Somatosensory Cortex Research Articles

The intrinsic propagation directionality of fMRI infra-slow activity during visual tasks

The temporal order of propagation in the blood-oxygen-level-dependent (BOLD) infra-slow activity (ISA, 0.01–0.1 Hz) of functional magnetic resonance imaging (fMRI) can indicate the functional organization of the brain. While prior studies have revealed the temporal order of propagation of BOLD ISA during rest, how it emerges during cognitive tasks remains unclear. Furthermore, its differences between the gray and white matters at the whole-brain scale are unexplored. In this study, we probed the propagation of BOLD ISA using a publicly available fMRI dataset from participants performing visual detection and discrimination tasks (N = 46, 29 females). We examined the temporal order of propagation based on ISA oscillatory phase differences among brain parcels. During visual task performance, ISA in both the gray and white matters propagated in a direction from the visual cortex to the association cortex, including the default mode network (DMN). This result differs from the previously reported propagation direction during rest that traveled from the visual and somatosensory cortices to the DMN, suggesting that the functional organization may change when performing cognitive tasks. In addition, the propagation in the white matter represented more complex patterns than that in the gray matter, exhibiting that the cingulum preceded DMN. Our results may help the understanding of how task performance alters the sensory-DMN propagation according of ISA.

Lack of Brain Asymmetry in the Alpha Band During the Observation of Object Grasping in Reality Versus on Screen

The way audiovisuals are perceived is not completely understood. Previous works have shown that attention increases when watching audiovisuals compared with looking at real events, but depending on the editing style, and the interpreter, the understanding of the content may be different. The study of brain asymmetries in this context aims to identify potential lateralizations in audiovisual perception. Previous studies have proven that seeing others grasp objects has a contralateral impact on somatosensory areas (C3 and C4) in the alpha band (8–12 Hz). In this work, we investigated whether brain activity could be asymmetrical in that band when looking at real grasping compared with watching grasping on a screen, and whether media expertise would be a determinant in this regard and presented the same narrative content both through live performance and as a movie to 40 participants (half of them media professionals) while recording their electroencephalography (EEG) activity. We conclude that the asymmetry in the alpha band in the somatosensory cortex is not affected by the medium through which the grasping actions are presented, that is, in reality or on screen. We also conclude that media expertise does not impact this asymmetry.

Neurprotective Role of Amaranthus Dubius on Penicillin Induced Experimental Epileptic Rat Model by Combating the Multineurotransmitter Deficiency

Objective: The study aims to clarify the protective effects of Amaranthus dubius (AD) in penicillin (PCN)-induced experimental epilepsy models in rats. Method: In this study, twenty-four adult male Wistar albino rats, each weighing between 200-250 grams, were utilized. The rats were allocated into four groups: a control group, an Amaranthus dubius (AD) treated control group, a PCN-induced experimental epileptic rat model group, and an AD pretreated PCN-induced experimental epileptic rat model group. All groups were administered a daily oral dosage of 400 mg/kg body weight of AD aqueous leaf extract for fourteen days via an orogastric cannula. For the experimental epileptic model, PCN was injected into designated areas of the somatosensory cortex. On the concluding fifteenth day, subsequently, the rats were humanely euthanized. Tissue specimens from the cerebral cortex (CC), cerebellum (CB), caudate nucleus (CN), pons and medulla (PM), and midbrain (MB) were extracted, measured, and homogenized to facilitate subsequent biochemical analyses. Result: Pretreatment with AD has demonstrated significant changes in the levels of antioxidants and neurotransmitters in the brain. Conclusion: Amaranthus Dubius aids in combating multi-neurotransmitter deficiencies and enhances the body's antioxidant capabilities.

Altered parasympathetic outflow and central sensitization response to continuous pain in cyclic vomiting syndrome: a functional magnetic resonance imaging study.

Cyclic vomiting syndrome (CVS) is a disorder of brain-gut interaction characterized by recurrent episodes of nausea and vomiting interspersed with asymptomatic periods and associated with autonomic nervous system dysfunction. We examined the dysautonomic response to noxious stimuli seen in CVS patients using our previously validated approach to integrate peripheral autonomic outflow metrics, temporal summation of pain, and brain fMRI. BOLD fMRI and ECG were acquired from CVS patients and healthy adults during a rest condition and a sustained cuff pressure pain stimulus at the leg. After the latter scan, participants rated pain for the full 6-minute pain stimulus as well as first, middle, and last two-minutes to calculate temporal summation. During sustained pain, patients (n=13) exhibited greater reduction in heart rate variability within the high-frequency range (HF-HRV) and reduced anticorrelation between HF-HRV and fMRI signal in the anterior insula, pregenual anterior cingulate cortex, and ventrolateral and dorsolateral prefrontal cortex relative to healthy adults (n=13). Compared to healthy adults (n=14), patients (n=14) exhibited increasing pain intensity over the course of sustained cuff pressure. Seed-based functional connectivity analysis revealed for healthy adults (n=13), pain sensitization correlated with pain-induced increases in connectivity between primary somatosensory cortex and regions of interest in both left anterior insula/posterior orbitofrontal cortex and right pre-supplementary motor area, while this correlation was disrupted in CVS (n=10). Our results support altered central coding of nociceptive stimuli and autonomic responsivity of CVS patients in key brain regions implicated in autonomic control and interoception.

Abstract 4121198: Structural Network Alterations After Cardiopulmonary Bypass In a Juvenile Porcine Model

Background: Cardiopulmonary bypass (CPB) can trigger inflammatory and oxidative stresses in the developing brain. Clinical studies showed altered brain network structure in children after infant cardiac surgery. However, the impact of CPB on structural connectivity remains poorly understood. This study aims to determine the effects of CPB on structural connectivity and underlying cellular events using a juvenile porcine model. Methods: CPB (150 min total) was performed on 2-week-old Yorkshire piglets. High-resolution diffusion tensor imaging (DTI) and neurite orientation dispersion and density (NODDI) imaging were performed 4 weeks post-CPB in a total of 12 animals (Control; n=7, CPB; n=5). Structural connectivity assay together with histological analysis was conducted to assess the brain network organization. Results: Our network analysis (Image 1) revealed a CPB-induced reduction of structural connections in particular nodes, such as in the anterior prefrontal cortex (APC), primary somatosensory cortex, substantia nigra (SN), and globus pallidus (GP). In contrast, there was an increase in the premotor cortex (PreMC), primary motor cortex (PriMC), dorsal posterior cingulate cortex (DPCC), and somatosensory cortex (SAC). Three-dimensional images were generated based on these altered nodes, and tractography was generated to indicate changed fiber tracking (Image 2). We found reduced network connections between the basal ganglia and frontal cortex, and increased connections between the motor and posterior region. DTI and NODDI indicated that microstructures of the superior corona radiata (SCR), internal capsule (PLIC), and anterior prefrontal (AP-WM), motor (PreM-/PriM-WM), and somatosensory white matter (SA-WM) were significantly altered after CPB (Image 3). While Iba1+ microglia was activated across all brain regions after CPB (P<.05), CPB-induced oligodendrocyte immatureness was identified in the WMs involved in APC-SN and APC-GP pathways (P<.05). Notably, CPB increased the number of mature oligodendrocytes in motor and SA-WMs (P<.05) where structural connections were increased after CPB. In addition, we found SN dopaminergic neuron injury after CPB (P<.05). Conclusion: CPB altered structural network organization in the developing brain. Spatial differences in oligodendrocyte responses and susceptibility of specific subpopulations of neurons may contribute to the unique connectivity alterations observed after CPB.

CNSC-64. BEYOND THE LOCAL TUMOR MICROENVIRONMENT: CHARACTERIZING CHANGES TO NEURONAL ACTIVITY INDUCED BY PEDIATRIC HIGH-GRADE GLIOMA

Abstract Bidirectional electrochemical signaling between neurons and tumor cells is emerging as a critical regulator of pediatric high-grade glioma (HGG) pathology. Neuron-tumor interactions are known to induce local neuronal hyperactivity. However, recent work tracing the projections of these neuron-tumor networks revealed that HGG neuronal recruitment extends beyond the local tumor microenvironment (TME). These findings suggest that tumor-induced hyperexcitability may spread beyond the local TME and drive brain-wide circuit-level changes. To elucidate how non-tumor innervated brain regions are affected by TME hyperactivity we first characterized neuronal hyperactivity induced by a cortical patient-derived pediatric high-grade cell line in vitro on human iPSC-derived neurons. In vitro calcium imaging experiments demonstrated an increase in the number of calcium fluctuations in glioma co-cultured neurons. In parallel, multi-electrode recordings revealed increased population spiking activity and amplitude in neurons co-cultured with glioma cells. We then xenografted these HGG cells into the prefrontal cortex of mice and performed whole brain-clearing and cFos staining on tumor-bearing vs saline-injected control samples. As cFos is an immediate early gene activated by neuronal activity, we utilized the density of cFos expression as a readout-out of neuronal activation in our atlas-aligned segmented brain section analyses. We expectedly observed increased cFos expression within the ipsilateral primary and secondary motor region, which collectively comprise the local TME. Interestingly, we additionally observed elevated cFos in non-tumor bearing brain regions on both the ipsilateral and contralateral hemispheres, largely in layer 2/3 cortical neurons. These neurons form extensive cortico-cortical projections, and we coincidingly observed increased cFos expression in known cortical projection targets of the prefrontal xenograft location, such as somatosensory, visual, and retrosplenial cortices. Our findings suggest that tumor-induced neuronal hyperactivity extends beyond the local TME in a brain-wide manner and potentially follows established neuronal circuits, rendering these connected regions vulnerable to alterations in neuronal activity.

Early movement restriction impairs the development of sensorimotor integration, motor skills and memory in rats: Towards a preclinical model of developmental coordination disorder?

Children with neurodevelopmental disorders, such as developmental coordination disorder (DCD), exhibit gross to fine sensorimotor impairments, reduced physical activity and interactions with the environment and people. This disorder co-exists with cognitive deficits, executive dysfunctions and learning impairments. Previously, we demonstrated in rats that limited amounts and atypical patterns of movements and somatosensory feedback during early movement restriction manifested in adulthood as degraded postural and locomotor abilities, and musculoskeletal histopathology, including muscle atrophy, hyperexcitability within sensorimotor circuitry and maladaptive cortical plasticity, leading to functional disorganization of the primary somatosensory and motor cortices in the absence of cortical histopathology. In this study, we asked how this developmental sensorimotor restriction (SMR) started to impact the integration of multisensory information and the emergence of sensorimotor reflexes in rats. We also questioned the enduring impact of SMR on motor activities, pain and memory. SMR led to deficits in the emergence of swimming and sensorimotor reflexes, the development of pain and altered locomotor patterns and posture with toe-walking, adult motor performance and night spontaneous activity. In addition, SMR induced exploratory hyperactivity, short-term impairments in object-recognition tasks and long-term deficits in object-location tasks. SMR rats displayed minor alterations in histological features of the hippocampus, entorhinal, perirhinal and postrhinal cortices yet no obvious changes in the prefrontal cortex. Taken all together, these results show similarities with the symptoms observed in children with DCD, although further exploration seems required to postulate whether developmental SMR corresponds to a rat model of DCD.

Characterising the power spectrum dynamics of the non-REM to REM sleep transition.

The transition from non-rapid eye movement (NREM) to rapid eye movement (REM) sleep is considered a transitional or intermediate stage (IS), characterised by high amplitude spindles in the frontal cortex and theta activity in the occipital cortex. Early reports in rats showed an IS lasting from 1 to 5 s, but recent studies suggested a longer duration of this stage of up to 20 s. To further characterise the IS, we analysed its spectral characteristics on electrocorticogram (ECoG) recordings of the olfactory bulb (OB), primary motor (M1), primary somatosensory (S1), and secondary visual cortex (V2) in 12 Wistar male adult rats. By comparing the IS with consolidated NREM/REM epochs, our results reveal that the IS has specific power spectral patterns that fall out of the NREM and REM sleep state power distribution. Specifically, the main findings were that sigma (11-16 Hz) power in OB, M1, S1, and V2 increased during the IS compared with NREM and REM sleep, which started first in the frontal part of the brain (OB -54 s, M1 -53 s) prior to the last spindle occurrence. The beta band (17-30 Hz) power showed a similar pattern to that of the sigma band, starting -54 s before the last spindle occurrence in the M1 cortex. Notably, sigma infraslow coupling (~0.02 Hz) increased during the IS but occurred at a slower frequency (~0.01 Hz) compared with NREM sleep. Thus, we argue that the NREM to REM transition contains its own local spectral profile, in accordance with previous reports, and is more extended than described previously.

Multiplexed expansion revealing for imaging multiprotein nanostructures in healthy and diseased brain

Proteins work together in nanostructures in many physiological contexts and disease states. We recently developed expansion revealing (ExR), which expands proteins away from each other, in order to support better labeling with antibody tags and nanoscale imaging on conventional microscopes. Here, we report multiplexed expansion revealing (multiExR), which enables high-fidelity antibody visualization of >20 proteins in the same specimen, over serial rounds of staining and imaging. Across all datasets examined, multiExR exhibits a median round-to-round registration error of 39 nm, with a median registration error of 25 nm when the most stringent form of the protocol is used. We precisely map 23 proteins in the brain of 5xFAD Alzheimer’s model mice, and find reductions in synaptic protein cluster volume, and co-localization of specific AMPA receptor subunits with amyloid-beta nanoclusters. We visualize 20 synaptic proteins in specimens of mouse primary somatosensory cortex. multiExR may be of broad use in analyzing how different kinds of protein are organized amidst normal and pathological processes in biology.

Comparison of head posture and neck proprioceptive sense of individuals with chronic neck pain and healthy controls: A cross-sectional study.

Chronic pain can affect body perception at the central level by causing the somatosensory cortex to rearrange. Additionally, cervical afferent abnormalities in individuals with neck pain can impair proprioceptive sensitivity, potentially leading to alterations in body alignment and biomechanics. Nevertheless, there are insufficient studies exploring these notions. The main objective of this study was to compare the head posture and neck proprioceptive sense of individuals with chronic neck pain and healthy controls. Utilizing a cross-sectional study, a total of 76 volunteers comprising 38 individuals with neck pain and 38 matched healthy controls participated in the study. Head posture and cervical joint position sense were measured using a Cervical Range of Motion Deluxe (CROM) device. Firstly, the deviation angles of the head in three planes were evaluated, then the Head Repositioning Accuracy (HRA) test was performed to determine the joint position error. Visual Analogue Scale (VAS) was used to determine the severity of pain in individuals with neck pain. The deviation angles of the head in all three planes were significantly lower in the healthy control group (p< 0.05). Joint position error values were significantly higher in all directions (flexion-extension, right-left lateral flexion, and rotation) in the neck pain group (p< 0.001). The findings show that the proprioceptive sensation of the cervical region in individuals with neck pain was adversely affected, with changes were observed in the head posture. The abstract of this study was presented as a verbal declaration at the International Congress of Health Sciences-ICHES-IDU 2020 that was held in İzmir on 20-21 June 2020.

Projection-specific circuits of retrosplenial cortex with differential contributions to spatial cognition.

Retrosplenial cortex (RSC) is a brain region involved in neuropsychiatric and neurodegenerative disorders. It has reciprocal connections with a diverse set of cortical and subcortical brain regions, but the afferent structure and behavioral function of circuits defined by its projection-specific sub-populations have yet to be determined. The corticocortical connections between RSC and secondary motor cortex (M2), as well as corticothalamic connections between RSC and anterodorsal thalamus (AD) have been hypothesized to function as semi-independent, but parallel pathways that impact spatial information processing in distinct ways. We used retrograde and anterograde viral tracers and monosynaptic retrograde rabies virus to quantitatively characterize and compare the afferent and efferent distributions of retrosplenial neuron sub-populations projecting to M2 and AD. AD-projecting and M2-projecting RSC neurons overlap in their collateral projections to other brain regions, but not in their projections to M2 and AD, respectively. Compared with AD-projecting RSC neurons, M2-projecting RSC neurons received much greater afferent input from the dorsal subiculum, AD, lateral dorsal and lateral posterior thalamus, and somatosensory cortex. AD-projecting RSC neurons received greater input from the anterior cingulate cortex and medial septum. We performed chemogenetic inhibition of M2- and AD-projecting RSC neurons and examined its impact on object-location memory, object-recognition, open-field exploration, and place-action association. Our findings indicate that inhibition of M2-projecting RSC neurons impairs object location memory as well as place-action association, while the RSC to AD pathway impacts only object-location memory. The findings indicate that RSC is composed of semi-independent circuits distinguishable by their afferent/efferent distributions and differing in the cognitive functions to which they contribute.

Repetitive sensory stimulation potentiates and recruits sensory-evoked cortical population activity.

Sensory experience and learning are thought to be associated with plasticity of neocortical circuits. Repetitive sensory stimulation can induce long-term potentiation (LTP) of cortical excitatory synapses in anesthetized mice; however, it is unclear if these phenomena are associated with sustained changes in activity during wakefulness. Here we used time-lapse, calcium imaging of layer (L) 2/3 neurons in the primary somatosensory cortex (S1), in awake male mice, to assess the effects of a bout of rhythmic whisker stimulation (RWS) at a frequency by which rodents sample objects. We found that RWS induced a 1h-increase in whisker-evoked L2/3 neuronal activity in most cells. This was not observed for whiskers functionally connected to distant cortical columns. We also found that RWS could heterogeneously recruit or suppress whisker-evoked activity in different populations of neurons. Vasoactive intestinal-peptide-expressing (VIP) interneurons, which promote plasticity through disinhibition of pyramidal neurons, were found to exclusively elevate activity during RWS. These findings indicate that cortical neurons' representation of sensory input can be modulated over hours through repetitive sensory stimulation, which may be gated by activation of disinhibitory circuits.Significance statement Sensory experience and learning are thought to be associated with the plasticity of cortical synaptic circuits. Here, we tested how repeated sensory stimulation changes subsequent sensory-evoked responses, using the mouse somatosensory cortex as a model. This cortical area processes, among others, sensory information from the whiskers. We found that rhythmic whisker stimulation potentiated excitatory neuronal activity for an hour, and identified a disinhibitory interneuron-mediated mechanism that could gate this plasticity. This work increases our understanding of sensory learning and experience-dependent plasticity processes by demonstrating that cortical representations of sensory input are dynamic and are effectively modulated by repeated sensory stimulation.

Electroacupuncture may alleviate inflammatory pain by downregulating the expression of P2Y14 receptor in the primary somatosensory cortex.

Increasing evidence indicated that purinergic signalling involved in electroacupuncture (EA)-induced analgesia. Whether purinergic P2Y14 receptor contributes to EA-mediated analgesia remains unclear. Here, we report that the expression of P2Y14 receptor in the hindlimb region of the primary somatosensory cortex (S1HL) was significantly upregulated on Complete Freund's Adjuvant (CFA)-induced pain model mice, while was downregulated after EA treatment (2Hz frequency, 1mA intensity, and 30min duration) at "Zusanli" (also named ST36 acupoint). EA-mediated analgesia could be reversed by injection of P2RY14 agonist uridine diphosphate glucose (UDPG) into the bilateral S1HL, while prolonged by injection of P2RY14 antagonist pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid (PPTN). It suggested that EA may alleviate inflammatory pain by downregulating the expression of P2RY14 in the S1HL.

Extracellular glutamate is not modulated by cannabinoid receptor activity.

Cannabinoid receptor activation has been proposed to trigger glutamate release from astrocytes located in cortical layer 2/3. Here, we measure the basal concentration of extracellular glutamate in layer 2/3 of mouse somatosensory cortex and find it to be 20-30 nM. We further examine the effect of cannabinoid receptor signaling on extracellular glutamate, and find no evidence for increased extracellular glutamate upon cannabinoid receptor agonist application.

Simultaneous 2-photon and 3-photon excitation with a red fluorescent protein-cyanine dye probe pair in the 1700-nm excitation window for deep in vivo neurovascular imaging

In vivo imaging of the neurovascular network is considered to be one of the most powerful approaches for understanding brain functionality. Nevertheless, simultaneously imaging the biological neural network and blood vessels in deep brain layers in a non-invasive manner remains to a major challenge due to the lack of appropriate labeling fluorescence probe pairs. Herein, we proposed a 2-photon and 3-photon fluorescence probe pair for neurovascular imaging. Specifically, the red fluorescence protein (RFP) with an absorption maximum of around 550 nm is used as a 3-photon excited probe to label neurons, and a cyanine derivative dye Q820@BSA has a NIR absorption maximum of 825 nm as a 2-photon excited probe to label the vasculature, enabling single wavelength excitation at 1650 nm for neurovascular imaging with high emission spectral separation (&gt;250 nm). In particular, the 2-photon action cross-section of Q820@BSA was found to be about 2-fold larger than that of indocyanine green (ICG), a commonly used red 2-photon fluorescence labeling agent, at the same excitation wavelength. Benefiting from the long wavelength advantage in reducing scattering in both 2 and 3-photon excitation of the fluorescence pairs, we demonstrated in vivo neurovascular imaging in intact adult mouse brains through white matter and deep into the hippocampus in the somatosensory cortex.

Chronic Aromatase Inhibition Attenuates Synaptic Plasticity in Ovariectomized Mice.

Brain-derived estrogen (17β-estradiol, E2) is a neuromodulator that plays important roles in neural plasticity and network excitability. Chronic inhibition of estrogen synthesis is used in adjuvant breast cancer therapy for estrogen receptor-positive tumors and may have been associated with cognitive and affective side effects. Here, we have developed a model of adjuvant therapy in female ovariectomized mice in which the E2 biosynthetic enzyme aromatase is inhibited by letrozole (1 mg/kg/day, i.p., for up to 3 weeks), Using two-photon longitudinal in vivo imaging in Thy1-GFP-M mice, we found that spine density in the apical dendrites of neocortical layer 5 pyramidal cells was unaffected by letrozole treatment but spine turnover was reduced. LTP in layer 4 to layer 2/3 synapses in the somatosensory cortex was also reduced in slices from letrozole-treated mice, showing deficits in structural and functional plasticity resulting from aromatase inhibition. Ovariectomized mice performed worse than intact control mice in the novel object recognition test but, surprisingly, letrozole treatment rescued this deficit.

Relationships of functional connectivity of motor cortex, primary somatosensory cortex, and cerebellum to balance performance in middle-aged and older adults

Connectivity of somatosensory cortex (S1) and cerebellum with the motor cortex (M1) is critical for balance control. While both S1-M1 and cerebellar-M1 connections are affected with aging, the implications of altered connectivity for balance control are not known. We investigated the relationship between S1-M1 and cerebellar-M1 connectivity and standing balance in middle-aged and older adults. Our secondary objective was to investigate how cognition affected the relationship between connectivity and balance. Our results show that greater S1-M1 and cerebellar-M1 connectivity was related to greater postural sway during standing. This may be indicative of an increase in functional recruitment of additional brain networks to maintain upright balance despite differences in network connectivity. Also, cognition moderated the relationship between S1-M1 connectivity and balance, such that those with lower cognition had a stronger relationship between connectivity and balance performance. It may be that individuals with poor cognition need increased recruitment of brain regions (compensation for cognitive declines) and in turn, higher wiring costs, which would be associated with increased functional connectivity.

Learning-induced remodelling of inhibitory synapses in the motor cortex.

Robust structural and functional plasticity occurs at excitatory synapses in the motor cortex in response to learning. It is well established that local spinogenesis and the subsequent maintenance of newly formed spines are crucial for motor learning. However, despite local synaptic inhibition being essential for shaping excitatory synaptic input, less is known about the structural rearrangement of inhibitory synapses following learning. In this study, we co-expressed the structural marker tdTomato and a mEmerald-tagged intrabody against gephyrin to visualize inhibitory synapses in layer 2/3 cortical neurons of wild-type CD1 mice. We found that a 1-day accelerated rotarod paradigm induced robust motor learning in male and female adult CD1 mice. Histological analyses revealed a significant increase in the surface area of gephyrin puncta in neurons within the motor cortex but not in the somatosensory cortex upon motor learning. Furthermore, this learning-induced reorganization of inhibitory synapses only occurred in dendritic shafts and not in the spines. These data suggest that learning induces experience-dependent remodelling of existing inhibitory synapses to fine-tune intrinsic plasticity and input-specific modulation of excitatory connections in the motor cortex.

Lack of habituation in somatosensory cortex but not in visual cortex of ALS patients

Objective Amyotrophic lateral sclerosis (ALS) is a multisystem degenerative disease with extra-motor components. In ALS, there is also hyperexcitability of extra-motor areas. Habituation is defined as ‘‘a response decrement” caused by repeated stimulations. Studies on evoked potential habituation can be conducted to detect cortical excitability. This study aimed to explore lack of habituation in non-motor cortical structures in ALS. Methods Twenty-one ALS patients and 14 controls were enrolled. Recordings were obtained in 3 and 10 consecutive blocks (each containing 100 responses) during right median somatosensory evoked potential (SEP) and bilateral visual evoked potential (VEP), respectively. “Habituation” and “lack of habituation” were defined as the amount of increase or decrease in the average N20 or N75-P100 amplitude of the last blocks compared to the first blocks, respectively. Comparative analyses were performed between patient and control groups, as well as the first and last block within groups. Results Paired sample t-test showed that in control group N20 peak amplitude of last blocks were significantly lower than first block values (p = 0.025) that indicate the physiological habituation as expected. On the other hand, there was not such a difference in ALS group (p = 0.239) which indicated lack of habituation. Conclusions Our study results suggest somatosensory hyperexcitability in line with cortical reorganization in ALS patients.

Pain-Discriminating Information Decoded From Spatiotemporal Patterns of Hemodynamic Responses Measured by fMRI in the Human Brain.

Functional magnetic resonance imaging (fMRI) has been widely used in studying the neural mechanisms of pain in the human brain, primarily focusing on where in the brain pain-elicited neural activities occur (i.e., the spatial distribution of pain-related brain activities). However, the temporal dynamics of pain-elicited hemodynamic responses (HDRs) measured by fMRI may also contain information specific to pain processing but have been largely neglected. Using high temporal resolution fMRI (TR = 0.8 s) data acquired from 62 healthy participants, in the present study we aimed to test whether pain-distinguishing information could be decoded from the spatial pattern of the temporal dynamics (i.e., the spatiotemporal pattern) of HDRs elicited by painful stimuli. Specifically, the peak latency and the response duration were used to characterize the temporal dynamics of HDRs to painful laser stimuli and non-painful electric stimuli, and then were compared between the two conditions (i.e., pain and no-pain) using a voxel-wise univariate analysis and a multivariate pattern analysis. Furthermore, we also tested whether the two temporal characteristics of pain-elicited HDRs and their spatial patterns were associated with pain-related behaviors. We found that the spatial patterns of HDR peak latency and response duration could successfully discriminate pain from no-pain. Interestingly, we also observed that the Pain Vigilance and Awareness Questionnaire (PVAQ) scores were correlated with the average response duration in bilateral insula and secondary somatosensory cortex (S2) and could also be predicted from the across-voxel spatial patterns of response durations in the middle cingulate cortex and middle frontal gyrus only during painful condition but not during non-painful condition. These findings indicate that the spatiotemporal pattern of pain-elicited HDRs may contain pain-specific information and highlight the importance of studying the neural mechanisms of pain by taking advantage of the high sensitivity of fMRI to both spatial and temporal information of brain responses.