Transcranial magnetic stimulation and functional magnet resonance imaging evaluation of adductor spasmodic dysphonia during phonation

BackgroundReduced intracortical inhibition is a neurophysiologic finding in focal dystonia that suggests a broader problem of impaired cortical excitability within the brain. A robust understanding of the neurophysiology in dystonia is essential to elucidate the pathophysiology of the disorder and develop new treatments. The cortical silent period (cSP) is a reliable, non-invasive method to measure intracortical inhibition in the primary motor cortex associated with a muscle of interest. In adductor spasmodic dysphonia (AdSD), cSP of the laryngeal motor cortex (LMC) which directly corresponds to the affected musculature, the thyroarytenoid (TA), has not been examined.ObjectiveThis work evaluated the cSP of the LMC and the relationship between cSP and functional magnetic resonance imaging (fMRI) blood-oxygen-level dependent (BOLD) activation in people with AdSD (n = 12) compared to healthy controls (CTL, n = 14).ResultsShortened LMC cSP were observed bilaterally in people with AdSD vs CTL (F_{(1, 99)} = 19.5226, p < 0.0001), with a large effect size (η² = 0.1834). Between-group fMRI analysis revealed greater activation in bilateral LMC in the AdSD > CTL contrast as compared to CTL > AdSD contrast. Correlation analysis showed that people with AdSD have positive correlation of left LMC BOLD activation and the cSP. Further, the right LMC cSP lacks either positive or negative associations with BOLD activation. CTL individuals displayed both positive and negative correlations between cSP and BOLD activation in the left LMC. In CTL, the LMC cSP and BOLD activation showed exclusively negative correlations in both hemispheres.ConclusionIn AdSD, the cortical activation during phonation may not be efficiently or effectively associated with inhibitory processes, leading to muscular dysfunction. These findings may give insight into the maladaptive cortical control during phonation in people with AdSD.     

Are there differences in cortical excitability between akinetic-rigid and tremor-dominant subtypes of Parkinson's disease?

ObjectiveTo assess by transcranial magnetic stimulation (TMS) the excitability of various cortical circuits in akinetic-rigid and tremor-dominant subtypes of Parkinson's disease (PD).MethodsThe study included 92 patients with PD according to UK Brain Bank criteria, with akinetic-rigid (n = 64) or tremor-dominant (n = 28) subtype. Cortical excitability study, including resting and active motor thresholds (rMT and aMT), input—output curve of motor evoked potentials, contralateral and ipsilateral silent periods (cSP and iSP), short and long-interval intracortical inhibition (SICI and LICI), and intracortical facilitation (ICF) were measured. The results obtained were compared to a control group of 30 age- and sex-matched healthy subjects.ResultsThe patients in the tremor group had significantly lower rMT and aMT compared to controls and akinetic-rigid patients and significantly shorter iSP duration compared to akinetic-rigid patients, while iSP latency tended to be longer in akinetic-rigid patients compared to controls. There were no significant differences between the two PD subgroups regarding other cortical excitability parameters, including paired-pulse TMS parameters.ConclusionsOnly subtle differences of cortical excitability were found between patients with akinetic-rigid vs. tremor-dominant subtype of PD.SignificanceThe clinical heterogeneity of PD patients probably has an impact on cortical excitability measures, far beyond the akinetic-rigid versus tremor-dominant profile.     

Motor pathway excitability in ATP13A2 mutation carriers: a transcranial magnetic stimulation study

ObjectiveTo describe excitability of motor pathways in Kufor-Rakeb syndrome (PARK9), an autosomal recessive nigro-striatal-pallidal-pyramidal neurodegeneration caused by a mutation in the ATP13A2 gene, using transcranial magnetic stimulation (TMS).MethodsFive members of a Chilean family with an ATP13A2 mutation (one affected mutation carrier (MC) with a compound heterozygous mutation, 4 asymptomatic MC with a single heterozygous mutation) and 11 healthy subjects without mutations were studied. We measured motor evoked potentials (MEP), the contralateral silent period (cSP), short interval intracortical inhibition (SICI), intracortical facilitation (ICF), short latency afferent inhibition (SAI) as markers of intracortical intrahemispheric inhibition/facilitation and the ipsilateral silent period (iSP) and paired-pulse interhemispheric inhibition (IHI) to probe interhemispheric motor interactions.ResultsCSP duration was increased in the symptomatic ATP13A2 MC. The iSP measurements revealed increased interhemispheric inhibition in both the compound heterozygous and the heterozygous MC.ConclusionA compound heterozygous mutation in the ATP13A2 gene is associated with increased intracortical inhibition. In addition, some aspects of interhemispheric inhibition are increased in the presence of a single ATP13A2 mutation.     

Disturbed transcallosally mediated motor inhibition in children with attention deficit hyperactivity disorder (ADHD).

OBJECTIVE: The aim of this study was to investigate mechanisms of motor-cortical excitability and inhibition which may contribute to motor hyperactivity in children with attention deficit hyperactivity disorder (ADHD). METHODS: Using transcranial magnetic stimulation (TMS), involvement of the motor cortex and the corpus callosum was analysed in 13 children with ADHD and 13 sex- and age-matched controls. Contralateral silent period (cSP) and transcallosally mediated ipsilateral silent period (iSP) were investigated. RESULTS: Resting motor threshold (RMT), amplitudes of motor evoked potentials (MEP) and cSP were similar in both groups whereas iSP-latencies were significantly longer (p<0.05) and their duration shorter (p<0.01) in the ADHD group. For the ADHD group iSP duration tended to increase and iSP latency to decrease with age (n.s.). Conners-Scores did neither correlate with iSP-latencies and -duration nor with children's age. CONCLUSIONS: The shortened duration of iSP in ADHD children could be explained by an imbalance of inhibitory and excitatory drive on the neuronal network between cortex layer III-the projection site of transcallosal motor-cortical fibers-and layer V, the origin of the pyramidal tract. The longer iSP-latencies might be the result of defective myelination of fast conducting transcallosal fibers in ADHD. iSP may be a useful supplementary diagnostic tool to discriminate between ADHD and normal children.     

Abnormal interhemispheric inhibition in musician's dystonia – Trait or state?

IntroductionA clustering of relatives with dystonia has been reported in families with musician's dystonia suggesting a genetic contribution to this disease. The aim of the present study was to determine whether interhemispheric inhibition (IHI) measured with transcranial magnetic stimulation is impaired in healthy family members rendering it a suitable endophenotypic marker for musician's dystonia.MethodsPatients with musician's hand dystonia (n = 21), patients with sporadic writer's cramp (n = 15), their healthy family members (n = 27), healthy musicians (n = 12) and healthy non-musicians (n = 12) were included. An extended interview about the family history and musical activity was performed. IHI in both hemispheres was measured using transcranial magnetic stimulation.ResultsA stepwise regression analysis revealed musical activity (p = 0.001) and a family history of dystonia (p = 0.008) but not dystonia per se, age, handedness or gender as relevant factors modulating IHI.ConclusionThese data support the notion of a genetic background of musician's hand dystonia and suggests that reduced IHI is a possible endophenotypic marker of this disorder.     

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.     

Corticospinal excitability in patients with secondary dystonia due to focal lesions of the basal ganglia and thalamus

ObjectiveTo investigate the possible correlations between clinico-radiological features and pathophysiological mechanisms in patients with dystonia secondary to focal brain lesions.MethodsSingle and paired-pulse transcranial magnetic stimulation was used to assess corticospinal excitability in 10 patients (4 females; mean age 61) and a group of normal controls. Active threshold, latency and amplitude of motor evoked potentials (MEPs), silent period (SP) duration and short-interval intracortical inhibition (SICI) were evaluated.ResultsPatients with lesions involving the putamen and caudate presented with dystonic postures at rest. TMS assessment in these subjects showed increased MEP amplitude on the affected side and a bilateral decrease of SP duration and SICI. When the lesion spared the putamen and caudate, mainly involving the thalamus, the clinical picture was dominated by slow repetitive involuntary movements and tremor. In the affected side of these subjects the MEP amplitude was reduced and the MEP threshold was increased.ConclusionsWhen putamen and caudate were lesioned, the patients presented with dystonic postures at rest; furthermore the patients showed changes of corticospinal excitability in comparison to both healthy subjects and other dystonic patients.SignificanceThere are correlations between type of dystonia, site of the lesion and neurophysiological findings.     

Motor cortical excitability and plasticity in patients with neurofibromatosis type 1

ObjectiveNeurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder that is associated with cognitive disabilities. Based on studies involving animals, the hypothesized cause of these disabilities results from increased activity of inhibitory interneurons that decreases synaptic plasticity. We obtained transcranial magnetic stimulation (TMS)-based measures of cortical inhibition, excitability and plasticity in individuals with NF1.MethodsWe included 32 NF1 adults and 32 neurotypical controls. Cortical inhibition was measured with short-interval intracortical inhibition (SICI) and cortical silent period (CSP). Excitability and plasticity were studied with intermittent theta burst stimulation (iTBS).ResultsThe SICI and CSP response did not differ between NF1 adults and controls. The response upon iTBS induction was significantly increased in controls (70%) and in NF1 adults (83%). This potentiation lasted longer in controls than in individuals with NF1. Overall, the TMS response was significantly lower in NF1 patients (F(1, 41) = 7.552, p = 0.009).ConclusionsIndividuals with NF1 may have reduced excitability and plasticity, as indicated by their lower TMS response and attenuation of the initial potentiated response upon iTBS induction. However, our findings did not provide evidence for increased inhibition in NF1 patients.SignificanceThese findings have potential utility as neurophysiological outcome measures for intervention studies to treat cognitive deficits associated with NF1.     

Magnetic evoked potential polyphasia in idiopathic/genetic generalized epilepsy: An endophenotype not associated with treatment response

ObjectiveIncreased Motor Evoked Potential (MEP) polyphasia was recently described in idiopathic/genetic generalized epilepsy (IGE). Here, we studied the association of MEP polyphasia with treatment response and other clinical characteristics in patients with IGE.MethodsMEPs were recorded from the biceps brachii, flexor carpi radialis and interosseus dorsalis muscles bilaterally during tonic contraction in IGE patients (n = 72) and historical controls (n = 54) after single pulse transcranial magnetic stimulation. Detailed clinical data was available for all IGE patients; predefined endpoint was the association of MEP polyphasia with treatment response.ResultsThe mean number of phases was higher in the interosseus dorsalis muscle (2.33 vs. 2.13, p = 0.002) in IGE patients as compared to normal controls, as was the proportion of MEPs with more than two phases in at least one test (59.4% vs. 30%, p < 0.002). MEP polyphasia did not differ between IGE patients and controls in the biceps brachii or the flexor carpi radialis muscles and was not associated with treatment response. Extensive exploratory analyses unveiled fewer phases under valproic acid treatment (p = 0.04) but no additional associations of MEP polyphasia in the interosseous muscle with other clinical characteristics.ConclusionMEP polyphasia is a subclinical symptom of IGE patients but is not associated with treatment response or other routinely assessed clinical characteristics.SignificanceMEP polyphasia is a fixed feature of IGE not modified by clinical variables.     

Impact of pulse duration in single pulse TMS

Objective

The intensity of transcranial magnetic stimulation (TMS) is typically adjusted by changing the amplitude of the induced electrical field, while its duration is fixed. Here we examined the influence of two different pulse durations on several physiological parameters of primary motor cortex excitability obtained using single pulse TMS.

Methods

A Magstim Bistim² stimulator was used to produce TMS pulses of two distinct durations. For either pulse duration we measured, in healthy volunteers, resting and active motor thresholds, recruitment curves of motor evoked potentials in relaxed and contracting hand muscles as well as contralateral (cSP) and ipsilateral (iSP) cortical silent periods.

Results

Motor thresholds decreased by 20% using a 1.4 times longer TMS pulse compared to the standard pulse, while there was no significant effect on threshold adjusted measurements of cortical excitability. The longer pulse duration reduced pulse-to-pulse variability in cSP.

Conclusions

The strength of a TMS pulse can be adjusted both by amplitude or pulse duration. TMS pulse duration does not affect threshold-adjusted single pulse measures of motor cortex excitability.

Significance

Using longer TMS pulses might be an alternative in subjects with very high motor threshold. Pulse duration might not be relevant as long as TMS intensity is threshold-adapted. This is important when comparing studies performed with different stimulator types.     

An age-related change in the ipsilateral silent period of a small hand muscle

ObjectiveTo establish the presence or absence of an age effect on the ipsilateral silent period (iSP) for the abductor pollicis brevis (APB) muscle in healthy subjects.MethodsTwenty young adults (10 men, 10 women; age range: 20–40) and 20 older adults (10 men, 10 women; age range: 50–70) were matched by age (+30 years), gender and height (±5 cm). All were right-handed. We investigated the iSP for the APB by applying transcranial magnetic stimulation (TMS) and recording surface electromyograms. The contralateral motor-evoked potential (MEP) onset latency, the iSP onset and end latency (iSPOL and iSPEL) were measured and the iSP duration (iSPD) and transcallosal conduction time (TCT) were calculated. We evaluated the correlation between age and iSP, the latter’s intra- and intersession reproducibility and potential influencing factors.ResultsMean iSPOL, iSPEL and TCT values were significantly greater in older adults (both men and women) than in young adults. Intra- and intersession reproducibility was good. The mean left-side iSPEL and iSPD were longer than the right-side mean values in young adults but not in older adults. In both age groups, women displayed shorter latencies than men.ConclusionsThere is a strong effect of age on iSP parameters.SignificanceOur iSP results may evidence a decrease in transcallosal excitability with age, rather than slowing of the transcallosal interneuron conduction velocity.     

Motor cortical excitability and pre-supplementary motor area neurochemistry in healthy adults with substantia nigra hyperechogenicity

Substantia nigra (SN) hyperechogenicity, viewed with transcranial ultrasound, is a risk marker for Parkinson's disease. We hypothesized that SN hyperechogenicity in healthy adults aged 50–70 years is associated with reduced short-interval intracortical inhibition in primary motor cortex, and that the reduced intracortical inhibition is associated with neurochemical markers of activity in the pre-supplementary motor area (pre-SMA). Short-interval intracortical inhibition and intracortical facilitation in primary motor cortex was assessed with paired-pulse transcranial magnetic stimulation in 23 healthy adults with normal (n = 14; 61 ± 7 yrs) or abnormally enlarged (hyperechogenic; n = 9; 60 ± 6 yrs) area of SN echogenicity. Thirteen of these participants (7 SN− and 6 SN+) also underwent brain magnetic resonance spectroscopy to investigate pre-SMA neurochemistry. There was no relationship between area of SN echogenicity and short-interval intracortical inhibition in the ipsilateral primary motor cortex. There was a significant positive relationship, however, between area of echogenicity in the right SN and the magnitude of intracortical facilitation in the right (ipsilateral) primary motor cortex (p = .005; multivariate regression), evidenced by the amplitude of the conditioned motor evoked potential (MEP) at the 10–12 ms interstimulus interval. This relationship was not present on the left side. Pre-SMA glutamate did not predict primary motor cortex inhibition or facilitation. The results suggest that SN hyperechogenicity in healthy older adults may be associated with changes in excitability of motor cortical circuitry. The results advance understanding of brain changes in healthy older adults at risk of Parkinson's disease.     

Low-intensity repetitive paired associative stimulation targeting the motor hand area at theta frequency causes a lasting reduction in corticospinal excitability

ObjectiveSub-motor threshold 5 Hz repetitive paired associative stimulation (5 Hz-rPAS_25ms) produces a long-lasting increase in corticospinal excitability. Assuming a spike-timing dependent plasticity-like (STDP-like) mechanism, we hypothesized that 5 Hz-rPAS at a shorter inter-stimulus interval (ISI) of 15 ms (5 Hz-rPAS_15ms) would exert a lasting inhibitory effect on corticospinal excitability.Methods20 healthy volunteers received two minutes of 5 Hz-rPAS_15ms. Transcranial magnetic stimulation (TMS) was applied over the motor hotspot of the right abductor pollicis brevis muscle at 90% active motor threshold. Sub-motor threshold peripheral electrical stimulation was given to the left median nerve 15 ms before each TMS pulse. We assessed changes in mean amplitude of the unconditioned motor evoked potential (MEP), short-latency intracortical inhibition (SICI), intracortical facilitation (ICF), short-latency afferent inhibition (SAI), long-latency afferent inhibition (LAI), and cortical silent period (CSP) before and for 60 minutes after 5-Hz rPAS_15ms.ResultsSubthreshold 5-Hz rPAS_15ms produced a 20–40% decrease in mean MEP amplitude along with an attenuation in SAI, lasting at least 60 minutes. A follow-up experiment revealed that MEP facilitation was spatially restricted to the target muscle.ConclusionsSubthreshold 5-Hz rPAS_15ms effectively suppresses corticospinal excitability. Together with the facilitatory effects of subthreshold 5-Hz rPAS_25ms (Quartarone et al., J Physiol 2006;575:657–670), the results show that sub-motor threshold 5-Hz rPAS induces STDP-like bidirectional plasticity in the motor cortex.SignificanceThe results of the present study provide a new short-time paradigm of long term depression (LTD) induction in human sensory-motor cortex.     

Determining optimal rTMS parameters through changes in cortical inhibition

ObjectivesEvidence shows that repetitive transcranial magnetic stimulation (rTMS) changes cortical inhibition (CI) and excitability and that these changes may relate to its therapeutic effects. This study aimed to investigate the effects of differing durations or ‘doses’ of rTMS on cortical inhibition and excitability in healthy subjects.MethodsFour different experiments were conducted: 1 session of 1200 pulses of 1 or 20 Hz active or sham rTMS; 10 sessions of 1 or 20 Hz active or sham rTMS, 1200 pulses/session; 1 session of 3600 pulses of 1 or 20 Hz active or sham rTMS; 1 session of 6000 pulses of 20 Hz active or sham rTMS. Measures of cortical inhibition and excitability included short-interval intracortical inhibition, long interval cortical inhibition, cortical silent period (CSP), motor evoked potential amplitude, resting motor threshold and intracortical facilitation.ResultsOnly 6000 pulses of 20 Hz rTMS lead to a significant lengthening of the CSP and therefore potentiation of CI. There were no changes to excitability measures.ConclusionOnly high frequency rTMS potentiated CI. Longer treatment durations are required to produce such changes.SignificanceStudies investigating the therapeutic effects of rTMS may benefit from extended dosing with increased number of pulses per session. CSP lengthening may be used to guide treatment response.     

Selective modulation of intracortical inhibition by low-intensity Theta Burst Stimulation

ObjectiveTheta Burst Stimulation (TBS) is a repetitive transcranial magnetic stimulation paradigm which has effects on both excitatory and inhibitory intracortical pathways when applied at an intensity of 80% of active motor threshold. As intracortical inhibitory pathways have a lower threshold for activation than excitatory pathways, we sought to determine whether it was possible to selectively target cortical inhibitory circuitry by reducing the intensity of TBS to 70% of active motor threshold.MethodsMotor evoked potentials (MEPs), short latency intracortical facilitation (SICF), intracortical facilitation (ICF) and short interval intracortical inhibition (SICI) were measured at baseline, 5–20 and 20–35 min following continuous (cTBS) and intermittent (iTBS) low-intensity TBS in nine healthy subjects.ResultsLow-intensity cTBS significantly reduced SICI 5–20 min following stimulation, whilst having no effect on MEPs, SICF or ICF. Low-intensity iTBS had no effect on SICI, MEPs, SICF or ICF.ConclusionsIt is possible to selectively target intracortical inhibitory networks for modulation by low-intensity TBS, however, responses may critically depend upon the particular paradigm chosen.SignificanceThese findings have important implications for the treatment of neurological disorders where abnormal levels of intracortical inhibition are present, such as Parkinson’s disease and focal hand dystonia and requires further investigation.     

Abnormal patterns of corticomuscular and intermuscular coherence in childhood dystonia

ObjectiveSensorimotor processing is abnormal in Idiopathic/Genetic dystonias, but poorly studied in Acquired dystonias. Beta-Corticomuscular coherence (CMC) quantifies coupling between oscillatory electroencephalogram (EEG) and electromyogram (EMG) activity and is modulated by sensory stimuli. We test the hypothesis that sensory modulation of CMC and intermuscular coherence (IMC) is abnormal in Idiopathic/Genetic and Acquired dystonias.MethodsParticipants: 11 children with Acquired dystonia, 5 with Idiopathic/Genetic dystonia, 13 controls (12–18 years). CMC and IMC were recorded during a grasp task, with mechanical perturbations provided by an electromechanical tapper. Coherence patterns pre- and post-stimulus were compared across groups.ResultsBeta-CMC increased post-stimulus in Controls and Acquired dystonia (p = 0.001 and p = 0.010, respectively), but not in Idiopathic/Genetic dystonia (p = 0.799). The modulation differed between groups, being larger in both Controls and Acquired dystonia compared with Idiopathic/Genetic dystonia (p = 0.003 and p = 0.022). Beta-IMC increased significantly post-stimulus in Controls (p = 0.004), but not in dystonia. Prominent 4–12 Hz IMC was seen in all dystonia patients and correlated with severity (rho = 0.618).ConclusionIdiopathic/Genetic and Acquired dystonia share an abnormal low-frequency IMC. In contrast, sensory modulation of beta-CMC differed between the two groups.SignificanceThe findings suggest that sensorimotor processing is abnormal in Acquired as well as Idiopathic/Genetic dystonia, but that the nature of the abnormality differs.     

Neuroplastic Modulation of Inhibitory Motor Cortical Networks by Spaced Theta Burst Stimulation Protocols

BackgroundContinuous theta burst stimulation (cTBS) suppresses the excitability of motor networks responsible for generating motor evoked potentials (MEPs), and may also modulates the excitability of inhibitory motor networks. However, its effects on intracortical inhibition are modest in comparison to the effects on MEPs. The repeated, spaced, application of cTBS protocols results in more MEP suppression than seen with a single cTBS protocol, but whether this approach is also effective at modulating intracortical inhibition has not been tested.ObjectiveTo determine whether the paired application of cTBS effectively modulates the excitability of intracortical inhibitory motor networks.MethodsSingle and paired-pulse transcranial magnetic stimulation (TMS) were used to assess resting motor threshold (RMT), MEP amplitude, short-interval intracortical inhibition (SICI), and long-interval intracortical inhibition (LICI) before and during two time periods (0–10 and 30–40 min) following application of either a single or paired cTBS protocols.ResultsBoth the single and paired cTBS conditions induced a significant reduction in both MEP amplitudes and the level of SICI. While paired cTBS produced a significantly greater MEP suppression than single cTBS, the effects on SICI were similar. Neither single nor paired cTBS had an effect on RMT or LICI.ConclusionsAlthough the repeated application of cTBS protocols may be effective for enhancing modulation of the MEP-generating excitatory motor networks, these findings suggest that this approach offers little advantage when targeting intracortical inhibitory networks.     

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.     

Stratifying chronic stroke patients based on the influence of contralesional motor cortices: An inter-hemispheric inhibition study

ObjectiveA recent “bimodal-balance recovery” model suggests that contralesional influence varies based on the amount of ipsilesional reserve: inhibitory when there is a large reserve, but supportive when there is a low reserve. Here, we investigated the relationships between contralesional influence (inter-hemispheric inhibition, IHI) and ipsilesional reserve (corticospinal damage/impairment), and also defined a criterion separating subgroups based on the relationships.MethodsTwenty-four patients underwent assessment of IHI using Transcranial Magnetic Stimulation (ipsilateral silent period method), motor impairment using Upper Extremity Fugl-Meyer (UEFM), and corticospinal damage using Diffusion Tensor Imaging and active motor threshold. Assessments of UEFM and IHI were repeated after 5-week rehabilitation (n = 21).ResultsRelationship between IHI and baseline UEFM was quadratic with criterion at UEFM 43 (95%conference interval: 40–46). Patients less impaired than UEFM = 43 showed stronger IHI with more impairment, whereas patients more impaired than UEFM = 43 showed lower IHI with more impairment. Of those made clinically-meaningful functional gains in rehabilitation (n = 14), more-impaired patients showed further IHI reduction.ConclusionsA criterion impairment-level can be derived to stratify patient-subgroups based on the bimodal influence of contralesional cortex. Contralesional influence also evolves differently across subgroups following rehabilitation.SignificanceThe criterion may be used to stratify patients to design targeted, precision treatments.     

Modeling motor-evoked potentials from neural field simulations of transcranial magnetic stimulation

ObjectiveTo develop a population-based biophysical model of motor-evoked potentials (MEPs) following transcranial magnetic stimulation (TMS).MethodsWe combined an existing MEP model with population-based cortical modeling. Layer 2/3 excitatory and inhibitory neural populations, modeled with neural-field theory, are stimulated with TMS and feed layer 5 corticospinal neurons, which also couple directly but weakly to the TMS pulse. The layer 5 output controls mean motoneuron responses, which generate a series of single motor-unit action potentials that are summed to estimate a MEP.ResultsA MEP waveform was generated comparable to those observed experimentally. The model captured TMS phenomena including a sigmoidal input–output curve, common paired pulse effects (short interval intracortical inhibition, intracortical facilitation, long interval intracortical inhibition) including responses to pharmacological interventions, and a cortical silent period. Changes in MEP amplitude following theta burst paradigms were observed including variability in outcome direction.ConclusionsThe model reproduces effects seen in common TMS paradigms.SignificanceThe model allows population-based modeling of changes in cortical dynamics due to TMS protocols to be assessed in terms of changes in MEPs, thus allowing a clear comparison between population-based modeling predictions and typical experimental outcome measures.