Exploring the pathophysiology of Mal de Debarquement

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

Transcranial magnetic stimulation (TMS) can produce effects not only at the site of stimulation but also at distant sites to which it projects. Here we examined the connection between supplementary motor area (SMA) and the hand area of the primary motor cortex (M1(Hand)) by testing whether prolonged repetitive TMS (rTMS) over the SMA can produce changes in excitability of the M1(Hand) after the end of the stimulus train. We evaluated motor-evoked potentials (MEPs) and the cortical silent period (CSP) evoked by a single-pulse TMS, short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) produced by a paired-pulse TMS, and forearm flexor H reflexes before and after 750 pulses of 5 Hz rTMS over SMA at an intensity of 110% active motor threshold (AMT) for the first dorsal interosseous (FDI) muscle. The amplitude of MEPs recorded from the right FDI muscle at rest as well as during voluntary contraction increased for at least 10 min after the end of rTMS, although the duration of the CSP, SICI and ICF did not change. There was no effect on H reflexes in the flexor carpi radialis muscle, even though the amplitude of the MEP obtained from the same muscle increased after rTMS. The effects on MEPs depended on the intensity of rTMS and were spatially specific to the SMA proper. We suggest that 5 Hz rTMS over SMA can induce a short-lasting facilitation in excitability of the M1(Hand) compatible with the anatomical connections between SMA and the M1(Hand).

Following a suprathreshold transcranial magnetic stimulation (TMS) to the primary motor cortex (M1) during voluntary muscle contraction, a motor evoked potential (MEP) occurs in the target muscle followed by a silent period (SP) in the electromyographic (EMG) activities. The present study investigated how short interval intracortical inhibition (SICI) and intracortical facilitation (ICF) change during the SP. The time course of MEP and motor threshold during the SP were examined in the right first dorsal interosseous muscle. Using a triple-pulse protocol, SICI and ICF were tested at different times during the SP. The effects of different intensities of the conditioning stimulation (CS) for SICI and ICF were also investigated during the SP and at rest. During the SP, MEP was inhibited and motor threshold was increased, whereas MEP latency and background EMG level were same as those at rest. SICI decreased during the SP over a wide range of CS intensities. ICF increased at higher CS intensity. We conclude that SICI is suppressed and ICF is facilitated during the SP and the effects are separate from the interruption of voluntary drive.

Theta-burst transcranial ultrasound stimulation (tbTUS) increases primary motor cortex (M1) excitability for at least 30min. However, the remote effects of focal M1 tbTUS on the excitability of other cortical areas are unknown. Here, we examined the effects of left M1 tbTUS on right M1 excitability. An 80s train of active or sham tbTUS was delivered to the left M1 in 20healthy subjects. Before and after the tbTUS, we measured: (1) corticospinal excitability using motor-evoked potential (MEP) amplitudes from single-pulse transcranial magnetic stimulation (TMS) of left and right M1; (2) interhemispheric inhibition (IHI) from left to right M1 and from right to left M1 using a dual-site paired-pulse TMS paradigm; and (3) intracortical circuits of the right M1 with short-interval intracortical inhibition and intracortical facilitation (ICF) using paired-pulse TMS. Left M1 tbTUS decreased right M1 excitability as shown by decreased MEP amplitudes, increased right M1 ICF and decreased short-interval IHI from left to right hemisphere at interstimulus interval (ISI) of 10ms but not long-interval IHI at interstimulus interval of 40ms. The study showed that left M1 tbTUS can change the excitability of remote cortical areas with decreased right M1 excitability and interhemispheric inhibition. The remote effects of tbTUS should be considered when it is used in neuroscience research and as a potential neuromodulation treatment for brain disorders. KEY POINTS: Transcranial ultrasound stimulation (TUS) is a novel non-invasive brain stimulation technique for neuromodulation with the advantages of being able to achieve high spatial resolution and target deep brain structures. A repetitive TUS protocol, with an 80s train of theta burst patterned TUS (tbTUS), has been shown to increase primary motor cortex (M1) excitability, as well as increase alpha and beta movement-related spectral power in distinct brain regions. In this study, we examined on the effects of the motor cortical tbTUS on the excitability of contralateral M1measured with MEPs elicited by transcranial magnetic stimulation. We showed that left M1 tbTUS decreased right M1 excitability and left-to-right M1 interhemispheric inhibition, and increased intracortical facilitation of right M1. These results lead to better understand the effects of tbTUS and can help the development of tbTUS for the treatment of neurological and psychiatric disorders and in neuroscience research.

Electrical Stimulation of Back Muscles Does Not Prime the Corticospinal Pathway

Intracortical inhibition in the human trigeminal motor system

Background: The muscle representations in non-primary motor area (NPMA) are located in the dorsal premotor area (PMd) and in the border region between the premotor area and the supplementary motor area (SMA).Objective: We characterized the plasticity of intracortical inhibitory and excitatory circuits in muscle representations in primary motor cortex (M1) and in NPMA related to acquired fine motor skills. We compared local cortical inhibition and facilitation balance in M1 and in NPMA between control subjects (n = 6) and right-handed string-instrument players (n = 5).Methods: Navigated transcranial magnetic stimulation (TMS) was used to compare motor thresholds (MTs), motor evoked potentials (MEPs), short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) in non-dominant hand muscle representations in M1 and NPMA.Results: String-instrument players showed reduced SICI in M1 in the actively used left hand abductor digiti minimi (ADM) muscle representation at 3 ms inter-stimulus interval (ISI) with a conditioning stimulus (CS) intensity of 80% of MT and increased SICI in NPMA in ADM representation at 2 ms ISI and CS intensity of 50% of MT in comparison with controls. No differences between string-instrument players and controls were found for the SICI in the left hand opponens pollicis (OP) muscle representation, which is a muscle not intensively trained in string-instrument players.Conclusions: These preliminary results indicate that the stronger inhibition in motor representations outside M1 in string-instrument players may be crucial when accurate movements of single muscles must be performed. In contrast, weaker inhibition in M1 in string-instrument players may benefit the performance of fast finger movements.

Short-interval intracortical inhibition (SICI), intracortical facilitation (ICF) and short-interval intracortical facilitation (SICF) were assessed in the cortical motor area of the first dorsal interosseous muscle (FDI) of 16 healthy subjects. Paired-pulse TMS was delivered to the left hemisphere at the following interstimulus intervals (ISIs): 2 and 3 ms for SICI, 10 and 15 ms for ICF and 1-5 ms for SICF. Motor-evoked potentials were recorded from the resting and active right FDI. The effects exerted on SICI and ICF by four intensities (60-90% of active motor threshold, AMT) of the conditioning stimulus (S1) and by three levels of muscle contraction (10%, 25%, 50% of maximal voluntary contraction, MVC) were evaluated. The effects exerted on SICF were evaluated with two intensities (90% and 70% of AMT) of the test stimulus (S2) and with the same levels of muscle contraction. Results showed that: (i) during 10% MVC, maximum SICI was observed with S1 = 70% AMT; (ii) the amount of SICI obtained with S1 = 70% AMT was the same at rest as during 10% MVC, but decreased at higher contraction levels; (iii) ICF was observed only at rest with S1 = 90% AMT; (iv) SICF was facilitated at 10% and 25% MVC, but not at 50% MVC. We conclude that during muscle activation, intracortical excitability reflects a balance between activation of SICI and SICF systems. Part of the reduction in SICI during contraction is due to superimposed recruitment of SICF. Low intensity (70% AMT) conditioning stimuli can test SICI independently of effects on SICF at low contraction levels.

What is the central question of this study? A transcranial magnetic stimulation (TMS)-induced twitch applied on isolated single breaths over the motor cortex somatotopic representation of the tongue briefly recruits submental muscles and improves airflow dynamics of flow-limited respiratory cycles without arousing sleep apnoea patients. However, the mechanical impact of the TMS-induced twitch applied during consecutive breathing cycles on airflow dynamics remains unknown. What is the main finding and what is its importance? Our results show that application of TMS with the stimulator output set at the sleep submental motor threshold intensity on consecutive respiratory cycles increases inspiratory flow and reduces the turbulent airflow component. These results indicate an improvement of airflow pattern after two single consecutive TMS-induced twitches without arousing sleep apnoea patients. Transcranial magnetic stimulation (TMS)-induced twitches applied on isolated breaths briefly recruit upper airway dilator muscles and improve airflow and inspiratory volume without arousing apnoeic patients from sleep, but the effects of applying such twitches consecutively on airflow dynamics is unknown. The objective of this study was to quantify the effects of five consecutive TMS-induced twitches applied on sleep-induced obstructive hypopnoeic breaths in 10 obstructive sleep apnoea patients. Submental muscle motor threshold (SUBMT) and motor-evoked potential were measured during wakefulness and sleep. The TMS-induced twitches were applied during stable non-rapid eye movement (NREM) sleep, at the beginning of inspiration of consecutive flow-limited respiratory cycles, with the stimulator output set at sleep SUBMT. Maximal inspiratory flow, inspiratory volume, inspiratory time, shifts of electroencephalogram frequency and pulse rate variability were assessed. During sleep, SUBMT increased (wakefulness, 25.3 ± 4.9%; NREM sleep, 27.0 ± 6.2%; P = 0.02). During each series of stimulations there was a rise in maximal inspiratory flow (from 306.7 ± 123.2 to 359.8 ± 154.1 ml s(-1); P = 0.0002) and in inspiratory volume (from 346.1 ± 128.1 to 414.9 ± 171.2 ml; P = 0.02) without differences in thoraco-abdominal efforts and inspiratory time. These responses were observed in the absence of arousals and ceased immediately after TMS interruption. Transcranial magnetic stimulation-induced cortical and/or autonomic arousal was observed in 30.2% of all series of stimulation. Consecutive twitch TMS of submental muscles may lead to arousals in a minority of patients but can be applied on consecutive respiratory cycles during sleep and can significantly improve maximal inspiratory flow and inspiratory volume of flow-limited cycles.

Increased facilitation of the primary motor cortex in de novo Parkinson's disease

Low amplitude muscle vibration (0.5 ms; 80 Hz; duration 1.5 s) was applied in turn to each of three different intrinsic hand muscles (first dorsal interosseus, FDI; abductor pollicis brevis, APB; and abductor digiti minimi, ADM) in order to test its effect on the EMG responses evoked by transcranial magnetic stimulation (TMS). Recordings were also taken from flexor and extensor carpi radialis (FCR and ECR, respectively). We evaluated the amplitude of motor evoked potentials (MEPs) produced by a single TMS pulse, short interval intracortical inhibition and facilitation (SICI and ICF) and long interval intracortical inhibition (LICI). TMS pulses were applied 1 s after the start of vibration with subjects relaxed throughout. Vibration increased the amplitude of MEPs evoked in the vibrated muscle (162 +/- 6 % of MEP with no vibration; mean +/- S.E.M.), but suppressed MEPs in the two non-vibrated hand muscles (72 +/- 9 %). Compared with no vibration (test response reduced to 51 +/- 5 % of control), there was less SICI in the vibrated muscle (test response reduced to 92 +/- 28 % of control) and more in the non-vibrated hand muscles (test response reduced to 27 +/- 5 % of control). The opposite occurred for LICI: compared with the no vibration condition (test response reduced to 33 +/- 6 % control), there was more LICI in the vibrated muscle (test response reduced to 17 +/- 3 % control) than in the non-vibrated hand muscles (test response reduced to 80 +/- 11 % control) even when the intensity of the test stimulus was adjusted to compensate for the changes in baseline MEP. There was no effect on ICF. Cutaneous stimulation of the index finger (80 Hz, 1.5 s duration, twice sensory threshold) had no consistent differential effect on any of the parameters. We conclude that vibratory input from muscle can differentially modulate excitability in motor cortical circuits.

Effects of negative autobiographical memories retrieval on corticospinal excitability and sensorimotor integration

Transcranial magnetic stimulation (TMS) can induce motor evoked potentials (MEPs). In TMS applications, near-threshold stimulation intensities (SIs) are often used for characterizing corticospinal excitability using MEPs. We aimed to characterize the individual near-threshold recruitment of MEPs and to test the assumptions related to selection of the suprathreshold SI. We utilized MEP data from a right-hand muscle induced at variable SIs. The single-pulse TMS (spTMS) data from previous studies (27 healthy volunteers), as well as data from new measurements (10 healthy volunteers) that included also MEPs modulated by paired-pulse TMS (ppTMS), were included. The probability of MEP (pMEP) was represented with individually fitted cumulative distribution function (CDF) with two parameters: resting motor threshold (rMT) and spread relative to rMT. MEPs were recorded with 110% and 120% of rMT as well as with Mills-Nithi upper threshold (UT). The individual near-threshold characteristics varied with CDF parameters: the rMT and the relative spread (median: 0.052). The rMT was lower with ppTMS than with spTMS (p < 0.001), while the relative spread remained similar (p = 0.812). At suprathreshold SIs, the probability of MEP was similar between UT and 110% of rMT (pMEP > 0.88), and higher for 120% of rMT (pMEP > 0.98). The individual near-threshold characteristics determine how probably MEPs are produced at common suprathreshold SIs. At the population level, the used SIs UT and 110% of rMT produced MEPs at similar probability. The individual variability in the relative spread parameter was large; therefore, the method of determining the proper suprathreshold SI for TMS applications is of crucial importance.

A model of the contribution of late I-waves to α-motoneuronal activation: implications for paired-pulse TMS

Further evidence for excitability changes in human primary motor cortex during ipsilateral voluntary contractions