Enzo Ortu

Effects of volitional contraction on intracortical inhibition and facilitation in the human motor cortex

Short‐interval intracortical inhibition (SICI), intracortical facilitation (ICF) and short‐interval intracortical facilitation (SICF) were assessed in the cortical motor area of the first dorsal interosseous muscle (FDI) of 16 healthy subjects. Paired‐pulse TMS was delivered to the left hemisphere at the following interstimulus intervals (ISIs): 2 and 3 ms for SICI, 10 and 15 ms for ICF and 1–5 ms for SICF. Motor‐evoked potentials were recorded from the resting and active right FDI. The effects exerted on SICI and ICF by four intensities (60–90% of active motor threshold, AMT) of the conditioning stimulus (S1) and by three levels of muscle contraction (10%, 25%, 50% of maximal voluntary contraction, MVC) were evaluated. The effects exerted on SICF were evaluated with two intensities (90% and 70% of AMT) of the test stimulus (S2) and with the same levels of muscle contraction. Results showed that: (i) during 10% MVC, maximum SICI was observed with S1 = 70% AMT; (ii) the amount of SICI obtained with S1 = 70% AMT was the same at rest as during 10% MVC, but decreased at higher contraction levels; (iii) ICF was observed only at rest with S1 = 90% AMT; (iv) SICF was facilitated at 10% and 25% MVC, but not at 50% MVC. We conclude that during muscle activation, intracortical excitability reflects a balance between activation of SICI and SICF systems. Part of the reduction in SICI during contraction is due to superimposed recruitment of SICF. Low intensity (70% AMT) conditioning stimuli can test SICI independently of effects on SICF at low contraction levels.

Theta burst stimulation induces after‐effects on contralateral primary motor cortex excitability in humans

Interhemispheric interactions between the primary motor cortices (M1) have been described with a variety of TMS methods. Here we give a detailed description of the interhemispheric interactions of a period of theta burst simulation (TBS), a rapid method of producing long lasting after‐effects on the excitability of the stimulated M1. A total of 18 right handed healthy subjects participated. In most experiments, continuous and intermittent TBS (cTBS and iTBS) were delivered over the right M1 using a coil orientated to induce antero‐posterior followed by postero‐anterior (AP–PA) currents in the brain. The intensity of stimulation was 80% of active motor threshold (AMT), and a total of 600 pulses were applied. The effects on the amplitude of motor evoked potentials (MEPs), short interval intracortical inhibition (SICI) and intracortical facilitation (ICF) were evaluated in the left and right M1 before and at three different times after TBS. We also tested long‐interval intracortical inhibition (LICI) in right M1 and interhemispheric inhibition (IHI) from right to left M1. Finally, to explore the effect of different polarities of cTBS over dominant and non‐dominant hemisphere we delivered AP–PA and postero‐anterior followed by antero‐posterior (PA–AP) cTBS over either right or left M1 and tested MEPs in both hemispheres. In the stimulated hemisphere, cTBS reduced MEPs and SICI whereas iTBS increased MEPs and SICI. In the non‐stimulated hemisphere cTBS increased MEPs and reduced SICI, while iTBS reduced MEPs and increased SICI. There were no effects on ICF, LICI or IHI. Although both AP–PA cTBS and PA–AP cTBS reduced MEPs in the stimulated M1, the former increased MEPs from non‐stimulated M1 whereas the latter did not. There was no difference in the effect of cTBS on the dominant or non‐dominant hemisphere.

Intracortical modulation of cortical-bulbar responses for the masseter muscle

Short interval intracortical inhibition (SICI) and intracortical facilitation (ICF) were evaluated in the masseter muscles of 12 subjects and the cortical silent period (SP) in nine subjects. Motor evoked potentials (MEPs) were recorded from contralateral (cMM) and ipsilateral (iMM) masseters, activated at 10% of maximal voluntary contraction (MVC). Interstimulus intervals (ISIs) were 2 and 3 ms for SICI, 10 and 15 ms for ICF. TMS of the left masseteric cortex induced MEPs that were larger in the cMM than the iMM; stimulation of right masseteric cortex produced a similar asymmetry in response amplitude. SICI was only observed using a CS intensity of 70% AMT and was equal in both cMM and iMM. SICI was stronger at higher TS intensities, was abolished by muscle activation greater than 10% MVC, and was unaffected by coil orientation changes. Control experiments confirmed that SICI was not contaminated by any inhibitory peripheral reflexes. However, ICF could not be obtained because it was masked by bilateral reflex depression of masseter EMG caused by auditory input from the coil discharge. The SP was bilateral and symmetric; its duration ranged from 35 to 70 ms depending on TS intensity and coil orientation. We conclude that SICI is present in the cortical representation of masseter muscles. The similarity of SICI in cMM and iMM suggests either that a single pool of inhibitory interneurons controls ipsi‐ and contralateral corticotrigeminal projections or that inhibition is directed to bilaterally projecting corticotrigeminal fibres. Finally, the corticotrigeminal projection seems to be weakly influenced by inhibitory interneurons mediating the cortical SP.

Origin of sound-evoked EMG responses in human masseter muscles

Sound is a natural stimulus for both cochlear and saccular receptors. At high intensities it evokes in active masseter muscles of healthy subjects two overlapping reflexes: p11/n15 and p16/n21 waves, whose origin has not yet been demonstrated. Our purpose was to test which receptor in the inner ear is responsible for these reflexes. We compared masseter EMG responses induced in normal subjects (n= 9) by loud clicks (70–100 dB normal hearing level (NHL), 0.1 ms, 3 Hz) to those evoked in subjects with a selective lesion of the cochlea (n= 5), of the vestibule (n= 1) or with mixed cochlear‐vestibular failure (n= 5). In controls, 100 dB clicks induced bilaterally, in the unrectified mean EMG (unrEMG), a clear p11 wave followed by a less clear n15 wave and a subsequent n21 wave. Lowering the intensity to 70 dB clicks abolished the p11/n15 wave, while a p16 wave appeared. Rectified mean EMG (rectEMG) showed, at all intensities, an inhibitory deflection corresponding to the p16/n21 wave in the unrEMG. Compared to controls, all deaf subjects had a normal p11 wave, together with more prominent n15 wave; however, the p16/n21 waves, and their corresponding inhibition in the rectEMG, were absent. The vestibular patient had bilaterally clear p11 waves only when 100 dB clicks were delivered bilaterally or to the unaffected ear. Stimulation of the affected ear induced only p16/n21 waves. Data from mixed patients were consistent with those of deaf and vestibular patients. We conclude that click‐induced masseter p11/n15 waves are vestibular dependent, while p16/n21 waves depend on cochlear integrity.

A comprehensive assessment of the cross-training effect in ankle dorsiflexors of healthy subjects: A randomized controlled study

PURPOSE To investigate the cross-training effect, induced on ankle dorsiflexors (AD) by unilateral strength-training of the contralateral muscles, as transfer of peak torque (PT) and muscle work (MW) and their relative contributions to muscle performance. METHODS Thirty healthy volunteers were randomly assigned to a training or control group. The trained group sustained a 4-week maximal isokinetic training of the stronger AD at 90 and 45°/s. At both angular velocities, PT, MW and MW/PT ratio were measured from both legs at baseline and after intervention (trained group) or no-intervention (controls). The familiarization/learning-effect was calculated and subtracted by PT and MW measures to obtain their net changes. RESULTS Net PT increased in both legs (untrained: +27.5% at 90°/s and +17.9% at 45°/s; trained: +15% at 90°/s and +16.3% at 45°/s). Similarly, net MW increased in both the untrained (90°/s: +29.6%; 45°/s: +37%) and trained (90°/s: +23.4%; 45°/s: +18.3%) legs. PT and MW gains were larger in the untrained than trained AD (p<0.0005), with MW improving more than PT at 45°/s (p=0.04). The MW/PT ratio increased bilaterally only in the trained group (p<0.05), depending on the angular velocity. CONCLUSIONS The cross-training effect occurred in AD muscles in terms of both PT and MW, with MW adding valuable information to PT-analysis in describing muscle performance. Moreover, the MW/PT ratio allowed estimating the contributions of these parameters to muscle capability and may represent a novel index in isokinetic testing. The greater improvements in the untrained than trained limb raises interesting clinical implications in asymmetric conditions.

Effect of Contralateral Strength Training on Muscle Weakness in People With Multiple Sclerosis: Proof-of-Concept Case Series

Background The contralateral strength training (CST) effect is a transfer of muscle performance to the untrained limb following training of the contralateral side. Objective The aim of this study was to explore, in individuals with multiple sclerosis (MS) presenting marked lower limb strength asymmetry, the effectiveness of CST on management of muscle weakness of the more-affected limb following training of the less-affected limb. Design A single-subject research design was used. Methods Eight individuals with MS underwent 16 to 18 high-intensity training sessions of the less-affected ankle dorsiflexor muscles. The primary outcome measure of this single-system case series was maximal strength expressed as peak moment and maximal work. Secondary outcome measures were: Six-Minute-Walk Test, Timed “Up & Go” Test, 10-Meter Timed Walk Test, and Multiple Sclerosis Quality of Life–54 questionnaire. Results After the 6-week intervention, the contralateral more affected (untrained) limb showed a 22% to 24% increase in maximal strength. From pretest-posttest measurements, participants also performed significantly better on the clinical and functional secondary outcome measures. At the 12-week follow-up, the strength levels of the weaker untrained limb remained significantly superior to baseline levels in the majority (5 out of 8) of the outcome parameters. Limitations Considering the design used, the absence of a control group, and the sample size, these findings should be cautiously generalized and will need confirmation in a properly planned randomized controlled trial. Conclusions The present proof-of-concept study shows, for the first time, the occurrence of the CST effect on muscle performance of ankle dorsiflexor muscles in people with MS. These preliminary findings reveal new potential implications for CST as a promising rehabilitation approach to those conditions where unilateral muscle weakness does not allow or makes difficult performing conventional strength training of the weaker limb.

Letter re: Alterations of functional connectivity of the motor cortex in Fabry disease: An RS-fMRI study

Cocozza et al.1 confirmed, by use of resting-state (RS)–fMRI, previous clinical and electrophysiologic studies showing involvement of cerebral motor circuits in Fabry disease (FD), independently of cerebrovascular signs/symptoms and brain MRI lesions.1–3 In particular, they showed alterations of functional connectivity in a polysynaptic motor circuit involving motor cortices, basal ganglia, and right cerebellar hemisphere.1 In metabolic/lysosomal storage diseases, a subclinical CNS impairment is common and may be related, regardless of brain MRI findings, either to a structural irreversible or to a biochemical reversible brain lesion.4,5 A crucial unsettled question in the article is the usefulness of RS-fMRI in detecting subtle and potentially reversible biochemical brain lesions in patients with FD at a rather early appearance. We investigated this question in a previous study by analyzing the effect of 1 year of enzyme replacement therapy (ERT) on cortical excitability in 5 patients with FD without brain MRI lesions, and an increase of excitatory neurotransmission in motor cortex circuits, documented by transcranial magnetic stimulation (TMS).3 We observed a reduction in motor cortex hyperexcitability in all patients after ERT, indicating the possible utility of TMS, and likely of other techniques such as RS-fMRI, in monitoring the disease course and the response to therapy.

Intracortical inhibitory and excitatory circuits of the human masseteric motor cortex

Short interval intracortical inhibition (SICI) and intracortical facilitation (ICF) were evaluated in the masseter muscles of 12 subjects and the cortical silent period (SP) as well as long interval intracortical inhibition (LICI) in 9 subjects.

Short interval paired pulse TMS during voluntary contraction: evidence of the balance between two antagonistic systems and importance of a low intensity conditioning stimulus

Muscle activation is usually reported to reduce the excitability of the inhibitory and facilitatory intracortical circuits tested in the SICI/ICF paradigm. The present work was to study these effects in more detail by examining how different levels of volitional contraction affect short interval intracortical inhibition (SICI) and short interval intracortical facilitation (SICF) evaluated with a range of stimulus intensities.

1.8. Sound-evoked p11/n15 and p16/n21 responses in human masseter muscles originate, respectively, in activation of vestibular and cochlear receptors

Background: Dysarthria is a frequent symptom of cerebral ischemia. The frequency, localisation and speech characteristics of ischemic brainstem infarcts leading to dysarthria are investigated in a prospective patient series. Methods: In a prospective study we included 106 consecutive patients with sudden onset of dysarthria due to a single, not space-occupying cerebral infarction confirmed by MRI. Out of these, in the last 64 consecutive patients we investigated the auditory perceptual features using standardized speech samples stored on a digital tape recorder within 72 h after stroke onset. Speech samples were assessed off-line independently by two experienced speech-language therapists which were unaware of the clinical and neuroradiological findings. Results: Out of 106 patients, dysarthria was due to a ventral brainstem infarction in 28.3% patients (midbrain: 0.9%, pontomesencephal: 1.9%, pons: 23.8%, pontomedullar: 1.9%). In 10.4% a combined brainstem and cerebellar infarction was responsible for dysarthria. Left-sided lesions were more oftenly (80.0%) found than right-sided infarctions (16.7%). Bilateral infarctions were present in 3.3% of the patients. Additionally, left-sided brainstem lesions were associated with a more severe impairment of speech, articulation and prosody than right-sided lesions (ANOVA, p < 0.001). Clinically, in patients with pure brainstem infarctions (n = 30) dysarthria was most oftenly associated with pyramidal tract signs (facial paresis: n = 18, upper limb paresis: n = 24, lower limb paresis: n = 19), ataxia of stance and gait: n = 14, limb ataxia: n = 6, hemihypesthesia: n = 8, while other typical brainstem signs were only rarely found (nystagmus: n = 4, INO: n = 2, horner-syndrome: n = 2, dysphagia: n = 2). Conclusions: The underlying cause of ischemic dysarthria was a brainstem lesion in only 28.3% of patients. We found that dysarthria was most commonly due to a ventral pontine infarction. The lesion localisation explains the frequent association of dysarthria with pyramidal tract signs and ataxia which is due to a lesion of the cerebro-ponto-cerebellar tract fibres. Left-sided lesions were more oftenly responsible for dysarthria and showed a more severe dysarthria and more severely affected articulatory and phonatory abnormalities as compared with the right side, supporting the assumption of a left hemispheric dominance for articulation.