Enhancing plasticity through repeated rTMS sessions: The benefits of a night of sleep

Objective

Previous work has demonstrated that corticospinal facilitation from 20 Hz repetitive transcranial magnetic stimulation (rTMS) was greater during a second rTMS session 24 h after the first. We sought to determine whether such metaplasticity is dependent on a particular phase of the normal sleep–wake/circadian cycle.

Methods

Twenty healthy participants received two sessions of 20 Hz rTMS over the hand motor cortex (M1) spaced 12 h apart, either over-day or overnight.

Results

Baseline corticospinal excitability did not differ by group or session. The time-of-day of Session 1 did not influence the relative increase in excitability following rTMS. However, the increase in excitability from the second rTMS session was 2-fold greater in the overnight group.

Conclusions

When a night with sleep follows rTMS to M1, the capacity to induce subsequent plasticity in M1 is enhanced, suggesting sleep–wake and/or circadian-dependent modulation of processes of metaplasticity.

Significance

TMS treatment of neuropsychiatric disorders entails repeated sessions of rTMS. Our findings suggest that the timing of sessions relative to the sleep–wake/circadian cycle may be a critical factor in the cumulative effect of treatment. Future studies using this paradigm may provide mechanistic insights into human metaplasticity, leading to refined strategies to enhance non-invasive stimulation therapies.     

Modulation of intracortical inhibition in response to acute psychosocial stress is impaired among individuals with chronic neck pain

Objective

Psychosocial stress has been associated with a variety of chronic pain disorders although the mechanisms responsible for this relationship are unknown. The purpose of this study was to compare the excitability of intracortical and corticospinal pathways to the trapezius muscle in individuals with and without chronic neck pain during exposure to low and high levels of psychosocial stress.

Methods

Single and paired-pulse transcranial magnetic stimulation was used to assess motor evoked potentials (MEPs) and short-interval intracortical inhibition (SICI) during mental math performed in the presence and absence of social evaluative threat.

Results

All participants demonstrated higher amplitude MEPs in the high stress compared to the low stress condition (p < 0.01). Participants with chronic neck pain had significantly greater SICI than healthy participants in the low stress condition (p = 0.03). During exposure to the stressor, healthy participants showed an increase in SICI, whereas participants with neck pain showed no change (group difference for change in SICI, p < 0.01).

Conclusions

These findings suggest that individuals with chronic neck pain inhibit motor output to the trapezius in the presence of minor stressors, and are unable to compensate for additional stress-evoked increases in corticospinal excitability through further modulation of SICI. This observation has potential implications for the management of patients who have difficulty relaxing painful muscles during times of stress.     

Cortico-conus motor conduction time (CCCT) for leg muscles

Objective

To measure the conduction time from the motor cortex to the conus medullaris (cortico-conus motor conduction time, CCCT) for leg muscles using magnetic stimulation.

Methods

Motor evoked potentials (MEPs) were recorded from tibialis anterior muscles in 51 healthy volunteers. To activate spinal nerves at the most proximal cauda equina level or at the conus medullaris level, magnetic stimulation was performed using a MATS coil. Transcranial magnetic stimulation of the motor cortex was also conducted to measure the cortical latency for the target muscle. To obtain the CCCT, the latency of MEPs to conus stimulation (conus latency) was subtracted from the cortical latency.

Results

MATS coil stimulation evoked reproducible MEPs in all subjects, yielding CCCT data for all studied tibialis anterior muscles.

Conclusions

MATS coil stimulation provides CCCT data for healthy subjects.

Significance

This novel method is useful for evaluation of corticospinal tract function for leg muscles because no peripheral component affects the CCCT.     

Reduced reciprocal inhibition during assisted stepping in human spinal cord injury

The aim of this study was to establish the modulation pattern of the reciprocal inhibition exerted from tibialis anterior (TA) group I afferents onto soleus motoneurons during body weight support (BWS) assisted stepping in people with spinal cord injury (SCI). During assisted stepping, the soleus H-reflex was conditioned by percutaneous stimulation of the ipsilateral common peroneal nerve at one fold TA M-wave motor threshold with a single pulse delivered at a short conditioning-test interval. To counteract movement of recording and stimulating electrodes, a supramaximal stimulus at 80–100 ms after the test H-reflex was delivered. Stimuli were randomly dispersed across the step cycle which was divided into 16 equal bins. The conditioned soleus H-reflex was significantly facilitated throughout the stance phase, while during swing no significant changes on the conditioned H-reflex were observed when compared to the unconditioned soleus H-reflex recorded during stepping. Spontaneous clonic activity in triceps surae muscle occurred in multiple phases of the step cycle at a mean frequency of 7 Hz for steps with and without stimulation. This suggests that electrical excitation of TA and soleus group Ia afferents did not contribute to manifestation of ankle clonus. Absent reciprocal inhibition is likely responsible for lack of soleus H-reflex depression in swing phase observed in these patients. The pronounced reduced reciprocal inhibition in stance phase may contribute to impaired levels of co-contraction of antagonistic ankle muscles. Based on these findings, we suggest that rehabilitation should selectively target to transform reciprocal facilitation to inhibition through computer controlled reflex conditioning protocols.     

Which electrophysiological measure is appropriate in predicting prognosis of facial paralysis?

Objective

The prognostic value of electrophysiology and its significance in the prediction facial function outcome in facial palsy patients remains unclear because of the different methodologies used in previous studies. We aimed to establish the prognostic value of electrophysiological testing in a group of patients with facial palsy.

Methods

We prospectively analyzed facial nerve electrophysiology results and compared them with the House–Brackmann scale in 65 patients. The treatment consisted of a standard corticosteroid plus antiviral regimen. Clinical evaluation comprised the House–Brackmann grading system and electrophysiological tests (nerve excitability, nerve conduction study (NCS), needle electromyography (EMG), and blink reflex) conducted on the 5th, 20th, and 90th days after paralysis onset.

Results

In predicting the prognosis, the nerve excitability test in the acute phase, NCS in the subacute phase, blink reflex in the acute and subacute phases and needle EMG in the subacute phase provided statistically significant results.

Conclusion

Prognosis can be determined, and excessive tests can be eliminated with proper timing and electrophysiological testing.

Significance

In determining the prognosis of facial paralysis, the nerve excitability test should be used in the acute phase, and NCS and needle EMG should be used in the subacute phase. Blink reflex studies are helpful in both the acute and subacute phases.     

Longitudinal changes of motor cortical excitability and transcallosal inhibition after subcortical stroke

Objective

A general lack of longitudinal studies on interhemispheric interactions following stroke led us to use transcranial magnetic stimulation (TMS) to examine changes in corticospinal/intracortical excitability and transcallosal inhibition over a 1-year period following subcortical stroke.

Methods

We measured TMS parameters such as motor threshold (MT), short-interval intracortical inhibition (SICI), and ipsilateral silent period (iSP) and evaluated clinical scores at three time-points (T1, T2, and T3) in 24 patients and 25 age-matched healthy subjects.

Results

At T1, we observed reduced MTs and SICIs with prolonged iSPs in the unaffected hemisphere (UH). In contrast, increased MTs and reduced SICIs were observed in the affected hemisphere (AH). These abnormalities gradually reduced and no MEP response to TMS at T1 predicted a worse prognosis. The prolonged iSP at T1 was associated with more severe impairments, but it did not necessarily predict a worse prognosis after 1 year.

Conclusions

UH excitability was increased at the post-acute time-period, which may have resulted in enhanced transcallosal inhibition to the AH. However, it is unclear whether there was a causal relationship between the enhanced transcallosal inhibition and the extent of clinical recovery.

Significance

This is the first study to demonstrate changes in transcallosal inhibition over a longitudinal period following stroke.     

Facilitation of corticospinal excitability in the tibialis anterior muscle during robot-assisted passive stepping in humans

Although phasic modulation of the corticospinal tract excitability to the lower limb muscles has been observed during normal walking, it is unclear to what extent afferent information induced by walking is related to the modulation. The purpose of this study was to test the corticospinal excitability to the lower limb muscles by using transcranial magnetic stimulation (TMS) and transcranial electrical stimulation of the motor cortex while 13 healthy subjects passively stepped in a robotic driven-gait orthosis. Specifically, to investigate the effect of load-related afferent inputs on the corticospinal excitability during passive stepping, motor evoked potentials (MEPs) in response to the stimulation were compared between two passive stepping conditions: 40% body weight unloading on a treadmill (ground stepping) and 100% body weight unloading in the air (air stepping). In the rectus femoris, biceps femoris and tibialis anterior (TA) muscles, electromyographic activity was not observed throughout the step cycle in either stepping condition. However, the TMS-evoked MEPs of the TA muscle at the early- and late-swing phases as well as at the early-stance phase during ground stepping were significantly larger than those observed during air stepping. The modulation pattern of the transcranial electrical stimulation-evoked MEPs was similar to that of the TMS-evoked MEPs. These results suggest that corticospinal excitability to the TA is facilitated by load-related afferent inputs. Thus, these results might be consistent with the notion that load-related afferent inputs play a significant role during locomotor training for gait disorders.     

Differential control of H-reflex amplitude in different weight-bearing conditions in young and elderly subjects

Objective

This study measured the modulation of conditioned (femoral nerve, paired-stimuli) and unconditioned soleus H-reflexes in young and elderly subjects when changing weight-bearing (WB) requirements and body position.

Methods

Conditioned and unconditioned H-reflexes were examined in 14 elderly subjects and 11 young subjects during six different WB conditions: (1) lying supine with no WB, (2) supine position inclined by 30° with 50% WB, (3) standing with 50%, (4) 75%, (5) 100% and (6) 125% WB.

Results

The elderly subjects had consistently higher background soleus EMG activity across the WB conditions compared to the young. Femoral nerve conditioning caused facilitation of the H-reflex that changed across WB conditions in the young subjects, but not in the elderly subjects. Finally, elderly subjects had less depression with paired-stimulation (PRD) across WB conditions, which was not observed in the young subjects.

Conclusions

The elderly may have more direct activation of motoneurons from descending pathways, coupled with less segmental spinal control of inhibitory interneurons, as evidenced by the increased background soleus activity, H/M-max ratios and the lack of modulatory control observed when conditioning the H-reflex.

Significance

There was an age-specific response from descending and segmental pathways during conditions that involved either different WB requirements or changes in body position.     

Potentiating paired corticospinal-motoneuronal plasticity after spinal cord injury

Background

Paired corticospinal-motoneuronal stimulation (PCMS) increases corticospinal transmission in humans with chronic incomplete spinal cord injury (SCI).Objective/Hypothesis: Here, we examine whether increases in the excitability of spinal motoneurons, by performing voluntary activity, could potentiate PCMS effects on corticospinal transmission.

Ascending beta oscillation from finger muscle to sensorimotor cortex contributes to enhanced steady-state isometric contraction in humans

Objective

β-Band corticomuscular coherence is suggested as an electrophysiological mechanism that contributes to sensorimotor functioning in the maintenance of steady-state contractions. Converging evidence suggests that not only the descending corticospinal pathway but the ascending sensory feedback pathway is involved in the generation of β-band corticomuscular coherence. The present study aimed to investigate which pathway, descending vs. ascending, contributes more to the stability of muscle contraction, especially for human intrinsic hand muscles.

Methods

In this study, we assessed directed transfer function (DTF) between magnetoencephalography signals over the sensorimotor cortex (SMC) and rectified electromyographic (EMG) signals recorded during steady-state isometric contraction of the right thumb muscle (flexor pollicis brevis, FPB) or right little finger muscle (flexor digiti minimi brevis, FDMB) in 15 right-handed healthy subjects.

Results

β-Band DTF was statistically significant in both descending (SMC → EMG) and ascending (EMG → SMC) directions, and mean phase delays for each direction were in agreement with the conduction time for the descending corticospinal and ascending sensory feedback pathways. The strengths of the β-band DTF (EMG → SMC direction) were greater in the FPB muscle than in the FDMB muscle, while the strengths of the β-band DTF (SMC → EMG direction) were not different between the two muscles. Moreover, the β-band DTF (EMG → SMC direction) was greater in the “Stable” period than in the “Less Stable” period within the FDMB muscle. Greater DTF (EMG → SMC direction) was positively associated with the stability of muscle contraction.

Conclusions

Our findings suggest that ascending β-band oscillatory activity may promote a steady-state isometric contraction by efficiently transmitting sensory feedback from finger muscles to the sensorimotor cortex.

Significance

The results show the differential contribution of the ascending part of the corticomuscular network depending on the functional organization.     

Synchronized finger exercise reduces surround inhibition

Objective

To investigate whether hand muscle repetitive use reduces surround inhibition (SI) as observed in patients with focal hand dystonia, we performed a transcranial magnetic stimulation (TMS) study in 15 healthy right-handed volunteers.

Methods

TMS was set to be triggered by self-initiated flexion of the index finger at 3 ms after movement onset. Motor evoked potentials (MEPs) of the abductor digiti minimi (ADM) were measured before and at 0, 10, 20 and 30 min after ‘single’ (little finger abduction) and ‘dual’ (both index finger flexion and little finger abduction) exercise at 0.5 Hz for 30 min. SI was calculated as (mean control MEP – mean self-triggered MEP) × 100/mean control MEP.

Results

Compared to single exercise, dual exercise produced significantly larger and longer-lasting enhancements of self-triggered MEPs, and greater reduction in calculated SIs.

Conclusions

This result demonstrates that synchronized finger exercise can reduce SI between the involved muscles possibly due either to the strengthening of the excitatory connections or to the weakening of the inhibitory connections between them, and may illustrate the association between hand muscle repetitive use and disturbed SI observed in FHD.

Significance

The operation of surround inhibition can be reduced by practicing synchronous movements.     

Distinguishing active from passive components of ankle plantar flexor stiffness in stroke,spinal cord injury and multiple sclerosis

Objective

Spasticity is a common manifestation of lesion of central motor pathways. It is essential for correct anti-spastic treatment that passive and active contributions to increased muscle stiffness are distinguished. Here, we combined biomechanical and electrophysiological evaluation to distinguish the contribution of active reflex mechanisms from passive muscle properties to ankle joint stiffness in 31 healthy, 10 stroke, 30 multiple sclerosis and 16 spinal cord injured participants. The results were compared to routine clinical evaluation of spasticity.

Methods

A computer-controlled robotic device applied stretches to the ankle plantar flexor muscles at different velocities (8–200 deg/s; amplitude 6°). The reflex threshold was determined by soleus EMG. Torque and EMG data were normalized to the maximal torque and EMG evoked by supramaximal stimulation of the tibial nerve. Passive resistance (the torque response to stretches) was confirmed to be a good representation of the passive stiffness also at higher velocities when transmission in the tibial nerve was blocked by ischemia.

Results

Passive torque tended to be larger in the neurological than in the healthy participants, but it did not reach statistical significance, except in the stroke group (p < 0.05). Following normalization to the maximal stimulus-evoked torque, the passive torque was found to be significantly larger in neurological participants identified with spasticity than in non-spastic participants (p < 0.01). There was no significant difference in the reflex threshold between the healthy and the neurological participants. The reflex evoked torque and EMG were significantly larger in all neurological groups than in the healthy group (p < 0.001). Twenty three participants with evidence of hypertonia in the plantar flexors (Ashworth score ? 1) showed normal reflex torque without normalization. With normalization this was only the case in 11 participants. Increased reflex mediated stiffness was detected in only 64% participants during clinical examination.

Conclusion

The findings confirm that the clinical diagnosis of spasticity includes changes in both active and passive muscle properties and the two can hardly be distinguished based on routine clinical examination.

Significance

The data suggest that evaluation techniques which are more efficient in distinguishing active and passive contributions to muscle stiffness than routine clinical examination should be considered before anti-spastic treatment is initiated.     

Intermittent theta-burst stimulation induces correlated changes in cortical and corticospinal excitability in healthy older subjects

Objective

We studied the correlation between motor evoked potentials (MEPs) and early TMS-evoked EEG potentials (TEPs) from single-pulse TMS before and after intermittent Theta Burst Stimulation (iTBS) to the left primary motor cortex (M1) in 17 healthy older participants.

Modification of altered ankle motor control after stroke using focal application of botulinum toxin type A

Study design

Blinded, placebo-controlled, prospective clinical trial.

Purpose

To examine the effects of botulinum toxin type A (BTX-A) injections into plantar flexor muscles in stroke patients with equinovarus gait.

Subjects

15 post-stroke and 10 matched neurologically intact subjects.

Methods

Modified Ashworth Scale (MAS) and Fugl–Meyer assessment of physical function scale scores along with surface EMG collected before and up to 12 weeks after BTX-A injections to plantar flexor muscle motor points in stroke subjects. Saline placebo injections were performed in a subset of stroke subject group.

Results

MAS scores were decreased at 4, 8 and 12 weeks but F–M scores did not improve until 12 weeks post injection. Multi-muscle EMG patterns showed the return of volitional dorsiflexor activity in 11 and a decrease of antagonistic and distant coactivation in all but one of the 15.

Conclusions

BTX-A is effective in reducing antagonistic and distant muscle activation that impedes volitional dorsiflexion.     

Age-related changes in the control of perturbation-evoked and voluntary arm movements

Objective

This study examined how handrail location predictability affects perturbation-evoked arm responses in young and older adults and whether age-related changes in perturbation-evoked arm responses are specific to mechanisms associated with reactive postural control.

Methods

Young and older adults reached for a handrail in response to a support surface translation (perturbation-evoked) or to a visual cue (voluntary). For both movement tasks, the handrail location was made predictable or unpredictable to the participant. Electromyographic (EMG) activity and kinematics of the reaching arm were recorded to quantify the arm response.

Results

Posterior deltoid EMG activity during perturbation-evoked and voluntary movements were delayed by 15–74 ms (p < 0.001) and 16% smaller (p = 0.024) when the handrail was in an unpredictable compared to a predictable location. While ageing resulted in a 12–16 ms delayed initiation of EMG activity during perturbation-evoked reaching (p = 0.003), the effects of handrail predictability and movement task did not interact with age.

Conclusions

Age-related differences in perturbation-evoked arm responses are independent of both handrail location predictability and movement task.

Significance

Age-related differences in perturbation-evoked arm responses cannot be solely attributed to declines in reactive postural control. Rather, ageing leads to a deterioration of neural mechanisms common to both perturbation-evoked and voluntary arm movements.     

Electrical stimulation site influences the spatial distribution of motor units recruited in tibialis anterior

Objective

To compare the spatial distribution of motor units recruited in tibialis anterior (TA) when electrical stimulation is applied over the TA muscle belly versus the common peroneal nerve trunk.

Methods

Electromyography (EMG) was recorded from the surface and from fine wires in superficial and deep regions of TA. Separate M-wave recruitment curves were constructed for muscle belly and nerve trunk stimulation.

Results

During muscle belly stimulation, significantly more current was required to generate M-waves that were 5% of the maximal M-wave (M_max; M_5%max), 50% M_max (M_50%max) and 95% M_max (M_95%max) at the deep versus the superficial recording site. In contrast, during nerve trunk stimulation, there were no differences in the current required to reach M_5%max, M_50%max or M_95%max between deep and superficial recording sites. Surface EMG reflected activity in both superficial and deep muscle regions.

Conclusions

Stimulation over the muscle belly recruited motor units from superficial to deep with increasing stimulation amplitude. Stimulation over the nerve trunk recruited superficial and deep motor units equally, regardless of stimulation amplitude.

Significance

These results support the idea that where electrical stimulation is applied markedly affects how contractions are produced and have implications for the interpretation of surface EMG data.     

The α-motoneuron pool as transmitter of rhythmicities in cortical motor drive

Objective

Investigate the effectiveness and frequency dependence of central drive transmission via the α-motoneuron pool to the muscle.

Methods

We describe a model for the simulation of α-motoneuron firing and the EMG signal as response to central drive input. The transfer in the frequency domain is investigated. Coherence between stochastical central input and EMG is also evaluated.

Results

The transmission of central rhythmicities to the EMG signal relates to the spectral content of the latter. Coherence between central input to the α-motoneuron pool and the EMG signal is significant whereby the coupling strength hardly depends on the frequency in a range from 1 to 100 Hz. Common central input to pairs of α-motoneurons strongly increases the coherence levels. The often-used rectification of the EMG signal introduces a clear frequency dependence.

Conclusions

Oscillatory phenomena are strongly transmitted via the α-motoneuron pool. The motoneuron firing frequencies do play a role in the transmission gain, but do not influence the coherence levels. Rectification of the EMG signal enhances the transmission gain, but lowers coherence and introduces a strong frequency dependency. We think that it should be avoided.

Significance

Our findings show that rhythmicities are translated into α-motoneuron activity without strong non-linearities.     

Paired associative stimulation increases motor cortex excitability more effectively than theta-burst stimulation

Objective

To examine the effects of theta burst stimulation (TBS) and paired associative stimulation (PAS) on excitability in the human motor cortex.

Methods

Sixteen healthy young participants received intermittent TBS (iTBS) or PAS to the primary motor cortex on two testing occasions, at least a week apart. Ten of the participants also received iTBS or PAS after conditioning with continuous TBS on two other occasions. Cortical excitability was assessed with single TMS pulses to the motor cortex. Motor evoked potentials (MEPs) were measured from the first dorsal interosseus (FDI) muscle before TBS or PAS stimulation, and every 10 min for 60 min after stimulation. Changes in excitability were compared against the potential for motor learning, assessed with the rotor pursuit task.

Results

After the PAS protocol MEP amplitudes were significantly increased. This increase was greater than after intermittent TBS, which did not change MEPs significantly. Conditioning with continuous TBS showed no significant effect. Participants’ responses were not correlated across protocols and were not correlated with rotor pursuit learning.

Conclusions

PAS was the only protocol which induced significant increases in MEP amplitude.

Significance

PAS is robust in inducing excitatory cortical change. This makes it a suitable protocol for testing plasticity in healthy and patient groups.     

Efferent and afferent evoked potentials in patients with adrenomyeloneuropathy

Objective

This paper investigates efferent and afferent conductions of the central nervous system by various evoked potentials in patients with adrenomyeloneuropathy (AMN).

Patients and methods

Ten pure AMN patients without cerebral involvement were studied. Motor evoked potentials (MEPs), somatosensory evoked potentials (SEPs), auditory brainstem response (ABR), and pattern reversal full-field visual evoked potentials (VEPs) were recorded. For MEP recording, single-pulse or double-pulse magnetic brainstem stimulation (BST) was also performed.

Results

Abnormal MEP was observed in all ten patients, abnormal SEP in all ten, abnormal ABR in nine, and abnormal VEP in only one. Brainstem latency was measured in three of the seven patients with central motor conduction time (CMCT) prolongation. The cortical–brainstem conduction time was severely prolonged along the normal or mildly delayed brainstem–cervical conduction time in those three patients.

Conclusions

The pattern of normal VEP and abnormal MEP, SEP, ABR is a clinically useful electrophysiological feature for the diagnosis. BST techniques are helpful to detect, functionally, intracranial corticospinal tract involvement, probably demyelination, in pure AMN patients.     

Modulation of motor cortex excitability by paired peripheral and transcranial magnetic stimulation

Objective

Repetitive application of peripheral electrical stimuli paired with transcranial magnetic stimulation (rTMS) of M1 cortex at low frequency, known as paired associative stimulation (PAS), is an effective method to induce motor cortex plasticity in humans. Here we investigated the effects of repetitive peripheral magnetic stimulation (rPMS) combined with low frequency rTMS (‘magnetic-PAS’) on intracortical and corticospinal excitability and whether those changes were widespread or circumscribed to the cortical area controlling the stimulated muscle.