Afferent Facilitation Research Articles

Evidence of altered interhemispheric communication after pediatric concussion

ABSTRACT OBJECTIVES: To investigate neurophysiological alterations within the typical symptomatic period after concussion (1-month) and throughout recovery (6-months) in adolescents; and (2) to examine relationships between neurophysiological and upper limb kinematic outcomes. METHODS: 18 adolescents with concussion were compared to 17 healthy controls. Transcranial magnetic stimulation (TMS) was used to assess neurophysiological differences between groups including: short- and long-interval intracortical inhibition, intracortical facilitation, short- and long-latency afferent inhibition, afferent facilitation, and transcallosal inhibition (TCI). Behavioral measures of upper limb kinematics were assessed with a robotic device. RESULTS: Mixed model analysis of neurophysiological data identified two key findings. First, participants with concussion demonstrated delayed onset of interhemispheric inhibition, as indexed by TCI, compared to healthy controls. Second, our exploratory analysis indicated that the magnitude of TCI onset delay in adolescents with concussion was related to upper limb kinematics. CONCLUSIONS: Our findings indicate that concussion in adolescence alters interhemispheric communication. We note relationships between neurophysiological and kinematic data, suggesting an affinity for individuals with less concussion-related physiological change to improve their motor behavior over time. These data serve as an important step in future development of assessments (neurobiological and clinical) and interventions for concussion.

The influence of an acute bout of moderate-intensity cycling exercise on sensorimotor integration.

Acute cycling exercise can modulate motor cortical circuitry in the non-exercised upper-limb. Within the primary motor cortex, measures of intracortical inhibition are reduced and intracortical facilitation is enhanced following acute exercise. Further, acute cycling exercise decreases interhemispheric inhibition between the motor cortices and lowers cerebellar-to-motor cortex inhibition. Yet, investigations into the effects of acute exercise on sensorimotor integration, referring to the transfer of incoming afferent information from the primary somatosensory cortex to motor cortex, are lacking. The current work addresses this gap in knowledge with two experimental sessions. In the first session, we tested the exercise-induced changes in somatosensory and motor excitability by assessing somatosensory (SEP) and motor evoked potentials (MEPs). In the second session, we explored the effects of acute cycling exercise on short- (SAI) and long-latency afferent inhibition (LAI), and afferent facilitation. In both experimental sessions, neurophysiological measures were obtained from the non-exercised upper-limb muscle, tested at two time points pre-exercise separated by a 25-min period of rest. Next, a 25-min bout of moderate-intensity lower-limb cycling was performed with measures assessed at two time points post-exercise. Acute lower-limb cycling increased LAI, without modulation of SAI or afferent facilitation. Further, there were no exercise-induced changes to SEP or MEP amplitudes. Together, these results suggest that acute exercise has unique effects on sensorimotor integration, which are not accompanied by concurrent changes in somatosensory or motor cortical excitability.

Effect of the brain-derived neurotrophic factor gene Val66Met polymorphism on sensory-motor integration during a complex motor learning exercise

The brain-derived neurotrophic factor (BDNF) gene Val66Met polymorphism may cause impairment in short-term motor learning by reducing activity-dependent BDNF expression, which causes alterations in synaptic plasticity by changing glutamatergic and GABAergic synaptic transmissions. Sensory-motor integration (SMI) plays an important role in motor learning. In this study, we investigated the role of this polymorphism on SMI during a complex motor learning practice. Forty-three healthy participants performed standardized 5-day basketball shooting exercises under supervision. Electrophysiologic SMI studies were performed before the first day exercise (T0) and after the first and fifth day exercises (T1 and T2, respectively). SMI was studied using electrical median nerve stimulation at the wrist, followed by transcranial magnetic stimulation (TMS) of the contralateral motor cortex with various inter-stimulus intervals (ISIs). Recordings were made from the thenar and forearm flexor muscles. Participants were divided into two groups according to their BDNF genotype. Group 1 consisted of 26 subjects with the Val66Val genotype and group 2 included 17 subjects with the BDNF Met allele. Group 2 had a lower increase in basketball scores at day 5. Moreover, they had higher afferent facilitation for the responses recorded from both thenar and forearm flexor muscles at T1, but these changes could not be maintained until T2. This non-persistent early hyper-responsivity of the sensory-motor cortex in subjects with the BDNF Met allele might be explained by a transient upsurge of cortical excitability to compensate the insufficient cortical plasticity during motor learning, which could be considered as a sign of lower performance in motor skill learning.

P79-T Sensory-motor integration during a visuomotor sequence learning task

Background Sensory-motor integration (SMI) is an important process in the learning and execution of voluntary movements. This study aimed to test the electrophysiological course of SMI along with fMRI during visuomotor sequence learning (VMSL). Methods Nineteen healthy participants were included. They performed the VMSL task with their left hand. On the first day, they completed one training run and a test run. They repeated daily training tasks and were re-tested on the fifth day. Ipsilateral electrical median nerve stimulation followed by transcranial magnetic stimulation of the contralateral motor cortex with various interstimulus intervals (ISI) were performed. Recordings were made from left forearm flexor and extensor muscles. SMI studies were performed at before (T0) and after (T1) 1st-day training, and after 5th-day training (T2). Motor response (MEP) ratios for each ISI were calculated. Mean reaction time (RT) and mean error rate were measured. Results RTs (training: 283.37 ± 65.76; test: 235.20 ± 51.00; re-test: 194.26 ± 50.26 ms) and mean error rates (0.19 ± 0.16; 0.06 ± 0.06; 0.02 ± 0.03, respectively) improved significantly in the early and late stages. MEP ratios showed early afferent inhibition (SAI, ISIs 20–35 ms), late afferent inhibition (LAI, ISIs 80–200 ms) and intervening afferent facilitation (AF) for forearm flexors. Although MEP ratios at T0 andT1 were very similar, less SAI and more AF were observed at T2. Conclusions There was a tendency for decreased SAI and increased AF towards the end of the learning period. This may be caused by the learning task which requires a more prominent sensorimotor integration towards the end of the study.

Short-latency afferent-induced facilitation and inhibition as predictors of thermally induced variations in corticomotor excitability.

Recently (Ansari et al., PeerJ 6:e6163, 2018a; Somatosens Mot Res 35:69-79, 2018b), we showed using transcranial magnetic stimulation (TMS) that focal application of innocuous thermal stimuli to the distal hand produced variable responses in terms of motor-evoked potential (MEP) suppression or enhancement. Here, we sought to investigate possible causes of this variability by examining circuits mediating sensorimotor integration and intra-cortical inhibition. Participants (n = 21) first underwent TMS to assess baseline corticomotor excitability by measuring MEPs at rest with the index finger wrapped in a gel pack at room temperature (24°C). Then, conditioned protocols were applied to assess short-latency afferent inhibition (SAI), short-latency afferent facilitation (SAF) and short-interval intra-cortical inhibition (SICI). Following baseline measures, MEP modulation in response to distal cooling was recorded with the index finger wrapped ina gel pack at ~ 10°C. At baseline, participants exhibited variable levels of SAI, SAF and SICI. Participant also exhibited variable responses to cooling with about half of them (11/21) showing suppressed excitability and one-third showing enhanced excitability (7/21). A linear regression analysis revealed that SAI and SAF proved to be good predictors of cooling-induced variations in corticomotor excitability but not SICI. These results provide novel evidence linking variations in SAI and SAF with those in corticomotor excitability elicited in response to focal thermal stimulation, suggesting that these markers could be used to predict responses to sensory stimulation protocols.

Sensorimotor integration in chronic stroke: Baseline differences and response to sensory training.

The integration of somatosensory information from the environment into the motor cortex to inform movement is essential for motor function. As motor deficits commonly persist into the chronic phase of stroke recovery, it is important to understand potential contributing factors to these deficits, as well as their relationship with motor function. To date the impact of chronic stroke on sensorimotor integration has not been thoroughly investigated. The current study aimed to comprehensively examine the influence of chronic stroke on sensorimotor integration, and determine whether sensorimotor integration can be modified with an intervention. Further, it determined the relationship between neurophysiological measures of sensorimotor integration and motor deficits post-stroke. Fourteen individuals with chronic stroke and twelve older healthy controls participated. Motor impairment and function were quantified in individuals with chronic stroke. Baseline neurophysiology was assessed using nerve-based measures (short- and long-latency afferent inhibition, afferent facilitation) and vibration-based measures of sensorimotor integration, which paired vibration with single and paired-pulse TMS techniques. Neurophysiological assessment was performed before and after a vibration-based sensory training paradigm to assess changes within these circuits. Vibration-based, but not nerve-based measures of sensorimotor integration were different in individuals with chronic stroke, as compared to older healthy controls, suggesting that stroke differentially impacts integration of specific types of somatosensory information. Sensorimotor integration was behaviourally relevant in that it related to both motor function and impairment post-stroke. Finally, sensory training modulated sensorimotor integration in individuals with chronic stroke and controls. Sensorimotor integration is differentially impacted by chronic stroke based on the type of afferent feedback. However, both nerve-based and vibration-based measures relate to motor impairment and function in individuals with chronic stroke.

Sensorimotor Integration During Motor Learning: Transcranial Magnetic Stimulation Studies.

The effect of sensory signals coming from skin and muscle afferents on the sensorimotor cortical networks is entitled as sensory-motor integration (SMI). SMI can be studied electrophysiologically by the motor cortex excitability changes in response to peripheral sensory stimulation. These changes include the periods of short afferent inhibition (SAI), afferent facilitation (AF), and late afferent inhibition (LAI). During the early period of motor skill acquisition, motor cortex excitability increases and changes occur in the area covered by the relevant zone of the motor cortex. In the late period, these give place to the morphological changes, such as synaptogenesis. SAI decreases during learning the motor skills, while LAI increases during motor activity. In this review, the role of SMI in the process of motor learning and transcranial magnetic stimulation techniques performed for studying SMI is summarized.

Centre-surround organization of fast sensorimotor integration in human motor hand area

Using the short-latency afferent inhibition (SAI) paradigm, transcranial magnetic stimulation (TMS) of the primary motor hand area (M1HAND) can probe how sensory input from limbs modulates corticomotor output in humans. Here we applied a novel TMS mapping approach to chart the spatial representation of SAI in human hand-knob. We hypothesized SAI is somatotopically expressed in M1HAND depending on both the site of peripheral electrical nerve stimulation and the cortical spot targeted by TMS within M1HAND. The left index or little finger was stimulated 23 ms before focal single-pulse TMS of the right M1HAND. Using frameless stereotaxy, we applied biphasic-TMS pulses at seven stimulation positions above right M1HAND and recorded the motor evoked potentials (MEPs) from relaxed left first-dorsal-interosseous (FDI) and abductor-digiti-minimi (ADM) muscles. Homotopic stimulation of the finger close to the muscle targeted by TMS revealed a somatotopic expression of afferent inhibition matching the somatotopic representation of unconditioned MEPs (homotopic SAI). Conversely, heterotopic stimulation of a finger distant to the muscle targeted by TMS induced short-latency afferent facilitation (SAF) of MEPs in M1HAND. Like homotopic SAI, heterotopic SAF was somatotopically expressed in M1HAND. Together, the results provide first-time evidence that fast sensorimotor integration involves centre-inhibition and surround-facilitation in human M1HAND.

Effects of Passive Finger Movement on Cortical Excitability.

This study examined the effects of joint angle and passive movement direction on corticospinal excitability. The subjects were 14 healthy adults from whom consent could be obtained. We performed two experiments. In Experiment 1, we measured motor evoked potential (MEP) amplitude, F-wave and M-wave at 0° and 20° adduction during adduction or abduction movement, in the range of movement from 10° abduction to 30° adduction. In Experiment 2, MEPs were measured at static 0° and 20° adduction during passive adduction from 10° adduction to 30° adduction and static 20° adduction. MEP, F-waves and M-waves were recorded from the right first dorsal interosseous (FDI) muscle. Experiment 1 revealed significantly increased MEP amplitude at 0° during passive adduction compared to static 0° (p < 0.01). No other significant differences in MEP, M-wave and F-wave parameters were observed. In Experiment 2, MEP amplitude was significantly higher at 20° adduction during passive adduction compared with static 0° (p < 0.01). Based on these findings, it appears that fluctuations in MEP amplitude values during passive movement are not influenced by joint angle, but rather it is possible that it is due to intracortical afferent facilitation (AF) dependent on afferent input due to the start of movement and interstimulus interval (ISI) of transcranial magnetic stimulation (TMS).

The in vivo reduction of afferent facilitation induced by low frequency electrical stimulation of the motor cortex is antagonized by cathodal direct current stimulation of the cerebellum.

BackgroundLow-frequency electrical stimulation to the motor cortex (LFSMC) depresses the excitability of motor circuits by long-term depression (LTD)-like effects. The interactions between LFSMC and cathodal direct current stimulation (cDCS) over the cerebellum are unknown.MethodsWe assessed the corticomotor responses and the afferent facilitation of corticomotor responses during a conditioning paradigm in anaesthetized rats. We applied LFSMC at a frequency of 1 Hz and a combination of LFSMC with cDCS.ResultsLFSMC significantly depressed both the corticomotor responses and the afferent facilitation of corticomotor responses. Simultaneous application of cDCS over the cerebellum antagonized the depression of corticomotor responses and cancelled the depression of the afferent facilitation.ConclusionOur results demonstrate that cDCS of the cerebellum is a potent modulator the inhibition of the motor circuits induced by LFSMC applied in vivo. These results expand our understanding of the effects of cerebellar DCS on motor commands and open novel applications for a cerebellar remote control of LFSMC-induced neuroplasticity. We suggest that the cerebellum acts as a neuronal machine supervising not only long-term potentiation (LTP)-like effects, but also LTD-like effects in the motor cortex, two mechanisms which underlie cerebello-cerebral interactions and the cerebellar control of remote plasticity. Implications for clinical ataxiology are discussed.

ID 277 – The effects of BDNF Val66Met polymorphism on motor learning studied electrophysiologically by sensory-motor integration

Objective We previously found by performing sensory-motor integration (SMI) studies on sedentary subjects that there were less short latency afferent inhibition and higher facilitation after basketball shooting exercises which partially subsided after exercising for five days. We herein present the effect of brain-derived neurotrophic factor (BDNF) val66met polymorphisms on this motor learning process. Method Two groups of healthy sedentary subjects [16 Val66Val (group I); 10 Val66Met and 1 Met66Met (group 2)] performed standardized 5-day basketball shooting exercises under supervision. SMI studies were done before and after the exercise on day 1 (T0, T1) and after the exercise on day 5 (T2). SMI was studied by electrical median nerve stimulation at the wrist followed by transcranial magnetic stimulation (TMS) of the contralateral motor cortex. Recordings were made from thenar and flexor carpi radialis (FCR) muscles. Inter-stimulus intervals between the electrical stimulus and TMS were 20, 35, 50, 65, 80, 100 and 200 ms. Results Group 2 had significantly more reduced short afferent inhibition and increased facilitation at T2. Conclusion In group 2, persistently increased excitability in the sensory-motor cortex on day five might be the reflection of a defect in changing the learning process into a different mechanism.

Effect of Paired-Pulse Electrical Stimulation on the Activity of Cortical Circuits.

Objective: We investigated the transient effect of short-duration paired-pulse electrical stimulation (ppES) on corticospinal excitability and the after-effect of long-duration ppES on excitability, short-latency afferent inhibition (SAI), and afferent facilitation (AF).Methods: A total of 28 healthy subjects participated in two different experiments. In Experiment 1, motor-evoked potentials (MEPs) were measured in the abductor pollicis brevis (APB) and abductor digiti minimi (ADM) muscles before and immediately after short-duration ppES (5 s) at various inter-pulse intervals (2, 3, 4, 5, 6, 7, 10, 15, 20, and 30 ms). In Experiment 2, MEPs, SAI, and AF were measured before, immediately, and 20 and 40 min after long-duration ppES (20 min, inter-pulse interval of 5 and 15 ms) and peripheral electrical stimulation (20 min, 10 and 20 Hz).Results: Short-duration ppES with inter-pulse intervals of 5 and 20 ms significantly increased MEP measured in APB but not in ADM. Long-duration ppES with an inter-pulse interval of 5 ms significantly decreased SAI but not MEPs in APB. In contrast, long-duration ppES did not affect ADM.Conclusion: The afferent inputs induced by ppES-5 ms were effective for transiently increasing MEP and sustaining SAI reduction.

No relation between afferent facilitation induced by digital nerve stimulation and the latency of cutaneomuscular reflexes and somatosensory evoked magnetic fields.

Primary motor cortex (M1) excitability can be assessed using transcranial magnetic stimulation (TMS) and can be modulated by a conditioning electrical stimulus delivered to a peripheral nerve prior to TMS. This is known as afferent facilitation (AF). The aim of this study was to determine whether AF can be induced by digital nerve stimulation and to evaluate the relation between the interstimulus interval (ISI) required for AF and the latency of the E2 component of the cutaneomuscular reflex (CMR) and the prominent somatosensory evoked field (SEF) deflection that occurs approximately 70 ms after digital nerve stimulation (P60m). Stimulation of the digital nerve of the right index finger was followed, at various time intervals, by single-pulse TMS applied to the contralateral hemisphere. The ISI between digital nerve stimulation and TMS was 20, 30, 40, 50, 60, 70, 80, 100, 140, 180, 200, or 220 ms. Single-pulse TMS was performed alone as a control. SEFs were recorded following digital nerve stimulation of the index finger, and the equivalent current dipole of prominent deflections that occurred around 70 ms after the stimulation was calculated. CMRs were recorded following digital nerve stimulation during muscle contraction. Motor evoked potentials (MEPs) were facilitated at an ISI between 50 and 100 ms in 11 of 13 subjects, and the facilitated MEP amplitude was larger than the unconditioned MEP amplitude (p < 0.01). There was no significant correlation between the ISI at which AF was maximal and the latency of the P60m component of the SEF (r = −0.50, p = 0.12) or the E2 component of the CMR (r = −0.54, p = 0.88). These results indicate that the precise ISI required for AF cannot be predicted using SEF or CMR.

Acute effects of muscle vibration on sensorimotor integration

Projections from the somesthetic cortex are believed to be involved in the modulation of motor cortical excitability by muscle vibration. The aim of the present pilot study was to analyse the effects of a vibration intervention on short-latency afferent inhibition (SAI), long-latency afferent inhibition (LAI), and afferent facilitation (AF), three intracortical mechanisms reflecting sensorimotor integration. Abductor pollicis brevis (APB) SAI, AF and LAI were investigated on 10 subjects by conditioning test transcranial magnetic stimulation pulses with median nerve electrical stimulation at inter-stimuli intervals in the range 15–25ms, 25–60ms, and 100–200ms, respectively. Test motor evoked potentials (MEPs) were compared to unconditioned MEPs. Measurements were performed before and just after 15min of vibration applied to the muscle belly of APB at a frequency of 80Hz. SAI and LAI responses were significantly reduced compared to unconditioned test MEPs (P=0.039 and P<0.001, respectively). AF MEP amplitude was greater than SAI and LAI one (P=0.009 and P=0.004, respectively), but not different from test MEP (P=0.511). There was no significant main effect of vibration (P=0.905). However, 4 subjects were clearly identified as responders. Their mean vibration-induced increase was 324±195% in APB SAI MEP amplitude, and 158±53% and 319±80% in AF and LAI, respectively. Significant differences in SAI, AF and LAI vibration-induced changes were found for responders when compared to non-responders (P=0.019, P=0.038, and P=0.01, respectively). A single session of APB vibration may increase sensorimotor integration, via decreased inhibition and increased facilitation. However, such results were not observed for all subjects, suggesting that other factors (such as attention to the sensory inputs) may have played a role.

Loss of short-latency afferent inhibition and emergence of afferent facilitation following neuromuscular electrical stimulation

Neuromuscular electrical stimulation (NMES) increases the excitability of corticospinal (CS) pathways by altering circuits in motor cortex (M1). How NMES affects circuits interposed between the ascending afferent volley and descending CS pathways is not known. Presently, we hypothesized that short-latency afferent inhibition (SAI) would be reduced and afferent facilitation (AF) enhanced when NMES increased CS excitability. NMES was delivered for 40min over the ulnar nerve. To assess CS excitability, motor evoked potentials (MEPs) were evoked using transcranial magnetic stimulation (TMS) delivered at 120% resting threshold for first dorsal interosseus muscle. These MEPs increased by ∼1.7-fold following NMES, demonstrating enhanced CS excitability. SAI and AF were tested by delivering a “conditioning” electrical stimulus to the ulnar nerve 18–25ms and 28–35ms before a “test” TMS pulse, respectively. Conditioned MEPs were compared to unconditioned MEPs evoked in the same trials. TMS was adjusted so unconditioned MEPs were not different before and after NMES. At the SAI interval, conditioned MEPs were 25% smaller than unconditioned MEPs before NMES but conditioned and unconditioned MEPs were not different following NMES. At the AF interval, conditioned MEPs were not different from unconditioned MEPs before NMES, but were facilitated by 33% following NMES. Thus, when NMES increases CS excitability there are concurrent changes in the effect of afferent input on M1 excitability, resulting in a net increase in the excitatory effect of the ascending afferent volley on CS circuits. Maximising this excitatory effect on M1 circuits may help strengthen CS pathways and improve functional outcomes of NMES-based rehabilitation programs.

Abnormal sensory-motor integration in a patient with anti-NMDA-receptor encephalitis.

In this report, we describe the case of patient who showed abnormal corticomotor responses after peripheral afferent stimulation, namely sensory afferent inhibition (SAI) and sensory afferent facilitation (SAF), and its reversibility after treatment in a patient with anti-N-methyl D-aspartate receptor (NMDAR) encephalitis. A 26-year-old woman was admitted to a hospital after experiencing fever and headache for 11 days. Comprehensive serological studies, a brain magnetic resonance imaging scan, and cerebrospinal fluid (CSF) analysis were unremarkable. In the following days, she developed hallucinations and generalized tonic seizures. A repeat CSF analysis showed lymphocytic pleocytosis (261 white blood cells/ mm; 97% lymphocytes) and a normal protein concentration (63 mg/dl). She continued to have hyperkinetic movements and hyper-pyrexia despite receiving antibacterial and antiviral treatments. Electroencephalography showed diffuse slow waves with unremarkable somatosensory evoked potentials and brainstem auditory evoked potentials. After 30 days, she became unresponsive and had respiratory failure, and was then transferred to our hospital. On examination, she presented with dystonic posturing, oro-lingual-facial dyskinesia, and myoclonic movements. A computed tomography scan of the chest and abdomen and a trans-vaginal sonogram disclosed no abnormalities. Her serum and CSF studies were positive for anti-NMDAR antibodies. Transcranial magnetic stimulation (TMS) demonstrated intact corticospinal tracts with normal latencies and thresholds for motor-evoked potentials (MEPs). However, the conditioned peripheral afferent stimulation failed to show an SAI response at inter-stimulus intervals (ISIs) in the range of 15–25 ms, while exaggerated SAF responses were observed at ISIs between 30 and 70 ms. These data are contrasted to data from a healthy control subject in Fig. 1a, b and Table 1. The patient’s condition showed a little improvement in that she started to have some slow responses to verbal stimulation after steroid pulse therapy and plasmapheresis. Intravenous immunoglobulin was then started, and her condition improved dramatically. In a 3-week follow-up SAI/SAF study, the SAF had made notable progress toward normalization, but a normal SAI response was still absent (Fig. 1c; Table 1). NMDARs are expressed at high levels in the central nervous system, and play an important role in excitatory synaptic transmission and synaptic plasticity. Patients with anti-NMDAR antibodies usually present with various neurological symptoms presumably resulting from an AMPA receptor-mediated hyperglutamatergic state [1]. The MEP amplitude and latency of the patient described herein were similar to normal values. Impaired SAI and exaggerated SAF, such as observed in the presently described case, are suggestive of abnormal motor-sensory Y.-H. Dou K.-L. Lai K.-K. Liao S.-P. Chen (&) Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, 112 Taipei, Taiwan e-mail: chensp1977@gmail.com

Afferent facilitation of corticomotor responses is increased by IgGs of patients with NMDA-receptor antibodies

A severe subacute encephalitis associated with auto-antibodies to the NMDA receptor (NMDA-R) has been reported in humans. These antibodies are directed to NR1/NR2 heteromers of the NMDA receptor. We studied the effects of patients' cerebrospinal fluid (CSF) injected in rFr2 (the prefrontal area) on the afferent facilitation in a conditioning paradigm for corticomotor responses. The afferent facilitation was assessed in forelimbs and hindlimbs of rats, before and after application of trains of high-frequency stimulation (HFS) which are known to modulate the excitability of M1. Before HFS, patients' CSF did not modify afferent facilitation. After HFS, the amplitudes of corticomotor responses before conditioning were significantly larger in forelimbs and hindlimbs. There was an increase of the afferent facilitation in forelimbs. The same effect was observed after injection of purified IgGs from patients' sera. Our results highlight that IgGs of patients with NMDA-R antibodies induce a state of corticomotor hyperexcitability following application of HFS over the prefrontal area.

Peripheral sensory activation of cortical circuits in the human leg motor cortex

Inputs from lower leg afferents can access both spinal and/or cortical circuits to facilitated on-going motor commands and prune unwanted motor activity. In the leg, this afferent facilitation may contribute to obstacle avoidance and stability during gait, but cortical inhibition analogous to short-latency afferent inhibition (SAI) and the effect of sensory input on intracortical excitability have yet to be reported. The purpose of this study was to first characterize the effect of excitatory afferent inputs from the lower leg on intracortical circuits, and secondly, to investigate the occurrence of SAI in the leg motor cortex.

Effects of trains of high-frequency stimulation of the premotor/supplementary motor area on conditioned corticomotor responses in hemicerebellectomized rats

We studied the effects of low- and high-frequency premotor electrical stimulations on conditioned corticomotor responses, intra-cortical facilitation (ICF) and spinal excitability in hemicerebellectomized rats (left side). Trains of stimulation were applied in prefrontal region rFr2 (the equivalent of the premotor/supplementary motor area in primates) at a rate of 1 Hz (low-frequency stimulation LFS) or 20 Hz (high-frequency stimulation HFS). Test stimuli on the motor cortex were preceded by a conditioning stimulus in contralateral sciatic nerve (two inter-stimulus intervals ISIs were studied: 5 ms or 45 ms). (A) At ISI-5, conditioning increased amplitudes of MEPs (motor evoked potentials) in the left motor cortex. This afferent facilitation was enhanced if preceded by trains of stimuli administered over the ipsilateral rFr2 area, and HFS had higher effects than LFS. The facilitation was lower for the right motor cortex, for both LFS and HFS. (B) At ISI-45, conditioned motor evoked responses were depressed as compared to unconditioned responses in the left motor cortex (afferent inhibition). Following LFS, the degree of inhibition was unchanged while it increased with HFS. At baseline, inhibition was enhanced in the right motor cortex. Interestingly, the afferent inhibition decreased significantly following HFS. (C) ICF was depressed in the right motor cortex, but increased similarly on both sides following LFS/HFS. These results (1) confirm the increased inhibition in the motor cortex contralaterally to the hemicerebellar ablation, (2) demonstrate for the first time that the cerebellum is necessary for tuning amplitudes of corticomotor responses following a peripheral nerve stimulation, (3) show that the application of LFS or HFS does not cancel the defect of excitability in the motor cortex for short ISIs, and (4) suggest that for longer ISIs, HFS could have interesting properties for the modulation of afferent inhibition in case of extensive cerebellar lesion. Our study underlines that cerebellar ablation impacts on the efficacy of combined peripheral–motor cortex stimulation in an ISI-dependent manner.

The metabotropic glutamate receptors of the vestibular organs

This research sought to test the presence and function of metabotropic excitatory amino acid receptors (mGluR) in the frog semicircular canal (SCC). The mGluR agonist ±1-aminocyclopentane- trans-1,3-dicarboxylate (ACPD) produced an increase in afferent firing rates of the ampullar nerve of the intact posterior canal. This increase was not due to a stimulation of cholinergic efferent terminals or the acetylcholine (ACh) receptor, since atropine, in concentrations which blocked the response to exogenous acetylcholine, did not affect the response to ACPD. Likewise, ACPD effects were not due to stimulation of postsynaptic NMDA receptors, since the NMDA antagonist d(−)-2-amino-5-phosphonopentanoate (AP-5) did not affect the response to ACPD, reinforcing the reported selectivity of ACPD for mGluRs. When the SCC was superfused with artificial perilymph known to inhibit hair cell transmitter release (i.e. low Ca-high Mg), ACPD failed to increase afferent firing. This suggests that the receptor activated by ACPD is located on the hair cell. Pharmacological evidence suggested that the mGluRs involved in afferent facilitation belong to Group I (i.e. subtypes 1 and 5). In fact, the Group III agonist AP-4 had no effect, and the ACPD facilitatory effect was blocked by the Group I mGluR antagonists ( S)-4-carboxyphenylglycine (CPG) and ( RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA). Additional pharmacological evidence supported the presence of Group I mGluRs. Interestingly, the mGluR antagonists, AIDA and 4CPG, by themselves did not affect the resting firing rates of ampullar afferents. This may suggest that the mGluRs are not involved in resting activity but perhaps only in evoked activity (as suggested in Guth et al. (1991) Hear. Res. 56, 69–78). In addition, the mRNA for the mGluR 1 has been detected in hair cells of both SCC, utricle, and saccule. In summary, the evidence points to an mGluR localized to the hair cell (i.e. an autoreceptor) which may be activated to produce a positive feedback augmentation of evoked but not resting transmitter release and thus affect afferent activity.