Trains Of Electrical Stimuli Research Articles

Comparison of Motor Evoked Potentials Neuromonitoring Following Pre- and Postoperative Transcranial Magnetic Stimulation and Intraoperative Electrical Stimulation in Patients Undergoing Surgical Correction of Idiopathic Scoliosis.

The relationships between the results of pre- and intraoperative motor evoked potential recordings during neuromonitoring and whether idiopathic scoliosis (IS) surgical correction improves the spinal efferent transmission have not been specified in detail. This study aims to compare the results of surface-recorded electromyography (EMG), electroneurography (ENG, M, and F-waves), and especially motor evoked potential (MEP) recordings from tibialis anterior muscle (TA) bilaterally in 353 girls with right idiopathic scoliosis (types 1-3 according to Lenke classification). It has not yet been documented whether the results of MEP recordings induced by transcranial single magnetic stimulus (TMS, pre- and postoperatively) and trains of electrical stimuli (TES; intraoperatively in T0-before surgery, T1-after pedicle screws implantation, and T2-after scoliosis curvature distraction and derotation following two-rod implantation) can be compared for diagnostic verification of the improvement of spinal cord neural transmission. We attempted to determine whether the constant level of optimal anesthesia during certain surgical steps of scoliosis treatment affects the parameters of MEPs recorded during neuromonitoring procedures. No neurological deficits have been observed postoperatively. The values of amplitudes but not latencies in MEP recordings evoked with TMS in IS patients compared before and after surgery indicated a slight improvement in efferent neural transmission. The results of all neurophysiological studies in IS patients were significantly asymmetrical and recorded worse on the concave side, suggesting greater neurological motor deficits at p = 0.04. The surgeries brought significant improvement (p = 0.04) in the parameters of amplitudes of sEMG recordings; however, the consequences of abnormalities in the activity of TA motor units were still reflected. ENG study results showed the symptoms of the axonal-type injury in peroneal motor fibers improving only on the concave side at p = 0.04, in parallel with F-wave parameters, which suggests that derotation and distraction might result in restoring the proper relations of the lumbar ventral roots in the spinal central canal, resembling their decompression. There were no significant differences detected in the amplitudes or latencies of MEPs induced with TMS or TES when comparing the parameters recorded preoperatively and intraoperatively in T0. The amplitudes of TES-evoked MEPs increased gradually at p = 0.04 in the subsequent periods (T1 and T2) of observation. A reduction in MEP latency at p = 0.05 was observed only at the end of the IS surgery. Studies on the possible connections between the level of anesthesia fluctuations and the required TMS stimulus strength, as well as the MEP amplitude changes measured in T0-T2, revealed a lack of relationships. These might not be the factors influencing the efferent transmission in spinal pathways beside the surgical procedures. Pre- (TMS-evoked) and intraoperative (TES-evoked) recordings are reliable for evaluating the patient's neurological status before and during surgical scoliosis correction procedures. An increase in MEP amplitude parameters recorded on both sides after scoliosis surgery proves the immediate improvement of the total efferent spinal cord transmission. Considering comparative pre- and postoperative sEMG and ENG recordings, it can be concluded that surgeries might directly result in additional lumbar ventral root decompression. We can conclude that MEP parameter changes are determined by the surgery procedures during neuromonitoring, not the anesthesia conditions if they are kept stable, which influences a decrease in the number of false-positive neuromonitoring warnings.

Pudendal mapping of S1 rootlets in a functional posterior rhizotomy: when an S1 posterior root shows a high pudendal dorsal action potential-a technical note.

The standard level for lesioning in a functional posterior rhizotomy (FPR) ranges from L2 to S1/S2. Lesioning of the S1 and S2 rootlets strongly correlates with a reduction in ankle spasticity. In the Japanese population, the S2 root often shows the highest dorsal root action potentials (DAPs) in the afferent fibers of the pudendal nerve and is not lesioned to preserve postoperative urinary function. Thus, cutting of the S1 root plays a key role in reducing ankle spasticity in FPR. However, on rare occasions, even an S1 root may show high DAP in the afferent fibers of the pudendal nerve. The present, brief, technical note aimed to describe how an S1 root with a relatively high DAP in the afferent fibers of the pudendal nerve may be handed. In the procedure, the S1 root is divided into several rootlets, and each rootlet is tested for the pudendal mapping. A train of electrical stimuli is delivered to each rootlet in the standard FPR. If electromyography (EMG) findings after electrical stimulation are highly abnormal while the pudendal mapping demonstrates no or a relatively low DAPs, the rootlet is cut. In contrast, even if the rootlet shows highly abnormal EMG findings, it is preserved if mapping demonstrates a relatively high DAP. The S1 pudendal mapping is combined with EMG findings to achieve satisfactory reduction in ankle spasticity while preserving urological function.

Impaired Replenishment of Cortico-Striatal Synaptic Glutamate in Huntington's Disease Mouse Model.

Huntington's disease (HD) is an inherited neurodegenerative disorder caused by expansion of CAG repeats in the Huntingtin gene (HTT). Studies suggest cortical to striatal (C-S) projections, which regulate movement and provide cell survival signals to SPNs, are altered in the pre-manifest and early symptomatic stages of HD. But whether and how presynaptic cortical terminals are affected in HD is not well explored. Test size and replenishment of readily releasable pool (RRP), and assess glutamate refill of C-S synapses in HD models. Immunocytochemistry was applied in C-S co-cultures generated from FVB/N (WT: wildtype) mice and YAC128, an HD mouse model expressing human HTT with 128 CAG repeats on the FVB/N background; Whole-cell patch clamp recordings from striatal neurons were performed both in cultures, with or without osmotic stimuli, and in acute brain slices from 6-month-old early symptomatic YAC128 mice and WT following prolonged trains of electrical stimuli in corpus callosum. We found no change in the average size or vesicle replenishment rate of RRP in C-S synapses of YAC128, compared with WT, cultures at day in vitro 21, a time when immunocytochemistry showed comparable neuronal survival between the two genotypes. However, YAC128 C-S synapses showed a slowed rate of recovery of glutamate release in co-cultures as well as in acute brain slices. Mutant HTT expression impairs glutamate refill but not RRP size or replenishment in C-S synapses. This work provides a foundation for examining the contribution of deficits in presynaptic cortical terminals on HD progression.

Endogenous Glutamate Excites Myenteric Calbindin Neurons by Activating Group I Metabotropic Glutamate Receptors in the Mouse Colon.

Glutamate is a classic excitatory neurotransmitter in the central nervous system (CNS), but despite several studies reporting the expression of glutamate together with its various receptors and transporters within the enteric nervous system (ENS), its role in the gut remains elusive. In this study, we characterized the expression of the vesicular glutamate transporter, vGluT2, and examined the function of glutamate in the myenteric plexus of the distal colon by employing calcium (Ca2+)-imaging on Wnt1-Cre; R26R-GCaMP3 mice which express a genetically encoded fluorescent Ca2+ indicator in all enteric neurons and glia. Most vGluT2 labeled varicosities contained the synaptic vesicle release protein, synaptophysin, but not vesicular acetylcholine transporter, vAChT, which labels vesicles containing acetylcholine, the primary excitatory neurotransmitter in the ENS. The somata of all calbindin (calb) immunoreactive neurons examined received close contacts from vGluT2 varicosities, which were more numerous than those contacting nitrergic neurons. Exogenous application of L-glutamic acid (L-Glu) and N-methyl-D-aspartate (NMDA) transiently increased the intracellular Ca2+ concentration [Ca2+]i in about 25% of myenteric neurons. Most L-Glu responsive neurons were calb immunoreactive. Blockade of NMDA receptors with APV significantly reduced the number of neurons responsive to L-Glu and NMDA, thus showing functional expression of NMDA receptors on enteric neurons. However, APV resistant responses to L-Glu and NMDA suggest that other glutamate receptors were present. APV did not affect [Ca2+]i transients evoked by electrical stimulation of interganglionic nerve fiber tracts, which suggests that NMDA receptors are not involved in synaptic transmission. The group I metabotropic glutamate receptor (mGluR) antagonist, PHCCC, significantly reduced the amplitude of [Ca2+]i transients evoked by a 20 pulse (20 Hz) train of electrical stimuli in L-Glu responsive neurons. This stimulus is known to induce slow synaptic depolarizations. Further, some neurons that had PHCCC sensitive [Ca2+]i transients were calb immunoreactive and received vGluT2 varicosities. Overall, we conclude that electrically evoked release of endogenous glutamate mediates slow synaptic transmission via activation of group I mGluRs expressed by myenteric neurons, particularly those immunoreactive for calb.

Sodium-potassium pump assessment by submaximal electrical nerve stimulation

ObjectiveSodium-potassium pump dysfunction in peripheral nerve is usually assessed by determining axonal hyperpolarization following maximal voluntary contraction (MVC) or maximal electrical nerve stimulation. As MVC may be unreliable and maximal electrical stimulation too painful, we assessed if hyperpolarization can also be induced by submaximal electrical nerve stimulation. MethodsIn 8 healthy volunteers different submaximal electrical stimulus trains were given to the median nerve at the wrist, followed by 5 min assessment of thresholds for compound muscle action potentials of 20%, 40% or 60% of maximal. ResultsThreshold increase after submaximal electrical nerve stimulation was most prominent after an 8 Hz train of at least 5 min duration evoking submaximal CMAPs of 60%. It induced minimal discomfort and was not painful. Threshold increase after MVC was not significantly higher than this stimulus train. ConclusionsSubmaximal electrical stimulation evokes activity dependent hyperpolarization in healthy test subjects without causing significant discomfort. SignificanceSodium-potassium pump function may be assessed using submaximal electrical stimulation.

Cortical stimulation relieves parkinsonian pathological activity invitro.

Previously, we have shown that chemical excitatory drives such as N-methyl-d-aspartate (NMDA) are capable of activating the striatal microcircuit exhibiting neuronal ensembles that alternate their activity producing temporal sequences. One aim of this work was to demonstrate whether similar activity could be evoked by delivering cortical stimulation. Dynamic calcium imaging allowed us to follow the activity of dozens of neurons with single-cell resolution in mus musculus brain slices. A train of electrical stimuli in the cortex evoked network activity similar to the one induced by bath application of NMDA. Previously, we have also shown that the dopamine-depleted striatal microcircuit increases its spontaneous activity generating dominant recurrent ensembles that interrupt the temporal sequences found in control microcircuits. This activity correlates with parkinsonian pathological activity. Several cortical stimulation protocols such as transcranial magnetic stimulation reduce motor signs of Parkinsonism. Here, we show that cortical stimulation invitro temporarily eliminates the pathological activity from the dopamine-depleted striatal microcircuit by turning off some neurons that sustain this activity and recruiting new ones that allow transitions between network states, similar to the control circuit. When cortical stimulation is given in the presence of L-DOPA, parkinsonian activity is eliminated during the whole recording period. The present experimental evidence suggests that cortical stimulation such as that generated by transcranial magnetic stimulation, or otherwise, may allow reduce L-DOPA dosage.

Inflammatory Pain Reduces C Fiber Activity-Dependent Slowing in a Sex-Dependent Manner, Amplifying Nociceptive Input to the Spinal Cord.

C fibers display activity-dependent slowing (ADS), whereby repetitive stimulation (≥1 Hz) results in a progressive slowing of action potential conduction velocity, which manifests as a progressive increase in response latency. However, the impact of ADS on spinal pain processing has not been explored, nor whether ADS is altered in inflammatory pain conditions. To investigate, compound action potentials were made, from dorsal roots isolated from rats with or without complete Freund's adjuvant (CFA) hindpaw inflammation, in response to electrical stimulus trains. CFA inflammation significantly reduced C fiber ADS at 1 and 2 Hz stimulation rates. Whole-cell patch-clamp recordings in the spinal cord slice preparation with attached dorsal roots also demonstrated that CFA inflammation reduced ADS in the monosynaptic C fiber input to lamina I neurokinin 1 receptor-expressing neurons (1–10 Hz stimulus trains) without altering the incidence of synaptic response failures. When analyzed by sex, it was revealed that females display a more pronounced ADS that is reduced by CFA inflammation to a level comparable with males. Cumulative ventral root potentials evoked by long and short dorsal root stimulation lengths, to maximize and minimize the impact of ADS, respectively, demonstrated that reducing ADS facilitates spinal summation, and this was also sex dependent. This finding correlated with the behavioral observation of increased noxious thermal thresholds and enhanced inflammatory thermal hypersensitivity in females. We propose that sex/inflammation-dependent regulation of C fiber ADS can, by controlling the temporal relay of nociceptive inputs, influence the spinal summation of nociceptive signals contributing to sex/inflammation-dependent differences in pain sensitivity.SIGNIFICANCE STATEMENT The intensity of a noxious stimulus is encoded by the frequency of action potentials relayed by nociceptive C fibers to the spinal cord. C fibers conduct successive action potentials at progressively slower speeds, but the impact of this activity-dependent slowing (ADS) is unknown. Here we demonstrate that ADS is more prevalent in females than males and is reduced in an inflammatory pain model in females only. We also demonstrate a progressive delay of C fiber monosynaptic transmission to the spinal cord that is similarly sex and inflammation dependent. Experimentally manipulating ADS strongly influences spinal summation consistent with sex differences in behavioral pain thresholds. This suggests that ADS provides a peripheral mechanism that can regulate spinal nociceptive processing and pain sensation.

VPAC Receptor Subtypes Tune Purinergic Neuron-to-Glia Communication in the Murine Submucosal Plexus.

The enteric nervous system (ENS) situated within the gastrointestinal tract comprises an intricate network of neurons and glia which together regulate intestinal function. The exact neuro-glial circuitry and the signaling molecules involved are yet to be fully elucidated. Vasoactive intestinal peptide (VIP) is one of the main neurotransmitters in the gut, and is important for regulating intestinal secretion and motility. However, the role of VIP and its VPAC receptors within the enteric circuitry is not well understood. We investigated this in the submucosal plexus of mouse jejunum using calcium (Ca2+)-imaging. Local VIP application induced Ca2+-transients primarily in neurons and these were inhibited by VPAC1- and VPAC2-antagonists (PG 99-269 and PG 99-465 respectively). These VIP-evoked neural Ca2+-transients were also inhibited by tetrodotoxin (TTX), indicating that they were secondary to action potential generation. Surprisingly, VIP induced Ca2+-transients in glia in the presence of the VPAC2 antagonist. Further, selective VPAC1 receptor activation with the agonist ([K15, R16, L27]VIP(1-7)/GRF(8-27)) predominantly evoked glial responses. However, VPAC1-immunoreactivity did not colocalize with the glial marker glial fibrillary acidic protein (GFAP). Rather, VPAC1 expression was found on cholinergic submucosal neurons and nerve fibers. This suggests that glial responses observed were secondary to neuronal activation. Trains of electrical stimuli were applied to fiber tracts to induce endogenous VIP release. Delayed glial responses were evoked when the VPAC2 antagonist was present. These findings support the presence of an intrinsic VIP/VPAC-initiated neuron-to-glia signaling pathway. VPAC1 agonist-evoked glial responses were inhibited by purinergic antagonists (PPADS and MRS2179), thus demonstrating the involvement of P2Y1 receptors. Collectively, we showed that neurally-released VIP can activate neurons expressing VPAC1 and/or VPAC2 receptors to modulate purine-release onto glia. Selective VPAC1 activation evokes a glial response, whereas VPAC2 receptors may act to inhibit this response. Thus, we identified a component of an enteric neuron-glia circuit that is fine-tuned by endogenous VIP acting through VPAC1- and VPAC2-mediated pathways.

Lower limb flexor reflex: Comparisons between drug-induced akathisia and restless legs syndrome

Background and objectiveAkathisia is characterized by restlessness and crawling sensations similar to restless legs syndrome (RLS). Long latency flexor reflex (LLFR) which has helped to advance RLS pathophysiology has never been investigated in akathisia. Due to the clinical commonalities of akathisia and RLS, we investigated the behavior of LLFR in patients with akathisia aiming to understand pathophysiology of akathisia. Patients and methodsSeven patients with neuroleptic-induced akathisia, 12 drug-naïve patients with primary RLS and 17 healthy subjects were prospectively enrolled in the study. LLFR was recorded from unilateral tibialis anterior (TA) and long head of biceps femoris (BF) muscles after stimulating the sole by trains of electrical stimuli. We measured amplitude, latency, duration, presence of response and compared between three groups. ResultsOne-way ANOVA showed mean durations of early and late responses recorded over TA were the longest in akathisia group compared to both RLS group and healthy subjects (p=0.012). The spatial spread of LLFR in akathisia patients was comparable to those of healthy subjects whereas presence of response on BF was significantly less in akathisia than RLS group. ConclusionsOur findings indicate increased excitability of LLFR pathway in akathisia group. These findings are probably due to lack of inhibition originated in regions other than those known to downregulate in RLS.

Neurophysiological mechanism of possibly confounding peripheral activation of the facial nerve during corticobulbar tract monitoring

ObjectiveTo improve the recognition and possibly prevent confounding peripheral activation of the facial nerve caused by leaking transcranial electrical stimulation (TES) current during corticobulbar tract monitoring. MethodsWe applied a single stimulus and a short train of electrical stimuli directly to the extracranial portion of the facial nerve. We compared the peripherally elicited compound muscle action potential (CMAP) of the facial nerve with the responses elicited by TES during intraoperative monitoring of the corticobulbar tract. ResultsA single stimulus applied directly to the facial nerve at subthreshold intensities did not evoke a CMAP, whereas short trains of subthreshold stimuli repeatedly evoked CMAPs. This is due to the phenomenon of sub- or near-threshold super excitability of the cranial nerve. Therefore, the facial responses evoked by short trains TES, when the leaked current reaches the facial nerve at sub- or near-threshold intensity, could lead to false interpretation. ConclusionsOur results revealed a potential pitfall in the current methodology for facial corticobulbar tract monitoring that is due to the activation of the facial nerve by subthreshold trains of stimuli.This study proposes a new criterion to exclude peripheral activation during corticobulbar tract monitoring. SignificanceThe failure to recognize and avoid facial nerve activation due to leaking current in the peripheral portion of the facial nerve during TES decreases the reliability of corticobulbar tract monitoring by increasing the possibility of false interpretation.

The modulatory effect of electrical stimulation on the excitability of the corticospinal tract varies according to the type of muscle contraction being performed.

Afferent input caused by electrical stimulation of a peripheral nerve increases corticospinal excitability during voluntary contractions, indicating that proprioceptive sensory input arriving at the cortex plays a fundamental role in modulating corticospinal excitability. The purpose of this study was to investigate whether the effect of electrical stimulation on the corticospinal excitability varies according to the type of muscle contraction being performed. Motor-evoked potentials (MEPs) were elicited by transcranial magnetic stimulation (TMS) during a shortening contraction, an isometric contraction, or no contraction of the first dorsal interosseous (FDI) muscle. In some trials, electrical stimulation of the ulnar nerve was performed at 110% of the sensory threshold or 110% of the motor threshold prior to TMS. Electrical stimulation involved either a train of 50 pulses at 10 Hz or a single pulse. Shortening contraction with the train of electrical stimuli significantly increased MEP amplitudes, and the increase was dependent on the type of stimulation. Isometric contraction with the train of electrical stimuli and electrical stimulation without voluntary contraction did not affect MEP amplitudes. A single pulse of electrical stimulation did not affect MEP amplitudes in any condition. Thus, electrical-stimulation-induced modulation of corticospinal excitability varied according to the type of muscle contraction performed and the type of stimulation. These results show that the type of contraction should be considered when using electrical stimulation for rehabilitation in patients with central nervous system lesions.

Electrical Stimulation of Abdominal Muscles to Produce Cough in Spinal Cord Injury

Background. Surface electrical stimulation of the abdominal muscles, with electrodes placed in the posterolateral position, combined with a voluntary cough can assist clearance of airway secretions in individuals with high-level spinal cord injury (SCI). Objective. To determine whether an increase in stimulus intensity of the trains of electrical stimuli delivered to the expiratory muscles has an increasing effect on a stimulated voluntary cough and to determine at which stimulus intensity a plateau of cough peak expiratory flow occurs. Methods. In 7 healthy individuals with a SCI at and above C7, gastric pressure (Pga), esophageal pressure (Pes), peak expiratory cough flow (PEFcough), and expiratory volume were measured as participants coughed voluntarily with simultaneous trains of electrical stimuli delivered over the abdominal muscles (50 Hz, 1-s duration). The intensity of the stimulation was increased incrementally. Results: A plateau in PEFcough occurred in all 7 individuals at a mean of 211 ± 29 mA (range 120-360 mA). Peak values reached for Pga, Pes, and PEFcough were 83.0 ± 8.0 cm H2O, 66.1 ± 5.6 cm H2O, and 4.0 ± 0.4 l/s respectively. Conclusions. The plateau in expiratory cough flow that was associated with increasing expiratory pressures is indicative of dynamic airway compression. This suggests that the evoked cough will be effective in creating more turbulent airflow to further assist in dislodging mucus and secretions.

The nociceptive withdrawal reflex does not adapt to joint position change and short-term motor practice

The nociceptive withdrawal reflex is a protective mechanism to mediate interactions within a potentially dangerous environment. The reflex is formed by action-based sensory encoding during the early post-natal developmental period, and it is unknown if the protective motor function of the nociceptive withdrawal reflex in the human upper-limb is adaptable based on the configuration of the arm or if it can be modified by short-term practice of a similar or opposing motor action. In the present study, nociceptive withdrawal reflexes were evoked by a brief train of electrical stimuli applied to digit II, 1) in five different static arm positions and, 2) before and after motor practice that was opposite (EXT) or similar (FLEX) to the stereotyped withdrawal response, in 10 individuals. Withdrawal responses were quantified by the electromyography (EMG) reflex response in several upper limb muscles, and by the forces and moments recorded at the wrist. EMG onset latencies and response amplitudes were not significantly different across the arm positions or between the EXT and FLEX practice conditions, and the general direction of the withdrawal response was similar across arm positions. In addition, the force vectors were not different after practice in either the practice condition or between EXT and FLEX conditions. We conclude the withdrawal response is insensitive to changes in elbow or shoulder joint angles as well as remaining resistant to short-term adaptations from the practice of motor actions, resulting in a generalized limb withdrawal in each case. It is further hypothesized that the multisensory feedback is weighted differently in each arm position, but integrated to achieve a similar withdrawal response to safeguard against erroneous motor responses that could cause further harm. The results remain consistent with the concept that nociceptive withdrawal reflexes are shaped through long-term and not short-term action based sensory encoding.

Thinking of anything else does not always reduce pain: It depends on timing

In this issue, you will find a paper by Silvestrini and Rainville (2013), entitled ‘After-effects of Cognitive Control on Pain’. In their study, the authors investigated the effect of a cognitive task on subsequent pain perception and nociceptive flexion reflex (NFR). It was found that both pain rating and NFR score increased after a highly demanding cognitive task, as compared to a less demanding cognitive task. The subject is interesting and original. Indeed, it is widely accepted that employment of cognitive resources during a noxious stimulation may reduce the subjective perception of pain through a mechanism of distraction from the stimulation itself (Chen, 2009; Ossipov et al., 2010). In other words, if one suffering from pain is induced, automatically or by a voluntary process, to diverge his/her attention from his/her own painful feeling, he/she will downgrade the subjective pain perception. It has also been demonstrated that distraction from a painful stimulus can reduce an objective measure of pain, such as the laser-evoked potential amplitude (Lorenz and Garcia-Larrea, 2003). However, what happens when the cognitive task precedes the noxious stimulation? Is the level of cognitive task difficulty important in the interaction between the initial cognitive resource allocation and the subsequent pain perception? The study by Silvestrini and Rainville (2013) answers these questions since the authors show that performing a numerical Stroop task in a condition with a high cognitive demand increases the subsequent pain perception, as compared with the same task performed in a condition with a low cognitive demand. Previous papers demonstrated a reduced pain tolerance following acts of self-control (Muraven et al., 2006; Vohs et al., 2008; Schmeichel and Vohs, 2009). However, in all these studies, reduced pain tolerance was suggested by a faster withdrawal of subject's hand from the cold water following the self-control act. Therefore, there was not a direct pain measurement, nor an objective evidence of the level of the nociceptive sensitization. Silvestrini and Rainville (2013), beyond showing an increased subjective pain perception after a highly demanding cognitive task, demonstrated that the sensitization to the painful stimuli begins from the nociceptive input processing at the spinal cord level (increased NFR score). This last finding means that the increased pain perception is a top-down process, beginning with the allocation of cognitive resources (numerical Stroop task) and leading to a reduced efficiency of the descending pain control mechanisms. Some points remain to be elucidated and will have to be investigated in future studies. First, as was also underlined by Silvestrini and Rainville (2013), it is not clear whether the effective depletion of cognitive resources per se or merely the subjective perception of such depletion is responsible for the increased subsequent pain perception. Indeed, if submitted to a highly demanding cognitive task, one could feel less able to cope with a subsequent painful stimulus, independent of the effective consumption of cognitive resources. On the ground of the treatment of an expected pain, this is not a secondary point. While in the first hypothesis (quantitative effect of cognitive resource depletion), the subject could feel less pain only by reducing his/her own resource engagement in the prior cognitive task, in the other case (belief about one's own willpower), a psychological treatment encouraging the subject to downgrade his/her subjective perception of the preceding cognitive effort may make him/her less sensitive to following painful stimuli. This is nothing else than what sportsmen define as ‘mental energy recovery’ between two consecutive competitions. Second, in the study by Silvestrini and Raiville's (2013), the subjects were asked to rate pain due to a train of electrical stimuli. Each train was very short, lasting 30 ms. Such a phasic stimulus is very different from the far longer-lasting clinical pain referred by patients. This prevents any immediate application of Silvestrini and Rainville's (2013) results to the clinical practice. However, it will be very interesting to investigate whether also a more ecological expected pain, as compared to that due to electrical stimuli, is influenced by a preceding depletion of cognitive resources. In conclusion, the present study by Silvestrini and Rainville (2013) has the main merit to have highlighted an original field for the psychophysiological investigation on pain. In particular, the authors showed that the engagement of cognitive resources cannot only interfere with the cognitive activities devoted to elaborate the affective/emotional aspects of pain, thus reducing the perception of a painful stimulus, but it can also diminish the cognitive activities needed for subsequent endogenous pain control.

Adaptability of the nociceptive withdrawal reflex

The nociceptive withdrawal reflex is a protective mechanism to mediate interactions within a potentially dangerous environment. The reflex is formed by action-based sensory encoding during the early post-natal developmental period, and it is unknown if the protective motor function of the nociceptive withdrawal reflex in the human upper-limb is adaptable based on the configuration of the arm or if it can be modified by short-term practice of a similar or opposing motor action. In the present study, nociceptive withdrawal reflexes were evoked by a brief train of electrical stimuli applied to digit II, 1) in five different static arm positions and, 2) before and after motor practice that was opposite (EXT) or similar (FLEX) to the stereotyped withdrawal response, in 10 individuals. Withdrawal responses were quantified by the electromyography (EMG) reflex response in several upper limb muscles, and by the forces and moments recorded at the wrist. EMG onset latencies and response amplitudes were not significantly different across the arm positions or between the EXT and FLEX practice conditions, and the general direction of the withdrawal response was similar across arm positions. In addition, the force vectors were not different after practice in either the practice condition or between EXT and FLEX conditions. We conclude the withdrawal response is insensitive to changes in elbow or shoulder joint angles as well as remaining resistant to short-term adaptations from the practice of motor actions, resulting in a generalized limb withdrawal in each case. It is further hypothesized that the multisensory feedback is weighted differently in each arm position, but integrated to achieve a similar withdrawal response to safeguard against erroneous motor responses that could cause further harm. The results remain consistent with the concept that nociceptive withdrawal reflexes are shaped through long-term and not short-term action based sensory encoding.

Gamma oscillatory amplitude encodes stimulus intensity in primary somatosensory cortex.

Gamma oscillations have previously been linked to pain perception and it has been hypothesized that they may have a potential role in encoding pain intensity. Stimulus response experiments have reported an increase in activity in the primary somatosensory cortex (SI) with increasing stimulus intensity, but the specific role of oscillatory dynamics in this change in activation remains unclear. In this study, Magnetoencephalography (MEG) was used to investigate the changes in cortical oscillations during four different intensities of a train of electrical stimuli to the right index finger, ranging from low sensation to strong pain. In those participants showing changes in evoked oscillatory gamma in SI during stimulation, the strength of the gamma power was found to increase with increasing stimulus intensity at both pain and sub-pain thresholds. These results suggest that evoked gamma oscillations in SI are not specific to pain but may have a role in encoding somatosensory stimulus intensity.

PWE-062 Can magnetic neural stimulation improve anorectal sensitivity in IBS?

IntroductionVisceral pain is a major clinical problem being a primary feature of irritable bowel syndrome (IBS). Treatments for this condition are limited, but there is increasing evidence that neural stimulation...

Sensory Stimulation-Dependent Plasticity in the Cerebellar Cortex of Alert Mice

In vitro studies have supported the occurrence of cerebellar long-term depression (LTD), an interaction between the parallel fibers and Purkinje cells (PCs) that requires the combined activation of the parallel and climbing fibers. To demonstrate the existence of LTD in alert animals, we investigated the plasticity of local field potentials (LFPs) evoked by electrical stimulation of the whisker pad. The recorded LFP showed two major negative waves corresponding to trigeminal (broken into the N2 and N3 components) and cortical responses. PC unitary extracellular recording showed that N2 and N3 occurred concurrently with PC evoked simple spikes, followed by an evoked complex spike. Polarity inversion of the N3 component at the PC level and N3 amplitude reduction after electrical stimulation of the parallel fiber volley applied on the surface of the cerebellum 2 ms earlier strongly suggest that N3 was related to the parallel fiber–PC synapse activity. LFP measurements elicited by single whisker pad stimulus were performed before and after trains of electrical stimuli given at a frequency of 8 Hz for 10 min. We demonstrated that during this later situation, the stimulation of the PC by parallel and climbing fibers was reinforced. After 8-Hz stimulation, we observed long-term modifications (lasting at least 30 min) characterized by a specific decrease of the N3 amplitude accompanied by an increase of the N2 and N3 latency peaks. These plastic modifications indicated the existence of cerebellar LTD in alert animals involving both timing and synaptic modulations. These results corroborate the idea that LTD may underlie basic physiological functions related to calcium-dependent synaptic plasticity in the cerebellum.

A new model for studying focal and generalized chronic seizures in anesthetized rats

Seizure activity in anesthetized animals can be recorded in a number of different animal models. One such model uses urethane as an anesthetic and kainic acid as a convulsant. In addition, it is known that animals can be made epileptic using kainic acid by causing a period of status epilepticus and waiting for epileptogenesis to occur. We report an animal model to study seizure activity in kainic acid‐induced epileptic rats under urethane anesthesia. Sprague‐Dawley rats were injected with sufficient kainic acid to cause a period of status epilepticus. At ≥8 months post status epilepticus, at a time when behavioral seizures were evident, the rats were anesthetized with urethane. EEG recordings from CA1 and CA3 were performed together with recordings of EKG, BP, and vagus nerve. All rats exhibited abnormal spiking in the EEG and 42% (5/12) experienced spontaneous focal seizures while under anesthesia. Spontaneous generalized seizure activity occurred in a subset of these animals. In 56% (5/9 tested), focal and generalized seizures could be triggered with brief trains of electrical stimuli. Vagus nerve activity was found to be increased during focal and generalized seizures. These results demonstrate a new animal model to study seizures, especially focal seizures of limbic cortical origin, in anesthetized epileptic rats with a variety of applications, including the study of autonomic activity during seizures.

A continuous high frequency stimulation of the subthalamic nucleus determines a suppression of excitatory synaptic transmission in nigral dopaminergic neurons recorded in vitro

High frequency stimulation of the subthalamic nucleus (HFS-STN) has been successfully introduced to treat symptoms of advanced Parkinson's disease (PD) (rigidity, tremor and akinesia). In spite of its extensive clinical practice, little is known at cellular level about the effects of a continuous train of electrical stimuli (>100Hz) delivered in the STN. In this manuscript we examine the synaptic responses of substantia nigra pars compacta (SNpc) dopaminergic cells, upon continuous HFS-STN delivered in a rat brain slice preparation.We report that HFS-STN, delivered at frequencies resembling those used during DBS (100–130Hz), caused synaptic responses in SNpc dopaminergic neurons, which summated progressively, until they reached a plateau within few tens of ms. However, if the HFS was maintained, a rapid fading of the synaptic response was observed, with an almost complete loss after 10s. Accordingly, the postsynaptic excitability, evaluated by the tonic firing rate of the SNpc dopaminergic neurons, remained unaltered during a continuous HFS-STN. Upon HFS termination, there was a rapid recovery of synaptic function. Neither a converging synaptic input, evoked by intranigral stimulation, nor the depolarizing responses to locally-applied AMPA, were affected during HFS. The loss of synaptic response by continuous HFS-STN was not prevented by inhibition of AMPA receptor desensitization, nor by antagonists of a variety of neurotransmitter receptors, known to depress synaptic transmission in the SNpc. We conclude that a HFS in the STN, with patterns resembling in vivo DBS, induces a rapid and input-specific suppression of the synaptic transmission from STN to SNpc dopaminergic neurons, that is maintained during an ongoing stimulation. The deficit of transmission between the STN and the SNpc could have a role in the therapeutic effects of the DBS procedure.