Does pericentral mu-rhythm “power” corticomotor excitability? – A matter of EEG perspective

BackgroundElectroencephalography (EEG) and single-pulse transcranial magnetic stimulation (spTMS) of the primary motor hand area (M1-HAND) have been combined to explore whether the instantaneous expression of pericentral mu-rhythm drives fluctuations in corticomotor excitability, but this line of research has yielded diverging results.ObjectivesTo re-assess the relationship between the mu-rhythm power expressed in left pericentral cortex and the amplitude of motor potentials (MEP) evoked with spTMS in left M1-HAND.Methods15 non-preselected healthy young participants received spTMS to the motor hot spot of left M1-HAND. Regional expression of mu-rhythm was estimated online based on a radial source at motor hotspot and informed the timing of spTMS which was applied either during epochs belonging to the highest or lowest quartile of regionally expressed mu-power. Using MEP amplitude as dependent variable, we computed a linear mixed-effects model, which included mu-power and mu-phase at the time of stimulation and the inter-stimulus interval (ISI) as fixed effects and subject as a random effect. Mu-phase was estimated by post-hoc sorting of trials into four discrete phase bins. We performed a follow-up analysis on the same EEG-triggered MEP data set in which we isolated mu-power at the sensor level using a Laplacian montage centered on the electrode above the M1-HAND.ResultsPericentral mu-power traced as radial source at motor hot spot did not significantly modulate the MEP, but mu-power determined by the surface Laplacian did, showing a positive relation between mu-power and MEP amplitude. In neither case, there was an effect of mu-phase on MEP amplitude.ConclusionThe relationship between cortical oscillatory activity and cortical excitability is complex and minor differences in the methodological choices may critically affect sensitivity.     

Multimodal integration and modulation of visual and somatosensory inputs on the corticospinal excitability

ObjectiveCorticospinal excitability may be affected by various sensory inputs under physiological conditions. In this study, we aimed to investigate the corticospinal excitability by using multimodal conditioning paradigms of combined somatosensory electrical and visual stimulation to understand the sensory-motor integration.MethodsWe examined motor evoked potentials (MEP) obtained by using transcranial magnetic stimulation (TMS) that were conditioned by using a single goggle–light-emitting diode (LED) stimulation, peripheral nerve electrical stimulation (short latency afferent inhibition protocol), or a combination of both (goggle-LED+electrical stimulation) at different interstimulus intervals (ISIs) in 14 healthy volunteers.ResultsWe found MEP inhibition at ISIs of 50–60 ms using the conditioned goggle-LED stimulation. The combined goggle-LED stimulation at a 60 ms ISI resulted in an additional inhibition to the electrical stimulation.ConclusionsVisual inputs cause significant modulatory effects on the corticospinal excitability. Combined visual and somatosensory stimuli integrate probably via different neural circuits and/or interneuron populations. To our knowledge, multimodal integration of visual and somatosensory inputs by using TMS-short latency inhibition protocol have been evaluated via electrophysiological methods for the first time in this study.     

Excitability profile of motor evoked potentials and silent periods

The aim of this study was to confirm the excitability profile of human cortical circuits on the motor evoked potential (MEP) and the silent period (SP) after paired transcranial magnetic stimulation (TMS) with variable interstimulus intervals (ISI), and to compare the time courses of MEP and SP after paired TMS at variable ISIs. MEPs were elicited at the hypothenar muscles at rest, and during tonic muscle contraction by applying paired TMS to the motor cortex. The authors measured the MEP amplitude during rest and the duration of SP during tonic muscle contraction at various ISIs. The response to paired stimuli was inhibited by an ISI of 15 ms and facilitated by an ISI of 1020 ms. The SP at an ISI of 15 ms was shorter than that at the single suprathreshold stimulus, but the SP at an ISI of 1525 ms was longer than this. A significant correlation was observed between the MEP amplitude and the duration of SP at ISIs of 120 ms and for a CS of 80% of threshold. These results may provide useful data for the study of the function of cortical excitability in disease states and suggest that the neural circuits underlying MEP and SP differ partly.     

Excitability Profile of Motor Evoked Potentials and Silent Periods

The aim of this study was to confirm the excitability profile of human cortical circuits on the motor evoked potential (MEP) and the silent period (SP) after paired transcranial magnetic stimulation (TMS) with variable interstimulus intervals (ISI), and to compare the time courses of MEP and SP after paired TMS at variable ISIs. MEPs were elicited at the hypothenar muscles at rest, and during tonic muscle contraction by applying paired TMS to the motor cortex. The authors measured the MEP amplitude during rest and the duration of SP during tonic muscle contraction at various ISIs. The response to paired stimuli was inhibited by an ISI of 1–5 ms and facilitated by an ISI of 10–20 ms. The SP at an ISI of 1–5 ms was shorter than that at the single suprathreshold stimulus, but the SP at an ISI of 15–25 ms was longer than this. A significant correlation was observed between the MEP amplitude and the duration of SP at ISIs of 1–20 ms and for a CS of 80% of threshold. These results may provide useful data for the study of the function of cortical excitability in disease states and suggest that the neural circuits underlying MEP and SP differ partly.     

Bidirectional modulation of sensory cortical excitability by quadripulse transcranial magnetic stimulation (QPS) in humans

ObjectiveQuadripulse transcranial magnetic stimulation (QPS) is a newly designed patterned repetitive transcranial magnetic stimulation (TMS). Previous studies of QPS showed bidirectional effects on the primary motor cortex (M1), which depended on its inter-stimulus interval (ISI): motor evoked potentials (MEPs) were potentiated at short ISIs and depressed at long ISIs (homotopic effects). These physiological characters were compatible with synaptic plasticity. In this research, we studied effects of QPS on the primary sensory cortex (S1).MethodsOne burst consisted of four monophasic TMS pulses at an intensity of 90% active motor threshold. The ISI of four pulses was set at 5 ms (QPS-5) or at 50 ms (QPS-50). Same bursts were given every 5 s for 30 min. QPS-5 and QPS-50 were performed over three areas (M1, S1 and dorsal premotor cortex (dPMC)). One sham stimulation session was also performed. Excitability changes of S1 were evaluated by timeline of somatosensory evoked potentials (SEPs).ResultsQPS-5 over M1 or dPMC enhanced the P25–N33 component of SEP, and QPS-50 over M1 depressed it. By contrast, QPSs over S1 had no effects on SEPs.ConclusionsQPSs over motor cortices modulated the S1 cortical excitability (heterotopic effects). Mutual connections between dPMC or M1 and S1 might be responsible for these modulations.SignificanceQPSs induced heterotopic LTP or LTD-like cortical excitability changes.     

Assessment of cortical excitability using threshold tracking techniques

Conventional paired-pulse transcranial magnetic stimulation (TMS) techniques of assessing cortical excitability are limited by fluctuations in the motor evoked potential (MEP) amplitude. The aim of the present study was to determine the feasibility of threshold tracking TMS for assessing cortical excitability in a clinical setting and to establish normative data. Studies were undertaken in 26 healthy controls, tracking the MEP response from abductor pollicis brevis. Short-interval intracortical inhibition (SICI) occurred up to an interstimulus interval (ISI) of 7-10 ms, with two distinct peaks evident, at ISIs of < or =1 and 3 ms, followed by intracortical facilitation to an ISI of 30 ms. Long-interval intracortical inhibition (LICI) occurred at ISIs of 50-300 ms, peaking at 150 ms. The present study has confirmed the effectiveness of the threshold tracking TMS technique in reliably and reproducibly measuring cortical excitability. Simultaneous assessment of upper and lower motor neuronal function with threshold tracking techniques may help to determine the site of disease onset and patterns of progression in neurodegenerative diseases.     

Restoration of disturbed intracortical motor inhibition and facilitation in attention deficit hyperactivity disorder children by methylphenidate.

BACKGROUND: Previous investigations using transcranial magnetic stimulation (TMS) have shown that neural inhibitory motor circuits are disturbed in ADHD children. We sought to investigate the influence of methylphenidate (MPH) on inhibitory and facilitatory motor circuits of ADHD children with TMS paired pulse protocols using surplus long interval inter-stimulus intervals (ISI) not investigated so far. METHODS: Motorcortical modulation was tested with TMS paired pulse protocols employing ISI of 3, 13, 50, 100, 200, and 300 msec in 18 ADHD children before and on treatment with MPH. Clinical improvement by MPH was measured by the Conners score. RESULTS: Analysis of variance (ANOVA) revealed a significant three-way interaction "Group x Amplitude x ISI," p = .001. Subsequent two-factorial ANOVAs and t-tests showed group specific differences of motor evoked potential (MEP) amplitudes for inhibitory ISIs of 3 and 100 msec, and for facilitatory ISIs of 13 and 50 msec. Compared to controls, an adjustment of these parameters by MPH could be shown. On MPH, a significant bivariate correlation was found between the Conners score reduction and averaged MEP amplitude changes only for inhibitory ISIs (3 and 100 msec). CONCLUSIONS: In ADHD children, MPH modulates disturbed facilitatory and inhibitory motor circuits, which for the latter is associated with clinical improvement.     

Intracortical inhibition and facilitation in human facial motor area: difference between upper and lower facial area.

OBJECTIVE: To investigate the intracortical inhibitory and excitatory systems in the motor cortical representation of upper and lower facial muscles. METHODS: Paired-pulse transcranial magnetic stimulation (TMS) was applied to 7 healthy volunteers, with the interstimulus interval (ISI) between the conditioning stimulus (CS) and test stimulus, varied from 1 to 20 ms. CS was set at 90% of motor threshold. Muscle evoked potentials (MEPs) were recorded from first dorsal interosseus (FDI), orbicularis oculi (o. oculi) and mentalis muscles. RESULT: TMS evoked MEPs in o. oculi on both ipsi- and contralateral sides in all subjects. In the paired-pulse study, MEP amplitude in the mentalis decreased at short ISIs of 1-3 ms, followed by increases at 12-20 ms. These effects were similar to those in the FDI. O. oculi did not show a distinct inhibitory period at short ISIs and facilitation at long ISIs was detected but was significantly less than in FDI and mentalis. In o. oculi, there was no significant difference between the effects of ipsilateral and contralateral CS on the MEPs. CONCLUSION: The bi-hemispheric control of volitional movement and the modulation from brainstem projections appear to markedly influence intracortical inhibitory and excitatory systems in the motor cortical representation of o. oculi.     

Variation in the response to transcranial magnetic brain stimulation in the general population.

OBJECTIVES: The aim of this study is to describe the variability and other characteristics of the motor evoked potential (MEP) to transcranial magnetic stimulation (TMS) in a large database.METHODS: One hundred fifty one subjects, including 17 sib pairs, free of neurological or psychiatric disease and on no neuroactive medications were studied with uniform techniques. Nineteen were studied on 3 occasions. Measures included MEP threshold (N=141) during rest and voluntary muscle activation and the response to paired TMS (subthreshold conditioning stimulus) at interstimulus intervals (ISIs) of 3, 4, 10, and 15ms (N=53).RESULTS: There was a large variability in all the measures. Approximately 40-50% of this appeared to come from within-subjects variation or experimental error. The MEP threshold data were skewed downward, but normalized with log transformation. The paired-pulse ratios (conditioned/unconditioned MEP) were normally distributed except those from the 3ms ISI which had no lower tail and could not be normalized. There were subjects showing inhibition and others showing facilitation at all ISIs. There were no correlations in any of the data with age or sex, but MEP thresholds were highly correlated within sibs.CONCLUSIONS: These data should be useful for planning, analyzing, and interpreting TMS studies in healthy and patient populations.     

Effects of a photic input on the human cortico-motoneuron connection.

OBJECTIVES: Disease manifestations such as photic cortical reflex myoclonus or myoclonus due to intermittent light stimulation rely on a pathologic interaction between non-structured visual inputs and the corticospinal system. We wanted to assess the normal interaction, if any, between a prior photic input and the output of the cortico-motoneuron connection. METHODS: In 9 consenting healthy subjects we quantified the changes exerted by a sudden, unexpected bright light flash on (i) the motor potentials (MEPs) evoked in the right first dorsal interosseous muscle (FDI) by transcranial magnetic or electrical stimulation (TMS/TES) of the primary motor cortex, (ii) the FDI F-waves and (iii) the soleus H-wave. Separately, we measured the simple reaction times to the flash itself. All determinations were repeated twice with an interval of 2-24 months. RESULTS: When the flash preceded TMS by 55-70 ms, the MEP size was reduced, while at interstimulus intervals (ISIs) of 90-130 ms it was enlarged. Statistical significance (P<0.05) emerged at ISIs of 55, 70, 100, 105 and 120 ms. Conversely, the MEP latency was prolonged at ISIs of 55-70 ms and shortened at ISIs of 90-130 ms (P<0.05 at ISIs of 55, 110 and 130 ms). Electrical MEPs were enhanced at an ISI of 120 ms. The F-wave size showed a non-significant trend of enhancement at ISIs of 90-130 ms. The soleus H-wave showed significant enlargement at ISIs of 90-130 ms (P<0.05 at ISIs of 100 and 105 ms). The minimum reaction time was on average 120 ms. CONCLUSIONS: An unexpected photic input, to which no reaction is planned, can cause an early inhibition of the responses to TMS. We think its origin lies within the primary motor cortex, since it is not associated with changes in spinal excitability or electrical MEPs. A later facilitation persists using TES and has a temporal relationship with an enlargement of the soleus H-wave. Thus, it likely results from activation of descending (possibly reticulospinal) fibers that excite the spinal motor nucleus.     

An initial transient-state and reliable measures of corticospinal excitability in TMS studies

ObjectiveThe objective of this study was to determine if an initial transient state influences the acquisition of reliable estimates of corticospinal excitability in transcranial magnetic stimulation (TMS) studies. Whereas muscle evoked potential (MEP) amplitudes are an important index of cortical excitability, these are severely limited by sweep-to-sweep variability. Interesting in this context is the experimental observation that the first MEP amplitudes might be much larger than subsequent responses [Brasil-Neto JP, Cohen LG, Hallet M. Central fatigue as revealed by postexercise decrement of motor evoked potentials. Muscle Nerve 1994;17:713–9]. This led to the hypothesis that an initial transient-state of increased excitability affects MEP amplitude derived estimates of corticospinal excitability.MethodsTo address this issue we acquired repeated measures of single pulse MEP amplitudes over the primary motor cortex with and without navigated brain stimulation (NBS) and with various TMS-coils. Importantly, NBS allows for the sweep-to-sweep differentiation of physical and physiological variability.ResultsWe found a significant decline in estimates of corticospinal excitability and a transition from log-Normal to Normal distributed state, after which reliable measures (British Standards Institute) could be acquired.ConclusionsWe argue that an initial transient state of physiological origin influences measures of corticospinal excitability.SignificanceThis has important implications for investigations of cortical excitability. For example, it could reduce variability over studies and within small group comparisons.     

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.     

Modulation of motor learning by a paired associative stimulation protocol inducing LTD-like effects

BackgroundPaired associative stimulation (PAS) induces long-term potentiation (LTP)-like effects when interstimulus intervals (ISIs) between electrical peripheral nerve stimulation and transcranial magnetic stimulation (TMS) to M1 are approximately 21–25 ms (PAS_LTP). It was previously reported that two forms of motor learning (i.e., mode-free and model-based learning) can be differentially modulated by PAS_LTP depending on the different synaptic inputs to corticospinal neurons (CSNs), which relate to posterior-to-anterior (PA) or anterior-to-posterior (AP) currents induced by TMS (PA or AP inputs, respectively). However, the effects of long-term depression (LTD)-inducing PAS with an ISI of approximately 10 ms (PAS_LTD) on motor learning and its dependency on current direction have not yet been tested.ObjectiveTo investigate whether, and how, PAS_LTD affects distinct types of motor learning.MethodsEighteen healthy volunteers participated. We adopted the standard PAS using suprathreshold TMS with the target muscle relaxed, as well as subthreshold PAS during voluntary contraction, which was suggested to selectively recruit PA or AP inputs depending on the orientation of the TMS coil. We examined the effects of suprathreshold and subthreshold PAS_LTD on the performance of model-free and model-based learning, as well as the corticospinal excitability, indexed as the amplitudes of motor evoked potentials (MEPs).ResultsPAS_LTD inhibited model-free learning and MEPs only when subthreshold AP currents were applied. The PAS_LTD protocols tested here showed no effects on model-based learning.ConclusionsPAS_LTD affected model-free learning, presumably by modulating CSN excitability changes, rather than PA inputs, which are thought to be related to model-free learning.     

Parietal transcranial direct current stimulation modulates primary motor cortex excitability

The posterior parietal cortex is part of the cortical network involved in motor learning and is structurally and functionally connected with the primary motor cortex (M1). Neuroplastic alterations of neuronal connectivity might be an important basis for learning processes. These have however not been explored for parieto‐motor connections in humans by transcranial direct current stimulation (tDCS). Exploring tDCS effects on parieto‐motor cortical connectivity might be functionally relevant, because tDCS has been shown to improve motor learning. We aimed to explore plastic alterations of parieto‐motor cortical connections by tDCS in healthy humans. We measured neuroplastic changes of corticospinal excitability via motor evoked potentials (MEP) elicited by single‐pulse transcranial magnetic stimulation (TMS) before and after tDCS over the left posterior parietal cortex (P3), and 3 cm posterior or lateral to P3, to explore the spatial specificity of the effects. Furthermore, short‐interval intracortical inhibition/intracortical facilitation (SICI/ICF) over M1, and parieto‐motor cortical connectivity were obtained before and after P3 tDCS. The results show polarity‐dependent M1 excitability alterations primarily after P3 tDCS. Single‐pulse TMS‐elicited MEPs, M1 SICI/ICF at 5 and 7 ms and 10 and 15 ms interstimulus intervals (ISIs), and parieto‐motor connectivity at 10 and 15 ms ISIs were all enhanced by anodal stimulation. Single pulse‐TMS‐elicited MEPs, and parieto‐motor connectivity at 10 and 15 ms ISIs were reduced by cathodal tDCS. The respective corticospinal excitability alterations lasted for at least 120 min after stimulation. These results show an effect of remote stimulation of parietal areas on M1 excitability. The spatial specificity of the effects and the impact on parietal cortex–motor cortex connections suggest a relevant connectivity‐driven effect.     

Region-dependent bidirectional plasticity in M1 following quadripulse transcranial magnetic stimulation in the inferior parietal cortex

BackgroundThe ability to manipulate the excitability of the network between the inferior parietal lobule (IPL) and primary motor cortex (M1) may have clinical value.ObjectiveTo investigate the possibility of inducing long-lasting changes in M1 excitability by applying quadripulse transcranial magnetic stimulation (QPS) to the IPL, and to ascertain stimulus condition- and site-dependent differences in the effects.MethodsQPS was applied to M1, the primary somatosensory cortex (S1), the supramarginal gyrus (SMG) and angular gyrus (AG) IPL areas, with the inter-stimulus interval (ISI) in the train of pulses set to either 5 ms (QPS-5) or 50 ms (QPS-50). QPS was repeated at 0.2 Hz for 30 min, or not presented (sham condition). Excitability changes in the target site were examined by means of single-pulse transcranial magnetic stimulation (TMS).ResultsQPS-5 and QPS-50 at M1 increased and decreased M1 excitability, respectively. QPS at S1 induced no obvious change in M1 excitability. However, QPS at the SMG induced mainly suppressive effects in M1 for at least 30 min, regardless of the ISI length. Both QPS ISIs at the AG yielded significantly different MEP compared to those at the SMG. Thus, the direction of the plastic effect of QPS differed depending on the site, even under the same stimulation conditions.ConclusionsQPS at the IPL produced long-lasting changes in M1 excitability, which differed depending on the precise stimulation site within the IPL. These results raise the possibility of noninvasive induction of functional plasticity in M1 via input from the IPL.     

Analogous corticocortical inhibition and facilitation in ipsilateral and contralateral human motor cortex representations of the tongue.

How the human brain controls activation of the ipsilateral part of midline muscles is unknown. We studied corticospinal and corticocortical network excitability of both ipsilateral and contralateral motor representations of the tongue to determine whether they are under analogous or disparate inhibitory and facilitatory corticocortical control. Motor evoked potentials (MEPs) to unilateral focal transcranial magnetic stimulation (TMS) of the tongue primary motor cortex were recorded simultaneously from the ipsilateral and contralateral lingual muscles. Single-pulse TMS was used to assess motor threshold (MT) and MEP recruitment. Paired-pulse TMS was used to study intracortical inhibition (ICI) and intracortical facilitation (ICF) at various interstimulus intervals (ISIs) between the conditioning stimulus (CS) and the test stimulus (TS), and at different CS and TS intensities, respectively. Focal TMS invariably produced MEPs in both ipsilateral and contralateral lingual muscles. MT was lower and MEP recruitment was steeper when recorded from the contralateral muscle group. ICI and ICF were identical in the ipsilateral and contralateral representations, with inhibition occurring at short ISIs (2 and 3 ms) and facilitation occurring at longer ISIs (10 and 15 ms). Moreover, changing one stimulus parameter regularly produced analogous changes in MEP size bilaterally, revealing strong linear correlations between ipsilateral and contralateral ICI and ICF (P < 0.0001). These findings indicate that the ipsilateral and contralateral representations of the tongue are under analogous inhibitory and facilitatory control, possibly by a common intracortical network.     

Influence of Waveform and Current Direction on Short-Interval Intracortical Facilitation: A Paired-Pulse TMS Study

BackgroundTranscranial magnetic stimulation (TMS) of the human primary motor hand area (M1-HAND) can produce multiple descending volleys in fast-conducting corticospinal neurons, especially so-called indirect waves (I-waves) resulting from trans-synaptic excitation. Facilitatory interaction between these I-waves can be studied non-invasively using a paired-pulse paradigm referred to as short-interval intracortical facilitation (SICF).Objective/hypothesisWe examined whether SICF depends on waveform and current direction of the TMS pulses.MethodsIn young healthy volunteers, we applied single- and paired-pulse TMS to M1-HAND. We probed SICF by pairs of monophasic or half-sine pulses at suprathreshold stimulation intensity and inter-stimulus intervals (ISIs) between 1.0 and 5.0 ms. For monophasic paired-pulse stimulation, both pulses had either a posterior–anterior (PA) or anterior–posterior (AP) current direction (AP–AP or PA–PA), whereas current direction was reversed between first and second pulse for half-sine paired-pulse stimulation (PA–AP and AP–PA).ResultsMonophasic AP–AP stimulation resulted in stronger early SICF at 1.4 ms relative to late SICF at 2.8 and 4.4 ms, whereas monophasic PA–PA stimulation produced SICF of comparable size at all three peaks. With half-sine stimulation the third SICF peak was reduced for PA–AP current orientation compared with AP–PA.ConclusionSICF elicited using monophasic as well as half-sine pulses is affected by current direction at clearly suprathreshold intensities. The impact of current orientation is stronger for monophasic compared with half-sine pulses. The direction-specific effect of paired-pulse TMS on the strength of early versus late SICF shows that different cortical circuits mediate early and late SICF.     

A Novel Model Incorporating Two Variability Sources for Describing Motor Evoked Potentials

ObjectiveMotor evoked potentials (MEPs) play a pivotal role in transcranial magnetic stimulation (TMS), e.g., for determining the motor threshold and probing cortical excitability. Sampled across the range of stimulation strengths, MEPs outline an input–output (IO) curve, which is often used to characterize the corticospinal tract. More detailed understanding of the signal generation and variability of MEPs would provide insight into the underlying physiology and aid correct statistical treatment of MEP data.MethodsA novel regression model is tested using measured IO data of twelve subjects. The model splits MEP variability into two independent contributions, acting on both sides of a strong sigmoidal nonlinearity that represents neural recruitment. Traditional sigmoidal regression with a single variability source after the nonlinearity is used for comparison.ResultsThe distribution of MEP amplitudes varied across different stimulation strengths, violating statistical assumptions in traditional regression models. In contrast to the conventional regression model, the dual variability source model better described the IO characteristics including phenomena such as changing distribution spread and skewness along the IO curve.ConclusionsMEP variability is best described by two sources that most likely separate variability in the initial excitation process from effects occurring later on. The new model enables more accurate and sensitive estimation of the IO curve characteristics, enhancing its power as a detection tool, and may apply to other brain stimulation modalities. Furthermore, it extracts new information from the IO data concerning the neural variability—information that has previously been treated as noise.     

Lack of evidence for interhemispheric inhibition in the lower face primary motor cortex

ObjectiveTo investigate interhemispheric inhibition (IHI) between the facial primary motor cortices (fM1s).MethodsIHI was investigated in 10 healthy subjects using paired-pulse TMS in the depressor anguli oris (DAO), upper trapezius (UT) and first dorsal interosseous (FDI) muscles. Conditioning stimuli (CS) of 90–130% resting motor threshold (RMT) preceded test motor evoked potentials (MEPs) by 7 interstimulus intervals (ISIs) ranging 4–12 ms. In the DAO, we also examined IHI at 1–2 ms ISIs.ResultsIHI was detected in the UT (CS 130% RMT; ISI 8 ms; p = 0.02) and FDI (CS 120% and 130% RMT, at 8–10 ms ISIs; p = 0.004), but not in DAO at any ISI, instead, there was facilitation at 1–4 ms ISIs and 110–130% RMT CS. In the DAO, conditioned responses at 1–4 ms ISIs were significantly larger than both test MEPs and the response induced by the CS alone.ConclusionIn the DAO there was no evidence of IHI even though this was clear in hand and axial muscles. Control experiments excluded a transcallosal origin of the facilitation observed at the shortest intervals.SignificanceData suggest that integrated bilateral control of facial muscles occurs mainly at the level of brainstem circuits engaged by corticobulbar output from fM1.     

EEG oscillations and magnetically evoked motor potentials reflect motor system excitability in overlapping neuronal populations

ObjectiveTo understand the relationship between neuronal excitability reflected by transcranial magnetic stimulation (TMS) evoked motor potentials (MEPs) and spontaneous oscillation amplitude and phase.MethodsWe combined spontaneous EEG measurement with motor cortex TMS and recorded MEP amplitudes from abductor digiti minimi (ADM).ResultsMidrange-beta oscillations over the stimulated left motor cortex were, on average, weaker before large- than small-amplitude MEPs. The phase of occipital midrange-beta oscillations was related to the MEP amplitudes.ConclusionsThe present results support the view that MEP and Rolandic beta oscillation amplitudes are associated with motor cortical excitability. However, oscillations seen in EEG reflect the excitability of a large population of cortical neurons, and MEP amplitude is affected also by spinal excitability and action potential desynchronization. Thus, MEP and EEG oscillation amplitudes are not strongly correlated. In addition, even during rest, motor system excitability appears to be related to activity in occipital areas at frequency ranges associated with visuomotor processing.SignificanceThe ability of spontaneous oscillations and MEPs to inform us about cortical excitability is clarified. For example, it is suggested that oscillatory activity at non-motor sites might be related to motor system excitability at rest.