the palm and sole. Posttraining transfer of tactile learning was greater from the trained right sole to the untrained right palm than from the trained right palm to the untrained right sole. Functional magnetic resonance imaging (fMRI) and multivariate pattern classification analysis revealed that the somatotopic representation of the right palm in contralateral primary somatosensory cortex (SI) was coactivated during tactile stimulation of the right sole. More pronounced coactivation in the cortical representation of the right palm was associated with lower tactile performance for tactile stimulation of the right sole and more pronounced subsequent transfer of tactile learning from the trained right sole to the untrained right palm. In contrast, coactivation of the cortical sole representation during tactile stimulation of the palm was less pronounced and no association with tactile performance and subsequent transfer of tactile learning was found. These results indicate that tactile learning may transfer to untrained body parts that are coactivated to support tactile learning with the trained body part. [ABSTRACT FROM AUTHOR]

The primary somatosensory cortex (S1) plays a key role in the discrimination of somatic sensations. Among subdivisions in S1, the dysgranular zone of rodent S1 (S1DZ) is homologous to Brodmann's area 3a of primate S1, which is involved in the processing of noxious signals from the body. However, molecular changes in this region and their role in the pathological pain state have never been studied. In this study, we identified molecular alteration of the S1DZ in a rat model of neuropathic pain induced by right L5 spinal nerve ligation (SNL) surgery and investigated its functional role in pain symptoms. Brain images acquired from SNL group and control group in our previous study were analyzed, and behaviors were measured using the von Frey test, acetone test, and conditioned place preference test. We found that metabotropic glutamate receptor 5 (mGluR5) levels were significantly upregulated in the S1DZ contralateral to the nerve injury in the SNL group compared to the sham group. Pharmacological deactivation of mGluR5 in S1DZ ameliorated symptoms of neuropathic allodynia, which was shown by a significant increase in the mechanical paw withdrawal threshold and a decrease in the behavioral response to cold stimuli. We further confirmed that this treatment induced relief from the tonic-aversive state of chronic neuropathic pain, as a place preference memory associated with the treatment-paired chamber was formed in rats with neuropathic pain. Our data provide evidence that mGluR5 in the S1DZ is involved in the manifestation of abnormal pain sensations in the neuropathic pain state. [ABSTRACT FROM AUTHOR]

The integration of somatosensory signals across fingers is essential for dexterous object manipulation. Previous experiments suggest that this integration occurs in neural populations in the primary somatosensory cortex (S1). However, the integration process has not been fully characterized, as previous studies have mainly used 2-finger stimulation paradigms. Here, we addressed this gap by stimulating all 31 single- and multifinger combinations. We measured population-wide activity patterns evoked during finger stimulation in human S1 and primary motor cortex (M1) using 7T fMRI in female and male participants. Using multivariate fMRI analyses, we found clear evidence of unique nonlinear interactions between fingers. In Brodmann area (BA) 3b, interactions predominantly occurred between pairs of neighboring fingers. In BA 2, however, we found equally strong interactions between spatially distant fingers, as well as interactions between finger triplets and quadruplets. We additionally observed strong interactions in the hand area of M1. In both M1 and S1, these nonlinear interactions did not reflect a general suppression of overall activity, suggesting instead that the interactions we observed reflect rich, nonlinear integration of sensory inputs from the fingers. We suggest that this nonlinear finger integration allows for a highly flexible mapping from finger sensory inputs to motor responses that facilitates dexterous object manipulation. [ABSTRACT FROM AUTHOR]

The periodontal ligaments are very important sensory organ for our daily life such as perception of food size or hardness, determination of jaw position, and adjustment of masticatory strength. The sensory properties of the periodontal ligament, especially those of the maxillary and mandibular molars, have not yet been fully investigated. Somatosensory evoked magnetic fields (SEFs) can be measured and evaluated for latency and intensity to determine the sensory transmission characteristics of each body parts. However, previous reports on SEFs in the oral region have only reported differences in upper and lower gingival and lip sensations. In this study, the aim was to clarify these sensory characteristics by measuring SEFs during mechanical stimulation of the periodontal ligament in the maxillary and mandibular first molars. Somatosensory evoked magnetic fields were measured in the contralateral hemispheres of 33 healthy volunteers. Mechanical stimulation of the maxillary and mandibular right first molars, and the left wrist was performed with a specific handmade tool. The first peak latency for the mandibular first molars was 41.7 ± 5.70 ms (mean ± SD), significantly shorter than that for the maxillary first molars at 47.7 ± 7.36 ms. The peak intensity for the mandibular first molars was 13.9 ± 6.06 nAm, significantly larger than that for the maxillary first molars at 7.63 ± 3.55 nAm. The locations in the contralateral hemispheres showed no significant difference between the maxillary first molars and mandibular first molars. These locations were more anteroinferior and exterior than that of the wrist, as suggested by the brain homunculus. Neural signals from the mandibular periodontal ligaments pass faster and more intensely to the central nervous system than those from the maxillary periodontal ligaments, and may preferentially participate in adjustment of the occlusal force and the occlusal position.