Longer transcranial magnetic stimulation intertrial interval increases size, reduces variability, and improves the reliability of motor evoked potentials

High rates of variability in the amplitude of transcranial magnetic stimulation (TMS)-induced motor evoked potentials (MEPs), a popular method for assessing corticospinal excitability (CSE), make it essential to examine inherent reliability of the MEP amplitude. We aimed to investigate the effects of different intertrial intervals (ITIs) of single-pulse TMS on the amplitude, variability, and test-retest reliability of MEPs. Twenty-five TMS single pulses were recorded at four different ITIs of 5, 10, 15, and 20 sec from 15 healthy participants who attended two experimental sessions. Repeated measures analysis of variance (rmANOVA) and standardized -value standard deviations (SDs) were used to investigate the effects of ITIs on MEP amplitudes and variability. Test-retest reliability of MEP amplitudes was also assessed using rmANOVA and intraclass correlation (ICC). rmANOVA revealed significantly larger MEP amplitudes following ITIs of 10, 15, and 20 sec compared with ITI 5, with no significant increases between ITIs of 15 and 20 sec. Standardized -value SDs revealed variability rate reduction following longer ITIs with significant reductions occurring following ITIs of 10, 15, and 20 sec compared with ITI 5 with no significant difference between ITIs of 15 and 20 sec. rmANOVA showed no significant Time main effect on the MEP changes confirming within- and between-session agreement. ICCs reported significant within- and between-session reliability in all selected ITIs. The findings of the current study indicate that longer ITIs up to 15 sec can significantly induce larger MEPs with lower variability and higher reliability. The increase in ITIs not only reduces the chance of TMS-induced changes in CSE but also helps us to use this assessment tool in studies with smaller sample sizes

How different priming stimulations affect the corticospinal excitability induced by noninvasive brain stimulation techniques: a systematic review and meta-analysis

Noninvasive brain stimulation (NIBS) techniques could induce changes in corticospinal excitability (CSE) and neuroplasticity. These changes could be affected by different factors, including having a session of stimulation called the 'priming' protocol before the main stimulation session called the 'test' protocol. Literature indicates that a priming protocol could affect the activity of postsynaptic neurons, form a neuronal history, and then modify the expected effects of the test protocol on CSE indicated by the amplitude of transcranial magnetic stimulation-induced motor-evoked potentials. This prior history affects a threshold to activate the necessary mechanism stabilizing the neuronal activity within a useful dynamic range. For studying the effects of this history and related metaplasticity mechanisms in the human primary motor cortex (M1), priming-test protocols are successfully employed. Thirty-two studies were included in this review to investigate how different priming protocols could affect the induced effects of a test protocol on CSE in healthy individuals. The results showed that if the history of synaptic activity were high or low enough to displace the threshold, the expected effects of the test protocol would be the reverse. This effect reversal is regulated by homeostatic mechanisms. On the contrary, the effects of the test protocol would not be the reverse, and at most we experience a prolongation of the lasting effects if the aforementioned history is not enough to displace the threshold. This effect prolongation is mediated by nonhomeostatic mechanisms. Therefore, based on the characteristics of priming-test protocols and the interval between them, the expected results of priming-test protocols would be different. Moreover, these findings could shed light on the different mechanisms of metaplasticity involved in NIBS. It helps us understand how we can improve the expected outcomes of these techniques in clinical approaches

How different priming stimulations affect the corticospinal excitability induced by noninvasive brain stimulation techniques: a systematic review and meta-analysis

Noninvasive brain stimulation (NIBS) techniques could induce changes in corticospinal excitability (CSE) and neuroplasticity. These changes could be affected by different factors, including having a session of stimulation called the 'priming' protocol before the main stimulation session called the 'test' protocol. Literature indicates that a priming protocol could affect the activity of postsynaptic neurons, form a neuronal history, and then modify the expected effects of the test protocol on CSE indicated by the amplitude of transcranial magnetic stimulation-induced motor-evoked potentials. This prior history affects a threshold to activate the necessary mechanism stabilizing the neuronal activity within a useful dynamic range. For studying the effects of this history and related metaplasticity mechanisms in the human primary motor cortex (M1), priming-test protocols are successfully employed. Thirty-two studies were included in this review to investigate how different priming protocols could affect the induced effects of a test protocol on CSE in healthy individuals. The results showed that if the history of synaptic activity were high or low enough to displace the threshold, the expected effects of the test protocol would be the reverse. This effect reversal is regulated by homeostatic mechanisms. On the contrary, the effects of the test protocol would not be the reverse, and at most we experience a prolongation of the lasting effects if the aforementioned history is not enough to displace the threshold. This effect prolongation is mediated by nonhomeostatic mechanisms. Therefore, based on the characteristics of priming-test protocols and the interval between them, the expected results of priming-test protocols would be different. Moreover, these findings could shed light on the different mechanisms of metaplasticity involved in NIBS. It helps us understand how we can improve the expected outcomes of these techniques in clinical approaches

Determination of anodal tDCS intensity threshold for reversal of corticospinal excitability:an investigation for induction of counter-regulatory mechanisms

Transcranial direct current stimulation is applied to modulate activity, and excitability of the brain. Basically, LTP-like plasticity is induced when anodal tDCS (a-tDCS) is applied over the primary motor cortex. However, it has been shown that specific parameters of a-tDCS can induce a plasticity reversal. We aimed to systematically assess the intensity threshold for reversal of the direction of plasticity induced by a-tDCS, monitored by corticospinal excitability (CSE), and explored mechanisms regulating this reversal. Fifteen healthy participants received a-tDCS in pseudo-random order for 26 min with four intensities of 0.3, 0.7, 1, and 1.5 mA. To measure CSE changes, single-pulse TMS was applied over the left M1, and motor evoked potentials of a contralateral hand muscle were recorded prior to a-tDCS, immediately and 30-min post-intervention. Paired-pulse TMS was used to evaluate intracortical excitation and inhibition. CSE increased significantly following a-tDCS with an intensity of 0.7 mA; however, the expected effect decreased and even reversed at intensities of 1 and 1.5 mA. ICF was significantly increased while SICI and LICI decreased at 0.7 mA. On the other hand, a significant decrease of ICF, but SICI and LICI enhancement was observed at intensities of 1, and 1.5 mA. The present findings show an intensity threshold of ≥ 1 mA for 26 min a-tDCS to reverse LTP- into LTD-like plasticity. It is suggested that increasing stimulation intensity, with constant stimulation duration, activates counter-regulatory mechanisms to prevent excessive brain excitation. Therefore, stimulation intensity and plasticity induced by a-tDCS might non-linearly correlate in scenarios with prolonged stimulation duration

Determination of anodal tDCS duration threshold for reversal of corticospinal excitability:An investigation for induction of counter-regulatory mechanisms

BACKGROUND: Transcranial direct current stimulation (tDCS) is used to induce neuroplasticity in the human brain. Within certain limits of stimulation duration, anodal tDCS (a-tDCS) over the primary motor cortex induces long term potentiation- (LTP) like plasticity. A reversal of the direction of plasticity has however been described with prolonged a-tDCS protocols. OBJECTIVE: We aimed to systematically investigate the intervention duration threshold for reversal of a-tDCS-induced effects on corticospinal excitability (CSE) and to determine the probable mechanisms involved in these changes. METHODS: Fifteen healthy participants received a-tDCS of 1 mA for five different durations in pseudo-random session order. Transcranial magnetic stimulation (TMS) was delivered over the left M1, and motor evoked potentials (MEPs) of a contralateral hand muscle were recorded before, immediately and 30 min following intervention to measure CSE changes. Short-interval intracortical inhibition (SICI), intracortical facilitation (ICF), and long interval facilitation (LIF) were assessed via paired-pulse TMS protocols. RESULTS: A-tDCS significantly increased CSE as expected at stimulation durations of 22 and 24 min. However, this effect of a-tDCS on CSE decreased and even reversed when stimulation duration increased to 26, 28, and 30 min. Respective alterations of ICF, LIF, and SICI indicate the involvement of glutamatergic, and GABAergic systems in these effects. CONCLUSIONS: These results confirm a duration threshold for reversal of the excitability-enhancing effect of a-tDCS with stimulation durations ≥ 26 min. Counter-regulatory mechanisms are discussed as a mechanistic foundation for these effects, which might prevent excessive brain activation