Effects of incisor extraction on jaw and tongue motor representations within face sensorimotor cortex of adult rats

Loss of teeth is associated with changes in somatosensory inputs and altered patterns of mastication, but it is unclear whether tooth loss is associated with changes in motor representations within face sensorimotor cortex of rats. We used intracortical microstimulation (ICMS) and recordings of cortically evoked muscle electromyographic (EMG) activities to test whether changes occur in the ICMS‐defined motor representations of the left and right jaw muscles [masseter, anterior digastric (LAD, RAD)] and tongue muscle [genioglossus (GG)] within the cytoarchitectonically defined face primary motor cortex (face‐M1) and adjacent face primary somatosensory cortex (face‐S1) 1 week following extraction of the right mandibular incisor in anesthetized (ketamine‐HCl) adult male Sprague‐Dawley rats. Under local and general anesthesia, an “extraction” group (n = 8) received mucoalveolar bone surgery and extraction of the mandibular right incisor. A “sham‐extraction” group (n = 6) received surgery with no extraction. A “naive” group (n = 6) had neither surgery nor extraction. Data were compared by using mixed‐model repeated‐measures ANOVA. Dental extraction was associated with a significantly increased number of sites within face‐M1 and face‐S1 from which ICMS evoked RAD EMG activities, a lateral shift of the RAD and LAD centers of gravity within face‐M1, shorter onset latencies of ICMS‐evoked GG activities within face‐M1 and face‐S1, and an increased number of sites within face‐M1 from which ICMS simultaneously evoked RAD and GG activities. Our novel findings suggest that dental extraction may be associated with significant neuroplastic changes within the rat's face‐M1 and adjacent face‐S1 that may be related to the animal's ability to adapt to the altered oral state. J. Comp. Neurol. 518:1030–1045, 2010. © 2009 Wiley‐Liss, Inc.     

Neuroplastic changes in the sensorimotor cortex associated with orthodontic tooth movement in rats

Orthodontic tooth movement (OTM) causes transient pain and changes in the dental occlusion that may lead to altered somatosensory inputs and patterns of mastication. This study used intracortical microstimulation (ICMS) and electromyographic (EMG) recordings to test whether neuroplastic changes occur in the ICMS‐defined motor representations of left and right anterior digastric (LAD, RAD), masseter, buccinator, and genioglossus (GG) muscles within the rat's face primary motor cortex (face‐M1) and adjacent face primary somatosensory cortex (face‐S1) during OTM. Analyses included any changes in the number of ICMS sites representing these muscles and in the onset latencies of ICMS‐evoked responses in the muscles. Sprague–Dawley rats were divided into experimental (E), sham (S), and naive (N) groups; OTM was induced in the E group. Statistical analyses involved a mixed model repeated‐measures analysis of variance (MMRM ANOVA). OTM resulted in significant neuroplastic changes in the number of positive sites in the E group for LAD, RAD, and GG muscles in face‐M1 and face‐S1 at days 1, 7, and 28 of continuous orthodontic force application, and in the number of sites in face‐M1 from which ICMS could simultaneously evoke EMG responses in different combinations of LAD, RAD, and GG muscles. However, the onset latencies of ICMS‐evoked responses were not significantly different between groups or between face‐M1 and face‐S1. The neuroplastic changes documented in this study may reflect adaptive sensorimotor changes in response to the altered environment in the oral cavity induced by OTM. J. Comp. Neurol. 523:1548–1568, 2015. © 2015 Wiley Periodicals, Inc.     

Suppression of activity in the forelimb motor cortex temporarily enlarges forelimb representation in the homotopic cortex in adult rats

After forelimb motor cortex (FMC) damage, the unaffected homotopic motor cortex showed plastic changes. The present experiments were designed to clarify the electrophysiological nature of these interhemispheric effects. To this end, the output reorganization of the FMC was investigated after homotopic area activity was suppressed in adult rats. FMC output was compared after lidocaine-induced inactivation (L-group) or quinolinic acid-induced lesion (Q-group) of the contralateral homotopic cortex. In the Q-group of animals, FMC mapping was performed, respectively, 3 days (Q3D group) and 2 weeks (Q2W group) after cortical lesion. In each animal, FMC output was assessed by mapping movements induced by intracortical microstimulation (ICMS) in both hemispheres (hemisphere ipsilateral and contralateral to injections). The findings demonstrated that in the L-group, the size of forelimb representation was 42.2% higher than in the control group ( P  < 0.0001). The percentage of dual forelimb–vibrissa movement sites significantly increased over the controls ( P  < 0.0005). The dual-movement sites occupied a strip of the map along the rostrocaudal border between the forelimb and vibrissa representations. This form of interhemispheric diaschisis had completely reversed, with the recovery of the baseline map, 3 days after the lesion in the contralateral FMC. This restored forelimb map showed no ICMS-induced changes 2 weeks after the lesion in the contralateral FMC. The present results suggest that the FMCs in the two hemispheres interact continuously through predominantly inhibitory influences that preserve the forelimb representation and the border vs. vibrissa representation.     

Long‐term neuroplasticity of the face primary motor cortex and adjacent somatosensory cortex induced by tooth loss can be reversed following dental implant replacement in rats

Tooth loss is common, and exploring the neuroplastic capacity of the face primary motor cortex (face‐M1) and adjacent primary somatosensory cortex (face‐S1) is crucial for understanding how subjects adapt to tooth loss and their prosthetic replacement. The aim was to test if functional reorganization of jaw and tongue motor representations in the rat face‐M1 and face‐S1 occurs following tooth extraction, and if subsequent dental implant placement can reverse this neuroplasticity. Rats (n = 22) had the right maxillary molar teeth extracted under local and general anesthesia. One month later, seven rats had dental implant placement into healed extraction sites. Naive rats (n = 8) received no surgical treatment. Intracortical microstimulation (ICMS) and recording of evoked jaw and tongue electromyographic responses were used to define jaw and tongue motor representations at 1 month (n = 8) or 2 months (n = 7) postextraction, 1 month postimplant placement, and at 1–2 months in naive rats. There were no significant differences across study groups in the onset latencies of the ICMS‐evoked responses (P > 0.05), but in comparison with naive rats, tooth extraction caused a significant (P < 0.05) and sustained (1–2 months) decreased number of ICMS‐defined jaw and tongue sites within face‐M1 and ‐S1, and increased thresholds of ICMS‐evoked responses in these sites. Furthermore, dental implant placement reversed the extraction‐induced changes in face‐S1, and in face‐M1 the number of jaw sites even increased as compared to naive rats. These novel findings suggest that face‐M1 and adjacent face‐S1 may play a role in adaptive mechanisms related to tooth loss and their replacement with dental implants. J. Comp. Neurol. 523:2372–2389, 2015. © 2015 Wiley Periodicals, Inc.     

Plastic changes in the vibrissa motor cortex in adult rats after output suppression in the homotopic cortex

After motor cortex damage, the unaffected homotopic cortex shows changes in motor output. The present experiments were designed to clarify the nature of these interhemispheric effects. We investigate the vibrissa motor cortex (VMC) output after activity suppression of the homotopic area in adult rats. Comparison was made of VMC output after lidocaine inactivation (L-group) or quinolinic acid lesion (Q-group) of the homotopic cortex. In the Q-group, VMC mapping was performed 3 days (Q3Ds group), 2 weeks (Q2Ws group) and 4 weeks (Q4Ws group) after cortical lesion. In each animal, VMC output was assessed by mapping movements induced by intracortical microstimulation (ICMS) in both hemispheres (hemisphere ipsilateral and contralateral to injections). Findings demonstrated that, in the L-group, the size of vibrissal representation was 39.5% smaller and thresholds required to evoke vibrissa movement were 46.3% higher than those in the Control group. There was an increase in the percentage of ineffective sites within the medial part of the VMC and an increase in the percentage of forelimb sites within the lateral part. Both the Q3Ds group and the L-group led to a similar VMC reorganization (Q3Ds vs. L-group, P > 0.05). In the Q2Ws group the VMC representation showed improvement in size (83.4% recovery compared with controls). The VMC showed recovery to normal output at 4 weeks after lesion (Control vs. Q4Ws group, P > 0.05). These results suggest that the VMC of the two hemispheres continuously interact through excitatory influences, preserving the normal output and inhibitory influences defining the border with the forelimb representation.     

Stimulus intensity determines experience‐dependent modifications in neocortical neuron firing rates

Although subthreshold inputs of neocortical sensory neurons are broadly tuned, the spiking output is more restricted. These subthreshold inputs provide a substrate for stimulus intensity‐dependent changes their spiking output, as well as for experience‐dependent plasticity to alter firing properties. Here we investigated how different stimulus intensities modified the firing output of individual neurons in layer 2/3 of the mouse barrel cortex. Decreasing stimulus intensity over a 30‐fold range lowered the firing rates evoked by principal whisker stimulation and reduced the overall size of the responding ensemble in whisker‐undeprived animals. We then examined how these responses were changed after single‐whisker experience (SWE). After 7 days of SWE, the mean magnitude of response to spared whisker stimulation at the highest stimulus intensity was not altered. However, lower‐intensity whisker stimulation revealed a more than 10‐fold increase in mean firing output compared with control animals. Also, under control conditions, only ~15% of neurons showed any firing at low stimulus intensity, compared with more than 70% of neurons after SWE. However, response changes measured in the immediately surrounding representations were detected only for the highest stimulus intensity. Overall, these data showed that the measurement of experience‐dependent changes in the spike output of neocortical neurons was highly dependent upon stimulus intensity.     

Overlapping representations of the neck and whiskers in the rat motor cortex revealed by mapping at different anaesthetic depths

The primary motor cortex of mammals has an orderly representation of different body parts. Within the representation of each body part the organization is more complex, with groups of neurons representing movements of a muscle or a group of muscles. In rats, uncertainties continue to exist regarding organization of the primary motor cortex in the whisker and the neck region. Using intracortical microstimulation (ICMS) we show that movements evoked in the whisker and the neck region of the rat motor cortex are highly sensitive to the depth of anaesthesia. At light anaesthetic depth, whisker movements are readily evoked from a large medial region of the motor cortex. Lateral to this is a small region where movements of the neck are evoked. However, in animals under deep anaesthesia whisker movements cannot be evoked. Instead, neck movements are evoked from this region. The neck movement region thus becomes greatly expanded. An analysis of the threshold currents required to evoke movements at different anaesthetic depths reveals that the caudal portion of the whisker region has dual representation, of both the whisker and the neck movements. The results also underline the importance of carefully controlling the depth of anaesthesia during ICMS experiments.     

Increased occlusal vertical dimension induces cortical plasticity in the rat face primary motor cortex

Previous studies have demonstrated that functional plasticity in the primary motor cortex (M1) is related to motor-skill learning and changes in the environment. Increased occlusal vertical dimension (iOVD) may modulate mastication, such as in the masticatory cycle, and the firing properties of jaw-muscle spindles. However, little is known about the changes in motor representation within the face primary motor cortex (face-M1) after iOVD. The purpose of the present study was to determine the effect of iOVD on the face-M1 using intracortical microstimulation (ICMS). In an iOVD group, the maxillary molars were built-up by 2 mm with acrylic. The electromyographic (EMG) activities from the left (LAD) and right (RAD) anterior digastric (AD), masseter and genioglossus (GG) muscles elicited by ICMS within the right face-M1 were recorded 1, 2 and 8 weeks after iOVD. IOVD was associated with a significant increase in the number of sites within the face-M1 from which ICMS evoked LAD and/or GG EMG activities, as well as a lateral shift in the center of gravity of the RAD and LAD muscles at 1 and 2 weeks, but not at 8 weeks. These findings suggest that a time-dependent neuroplastic change within the rat face-M1 occurs in association with iOVD. This may be related to the animal's ability to adapt to a change in the oral environment.     

Temporal refinement of sensory‐evoked activity across layers in developing mouse barrel cortex

Rhythmic whisking behavior in rodents fully develops during a critical period about 2 weeks after birth, in parallel with the maturation of other sensory modalities and the onset of exploratory locomotion. How whisker‐related sensory processing develops during this period in the primary somatosensory cortex (S1) remains poorly understood. Here, we characterized neuronal activity evoked by single‐ or dual‐whisker stimulation patterns in developing S1, before, during and after the occurrence of active whisking. Employing multi‐electrode recordings in all layers of barrel cortex in urethane‐anesthetized mice, we find layer‐specific changes in multi‐unit activity for principal and neighboring barrel columns. While whisker stimulation evoked similar early responses (0–50 ms post‐stimulus) across development, the late response (50–150 ms post‐stimulus) decreased in all layers with age. Furthermore, peak onset times and the duration of the late response decreased in all layers across age groups. Responses to paired‐pulse stimulation showed increases in spiking precision and in paired‐pulse ratios in all cortical layers during development. Sequential activation of two neighboring whiskers with varying stimulus intervals evoked distinct response profiles in the activated barrel columns, depending on the direction and temporal separation of the stimuli. In conclusion, our findings indicate that the temporal sharpening of sensory‐evoked activity coincides with the onset of active whisking.     

Frontal eye field efferents in the macaque monkey: II. Topography of terminal fields in midbrain and pons

Frontal eye field (FEF) projections to the midbrain and pons were studied in nine macaque monkeys that were used to study FEF projections to the striatum and thalamus (Stanton et al.: J. Comp. Neurol. 271:473-492, '88). Injections of tritiated amino acids or WGA-HRP were made into FEF cortical locations where low-level microstimulation (less than or equal to 50 microA) elicited saccadic eye movements, and anterograde axonal labeling was mapped. The injections were made into the anterior bank of the arcuate sulcus from dorsomedial sites where large saccades were evoked (lFEF) to ventrolateral sites where small saccades were evoked (sFEF). The largest terminal fields of FEF fibers were located in the ipsilateral superior colliculus (SC). Projections to SC were topographically organized: lFEF sites projected to intermediate and deep layers of caudal SC, sFEF sites projected to intermediate and superficial layers of rostral SC, and FEF sites between these extremes projected to intermediate locations in SC. Patches of terminal labeling were located ipsilaterally in the lateral mesencephalic reticular formation near the parabigeminal nucleus and the ventrolateral pontine reticular formation. These patches were larger from lFEF injections. Small, dense terminal patches were seen in the ipsilateral pontine gray, mostly along the medial and dorsal borders of these nuclei but occasionally in central and dorsolateral regions. Patches of label like those in the pontine nuclei were located ipsilaterally in the reticularis tegmenti pontis nucleus in lFEF cases and bilaterally in sFEF cases. Small terminal patches were found in the nucleus of Darkschewitsch and dorsal and medial parts of the parvicellular red nucleus in most FEF cases. In the pretectal region, labeled terminal patches were consistently found in the nucleus limitans of the posterior thalamus, but we could not determine if label in the nucleus of the pretectal area and dorsal parts of the nucleus of the posterior commissure marked axon terminals or fibers of passage. We found small, lightly labeled terminal patches in the pontine raphe between the rootlets of the abducens nerve (three cases) or in the adjacent paramedian pontine reticular formation (one case). Omnipauser cells in this region are important in initiating saccades. In one sFEF case, very small patches of label were located in the supragenual nuclei anterior to the abducens nuclei and in the ipsilateral nucleus prepositus hypoglossi posterior to the abducens nucleus. Presaccadic burster neurons in the periabducens region are known to fire immediately before horizontal saccades.(ABSTRACT TRUNCATED AT 400 WORDS)     

Involvement of spinal α2‐adrenoceptors in prolonged modulation of hind limb withdrawal reflexes following acute noxious stimulation in the anaesthetized rabbit

The role of spinal α ₂‐adrenoceptors in mediating long‐lasting modulation of hind limb withdrawal reflexes following acute noxious chemical stimulation of distant heterotopic and local homotopic locations has been investigated in pentobarbitone‐anaesthetized rabbits. Reflexes evoked in the ankle extensor muscle medial gastrocnemius (MG) by electrical stimulation of the ipsilateral heel, and reflexes elicited in the ankle flexor tibialis anterior and the knee flexor semitendinosus by stimulation at the base of the ipsilateral toes, could be inhibited for over 1 h after mustard oil (20%) was applied to either the snout or into the contralateral MG. The heel–MG response was also inhibited after applying mustard oil across the plantar metatarsophalangeal joints of the ipsilateral foot, whereas this homotopic stimulus facilitated both flexor responses. Mustard oil also caused a significant pressor effect when applied to any of the three test sites. The selective α₂‐adrenoceptor antagonist, RX 821002 (100–300 μg, intrathecally), had no effect on reflexes per se, but did cause a decrease in mean arterial blood pressure. In the presence of the α₂‐blocker, inhibitory and facilitatory effects of mustard oil on reflexes were completely abolished. These data imply that long‐lasting inhibition of spinal reflexes following acute noxious stimulation of distant locations involves activation of supraspinal noradrenergic pathways, the effects of which are dependent on an intact α₂‐adrenoceptor system at the spinal level. These pathways and receptors also appear to be involved in facilitation (sensitization) as well as inhibition of reflexes following a noxious stimulus applied to the same limb.     

Effects of stimulus pulse rate on somatosensory adaptation in the human cortex

BackgroundIntracortical microstimulation (ICMS) of the somatosensory cortex can restore sensation to people with neurological diseases. However, many aspects of ICMS are poorly understood, including the effect of stimulation on percept intensity over time.ObjectiveHere, we evaluate how tactile percepts evoked by ICMS in the somatosensory cortex of a human participant adapt over time.MethodsWe delivered continuous and intermittent ICMS to the somatosensory cortex and assessed the reported intensity of tactile percepts over time in a human participant. Experiments were conducted over approximately one year and linear mixed effects models were used to assess significance.ResultsContinuous stimulation at high frequencies led to rapid decreases in intensity, while low frequency stimulation maintained percept intensity for longer periods. Burst-modulated stimulation extended the time before the intensity began to decrease, but all protocols ultimately resulted in complete sensation loss within 1 min. Intermittent stimulation paradigms with several seconds between stimulus trains evoked intermittent percepts and also led to decreases in intensity on many electrodes, but never resulted in extinction of the sensation after over 3 min of stimulation. Longer breaks between each pulse train resulted in some recovery in the intensity of the stimulus-evoked percepts. For several electrodes, intermittent stimulation had almost no effect on the perceived intensity.ConclusionsIntermittent ICMS paradigms were more effective at maintaining percepts. Given that transient neural activity dominates the response in somatosensory cortex during mechanical contact onsets and offsets, providing brief stimulation trains at these times may more closely represent natural cortical activity and have the additional benefit of prolonging the ability to evoke sensations over longer time periods.     

Neonatal frontal lesion in unilateral hemisphere enhances the development of the intact higher motor cortex in the rat

The influence of the neonatal frontal lesion in unilateral cerebral hemisphere for the organization of intact forelimb motor cortex in the rat was investigated by intracortical microstimulation (ICMS). The relative size of the rostral forelimb area (RFL) compared to the caudal forelimb area (CFL) in the ipsilateral motor field of lesioned rat was significantly greater than those of contralateral in normal and lesioned rats. The optimal sites of the stimulation for ipsilateral responses in lesioned rats were located in the RFL, while the optimal sites for contralateral were located caudolaterally, as for those of normal rats. At the ipsilateral optimal sites within the RFL in the lesioned animals, the threshold for the ipsilateral responses was lower than that for the contralateral responses. That is, the intact hemisphere of the animal preferentially developed the RFL rather than the CFL, for the ipsilateral forelimb. This may suggest a critical role for the RFL in individual forelimb motor control within the normal hemisphere.     

Experience‐dependent increase in spine calcium evoked by backpropagating action potentials in layer 2/3 pyramidal neurons in rat somatosensory cortex

In spines on basal dendrites of layer 2/3 pyramidal neurons in somatosensory barrel cortex, calcium transients evoked by back‐propagating action potentials (bAPs) were investigated (i) along the length of the basal dendrite, (ii) with postnatal development and (iii) with sensory deprivation during postnatal development. Layer 2/3 pyramidal neurons were investigated at three different ages. At all ages [postnatal day (P)8, P14, P21] the bAP‐evoked calcium transient amplitude increased with distance from the soma with a peak at around 50 μm, followed by a gradual decline in amplitude. The effect of sensory deprivation on the bAP‐evoked calcium was investigated using two different protocols. When all whiskers on one side of the rat snout were trimmed daily from P8 to P20‐24 there was no difference in the bAP‐evoked calcium transient between cells in the contralateral hemisphere, lacking sensory input from the whisker, and cells in the ipsilateral barrel cortex, with intact whisker activation. When, however, only the D‐row whiskers on one side were trimmed the distribution of bAP‐evoked calcium transients in spines was shifted towards larger amplitudes in cells located in the deprived D‐column. In conclusion, (i) the bAP‐evoked calcium transient gradient along the dendrite length is established at P8, (ii) the calcium transient increases in amplitude with age and (iii) this increase is enhanced in layer 2/3 pyramidal neurons located in a sensory‐deprived barrel column that is bordered by non‐deprived barrel columns.     

Complete protection from impending stroke following permanent middle cerebral artery occlusion in awake,behaving rats

Using a rodent model of ischemic stroke [permanent middle cerebral artery occlusion (pMCAO)], our laboratory has previously demonstrated that sensory‐evoked cortical activation via mechanical single whisker stimulation treatment delivered under an anesthetized condition within 2 h of ischemic onset confers complete protection from impending infarct. There is a limited time window for this protection; rats that received the identical treatment at 3 h following ischemic onset lost neuronal function and sustained a substantial infarct. Rats in these studies, however, were anesthetized with sodium pentobarbital or isoflurane, whereas most human stroke patients are typically awake. To optimize our animal model, the present study examined, using functional imaging, histological, and behavioral analysis, whether self‐induced sensorimotor stimulation is also protective in unrestrained, behaving rats that actively explore an enriched environment. Rats were revived from anesthesia either immediately or at 3 h after pMCAO, at which point they were allowed to freely explore an enriched environment. Rats that explored immediately after ischemic onset maintained normal cortical function and did not sustain infarct, even when their whiskers were clipped. Rats that were revived at 3 h post‐pMCAO exhibited eliminated cortical function and sustained cortical infarct. Further, the data suggested that the level of individual active exploration could influence the outcome. Thus, early activation of the ischemic cortical area via unrestrained exploration resulted in protection from ischemic infarct, whereas late activation resulted in infarct, irrespective of the level of arousal or whisker‐specific stimulation.     

Astrocyte‐restricted disruption of connexin‐43 impairs neuronal plasticity in mouse barrel cortex

There is intensive gap‐junctional coupling between glial processes, but their significance in sensory functions remains unknown. Connexin‐43 (Cx43), a major component of astrocytic gap‐junction channels, is abundantly expressed in astrocytes. To investigate the role of Cx43‐mediated gap junctions between astrocytes in sensory functions, we generated Cx43 knockout (KO) mice with a mouse line carrying loxP sites flanking exon 2 of the Cx43 gene and the transgenic line expressing Cre recombinase under control of the glial fibrillary acidic protein promoter, which exhibited a significant loss of Cx43 in astrocytes in the barrel cortex. Although Cx43 expression between the astrocytes measured by immunohistochemistry was virtually abolished in Cx43 KO mice, they had normal architecture in the barrel cortex but the intensity of cytochrome oxide histochemistry decreased significantly. In vivo electrophysiological analysis revealed that the long‐term potentiation of the vibrissal evoked responses in the barrel cortex evoked by high‐frequency rhythmic vibrissal stimuli (100 Hz, 1 s) was abolished in Cx43 KO mice. Current source density analysis also revealed that astrocytic Cx43 was important to the flow of excitation within the laminar connections in barrel cortex. Behavioral tests showed that the ability of Cx43 KO mice to sense the environment with their whiskers decreased. Even so, the jump‐stand experiment showed that they could still discriminate rough from smooth surfaces. Our findings suggest that Cx43‐mediated gap‐junctional coupling between astrocytes is important in the neuron–glia interactions required for whisker‐related sensory functions and plasticity.     

Descending modulation of visceral nociceptive transmission from the locus coeruleus/subcoeruleus in the rat

The purpose of the present investigation was to examine whether electrical stimulation in the locus coeruleus/subcoeruleus (LC/SC) could modulate visceral pain evoked by noxious colorectal distention (CRD). Experiments were performed on 40 pentobarbital anesthetized male Sprague–Dawley rats. Extracellular potentials of single L₆–S₂ spinal neuron were recorded with a carbon filament electrode. CRD (80 mmHg) was produced by inflating a balloon inside the descending colon and rectum. Electrical stimulation of the LC/SC (30, 50 and 70 μA, 100 Hz, 0.1 ms pulses) was delivered either ipsilaterally or contralaterally. Results showed that for 42/62 (68%) short-latency abrupt (SL-A) neurons, all of the short-latency sustained (SL-S) and long-latency (LL) neurons, LC/SC stimulation produced intensity-dependent attenuation of the CRD-evoked discharge. For 10/62 (16%) SL-A neurons, 6/8 (75%) inhibited (INHIB) neurons LC/SC stimulation increased the evoked discharge, for 10/62 (16%) SL-A neurons and 2/8 (25%) INHIB neurons, the evoked discharges were unaffected by the LC/SC stimulation. LC/SC stimulation also had different effects on the spontaneous activities of these neurons. The effects of LC/SC stimulation were the same both ipsilaterally and contralaterally either for the evoked discharges or for spontaneous activities. Following LC/SC lesions, LC/SC stimulation did not inhibit nociceptive responses, whereas inhibitory effects were observed by stimulation of the intact LC/SC contralateral to the recording site. These data suggest that the transmission of visceral pain was under the control of the centrifugal pathways from the LC/SC.     

Wireless pH‐motility capsule for colonic transit: prospective comparison with radiopaque markers in chronic constipation

Background Colon transit (CT) measurements are used in the management of significant constipation. The radiopaque marker (ROM) method provides limited information. Methods We proposed to validate wireless motility capsule (WMC), that measures pH, pressure and temperature, to ROM measurement of CT in patients with symptomatic constipation evaluated at multiple centers. Of 208 patients recruited, 158 eligible patients underwent simultaneous measurement of colonic transit time (CTT) using ROM (Metcalf method, cut off for delay >67 h), and WMC (cutoff for delay >59 h). The study was designed to demonstrate substantial equivalence, defined as diagnostic agreement >65% for patients who had normal or delayed ROM transit. Key Results Fifty‐nine of 157 patients had delayed ROM CT. Transit results by the two methods differed: ROM median 55.0 h [IQR 31.0–85.0] and WMC (43.5 h [21.7–70.3], P < 0.001. The positive percent agreement between WMC and ROM for delayed transit was ～80%; positive agreement in 47 by WMC/59 by ROM or 0.796 (95% CI = 0.67–0.98); agreement vs null hypothesis (65%) P = 0.01. The negative percent agreement (normal transit) was ～91%: 89 by WMC/98 by ROM or 0.908 (95% CI = 0.83–0.96); agreement vs null hypothesis (65%), P = 0.00001. Overall device agreement was 87%. There were significant correlations (P < 0.001) between ROM and WMC transit (CTT [r = 0.707] and between ROM and combined small and large bowel transit [r = 0.704]). There were no significant adverse events. Conclusions & Inferences The 87% overall agreement (positive and negative) validates WMC relative to ROM in differentiating slow vs normal CT in a multicenter clinical study of constipation.     

The caudal subnucleus caudalis (medullary dorsal horn) acts as an interneuronal relay site in craniofacial nociceptive reflex activity

We have recently documented that bilateral increases in electromyographic (EMG) activity of digastric (DIG) and masseter (MASS) muscles can be evoked by injection into the rat's temporomandibular joint (TMJ) region of the small-fiber excitant and inflammatory irritant mustard oil and that this increased jaw muscle activity can be significantly reduced by extensive lesions of the trigeminal subnucleus caudalis (Vc). This study was carried out in 34 anaesthetized rats to test whether neurones in the caudal Vc are indeed of critical importance in these craniofacial nociceptive reflexes. The effects of micro-injection of the cellular neurotoxic chemical ibotenic acid in histologically confirmed sites of the caudal brainstem on the mustard oil-evoked EMG activity of ipsilateral and contralateral DIG and MASS were tested. Ibotenic acid micro-injection in the left caudal Vc significantly reduced the increased EMG activity of all four muscles evoked by mustard oil injection into the left TMJ region whereas mustard oil injection into the right TMJ region in these same rats still readily evoked an increase in EMG activity. In other groups of rats, ibotenic acid micro-injection into the rostral Vc, the C2 segment or the reticular formation at the obex level did not produce any significant reduction in the reflexly evoked EMG activity. These findings suggest that neurones in the caudal Vc may be critical elements in neural pathways underlying the reflex responses evoked in jaw muscles by noxious stimulation of the TMJ region.     

Detection of convulsive seizures using surface electromyography

Bilateral (generalized) tonic–clonic seizures (TCS) increase the risk of sudden unexpected death in epilepsy (SUDEP), especially when patients are unattended. In sleep, TCS often remain unnoticed, which can result in suboptimal treatment decisions. There is a need for automated detection of these major epileptic seizures, using wearable devices. Quantitative surface electromyography (EMG) changes are specific for TCS and characterized by a dynamic evolution of low‐ and high‐frequency signal components. Algorithms targeting increase in high‐frequency EMG signals constitute biomarkers of TCS; they can be used both for seizure detection and for differentiating TCS from convulsive nonepileptic seizures. Two large‐scale, blinded, prospective studies demonstrated the accuracy of wearable EMG devices for detecting TCS with high sensitivity (76%‐100%). The rate of false alarms (0.7‐2.5/24 h) needs further improvement. This article summarizes the pathophysiology of muscle activation during convulsive seizures and reviews the published evidence on the accuracy of EMG‐based seizure detection.