Afferent Volley Research Articles

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.

Synaptic and Extrasynaptic NMDA Receptors Are Gated by Different Endogenous Coagonists

N-methyl-d-aspartate receptors (NMDARs) are located in neuronal cell membranes at synaptic and extrasynaptic locations, where they are believed to mediate distinct physiological and pathological processes. Activation of NMDARs requires glutamate and a coagonist whose nature and impact on NMDAR physiology remain elusive. We report that synaptic and extrasynaptic NMDARs are gated by different endogenous coagonists, d-serine and glycine, respectively. The regionalized availability of the coagonists matches the preferential affinity of synaptic NMDARs for d-serine and extrasynaptic NMDARs for glycine. Furthermore, glycine and d-serine inhibit NMDAR surface trafficking in a subunit-dependent manner, which is likely to influence NMDARs subcellular location. Taking advantage of this coagonist segregation, we demonstrate that long-term potentiation and NMDA-induced neurotoxicity rely on synaptic NMDARs only. Conversely, long-term depression requires both synaptic and extrasynaptic receptors. Our observations provide key insights into the operating mode of NMDARs, emphasizing functional distinctions between synaptic and extrasynaptic NMDARs in brain physiology.

Requirement of neuronal connexin36 in pathways mediating presynaptic inhibition of primary afferents in functionally mature mouse spinal cord

Electrical synapses formed by gap junctions containing connexin36 (Cx36) promote synchronous activity of interneurones in many regions of mammalian brain; however, there is limited information on the role of electrical synapses in spinal neuronal networks. Here we show that Cx36 is widely distributed in the spinal cord and is involved in mechanisms that govern presynaptic inhibition of primary afferent terminals. Electrophysiological recordings were made in spinal cord preparations from 8- to 11-day-old wild-type and Cx36 knockout mice. Several features associated with presynaptic inhibition evoked by conditioning stimulation of low threshold hindlimb afferents were substantially compromised in Cx36 knockout mice. Dorsal root potentials (DRPs) evoked by low intensity stimulation of sensory afferents were reduced in amplitude by 79% and in duration by 67% in Cx36 knockouts. DRPs were similarly affected in wild-types by bath application of gap junction blockers. Consistent with presynaptic inhibition of group Ia muscle spindle afferent terminals on motoneurones described in adult cats, conditioning stimulation of an adjacent dorsal root evoked a long duration inhibition of monosynaptic reflexes recorded from the ventral root in wild-type mice, and this inhibition was antagonized by bicuculline. The same conditioning stimulation failed to inhibit monosynaptic reflexes in Cx36 knockout mice. Immunofluorescence labelling for Cx36 was found throughout the dorsal and ventral horns of the spinal cord of juvenile mice and persisted in mature animals. In deep dorsal horn laminae, where interneurones involved in presynaptic inhibition of large diameter muscle afferents are located, cells were extensively dye-coupled following intracellular neurobiotin injection. Coupled cells displayed Cx36-positive puncta along their processes. Our results indicate that gap junctions formed by Cx36 in spinal cord are required for maintenance of presynaptic inhibition, including the regulation of transmission from Ia muscle spindle afferents. In addition to a role in presynaptic inhibition in juvenile animals, the persistence of Cx36 expression among spinal neuronal populations in the adult mouse suggests that the contribution of electrical synapses to integrative processes in fully mature spinal cord may be as diverse as that found in other areas of the CNS.

A new signalling pathway for parallel fibre presynaptic type 4 metabotropic glutamate receptors (mGluR4) in the rat cerebellar cortex

In the rodent cerebellum, pharmacological activation of mGluR4 acutely depresses excitatory synaptic transmission at parallel fibre–Purkinje cell synapses. This depression involves the inhibition of presynaptic calcium (Ca2+) influx that ultimately controls glutamate release. In this study, we investigate the molecular basis of mGluR4-mediated inhibition of presynaptic Ca2+ transients. Our results demonstrate that the mGluR4 effect does not depend on selective inhibition of a specific type of presynaptic voltage-gated Ca2+ channel, but rather involves modulation of all classes of Ca2+ channels present in the presynaptic terminals. In addition, this inhibitory effect does not involve the activation of G protein-activated inwardly rectifying potassium channels, TEA-sensitive potassium channels or two-pore-domain potassium channels. Furthermore, this inhibition does not require pertussis toxin-sensitive G proteins, and is independent of any effect on adenylyl cyclases, protein kinase A, mitogen-activated protein kinases or phosphoinositol-3 kinase activity. Interestingly we found that mGluR4 inhibition of presynaptic Ca2+ influx employs a newly defined signalling pathway, notably that involving the activation of phospholipase C and ultimately protein kinase C.

Short-term plasticity of human spinal inhibitory circuits after isometric and isotonic ankle training

The purpose of this study was to determine to what extent one session of isotonic and isometric ankle dorsi and plantar flexion training induces changes in the frequency-dependent depression of the soleus H-reflex. Further, adaptation of reciprocal Ia inhibition exerted from tibialis anterior flexor group I afferents on soleus motoneurons, and presynaptic inhibition of Ia afferent terminals induced by a conditioning afferent volley following stimulation of the antagonist nerve were established with subjects seated before and after training. The soleus H-reflexes evoked at the inter-stimulus intervals of 1, 2, 3, 5, and 8s were normalized to the mean amplitude of the H-reflex evoked every 10s. Conditioned H-reflexes were normalized to the associated control H-reflex evoked with subjects seated before and after training. Twenty-six subjects were randomly assigned to one or more of the 4 exercise groups. Isometric ankle dorsi flexion training decreased the reciprocal and presynaptic inhibition, while isotonic ankle dorsi flexion had no significant effects. Isotonic plantar flexion training decreased only the reciprocal inhibition, whilst isometric plantar flexion had no significant effects on the reciprocal or presynaptic inhibition. None of the training exercise protocols affected the amount of homosynaptic depression of the soleus H-reflex. Our findings support the notion that plastic changes of reciprocal and presynaptic inhibition due to exercise are transferrable to a resting state, and that homosynaptic depression remains unaltered after a single session of ankle training. Further research is needed to outline the time-course of plastic changes of spinal inhibitory mechanisms in humans.

Precise temporal association between cortical potentials evoked by motor imagination and afference induces cortical plasticity

In monkeys, the repeated activation of somatosensory afferents projecting onto the motor cortex (M1) has a pivotal role in motor skill learning. Here we investigate if sensory feedback that is artificially generated at specific times during imagination of a dorsiflexion task leads to reorganization of the human M1. The common peroneal nerve was stimulated to generate an afferent volley timed to arrive during specific phases of the cortical potential generated when a movement was imagined (50 repetitions). The change in the output of M1 was quantified by applying single transcranial magnetic stimuli to the area of M1 controlling the tibialis anterior muscle. The results demonstrated that the concomitance between the cognitive process of movement (motor imagination) and the ascending volley due to the peripheral nerve stimulation can lead to significant increases in cortical excitability. These increases were critically dependent on the timing between the peripherally generated afferent volley and the cortical potential generated during the imagined movement. Only if the afferent volley arrived during the peak negative deflection of the potential, were significant alterations in motor cortical output attained. These results demonstrate that an artificially generated signal (the peripheral afferent volley) can interact with a physiologically generated signal in humans leading to plastic changes within the M1, the final output stage for movement generation within the human brain. The results presented may have implications in systems for artificially inducing cortical plasticity in patients with motor impairments (neuromodulation).

Effects of Near-Threshold Stimulation of the Vestibular Apparatus on Postural Responses Evoked by Displacements of the Visualized Surrounding

In healthy subjects in the relaxed upward stance and perceiving a virtual visual environment (VVE), we recorded postural reactions to isolated visual and vestibular stimulations or their combinations. Lateral displacements of the visualized virtual scene were used as visual stimuli. The vestibular apparatus was stimulated by application of near-threshold galvanic current pulses to the proc. mastoidei of the temporal bones. Isolated VVE shifts evoked mild, nonetheless clear, body tilts readily distinguished in separate trials; at the same time, postural effects of isolated vestibular stimulation could be detected only after averaging of several trials synchronized with respect to the beginning of stimulation. Under conditions of simultaneous combined presentation of visual and vestibular stimuli, the direction of the resulting postural responses always corresponded to the direction of responses induced by VVE shifts. The contribution of an afferent volley from the vestibular organ depended on the coincidence/mismatch of the direction of motor response evoked by such a volley with the direction of response to visual stimulation. When both types of stimulations evoked unidirectional body tilts, postural responses were facilitated, and the resulting effect was greater than that of simple summation of the reactions to isolated actions of the above stimuli. In the case where isolated galvanic stimulation evoked a response opposite with respect to that induced by visual stimulation, the combined action of these stimuli of different modalities evoked postural responses identical in their magnitude, direction, and shape to those evoked by isolated visual stimulation. The above findings allow us to conclude that the effects of visual afferent input on the vertical posture under conditions of our experiments clearly dominate. In general, these results confirm the statement that neuronal structures involved in integrative processing of different afferent volleys preferably select certain type of afferentation carrying more significant or more detailed information on displacements (including oscillations) of the body in space.

Subthalamic nucleus stimulation reverses spinal motoneuron activity in parkinsonian patients

Although a cardinal symptom of Parkinsonian disease, up to now, rigidity has been investigated much less than spasticity in hemiplegic patients. Many pathophysiological mechanisms may at least theoretically contribute to Parkinsonian rigidity, from altered viscoelastic muscle properties to inability of parkinsonian patients to relax. However, as demonstrated many years ago, motoneuron responses to muscle afferent volleys are involved in rigidity since afferent volleys are suppressed after dorsal root section. To our knowledge, homosynaptic depression (i.e. the fact that motoneuron responses to Ia afferent volleys exhibit a frequency-related depression) has not been studied in parkinsonian disease, despite the fact that in spastic patients, changes in homosynaptic depression are significantly correlated at wrist and ankle levels with the severity of spasticity. Thus, in the present series of experiments, we investigated in parkinsonian patients with chronic implantation of both subthalamic motor nuclei, the amount of homosynaptic depression at wrist and ankle levels on and off deep brain stimulation. Off deep brain stimulation, the frequency-related depression disappeared, the patients became rigid and the amount of homosynaptic depression was significantly correlated with the severity of rigidity. On deep brain stimulation, the frequency-related depression was restored and the rigidity suppressed, suggesting that homosynaptic depression is one of the mechanisms underlying rigidity in Parkinson's disease. Moreover, the unexpected finding that changes in the rigidity score and the amount of homosynaptic depression are time-locked to the onset of deep brain stimulation leads us to reconsider the mechanisms underlying changes in homosynaptic depression.

Cutaneous afferent input does not modulate motor intracortical inhibition in ageing men

Afferent input has been shown to be a powerful modulator of cortical inhibition. Such modulation is likely to be important for the control of ongoing movement, but may also play a role in facilitating neuroplastic reorganisation. Human motor control and neuroplasticity both decline with ageing, whereas the efficacy of short-interval intracortical inhibition (SICI) appears not to. We examined if ageing alters the efficacy of afferent modulation of SICI. Previously, electrical cutaneous stimulation of a finger has been shown to reduce SICI in the motor cortices of young adults. Paired-pulse transcranial magnetic stimulation was used to assess SICI in the cortical representation of the first dorsal interosseous muscle. SICI was assessed separately under two conditions: with and without prior afferent input from electrical cutaneous stimulation of the index finger. Fifteen 'young' (20.1 ± 2.1 years) and 15 'old' male humans (65.5 ± 3.9 years) were studied. SICI did not differ when young and old males were compared. However, when preceded by electrical cutaneous finger stimulation, SICI was reduced in young men but not old men. Reflex testing indicated preservation of the afferent volley to the cortex. These findings suggest that a contributing factor in the decline of motor function, and possibly neuroplasticity, with ageing is loss of SICI modulation, probably due to altered cortical sensorimotor integration of afferent input.

Enhanced propriospinal excitation from hand muscles to wrist flexors during reach-to-grasp in humans

In humans, propriospinal neurons located at midcervical levels receive peripheral and corticospinal inputs and probably participate in the control of grip tasks, but their role in reaching movements, as observed in cats and primates, is still an open question. The effect of ulnar nerve stimulation on flexor carpi radialis (FCR) motor evoked potential (MEP) was tested during reaching tasks and tonic wrist flexion. Significant MEP facilitation was observed at the end of reach during reach-to-grasp but not during grasp, reach-to-point, or tonic contractions. MEP facilitation occurred at a longer interstimulus interval than expected for convergence of corticospinal and afferent volleys at motoneuron level and was not paralleled by a change in the H-reflex. These findings suggest convergence of the two volleys at propriospinal level. Ulnar-induced MEP facilitation was observed when conditioning stimuli were at 0.75 motor response threshold (MT), but not 1 MT. This favors an increased excitability of propriospinal neurons rather than depression of their feedback inhibition, as has been observed during tonic power grip tasks. It is suggested that the ulnar-induced facilitation of FCR MEP during reach may be due to descending activation of propriospinal neurons, assisting the early recruitment of large motoneurons for rapid movement. Because the feedback inhibitory control is still open, this excitation can be truncated by cutaneous inputs from the palmar side of the hand during grasp, thus assisting movement termination. It is concluded that the feedforward activation of propriospinal neurons and their feedback control may be involved in the internal model, motor planning, and online adjustments for reach-to-grasp movements in humans.

Quadrupedal coordination of bipedal gait: implications for movement disorders

During recent years, evidence has come up that bipedal locomotion is based on a quadrupedal limb coordination. A task-dependent neuronal coupling of upper and lower limbs allows one to involve the arms during gait but to uncouple this connection during voluntarily guided arm/hand movements. Hence, despite the evolution of a strong cortico-spinal control of hand/arm movements in humans, a quadrupedal limb coordination persists during locomotion. This has consequences for the limb coordination in movement disorders such as in Parkinson's disease (PD) and after stroke. In patients suffering PD, the quadrupedal coordination of gait is basically preserved. The activation of upper limb muscles during locomotion is strong, similar as in age-matched healthy subjects although arm swing is reduced. This suggests a contribution of biomechanical constraints to immobility. In post-stroke subjects a close interactions between unaffected and affected sides with an impaired processing of afferent input takes place. An afferent volley applied to a leg nerve of the unaffected leg leads to a normal reflex activation of proximal arm muscles of both sides. In contrast, when the nerve of the affected leg was stimulated, neither on the affected nor in the unaffected arm muscles EMG responses appear. Muscle activation on the affected arm becomes normalized by influences of the unaffected side during locomotion. These observations have consequences for the rehabilitation of patients suffering movement disorders.

SKF83959 suppresses excitatory synaptic transmission in rat hippocampus via a dopamine receptor‐independent mechanism

Dopamine (DA) profoundly modulates excitatory synaptic transmission and synaptic plasticity in the brain. In the present study the effects of SKF83959, the selective agonist of phosphatidylinositol (PI)-linked D(1) -like receptor, on the excitatory synaptic transmission were investigated in rat hippocampus. SKF83959 (10-100 μM) reversibly suppressed the field excitatory postsynaptic potential (fEPSP) elicited by stimulating the Schaffer's collateral-commissural fibers in CA1 area of hippocampal slices. However, the inhibition was not blocked by the D(1) receptor antagonist SCH23390, the D(2) receptor antagonist raclopride, the 5-HT(2A/2C) receptor antagonist mesulergine, or the α(1) -adrenoceptor antagonist prazosin. In addition, SKF83959 inhibited the afferent volley and significantly reduced the paired-pulse facilitation ratios. In dissociated hippocampal CA1 pyramidal neurons, SKF83959 had no detectable effect on glutamate-induced currents but potently inhibited voltage-activated Na(+) current (IC50 value = 26.9 ± 1.0 μM), which was not blocked by SCH23390 or by intracellular dialysis of GDP-β-S. These results demonstrate that SKF83959 suppressed the excitatory synaptic transmission in hippocampal CA1 area, which was independent of D(1) -like receptor. The mechanism underlying the effect could be mainly inhibition of Na(+) channel in the afferent fibers. The suppression of excitatory synaptic transmission and the Na(+) channel by SKF83959 may contribute to its therapeutic benefits in Parkinson's disease.

Effect of chronic undernourishment on the cord dorsum potentials and the primary afferent depolarization evoked by cutaneous nerves in the rat spinal cord

The effect of chronic undernourishment on the cord dorsum potentials (CDPs) and the dorsal root potential (DRP), closely related to primary afferent depolarization (PAD) and presynaptic inhibition in the spinal cord of the rat, was analyzed in this study. Single electrical pulses applied to the sural nerve (SU) of control ( n = 14) and chronically undernourished ( n = 16) Wistar rats produced CDPs, which are composed of four components: afferent volley (AV), two negative components (N 1 and N 2), and one positive component (P wave) and negative DRPs recorded in a small rootlet of the L6 segment of the rat. The CDPs of the control and undernourished rats with AV components of comparable amplitude (U AV/C AV = 0.96), showed N 1 components of similar amplitude ( U N 1 / C N 1 = 0.94 ), but smaller P wave (U PW/C PW = 0.23). A comparable reduction in the amplitude of the DRPs was obtained in the undernourished rats (U DRP/C DRP = 0.36). When normalized as a function of the body mass of the animals, the CDPs and DRPs produced in undernourished rats were of significantly smaller normalized amplitude than those evoked in the control. According to these results, it is suggested that chronic undernourishment induce a depressive effect on the mechanisms generating the P wave component in the CDP and the DRPs either by decreasing the sensory input and/or the excitability of the dorsal horn neurones involved in the generation of PAD and presynaptic inhibition in the spinal cord of the rat.

Locomotion in stroke subjects: interactions between unaffected and affected sides

The aim of this study was to evaluate the sensorimotor interactions between unaffected and affected sides of post-stroke subjects during locomotion. In healthy subjects, stimulation of the tibial nerve during the mid-stance phase is followed by electromyography responses not only in the ipsilateral tibialis anterior, but also in the proximal arm muscles of both sides, with larger amplitudes prior to swing over an obstacle compared with normal swing. In post-stroke subjects, the electromyography responses were stronger on both sides when the tibial nerve of the unaffected leg was stimulated compared with stimulation of the affected leg. This difference was more pronounced when stimuli were applied prior to swing over an obstacle than prior to normal swing. This indicates an impaired processing of afferent input from the affected leg resulting in attenuated and little task-modulated reflex responses in the arm muscles on both sides. In contrast, an afferent volley from the unaffected leg resulted in larger electromyography responses, even in the muscles of the affected arm. Arm muscle activations were stronger during swing over an obstacle than during normal swing, with no difference in electromyography amplitudes between the unaffected and affected sides. It is concluded that the deficits of the affected arm are compensated for by influences from the unaffected side. These observations indicate strong mutual influences between unaffected and affected sides during locomotion of post-stroke subjects, which might be used to optimize rehabilitation approaches.

Vision of the Body Modulates Somatosensory Intracortical Inhibition

The magnitude of somatosensory evoked potentials (SEPs) elicited by simultaneous electrical stimulation of adjacent digits is generally less than the sum of potentials evoked by stimulation of each digit individually. This under-additivity suggests suppression between representations of adjacent skin regions and may reflect a process of lateral inhibition by interneurons in somatosensory cortex. Given that simply viewing the body enhances tactile acuity and that tactile acuity depends on cortical lateral inhibition, we investigated how viewing the body modulates suppressive interactions between simultaneous afferent volleys from adjacent fingers. We recorded SEPs evoked by electrical stimulation of the right index and middle fingers, either individually or simultaneously, while participants viewed either their own hand or an object. In between trains of electrical stimuli, participants discriminated the orientation of tactile gratings applied to either finger. Consistent with previous findings, viewing the hand enhanced tactile acuity. Furthermore, viewing the hand increased the suppression of the P50 potential due to simultaneous electrical stimulation of both fingers. Moreover, the visual enhancement of tactile performance correlated across participants with the visual modulation of suppression. These results demonstrate that vision enhances somatosensation by modulating activity of inhibitory interneuronal circuits in the somatosensory cortex.

Neuromuscular electrical stimulation has a global effect on corticospinal excitability for leg muscles and a focused effect for hand muscles

The afferent volley generated during neuromuscular electrical stimulation (NMES) can increase the excitability of human corticospinal (CS) pathways to muscles of the leg and hand. Over time, such increases can strengthen CS pathways damaged by injury or disease and result in enduring improvements in function. There is some evidence that NMES affects CS excitability differently for muscles of the leg and hand, although a direct comparison has not been conducted. Thus, the present experiments were designed to compare the strength and specificity of NMES-induced changes in CS excitability for muscles of the leg and hand. Two hypotheses were tested: (1) For muscles innervated by the stimulated nerve (target muscles), CS excitability will increase more for the hand than for the leg. (2) For muscles not innervated by the stimulated nerve (non-target muscles), CS excitability will increase for muscles of the leg but not muscles of the hand. NMES was delivered over the common peroneal (CP) nerve in the leg or the median nerve at the wrist using a 1-ms pulse width in a 20 s on, 20 s off cycle for 40 min. The intensity was set to evoke an M-wave that was ~15% of the maximal M-wave in the target muscle: tibialis anterior (TA) in the leg and abductor pollicis brevis (APB) in the hand. Ten motor-evoked potentials (MEPs) were recorded from the target muscles and from 2 non-target muscles of each limb using transcranial magnetic stimulation delivered over the "hotspot" for each muscle before and after the NMES. MEP amplitude increased significantly for TA (by 45 ± 6%) and for APB (56 ± 8%), but the amplitude of these increases was not different. In non-target muscles, MEPs increased significantly for muscles of the leg (42 ± 4%), but not the hand. Although NMES increased CS excitability for target muscles to the same extent in the leg and hand, the differences in the effect on non-target muscles suggest that NMES has a "global" effect on CS excitability for the leg and a "focused" effect for the hand. These differences may reflect differences in the specificity of afferent projections to the cortex. Global increases in CS excitability for the leg could be advantageous for rehabilitation as NMES applied to one muscle could strengthen CS pathways and enhance function for multiple muscles.

The effects of paired associative stimulation on knee extensor motor excitability of individuals post-stroke: A pilot study

Objective Paired associative stimulation (PAS) modulates bilateral distal lower limb motor pathways during walking. We assessed the effects of inhibitory PAS applied to the vastus medialis (VM) motor pathways of chronic stroke patients. Methods PAS consisted of 120 electrical stimuli applied to the femoral nerve paired with transcranial magnetic stimulation (TMS) of the lower limb primary motor cortex so that the estimated arrival of the afferent volley occurred 8 ms after delivery of the magnetic stimulus. Stimulus pairs were delivered to the non-paretic VM motor system of 11 chronic stroke patients and the right limb motor system of 11 non-impaired subjects at 0.19 Hz. The effects of PAS on VM motor pathway excitability and muscle activity were assessed during pedaling. TMS-induced motor evoked potential (MEP) amplitudes and the percent of VM activity in the flexion phase of active pedaling (%FLEXVM) was examined before and after PAS. Results Inhibitory PAS reduced VM MEP amplitudes in the target limb ( p < 0.05) of both groups, while post-PAS paretic VM MEP amplitudes increased for some patients and decreased for others. Group mean paretic limb %FLEXVM was not altered by inhibitory PAS. Conclusions These results indicate PAS can be used to manipulate motor cortical excitability in proximal lower limb representations, however the sign of induced modulation was unpredictable and cyclic muscle activity was not modified. Significance The study has important implications for the development of therapies involving non-invasive brain stimulation to modify abnormal motor behavior following stroke.

First Trial Postural Reactions to Unexpected Balance Disturbances: A Comparison With the Acoustic Startle Reaction

Unexpected support-surface movements delivered during stance elicit "first trial" postural reactions, which are larger and cause greater instability compared with habituated responses. The nature of this first trial reaction remains unknown. We hypothesized that first trial postural reactions consist of a generalized startle reaction, with a similar muscle synergy as the acoustic startle response, combined with an automatic postural reaction. Therefore we compared acoustic startle responses to first trial postural reactions. Eight healthy subjects stood on a support surface that unexpectedly rotated backwards 10 times, followed by 10 startling acoustic stimuli, or vice versa. Outcome measures included full body kinematics and surface EMG from muscles involved in startle reactions or postural control. Postural perturbations and startling acoustic stimuli both elicited a clear first trial reaction, as reflected by larger kinematic and EMG responses. The ensuing habituation rate to repeated identical stimuli was comparable for neck and trunk muscles in both conditions. Onset latencies in neck muscles occurred significantly later for first trial perturbations compared with startle responses, but earlier in trunk muscles. Our results show that platform tilting initially induces reactions larger than needed to maintain equilibrium. For neck and trunk muscles, these first trial postural reactions resembled acoustic startle reflexes. First trial postural reactions may be triggered by interaction of afferent volleys formed by somatosensory and vestibular inputs. Acoustic startle reactions may also be partially triggered by vestibular inputs. Similar muscle activation driven by vestibular inputs may be the common element of first trial postural responses and acoustic startle reactions.

Changes in corticospinal excitability evoked by common peroneal nerve stimulation depend on stimulation frequency

The afferent volley generated during neuromuscular electrical stimulation (NMES) can increase the excitability of the human corticospinal (CS) pathway. This study was designed to determine the effect of different frequencies of NMES applied over the common peroneal nerve on changes in CS excitability for the tibialis anterior (TA) muscle. We hypothesized that higher frequencies of stimulation would produce larger increases in CS excitability than lower frequencies. NMES was applied at 10, 50, 100, or 200 Hz during separate sessions held at least 48 h apart. The stimulation was delivered in a 20 s on, 20 s off cycle for 40 min using a 1 ms pulse width. The intensity of stimulation was set to evoke an M-wave in response to a single pulse that was 15% of the maximal M-wave. CS excitability was evaluated by the amplitude of motor-evoked potentials (MEPs) in TA evoked by transcranial magnetic stimulation. MEPs were recorded immediately before and after the 40 min of NMES and in each 20 s "off" period. For each subject, MEPs recorded during three successive "off" periods were averaged together (n = 9 MEPs), providing a temporal resolution of 2 min for assessing changes in CS excitability. When delivering NMES at 100 Hz, MEPs became significantly elevated from those evoked before the stimulation at the 24th min, and there was a twofold increase in MEP amplitude after 40 min. NMES delivered at 10, 50, and 200 Hz did not significantly alter MEP amplitude. The amplitude of MEPs evoked in soleus and vastus medialis followed similar patterns as those evoked simultaneously in TA, but these changes were mostly not of statistical significance. There were no changes in the ratio of maximal H-reflex to maximal M-wave in TA or soleus. These experiments demonstrate a frequency-dependent effect of NMES on CS excitability for TA and show that, under the conditions of the present study, 100-Hz stimulation was more effective than 10, 50, and 200 Hz. This effect of NMES on CS excitability was strongest in the stimulated muscle and may be mediated primarily at a supraspinal level. These results contribute to a growing body of knowledge about how the afferent volley generated during NMES influences the CNS and have implications for identifying optimal NMES parameters to augment CS excitability for rehabilitation of dorsiflexion after CNS injury.

Face-Related Ictal Hallucinations and Illusions and Reflex-Type Phenomena

Face-Related Ictal Hallucinations and Illusions and Reflex-Type Phenomena