Effects of prolonged vibration to the flexor carpi radialis muscle on intracortical excitability.

Prolonged local vibration (LV) can induce neurophysiological adaptations thought to be related to long-term potentiation or depression. Yet, how changes in intracortical excitability may be involved remains to be further investigated as previous studies reported equivocal results. We therefore investigated the effects of 30 min of LV applied to the right flexor carpi radialis muscle (FCR) on both short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF). SICI and ICF were measured through transcranial magnetic stimulation before and immediately after 30 min of FCR LV (vibration condition) or 30 min of rest (control condition). Measurements were performed during a low-intensity contraction (n = 17) or at rest (n = 7). No significant SICI nor ICF modulations were observed, whether measured during isometric contractions or at rest (p = 0.2). Yet, we observed an increase in inter-individual variability for post measurements after LV. In conclusion, while intracortical excitability was not significantly modulated after LV, increased inter-variability observed after LV may suggest the possibility of divergent responses to prolonged LV exposure.

Approximating Nonlinear Functions With Latent Boundaries in Low-Rank Excitatory-Inhibitory Spiking Networks.

Deep feedforward and recurrent neural networks have become successful functional models of the brain, but they neglect obvious biological details such as spikes and Dale's law. Here we argue that these details are crucial in order to understand how real neural circuits operate. Towards this aim, we put forth a new framework for spike-based computation in low-rank excitatory-inhibitory spiking networks. By considering populations with rank-1 connectivity, we cast each neuron's spiking threshold as a boundary in a low-dimensional input-output space. We then show how the combined thresholds of a population of inhibitory neurons form a stable boundary in this space, and those of a population of excitatory neurons form an unstable boundary. Combining the two boundaries results in a rank-2 excitatory-inhibitory (EI) network with inhibition-stabilized dynamics at the intersection of the two boundaries. The computation of the resulting networks can be understood as the difference of two convex functions and is thereby capable of approximating arbitrary non-linear input-output mappings. We demonstrate several properties of these networks, including noise suppression and amplification, irregular activity and synaptic balance, as well as how they relate to rate network dynamics in the limit that the boundary becomes soft. Finally, while our work focuses on small networks (5-50 neurons), we discuss potential avenues for scaling up to much larger networks. Overall, our work proposes a new perspective on spiking networks that may serve as a starting point for a mechanistic understanding of biological spike-based computation.

Local origin of excitatory-inhibitory tuning equivalence in a cortical network.

The interplay between excitation and inhibition determines the fidelity of cortical representations. The receptive fields of excitatory neurons are often finely tuned to encoded features, but the principles governing the tuning of inhibitory neurons remain elusive. In this study, we recorded populations of neurons in the mouse postsubiculum (PoSub), where the majority of excitatory neurons are head-direction (HD) cells. We show that the tuning of fast-spiking (FS) cells, the largest class of cortical inhibitory neurons, was broad and frequently radially symmetrical. By decomposing tuning curves using the Fourier transform, we identified an equivalence in tuning between PoSub-FS and PoSub-HD cell populations. Furthermore, recordings, optogenetic manipulations of upstream thalamic populations and computational modeling provide evidence that the tuning of PoSub-FS cells has a local origin. These findings support the notion that the equivalence of neuronal tuning between excitatory and inhibitory cell populations is an intrinsic property of local cortical networks.

The pathobiology of psychomotor slowing in psychosis: altered cortical excitability and connectivity.

Psychomotor slowing is a frequent symptom of schizophrenia. Short-interval intracortical inhibition assessed by transcranial magnetic stimulation demonstrated inhibitory dysfunction in schizophrenia. The inhibitory deficit results from additional noise during information processing in the motor system in psychosis. Here, we tested whether cortical inhibitory dysfunction was linked to psychomotor slowing and motor network alterations. In this cross-sectional study, we included 60 patients with schizophrenia and psychomotor slowing determined by the Salpêtrière Retardation Rating Scale, 23 patients without slowing and 40 healthy control participants. We acquired single and double-pulse transcranial magnetic stimulation effects from the left primary motor cortex, resting-state functional connectivity and diffusion imaging on the same day. Groups were compared on resting motor threshold, amplitude of the motor evoked potentials, as well as short-interval intracortical inhibition. Regression analyses calculated the association between motor evoked potential amplitudes or cortical inhibition with seed-based resting-state functional connectivity from the left primary motor cortex and fractional anisotropy at whole brain level and within major motor tracts. In patients with schizophrenia and psychomotor slowing, we observed lower amplitudes of motor evoked potentials, while the short-interval intracortical inhibition/motor evoked potentials amplitude ratio was higher than in healthy controls, suggesting lower cortical inhibition in these patients. Patients without slowing also had lower amplitudes of motor evoked potentials. Across the combined patient sample, cortical inhibition deficits were linked to more motor coordination impairments. In patients with schizophrenia and psychomotor slowing, lower amplitudes of motor evoked potentials were associated with lower fractional anisotropy in motor tracts. Moreover, resting-state functional connectivity between the primary motor cortex, the anterior cingulate cortex and the cerebellum increased with stronger cortical inhibition. In contrast, in healthy controls and patients without slowing, stronger cortical inhibition was linked to lower resting-state functional connectivity between the left primary motor cortex and premotor or parietal cortices. Psychomotor slowing in psychosis is linked to less cortical inhibition and aberrant functional connectivity of the primary motor cortex. Higher neural noise in the motor system may drive psychomotor slowing and thus may become a treatment target.

Applications of information geometry to spiking neural network activity.

The space of possible behaviors that complex biological systems may exhibit is unimaginably vast, and these systems often appear to be stochastic, whether due to variable noisy environmental inputs or intrinsically generated chaos. The brain is a prominent example of a biological system with complex behaviors. The number of possible patterns of spikes emitted by a local brain circuit is combinatorially large, although the brain may not make use of all of them. Understanding which of these possible patterns are actually used by the brain, and how those sets of patterns change as properties of neural circuitry change is a major goal in neuroscience. Recently, tools from information geometry have been used to study embeddings of probabilistic models onto a hierarchy of model manifolds that encode how model outputs change as a function of their parameters, giving a quantitative notion of "distances" between outputs. We apply this method to a network model of excitatory and inhibitory neural populations to understand how the competition between membrane and synaptic response timescales shapes the network's information geometry. The hyperbolic embedding allows us to identify the statistical parameters to which the model behavior is most sensitive, and demonstrate how the ranking of these coordinates changes with the balance of excitation and inhibition in the network.

Effects of sensory afferent input on motor cortex excitability of agonist and antagonist muscles.

In this study, we aimed to analyze control mechanisms of short-latency afferent inhibition (SAI) during motor output exertion from an agonist or antagonist muscle. The motor task involved index finger abduction (agonist) and adduction (antagonist). In Experiment 1, motor-evoked potentials (MEPs) were recorded from the first dorsal interosseous (FDI) muscle with and without SAI at three output force levels. In Experiment 2, MEPs were recorded with and without SAI at various time points immediately before the muscle output. Experiment 1 showed that inhibition decreased with an increase in muscle output in the agonist muscle but increased in the antagonist muscle. Experiment 2 showed a decreasing trend of inhibition in the agonist muscle immediately before contraction but showed no significant change in the antagonist muscle. MEPs without electrical stimulation during the reaction time increased in both directions of movement as compared to those in the resting state. These results suggest that SAI modulation strongly influences smooth motor output. Analyzing the inhibitory or enhanced mechanisms during the performance of motor output by SAI in patients with motor impairment and comparing them with the mechanisms seen in healthy participants will improve our understanding of the neurophysiological mechanisms relevant to various situations (e.g., rehabilitation and sports).

A mean-field model of gamma-frequency oscillations in networks of excitatory and inhibitory neurons.

Gamma oscillations are widely seen in the cerebral cortex in different states of the wake-sleep cycle and are thought to play a role in sensory processing and cognition. Here, we study the emergence of gamma oscillations at two levels, in networks of spiking neurons, and a mean-field model. At the network level, we consider two different mechanisms to generate gamma oscillations and show that they are best seen if one takes into account the synaptic delay between neurons. At the mean-field level, we show that, by introducing delays, the mean-field can also produce gamma oscillations. The mean-field matches the mean activity of excitatory and inhibitory populations of the spiking network, as well as their oscillation frequencies, for both mechanisms. This mean-field model of gamma oscillations should be a useful tool to investigate large-scale interactions through gamma oscillations in the brain.

Hypothalamic Paraventricular Stimulation Inhibits Nociceptive Wide Dynamic Range Trigeminocervical Complex Cells via Oxytocinergic Transmission.

Oxytocinergic transmission blocks nociception at the peripheral, spinal, and supraspinal levels through the oxytocin receptor (OTR). Indeed, a neuronal pathway from the hypothalamic paraventricular nucleus (PVN) to the spinal cord and trigeminal nucleus caudalis (Sp5c) has been described. Hence, although the trigeminocervical complex (TCC), an anatomical area spanning the Sp5c, C1, and C2 regions, plays a role in some pain disorders associated with craniofacial structures (e.g., migraine), the role of oxytocinergic transmission in modulating nociception at this level has been poorly explored. Hence, in vivo electrophysiological recordings of TCC wide dynamic range (WDR) cells sensitive to stimulation of the periorbital or meningeal region were performed in male Wistar rats. PVN electrical stimulation diminished the neuronal firing evoked by periorbital or meningeal electrical stimulation; this inhibition was reversed by OTR antagonists administered locally. Accordingly, neuronal projections (using Fluoro-Ruby) from the PVN to the WDR cells filled with Neurobiotin were observed. Moreover, colocalization between OTR and calcitonin gene-related peptide (CGRP) or OTR and GABA was found near Neurobiotin-filled WDR cells. Retrograde neuronal tracers deposited at the meningeal (True-Blue, TB) and infraorbital nerves (Fluoro-Gold, FG) showed that at the trigeminal ganglion (TG), some cells were immunopositive to both fluorophores, suggesting that some TG cells send projections via the V1 and V2 trigeminal branches. Together, these data may imply that endogenous oxytocinergic transmission inhibits the nociceptive activity of second-order neurons via OTR activation in CGRPergic (primary afferent fibers) and GABAergic cells.

Modulation of intracortical circuits in primary motor cortex during automatic action tendencies.

Humans display automatic action tendencies toward emotional stimuli, showing faster automatic behavior (i.e., approaching a positive stimulus and avoiding a negative stimulus) than regulated behavior (i.e., avoiding a positive stimulus and approaching a negative stimulus). Previous studies have shown that the primary motor cortex is involved in the processing of automatic actions, with higher motor evoked potential amplitudes during automatic behavior elicited by single-pulse transcranial magnetic stimulation. However, it is unknown how intracortical circuits are involved with automatic action tendencies. Here, we measured short-interval intracortical inhibition and intracortical facilitation within the primary motor cortex by using paired-pulse transcranial magnetic stimulation protocols during a manikin task, which has been widely used to explore approaching and avoiding behavior. Results showed that intracortical facilitation was stronger during automatic behavior than during regulated behavior. Moreover, there was a significant negative correlation between reaction times and intracortical facilitation effect during automatic behavior: individuals with short reaction times had stronger faciliatory activity, as shown by higher intracortical facilitation. By contrast, no significant difference was found for short-interval intracortical inhibition between automatic behavior and regulated behavior. The results indicated that the intracortical facilitation circuit, mediated by excitatory glutamatergic neurons, in the primary motor cortex, plays an important role in mediating automatic action tendencies. This finding further supports the link between emotional perception and the action system.

Decreased short-latency afferent inhibition in individuals with mild cognitive impairment: A TMS-EEG study.

TMS combined with EEG (TMS-EEG) is a tool to characterize the neurophysiological dynamics of the cortex. Among the TMS paradigms, short-latency afferent inhibition (SAI) allows the investigation of inhibitory effects mediated by the cholinergic system. The aim of this study was to compare cholinergic function in the DLPFC between individuals with mild cognitive impairment (MCI) and healthy controls (HC) using TMS-EEG with the SAI paradigm. In this study, 30 MCI and 30 HC subjects were included. The SAI paradigm consisted of 80 single pulse TMS and 80 SAI stimulations applied to the left DLPFC. N100 components, global mean field power (GMFP) and total power were calculated. As a result, individuals with MCI showed reduced inhibitory effects on N100 components and GMFP at approximately 100 ms post-stimulation and on ß-band activity at 200 ms post-stimulation compared to HC. Individuals with MCI showed reduced SAI, suggesting impaired cholinergic function in the DLPFC compared to the HC group. We conclude that these findings underscore the clinical applicability of the TMS-EEG method as a powerful tool for assessing cholinergic function in individuals with MCI.

Short-latency afferent inhibition as a biomarker of cholinergic degeneration compared to PET imaging in Parkinson's disease.

INTRODUCTION: Short-latency afferent inhibition (SAI) is a relatively cheap and non-invasive method that has been proposed as a cholinergic marker in Parkinson's disease (PD). We aim to verify the clinical feasibility of SAI as a cholinergic marker in PD using positron emission tomography (PET) with the tracer (2R,3R)-5-(2-[18F]fluoroethoxy)benzovesamicol ([18F]FEOBV) as a reference. METHODS: We examined relations between SAI and [18F]FEOBV PET using linear regression analysis, with the primary motor cortex (M1) as primary region of interest. Additionally, we examined relations of both measures with clinical features. RESULTS: 30 PD patients with varying degrees of cognitive dysfunction and 10 healthy controls (HC) were included in the analysis. SAI was not related to tracer uptake in M1 in the PD group (p = .291) or the HC group (p = .206). We could not replicate the previously published relations between SAI and cholinergic symptoms, such as cognition, psychotic experiences and olfactory function. CONCLUSION: SAI was not related to [18F]FEOBV imaging parameters, nor to clinical measures of cholinergic dysfunction. Therefore, SAI may not be feasible as a clinically applied cholinergic marker in PD.

Beta rebound reduces subsequent movement preparation time by modulating of GABAA inhibition.

Post-movement beta synchronization is an increase of beta power relative to baseline, which commonly used to represent the status quo of the motor system. However, its functional role to the subsequent voluntary motor output and potential electrophysiological significance remain largely unknown. Here, we examined the reaction time of a Go/No-Go task of index finger tapping which performed at the phases of power baseline and post-movement beta synchronization peak induced by index finger abduction movements at different speeds (ballistic/self-paced) in 13 healthy subjects. We found a correlation between the post-movement beta synchronization and reaction time that larger post-movement beta synchronization prolonged the reaction time during Go trials. To probe the electrophysiological significance of post-movement beta synchronization, we assessed intracortical inhibitory measures probably involving GABAB (long-interval intracortical inhibition) and GABAA (short-interval intracortical inhibition) receptors in beta baseline and post-movement beta synchronization peak induced by index finger abduction movements at different speeds. We found that short-interval intracortical inhibition but not long-interval intracortical inhibition increased in post-movement beta synchronization peak compared with that in the power baseline, and was negatively correlated with the change of post-movement beta synchronization peak value. These novel findings indicate that the post-movement beta synchronization is related to forward model updating, with high beta rebound predicting longer time for the preparation of subsequent movement by inhibitory neural pathways of GABAA.

Attentional focus differentially modulates the corticospinal and intracortical excitability during dynamic and static exercise.

Although attentional focus affects motor performance, whether corticospinal excitability and intracortical modulations differ between focus strategies depending on the exercise patterns remains unclear. In the present study, using single- and paired-pulse transcranial magnetic stimulation and peripheral nerve stimulation, we demonstrated changes in the cortical and spinal excitability under external focus (EF) and internal focus (IF) conditions with dynamic or static exercise. Participants performed the ramp-and-hold contraction task of right index finger abduction against an object (sponge or wood) with both exercises. They were asked to concentrate on the pressure on the sponge/wood induced by finger abduction under the EF condition, and on the index finger itself under the IF condition. Motor-evoked potential (MEP) and F-wave in the premotor, phasic, or tonic phase, and short- and long-interval intracortical inhibition (SICI and LICI, respectively), and intracortical facilitation (ICF) in the premotor phase were examined by recording surface electromyographic activity in the right first dorsal interosseous muscle. Increments in the MEP amplitude were larger under the EF condition than under the IF condition in the dynamic, but not static, exercise. The F-wave, SICI, and LICI did not differ between focus conditions in both exercises. In the dynamic exercise, interestingly, ICF was greater under the EF condition than under the IF condition and positively correlated with the MEP amplitude. These results indicate that corticospinal excitability and intracortical modulations to attentional focus differ depending on exercise patterns, suggesting that attentional focus differentially affects the central nervous system responsible for diverse motor behaviors.NEW & NOTEWORTHY We investigated attentional focus-dependent corticospinal and intracortical modulations in dynamic or static exercise. The corticospinal excitability was modulated differentially depending on the focus of attention during dynamic, but not static exercise. Although the reduction of intracortical GABAergic inhibition was comparable between focus conditions in both exercises, intracortical facilitation was smaller when focusing on the internal environments in the dynamic exercise, resulting in lower activation of the corticospinal tract.

Long-interval afferent inhibition measurement using two different methods: Normative values, repeatability and reliability.

BACKGROUND: The mechanism of Short-Latency Afferent Inhibition (SAI) is relatively well understood. In contrast, Long-Latency Afferent Inhibition (LAI) has not been as extensively studied as SAI, and its underlying mechanism remains unclear. OBJECTIVE/HYPOTHESIS: This study had two primary objectives: first, to determine the optimal ISIs for LAI measured by amplitude changes (A-LAI) using high-resolution ISI ranges; and second, to compare measurements of LAI by threshold-tracking (T-LAI). METHODS: Twenty-eight healthy volunteers (12 males aged 24- 45 years) participated in the study. Paired peripheral electrical and transcranial magnetic stimulation (TMS) stimuli (TS1mv) were applied at varying (ISIs)- 100, 200, 250, 300, 350, 400, 450, 500, 550, 600, 700, 800, 900, 1000 ms. RESULTS: Both A-LAI and T-LAI showed that LAI decreased progressively from a peak at 200 or 250 ms to 1000 ms. Using the A-LAI method, pronounced inhibition was observed at three specific ISIs: 100 ms, 250 ms and 450 ms. When A-LAI values were converted to equivalent threshold changes, they did not differ significantly from T-LAI. Reliability at distinguishing individuals, as indicated by intraclass correlation coefficient (ICC) was greater for A-LAI, with a peak value of 0.82 at 250 ms. CONCLUSION(S): The study demonstrates that ISIs of 100 ms and 250 ms can be reliably used in amplitude measurement LAI. The study demonstrates that both LAI measurements record a similar decline of inhibition with increasing ISI.

Shared input and recurrency in neural networks for metabolically efficient information transmission.

Shared input to a population of neurons induces noise correlations, which can decrease the information carried by a population activity. Inhibitory feedback in recurrent neural networks can reduce the noise correlations and thus increase the information carried by the population activity. However, the activity of inhibitory neurons is costly. This inhibitory feedback decreases the gain of the population. Thus, depolarization of its neurons requires stronger excitatory synaptic input, which is associated with higher ATP consumption. Given that the goal of neural populations is to transmit as much information as possible at minimal metabolic costs, it is unclear whether the increased information transmission reliability provided by inhibitory feedback compensates for the additional costs. We analyze this problem in a network of leaky integrate-and-fire neurons receiving correlated input. By maximizing mutual information with metabolic cost constraints, we show that there is an optimal strength of recurrent connections in the network, which maximizes the value of mutual information-per-cost. For higher values of input correlation, the mutual information-per-cost is higher for recurrent networks with inhibitory feedback compared to feedforward networks without any inhibitory neurons. Our results, therefore, show that the optimal synaptic strength of a recurrent network can be inferred from metabolically efficient coding arguments and that decorrelation of the input by inhibitory feedback compensates for the associated increased metabolic costs.

Short-latency afferent inhibition is reduced in people with multiple sclerosis during fatiguing muscle contractions.

Understanding how inhibitory pathways influence motor cortical activity during fatiguing contractions may provide valuable insight into mechanisms associated with multiple sclerosis (MS) muscle activation. Short-latency afferent inhibition (SAI) reflects inhibitory interactions between the somatosensory cortex and the motor cortex, and although SAI is typically reduced with MS, it is unknown how SAI is regulated during exercise-induced fatigue. The current study examined how SAI modulates motor evoked potentials (MEPs) during fatiguing contractions. Fourteen people with relapsing-remitting MS (39 ± 6 years, nine female) and 10 healthy individuals (36 ± 6 years, six female) participated. SAI was induced by stimulation of the median nerve that was paired with TMS over the motor representation of the abductor pollicis brevis. A contraction protocol was employed that depressed force generating capacity using a sustained 3-min 15% MVC, immediately followed by a low-intensity (15% MVC) intermittent contraction protocol so that MEP and SAI could be measured during the rest phases of each duty cycle. Similar force, electromyography and MEP responses were observed between groups. However, the MS group had significantly reduced SAI during the contraction protocol compared to the healthy control group (p < .001). Despite the MS group reporting greater scores on the Fatigue Severity Scale and Modified Fatigue Impact Scale, these scales did not correlate with inhibitory measures. As there were no between-group differences in SSEPs, MS-related SAI differences during the fatiguing contractions were most likely associated with disease-related changes in central integration.

Enhancing GABAergic Tonic Inhibition Reduces Seizure-Like Activity in the Neonatal Mouse Hippocampus and Neocortex.

Approximately one-third of neonatal seizures do not respond to first-line anticonvulsants, including phenobarbital, which enhances phasic inhibition. Whether enhancing tonic inhibition decreases seizure-like activity in the neonate when GABA is mainly depolarizing at this age is unknown. We evaluated if increasing tonic inhibition using THIP [4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridin-3-ol, gaboxadol], a δ-subunit-selective GABAA receptor agonist, decreases seizure-like activity in neonatal C57BL/6J mice (postnatal day P5-8, both sexes) using acute brain slices. Whole-cell patch-clamp recordings showed that THIP enhanced GABAergic tonic inhibitory conductances in layer V neocortical and CA1 pyramidal neurons and increased their rheobase without altering sEPSC characteristics. Two-photon calcium imaging demonstrated that enhancing the activity of extrasynaptic GABAARs decreased neuronal firing in both brain regions. In the 4-aminopyridine and the low-Mg2+ model of pharmacoresistant seizures, THIP reduced epileptiform activity in the neocortex and CA1 hippocampal region of neonatal and adult brain slices in a dose-dependent manner. We conclude that neocortical layer V and CA1 pyramidal neurons have tonic inhibitory conductances, and when enhanced, they reduce neuronal firing and decrease seizure-like activity. Therefore, augmenting tonic inhibition could be a viable approach for treating neonatal seizures.

Functional specificity of recurrent inhibition in visual cortex.

In the neocortex, neural activity is shaped by the interaction of excitatory and inhibitory neurons, defined by the organization of their synaptic connections. Although connections among excitatory pyramidal neurons are sparse and functionally tuned, inhibitory connectivity is thought to be dense and largely unstructured. By measuring in vivo visual responses and synaptic connectivity of parvalbumin-expressing (PV+) inhibitory cells in mouse primary visual cortex, we show that the synaptic weights of their connections to nearby pyramidal neurons are specifically tuned according to the similarity of the cells' responses. Individual PV+ cells strongly inhibit those pyramidal cells that provide them with strong excitation and share their visual selectivity. This structured organization of inhibitory synaptic weights provides a circuit mechanism for tuned inhibition onto pyramidal cells despite dense connectivity, stabilizing activity within feature-specific excitatory ensembles while supporting competition between them.

Corticomotor Control of Lumbar Erector Spinae in Postural and Voluntary Tasks: The Influence of Transcranial Magnetic Stimulation Current Direction.

Lumbar erector spinae (LES) contribute to spine postural and voluntary control. Transcranial magnetic stimulation (TMS) preferentially depolarizes different neural circuits depending on the direction of electrical currents evoked in the brain. Posteroanterior current (PA-TMS) and anteroposterior (AP-TMS) current would, respectively, depolarize neurons in the primary motor cortex (M1) and the premotor cortex. These regions may contribute differently to LES control. This study examined whether responses evoked by PA- and AP-TMS are different during the preparation and execution of LES voluntary and postural tasks. Participants performed a reaction time task. A Warning signal indicated to prepare to flex shoulders (postural; n = 15) or to tilt the pelvis (voluntary; n = 13) at the Go signal. Single- and paired-pulse TMS (short-interval intracortical inhibition-SICI) were applied using PA- and AP-TMS before the Warning signal (baseline), between the Warning and Go signals (preparation), or 30 ms before the LES onset (execution). Changes from baseline during preparation and execution were calculated in AP/PA-TMS. In the postural task, MEP amplitude was higher during the execution than that during preparation independently of the current direction (p = 0.0002). In the voluntary task, AP-MEP amplitude was higher during execution than that during preparation (p = 0.016). More PA inhibition (SICI) was observed in execution than that in preparation (p = 0.028). Different neural circuits are preferentially involved in the two motor tasks assessed, as suggested by different patterns of change in execution of the voluntary task (AP-TMS, increase; PA-TMS, no change). Considering that PA-TMS preferentially depolarize neurons in M1, it questions their importance in LES voluntary control.

The paired-pulse TMS paradigm of short intracortical inhibition is mediated by a reduction of repetitive motor neuron discharges.

Transcranial magnetic stimulation (TMS) causes repetitive spinal motoneuron discharges (repMNDs), but the effects of short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) on repMNDs remain unknown. Triple stimulation technique (TST) and the extended TST-protocols that include a fourth and fifth stimulation, the Quadruple (QuadS) and Quintuple (QuintS) stimulation, respectively, offer a precise estimate of cortical and spinal motor neuron discharges, including repMNDs. The objective of our study was to explore the effects of SICI and ICF on repMNDs. We explored conventional paired-pulse TMS protocols of SICI and ICF with the TMS, TST, the QuadS, and the QuintS protocols, in a randomized study design in 20 healthy volunteers. We found significantly less repMNDs in the SICI paradigm compared with a single-pulse TMS (SP-TMS). No significant difference was observed in the ICF paradigm. There was a significant inter- and intrasubject variability in both SICI and ICF. We demonstrate a significant reduction of repMNDs in SICI, which may result from the suppression of later I-waves and mediate the inhibition of motor-evoked potential (MEP). There is no increase in repMNDs in ICF suggesting another mechanism underlying facilitation. This study provides the proof that a reduction of repMNDs mediates the inhibition seen in SICI.NEW & NOTEWORTHY Significant reduction of repetitive motor neuron discharges (repMNDs) in short-interval intracortical inhibition (SICI) may result from the suppression of later I-waves and mediate the inhibition of motor-evoked potential (MEP). There is no change in the number of repMNDs in intracortical facilitation (ICF). There was a significant variability in SICI and ICF in healthy subjects.