A comparison of relative-frequency and threshold-hunting methods to determine stimulus intensity in transcranial magnetic stimulation

ObjectiveStimulation intensity (SI) in transcranial magnetic stimulation is commonly set in relation to motor threshold (MT), or to achieve a motor-evoked potential (MEP) of predefined amplitude (usually 1 mV). Recently, IFCN recommended adaptive threshold-hunting over the previously endorsed relative-frequency method. We compared the Rossini–Rothwell (R–R) relative-frequency method to an adaptive threshold-hunting method based on parameter estimation by sequential testing (PEST) for determining MT and the SI to target a MEP amplitude of 1 mV (I_1 mV).MethodsIn 10 healthy controls we determined MT and I_1 mV with R–R and PEST using a blinded crossover design, and performed within-session serial PEST measurements of MT.ResultsThere was no significant difference between methods for MT (52.6 ± 2.6% vs. 53.7 ± 3.1%; p = 0.302; % maximum stimulator output; R–R vs. PEST, respectively) or I_1 mV (66.7 ± 3.0% vs. 68.8 ± 3.8%; p = 0.146). There was strong correlation between R–R and PEST estimates for both MT and I_1 mV. R–R required significantly more stimuli than PEST. Serial measurements of MT with PEST were reproducible.ConclusionsPEST has the advantage of speed without sacrificing precision when compared to the R–R method, and is adaptable to other SI targets.SignificanceOur results in healthy controls add to increasing evidence in favour of adaptive threshold-hunting methods for determining SI.     

Acute effects of lithium on excitability of human motor cortex

ObjectiveLithium has been widely used to treat bipolar affective disorder for over 60 years. Still, its acute effects in human cerebral cortex are poorly understood. This study aimed at investigating the acute effects of lithium on motor cortex excitability as measured by transcranial magnetic stimulation (TMS).MethodsTen healthy young adults participated in a double-blind placebo-controlled randomized crossover study with four sessions, where a single oral dose of lithium carbonate (450 mg, 900 mg, or 1350 mg) or placebo was tested. Focal TMS of the hand area of left motor cortex was used to test resting and active motor thresholds, motor evoked potential input–output curve (MEP IO-curve), slope of the MEP IO-curve and paired-pulse measures of intracortical inhibition and facilitation before, and two and four hours after drug administration.ResultsTwo hours post drug administration, 450 mg of lithium carbonate increased the slope of the MEP IO-curve while 1350 mg tended to decrease it. Lithium had no effect on motor thresholds, or intracortical inhibition or facilitation.ConclusionsThe acute effects of lithium on MEP IO-curve, a marker of corticospinal excitability, are consistent with an inverted U-shaped dose–response relationship.SignificanceFindings are important for our understanding of the therapeutic and toxic effects of lithium on the human central nervous system.     

Effects of continuous theta burst transcranial magnetic stimulation on cortical excitability in patients with idiopathic generalized epilepsy

IntroductionTranscranial magnetic stimulation (TMS) is a noninvasive technique for investigating cortical physiologic functions in the brain. In this study, the effects of continuous theta burst stimulation (cTBS) on motor evoked potential (MEP) parameters in patients with idiopathic generalized epilepsy (IGE) were investigated.Materials and methodsFifteen patients with IGE were included. Motor threshold (MT) and cortical silent period (CSP) were determined before cTBS application. Next, cTBS was applied to the dominant (left) hemisphere M1 hand area as the first application. After 1 day, cTBS was applied first to the left M1 hand area and then to the right lateral cerebellar area as the second application. Parameters were again determined after the applications.ResultsThere was no difference in resting MT values before and after cTBS application (p > 0.05). Although CSP increased after stimulation (p < 0.05), it was not significantly different between applications (p > 0.05).ConclusionFor patients with epilepsy, cTBS is a safe technique when applied at a low intensity. The inhibitory effect of cTBS, a noninvasive technique, on cortical excitability in patients with IGE was determined using MEP parameters. The effect lasted at least 1 h. To our knowledge, this is the first study to assess the effect of cTBS on cortical excitability in patients with IGE. Our findings indicate that cTBS decreases cortical excitability in patients with IGE.     

Reduced plastic brain responses to repetitive transcranial magnetic stimulation in severe obstructive sleep apnea syndrome

ObjectivesAbnormalities in cortical excitability have been proposed to underlie the pathophysiology of various neurocognitive manifestations of obstructive sleep apnea syndrome (OSAS). Transcranial magnetic stimulation (TMS) provides a noninvasive method for study and modulation of cortical excitability in the human brain, and repetitive TMS (rTMS) has been proven useful for neurophysiologic investigation in various neurologic conditions. We aimed to investigate cortical excitability in patients with OSAS during wakefulness and to determine if rTMS would change the abnormal excitability patterns.MethodsMeasures of motor cortical and corticospinal excitability (resting motor threshold [RMT], motor-evoked potential [MEP] amplitude, and cortical silent period [CSP]) were taken before and after a session of 10-Hz rTMS applied to the motor cortex in 13 individuals with untreated severe OSAS (apnea–hypopnea index [AHI] > 30) and 12 age- and sex-matched healthy controls (HC).ResultsOSAS subjects had a significantly higher RMT (P < .003) and a longer CSP duration (P < .002) compared to HC. No difference was observed between MEP values of OSAS subjects and HC (P > .05). In response to rTMS, the HC group had a significant increase in CSP and MEP values from baseline, which were absent in OSAS subjects.ConclusionsIndividuals with OSAS demonstrated increased motor cortex inhibition, which did not respond to 10-Hz rTMS. As rTMS-induced changes in MEP and CSP involve a separate neurotransmitter system (N-methyl-d-aspartate [NMDA] and gamma-aminobutyric acid [GABA], respectively), these findings suggest a widespread alteration in cortical neurophysiology in severe OSAS subjects that requires clarification with further exploration.     

Effects of persistent Mal de debarquement syndrome on balance,psychological traits,and motor cortex exctiability

Mal de debarquement syndrome (MdDS) is a poorly characterized and understood disorder of perceived motion. We sought to characterize postural control and the psychological impact of MdDS. Additionally, we explored whether patients with MdDS exhibit altered corticospinal and intracortical excitability. In a case-control study we compared patients with MdDS to age- and sex-matched controls (n = 8/group). Postural stability (σ_r) was quantified from plane phase plots based on center or pressure, and psychological indices of depression, fatigue and kinesiophobia were obtained. Transcranial magnetic stimulation (TMS) was used to assess corticospinal excitability by quantifying the motor evoked potential (MEP) amplitude of the flexor carpi radialis, and intracortical excitability was assessed by quantifying indices of intracortical facilitation (ICF), and short-interval and long-interval intracortical inhibition using a paired-pulse TMS paradigm. The patients with MdDS exhibited greater mean (±standard error of the mean) σ_r during semi-tandem stance (10.9 ± 1.5 compared to 7.1 ± 0.7, p = 0.04), higher levels of kinesiophobia (41.6 ± 2.8 compared to 27.3 ± 2.2), and higher levels of fatigue (27.0 ± 4.1 compared to 48.4 ± 1.0). Patients with MdDS exhibited a higher mean motor threshold (MT) (58.1 ± 2.5 compared to 47.4 ± 2.7% of stimulator output), and larger MEP (13.1 ± 3.1 compared to 5.1 ± 1.2% of maximal compound muscle action potential) but there was no difference in measures of intracortical excitability. These findings suggest that patients with MdDS exhibit impaired postural stability, and high levels of kinesiophobia and fatigue. Additionally, we observed that patients with MdDS exhibit higher MT and large MEP amplitudes, but do not exhibit differences in measures of intracortical excitability, compared to controls. These findings help characterize MdDS, and provide insight into the physiology of MdDS.     

The effect of modafinil on cortical excitability in patients with narcolepsy: A randomized,placebo-controlled,crossover study

ObjectiveTo investigate the effect of modafinil on cortical excitability in patients with narcolepsy using transcranial magnetic stimulation (TMS).MethodsNineteen drug-naïve narcolepsy patients with cataplexy (10 males, 9 females, and mean age 28.5 years) and 25 age- and sex-matched healthy controls were recruited. In this double-blind, randomized, crossover study, patients and controls received a single dose of 400 mg modafinil or placebo. Modafinil and placebo administrations were separated by a 2-week washout period. TMS parameters, such as resting motor thresholds (RMT), motor-evoked potential (MEP) amplitudes, cortical silent periods (CSP), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF), were measured before and 3 h after administering modafinil or placebo. The differences of TMS parameters were statistically tested between patients and controls and between before and after modafinil or placebo administration.ResultsNarcolepsy patients had significantly increased CSP durations compared to controls (independent t-test, P < 0.05), indicating decreased excitability of cortical networks in human narcolepsy. In patients after modafinil administration, MEP amplitudes, SICI, and ICF increased, and CSP duration shortened significantly, meaning enhanced motor excitability, whereas in controls modafinil did not change TMS parameters significantly. Placebo administration did not affect TMS parameters both in patients or controls.ConclusionsNarcolepsy patients with cataplexy showed decreased cortical excitability than normal healthy controls. Single dose modafinil significantly increased motor excitability in narcolepsy patients but had no effect in healthy controls.     

Neuromagnetic activation of primary and secondary somatosensory cortex following tactile-on and tactile-off stimulation

ObjectiveMagnetoencephalography (MEG) recordings were performed to investigate the cortical activation following tactile-on and tactile-off stimulation.MethodsWe used a 306-ch whole-head MEG system and a tactile stimulator driven by a piezoelectric actuator. Tactile stimuli were applied to the tip of right index finger. The interstimulus interval was set at 2000 ms, which included a constant stimulus of 1000 ms duration.ResultsProminent somatosensory evoked magnetic fields were recorded from the contralateral hemisphere at 57.5 ms and 133.0 ms after the onset of tactile-on stimulation and at 58.2 ms and 138.5 ms after the onset of tactile-off stimulation. All corresponding equivalent current dipoles (ECDs) were located in the primary somatosensory cortex (SI). Moreover, long-latency responses (168.7 ms after tactile-on stimulation, 169.8 ms after tactile-off stimulation) were detected from the ipsilateral hemisphere. The ECDs of these signals were identified in the secondary somatosensory cortex (SII).ConclusionsThe somatosensory evoked magnetic fields waveforms elicited by the two tactile stimuli (tactile-on and tactile-off stimuli) with a mechanical stimulator were strikingly similar. These mechanical stimuli elicited both contralateral SI and ipsilateral SII activities.SignificanceTactile stimulation with a mechanical stimulator provides new possibilities for experimental designs in studies of the human mechanoreceptor system.     

Hysteresis effects on the input–output curve of motor evoked potentials

ObjectiveInput–output (IO) curves of motor evoked potentials (MEP) are widely used to assess corticospinal excitability by transcranial magnetic stimulation (TMS). Here we sought to determine hysteresis effects on IO curves, i.e. their short-term dependence on prior corticospinal activation.MethodsIO curves were measured from the first dorsal interosseous (FDI) muscle of 14 healthy volunteers in three different conditions of stimulus intensity order: increase from lowest to highest, decrease from highest to lowest, and random. Intensities ranged from 80% to 170% of the resting motor threshold (RMT). IO curves were measured in the resting vs. active FDI and at two different intertrial intervals (ITI, 5 s and 20 s).ResultsIn the resting FDI and at ITI = 5 s, the IO curve in condition “decrease” shifted significantly to the left compared to condition “increase”. The IO curve in condition “random” ran in between the other two curves. Hysteresis was most pronounced in the high intensity part of the IO curves. Hysteresis did not occur at ITI = 20 s or in the active FDI.ConclusionsFindings implicate that hysteresis can influence IO curves significantly. One possible underlying mechanism might be short-term synaptic enhancement.SignificanceConsideration of IO curve hysteresis effects is important to avoid systematic data bias in clinical and research TMS applications.     

Corticospinal activation confounds cerebellar effects of posterior fossa stimuli

ObjectiveTo investigate the efficacy of magnetic stimulation over the posterior fossa (PF) as a non-invasive assessment of cerebellar function in man.MethodsWe replicated a previously reported conditioning-test paradigm in 11 healthy subjects. Transcranial magnetic stimulation (TMS) at varying intensities was applied to the PF and motor cortex with a 3, 5 or 7 ms interstimulus interval (ISI), chosen randomly for each trial. Surface electromyogram (EMG) activity was recorded from two intrinsic hand muscles and two forearm muscles. Responses were averaged and rectified, and MEP amplitudes were compared to assess whether suppression of the motor output occurred as a result of the PF conditioning pulse.ResultsCortical MEPs were suppressed following conditioning-test ISIs of 5 or 7 ms. No suppression occurred with an ISI of 3 ms. PF stimuli alone also produced EMG responses, suggesting direct activation of the corticospinal tract (CST).ConclusionsCST collaterals are known to contact cortical inhibitory interneurones; antidromic CST activation could therefore contribute to the observed suppression of cortical MEPs.SignificancePF stimulation probably activates multiple pathways; even at low intensities it should not be regarded as a selective assessment of cerebellar function unless stringent controls can confirm the absence of confounding activity in other pathways.     

Increased motor cortical excitability after whole-hand electrical stimulation: A TMS study

ObjectiveTo examine the neuromodulatory effect of whole-hand mesh-glove (MG) stimulation on motor cortical pathways, we explored motor cortical excitability before and after suprathreshold whole-hand MG stimulation using transcranial magnetic stimulation (TMS).MethodsTwenty-eight healthy volunteers (14 controls) were studied at baseline, immediately post and 1 h post-MG stimulation for 30 min. Motor thresholds (MTs), motor evoked potentials (MEPs) recruitment curve, short intracortical inhibition (SICI) and intracortical facilitation (ICF) after paired magnetic stimuli were evaluated.ResultsAfter MG stimulation the MTs were significantly reduced and slope of MEP recruitment curve significantly increased; furthermore, the stimulation led to a sustained decrease of SICI and increase of ICF in the contralateral motor cortex. These effects lasted for at least 60 min and were stronger 1 h post-stimulation compared with testing immediately after stimulation. A sham group did not show any differences before and after MG stimulation.ConclusionsWe provide a first demonstration that MG whole-hand stimulation induces increases in motor cortical excitability lasting at least 1 h. Both the strength of the corticospinal projections and the inhibitory and facilitatory intracortical mechanisms are involved. Synaptic modifications such as long-term potentiation mechanisms may underlie this stimulation-induced cortical plasticity changes.SignificancePresent results prove the MG stimulation to be a promising tool in neurorehabilitation.     

Reliability of lower limb motor evoked potentials in stroke and healthy populations: How many responses are needed?

ObjectiveTo determine the intra- and inter-session reliability of motor evoked potential (MEP) size parameters in the lower limb of patients with stroke, focussing on the number of MEPs collected and the method of measuring MEP size.MethodsTranscranial magnetic stimulation was used to elicit MEPs in the soleus muscle of patients with stroke (n = 13) and age-matched healthy participants (n = 13) during low level muscle activation. Two sets of 10 responses were collected in the first session and a further 10 responses collected in a second session held 7 days later. Four MEP size measurements were made using 4, 6, 8, or all 10 of the MEPs collected. Intra- and inter-session reliability was examined using intraclass correlation coefficients (ICC) and typical percentage error.ResultsIntrasession ICC statistics using 6 or more MEPs were >0.85 in the stroke group but intersession values were all <0.5. Reliability was best when measuring parameters from individual MEPs rather than averaged responses.ConclusionsReliability of intrasession MEP size is excellent in the lower limb of patients with stroke using as few as 6 MEPs but intersession reliability is poor.SignificanceComparing MEP size measures across two or more sessions is questionable in the lower limb of patients with stroke.     

Exercise-induced strengthening of inter-digital connections in musicians

ObjectiveTo investigate whether finger exercise affects surround inhibition in professional musicians as it was previously observed in non-musicians, we performed a transcranial magnetic stimulation (TMS) study in 13 healthy right-handed professional musicians.MethodsTMS was set to be triggered by self-initiated flexion of the index finger at 3 ms after electromyography onset (self-triggered TMS). 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.ResultsControl and self-triggered MEPs were not different between the two exercise sessions. MEP enhancements were significantly greater in self-triggered TMS than control TMS after single exercise as well as dual exercise.ConclusionThis result demonstrates that MEP enhancement in self-triggered TMS was comparable between two exercise sessions in professional musicians, a result different from that observed in healthy non-musicians. Enhanced self-triggered MEPs after isolated finger exercise suggest that inter-digital cortical connections are strengthened in musicians, presumably due to previous musical training.SignificanceInter-digital cortical connections are strengthened in musicians and are not differently modulated by different types of short-term finger exercise.     

Galvanic ocular vestibular evoked myogenic potentials provide new insight into vestibulo-ocular reflexes and unilateral vestibular loss

ObjectiveSynchronous extraocular muscle activity can be recorded from around the eyes at the beginning of a vestibular-evoked eye movement (ocular vestibular evoked myogenic potentials, OVEMPs). As galvanic vestibular stimulation (GVS) evokes the vestibulo-ocular reflex, we wished to investigate GVS-evoked OVEMPs.MethodsWe stimulated 10 normals and 6 patients with unilateral vestibular loss (uVL) with bi/unipolar 4 mA, 2 ms current steps at the mastoid. OVEMPs were recorded from electrodes placed superior and inferior to the eyes.ResultsOVEMPs were present beneath both eyes in all normal subjects: an initial positivity ipsilateral to the cathodal electrode (peak latency 9.9 ms, amplitude 1.3 μV) and an initial negativity contralateral to the cathode (8.8 ms, 2.4 μV). In the patients, stimulation of the affected side produced little or no response. Stimulation of the intact side produced only contralateral responses.ConclusionsThe infra-orbital response is likely produced primarily by the inferior obliques, producing conjugate torsion away from the cathode. The projection to the ipsilateral eye depends upon normal vestibular function on the contralateral side.SignificanceOVEMPs can be evoked by GVS. While bilateral effects are obtained with unilateral stimulation in normals, the primary vestibular pathway to the inferior oblique in humans is crossed.     

Origin of the low-level EMG during the silent period following transcranial magnetic stimulation

ObjectiveThe cortical silent period refers to a period of near silence in the electromyogram (EMG) after transcranial magnetic stimulation (TMS) of the motor cortex during contraction. However, low-level EMG of unknown origin is often present. We hypothesised that it arises through spinal reflexes. Sudden lengthening of the muscle as force drops during the silent period could excite muscle spindles and facilitate motoneurones.MethodsSubjects (n = 8) performed maximal isometric, shortening and lengthening contractions of the elbow flexors during which TMS (90–100% output) was delivered over the motor cortex. The rate of flexion during shortening contractions reduced muscle lengthening caused by muscle relaxation. Surface EMG was recorded from biceps brachii and brachioradialis, and the low-level EMG during silent periods produced by TMS was measured.ResultsLow-level EMG activity was reduced on average by 68% in biceps and 63% in brachioradialis in the shortening contraction compared to all other contraction conditions (p < 0.001). Levels of pre-stimulus EMG were similar between conditions.ConclusionsMuscle lengthening contributes to low-level EMG activity in the silent period, through spinal reflex facilitation by muscle spindle afferents.SignificanceThe silent period depth is not only dependent on cortical output but also reflex effects evoked by muscle lengthening.     

Determination of motor threshold using visual observation overestimates transcranial magnetic stimulation dosage: Safety implications

ObjectiveWhile the standard has been to define motor threshold (MT) using EMG to measure motor cortex response to transcranial magnetic stimulation (TMS), another method of determining MT using visual observation of muscle twitch (OM-MT) has emerged in clinical and research use. We compared these two methods for determining MT.MethodsLeft motor cortex MTs were found in 20 healthy subjects. Employing the commonly-used relative frequency procedure and beginning from a clearly suprathreshold intensity, two raters used motor evoked potentials and finger movements respectively to determine EMG-MT and OM-MT.ResultsOM-MT was 11.3% higher than EMG-MT (p < 0.001), ranging from 0% to 27.8%. In eight subjects, OM-MT was more than 10% higher than EMG-MT, with two greater than 25%.ConclusionsThese findings suggest using OM yields significantly higher MTs than EMG, and may lead to unsafe TMS in some individuals. In more than half of the subjects in the present study, use of their OM-MT for typical rTMS treatment of depression would have resulted in stimulation beyond safety limits.SignificanceFor applications that involve stimulation near established safety limits and in the presence of factors that could elevate risk such as concomitant medications, EMG–MT is advisable, given that safety guidelines for TMS parameters were based on EMG-MT.     

Altered cortical excitability in patients with untreated obstructive sleep apnea syndrome

ObjectiveTo investigate cortical excitability in patients with obstructive sleep apnea syndrome (OSAS) during wakefulness.MethodsThe authors recruited 45 untreated severe OSAS (all males, mean age 47.2 years, mean apnea–hypopnea index = 44.6 h^?1) patients and 44 age-matched healthy male volunteers (mean apnea–hypopnea index = 3.4 h^?1). The TMS parameters measured were resting motor threshold (RMT), motor evoked potential (MEP) amplitude, cortical silent period (CSP), and short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF). These parameters were measured in the morning (9–10 am) more than 2 h after arising and the parameters of patients and controls were compared. The Epworth Sleepiness Scale (ESS) and the Stanford Sleepiness Scale (SSS) were also measured before the TMS study.ResultsOSAS patients had a significantly higher RMT and a longer CSP duration (t-test, p < 0.001) compared to healthy volunteers. No significant difference was observed between MEP amplitudes at any stimulus intensity or between the SICI (2, 3, 5 ms) and ICF (10, 15, 20 ms) values of OSAS patients and healthy volunteers (p > 0.05).ConclusionsThis TMS-based study suggests that untreated severe OSAS patients have imbalanced cortical excitabilities that enhanced inhibition or decreased brain excitability when awake during the day.     

Sensory afferent inhibition within and between limbs in humans

ObjectiveTo examine the distribution and inter-limb interaction of short-latency afferent inhibition (SAI) in the arm and leg.MethodsMotor evoked potentials (MEPs) in distal and proximal arm, shoulder and leg muscles induced with ranscranial magnetic stimulation (TMS) were conditioned by painless electrical stimuli applied to the index finger (D2) and great toe (T1) at interstimulus intervals (ISIs) of 15, 25–35, 80 ms (D2) and 35, 45, 55, 65 and 100 ms (T1) in 27 healthy human subjects. TMS was delivered over primary motor cortex (M1) arm and leg areas. Electrical stimulus intensities were varied between 1 and 3 times the sensory perception thresholds. We also tested effects of posterior cutaneous brachial nerve (PCBN) stimulation on MEPs in arm muscles at ISIs of 18 and 28 ms.ResultsD2 but not PCBN electrical conditioning reduced MEP amplitudes in upper limb muscles at ISIs of 25 and 35 ms. SAI was more pronounced in distal as compared to proximal arm muscles. Also, SAI following D2 stimulation increased with higher conditioning intensities. D2 stimulation did not change lower limb muscles MEPs. In ontrast, T1 stimulation did not induce SAI in any muscles but caused MEP facilitation in a foot muscle at an ISI of 55 ms and in upper limb muscles at ISIs of 35 and 55 ms. Short interval intracortical inhibition (SICI) and intracortical facilitation (ICF) were not affected by electrical T1 conditioning.ConclusionD2 stimulation causes segmental SAI in upper limb muscles with a distal to proximal attenuation without affecting leg muscles. In contrast, toe stimulation facilitates motor output both in foot and upper arm muscles.SignificanceOur data suggest that cutaneo-motor pathways in arms and legs are functionally organized in a different way with cutaneo-motor interactions induced by toe stimulation probably relayed at a thalamic level. Abnormal cutaneo-motor interactions following electrical toe stimulation may serve as an electrophysiological marker of thalamic dysfunction, e.g. in neurodegenerative diseases.     

Short-latency crossed spinal responses are impaired differently in sub-acute and chronic stroke patients

ObjectiveInvestigate if patients with supraspinal lesions have impaired interlimb spinal reflex pathways. The short-latency crossed spinal response will be investigated during sitting from the non-paretic to paretic and paretic to non-paretic extremities at different stimulation intensities in chronic and sub-acute stroke patients.MethodsThe ipsilateral tibial nerve of the paretic and non-paretic extremities were stimulated at motor threshold, 35% M-max and 85% M-max of the ipsilateral soleus while the contralateral soleus was contracted from 5% to 15% of the maximum voluntary contraction of the paretic soleus.ResultsChronic patients (from both extremities) had significantly less prominent inhibitory responses than healthy controls (post hoc tests: P < .01–P < .05). The responses were significantly modulated by stimulus intensity in healthy controls and chronic patients (P < .001–P < .05) but not sub-acute patients (P > .05). Some sub-acute patients had significantly more variable responses than chronic patients and healthy controls (P < .001–P ? .05).ConclusionsShort-latency interlimb reflexes are impaired differently in sub-acute vs. chronic patients, are impaired from the non-paretic and paretic extremity, and abnormal when compared to healthy controls.SignificanceThe inappropriate coordination could result in an inability to quickly avoid obstacles following a mechanical disturbance to the ipsilateral extremity. It also indicates that bilateral descending projections affect the response.     

Ipsilesional motor-evoked potential absence in pediatric hemiparesis impacts tracking accuracy of the less affected hand

This study analyzed the relationship between electrophysiological responses to transcranial magnetic stimulation (TMS), finger tracking accuracy, and volume of neural substrate in children with congenital hemiparesis. Nineteen participants demonstrating an ipsilesional motor-evoked potential (MEP) were compared with eleven participants showing an absent ipsilesional MEP response. Comparisons of finger tracking accuracy from the affected and less affected hands and ipsilesional/contralesional (I/C) volume ratio for the primary motor cortex (M1) and posterior limb of internal capsule (PLIC) were done using two-sample t-tests. Participants showing an ipsilesional MEP response demonstrated superior tracking performance from the less affected hand (p = 0.016) and significantly higher I/C volume ratios for M1 (p = 0.028) and PLIC (p = 0.005) compared to participants without an ipsilesional MEP response. Group differences in finger tracking accuracy from the affected hand were not significant. These results highlight differentiating factors amongst children with congenital hemiparesis showing contrasting MEP responses: less affected hand performance and preserved M1 and PLIC volume. Along with MEP status, these factors pose important clinical implications in pediatric stroke rehabilitation. These findings may also reflect competitive developmental processes associated with the preservation of affected hand function at the expense of some function in the less affected hand.     

Occlusion of bidirectional plasticity by preceding low-frequency stimulation in the human motor cortex

ObjectiveLow-frequency stimulation, which does not induce long-term potentiation (LTP) or long-term potentiation (LTD) by itself, suppresses consecutive LTP or LTD induction in vitro. We tested whether a similar interaction occurs in the human motor cortex.MethodsLTP- or LTD-like plasticity was induced using paired associative stimulation (PAS) with 25 and 10 ms interstimulus interval and conditioned by suprathreshold repetitive transcranial magnetic stimulation (rTMS) at a frequency of 0.1 Hz.ResultsRTMS completely abolished the significant increase of motor-evoked potential (MEP) amplitudes after PAS_25ms (PAS_25ms only: 1.05 ± 0.14 to 1.76 ± 0.66 mV, p = 0.001; rTMS + PAS_25ms: 1.08 ± 0.18 to 1.02 ± 0.44 mV, n.s.) and also abolished the significant decrease of MEP amplitudes after PAS_10ms (PAS_10ms only: 1.00 ± 0.14 to 0.73 ± 0.32 mV; rTMS + PAS_10ms: 1.15 ± 0.35 to 1.25 ± 0.43 mV, p = 0.006). RTMS alone did not significantly alter MEP amplitudes but increased SICI and LICI.ConclusionsLow frequency stimulation increases intracortical inhibition and occludes LTP- and LTD-like plasticity in the human motor cortex.SignificanceThis finding supports the concept that metaplasticity in the human motor cortex follows similar rules as metaplasticity in in vitro experiments.