Sebastian H. Doeltgen

Low-intensity, short-interval theta burst stimulation modulates excitatory but not inhibitory motor networks.

OBJECTIVE Continuous theta burst stimulation (cTBS) administered at a low stimulus intensity can reduce the excitability of short interval intracortical inhibitory (SICI) networks without affecting the facilitatory intracortical motor networks involved in motor evoked potential (MEP) generation. We sought to determine whether low-intensity, facilitatory, short duration cTBS (300 stimuli over 20 s; cTBS(300)) could modulate SICI without influencing cortical circuits involved in MEP generation. METHODS MEPs and SICI were assessed at baseline and 5 min and 20 min following cTBS(300) applied at intensities of 60%, 65% or 70% of resting motor threshold (RMT). In addition, the effect of cTBS(300) applied at 60% RMT on low level SICI (20% test MEP suppression) was examined. RESULTS Low-intensity cTBS(300) facilitated MEP amplitude when applied at 70% RMT, and inhibited MEP amplitude when applied at 65% RMT. In contrast, none of the cTBS(300) protocols had significant effects on moderate or low levels of SICI. CONCLUSIONS The effects of cTBS(300) on MEP generating motor networks are highly sensitive to stimulation intensity. Low-intensity cTBS(300) does not have isolated, facilitatory effects on SICI networks. SIGNIFICANCE These results further highlight the difficulties of selectively facilitating the inhibitory circuits within M1 that are responsible for SICI with currently available rTMS paradigms.

Physiological Evidence Consistent with Reduced Neuroplasticity in Human Adolescents Born Preterm

Preterm-born children commonly experience motor, cognitive, and learning difficulties that may be accompanied by altered brain microstructure, connectivity, and neurochemistry. However, the mechanisms linking the altered neurophysiology with the behavioral outcomes are unknown. Here we provide the first physiological evidence that human adolescents born preterm at or before 37 weeks of completed gestation have a significantly reduced capacity for cortical neuroplasticity, the key overall mechanism underlying learning and memory. We examined motor cortex neuroplasticity in three groups of adolescents who were born after gestations of ≤32 completed weeks (early preterm), 33–37 weeks (late preterm), and 38–41 weeks (term) using a noninvasive transcranial magnetic brain stimulation technique to induce long-term depression (LTD)-like neuroplasticity. Compared with term-born adolescents, both early and late preterm adolescents had reduced LTD-like neuroplasticity in response to brain stimulation that was also associated with low salivary cortisol levels. We also compared neuroplasticity in term-born adolescents with that in term-born young adults, finding that the motor cortex retains a relatively enhanced neuroplastic capacity in adolescence. These findings provide a possible mechanistic link between the altered brain physiology of preterm birth and the subsequent associated behavioral deficits, particularly in learning and memory. They also suggest that altered hypothalamic–pituitary–adrenal axis function due to preterm birth may be a significant modulator of this altered neuroplasticity. This latter finding may offer options in the development of possible therapeutic interventions.

The Effect of Effortful Swallow on Pharyngeal Manometric Measurements During Saliva and Water Swallowing in Healthy Participants

OBJECTIVE To evaluate the effect of effortful swallow on pharyngeal manometric pressure measurements during saliva and water swallowing. DESIGN Comparative analysis of pharyngeal pressure generation under 2 bolus and 2 task conditions. SETTING Swallowing rehabilitation research laboratory. PARTICIPANTS Healthy participants (N=40), sex equally represented, with a mean age of 25.8 years. INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES Manometric peak and nadir amplitude and duration measures at 3 locations in the pharynx. RESULTS Significantly higher peak pressures were measured for saliva swallows compared with water swallows under both swallowing conditions at the proximal pharyngeal sensor only (P=.011). No significant differences were observed between the effortful versus noneffortful conditions at the proximal and midpharyngeal sensors; however, upper esophageal sphincter (UES) nadir pressures were significantly lower for effortful than noneffortful swallows (P=.034) with significantly lower pressure measurements in saliva effortful swallows (P=.008) compared with water effortful swallows. Saliva swallows resulted in significantly longer pressure durations than water swallows at the proximal (P=.003) and middle (P=.048) sensors. Pressure-generation duration was significantly longer in effortful versus noneffortful swallows for the middle sensor (P=.036) only. CONCLUSIONS The results indicate that the effect of effortful swallow on pharyngeal peak pressure measurement is not altered by bolus type (saliva vs water). However, this is not the case for nadir pressure measurements in the UES, which were significantly lower in effortful saliva swallows than in effortful water swallows.

Differential Effects of Neuromuscular Electrical Stimulation Parameters on Submental Motor-Evoked Potentials

Background. Neuromuscular electrical stimulation (NMES) of the muscles underlying the pharynx and faucial pillars affects the excitability of corticobulbar projections in a frequency- and duration-specific manner. The anterior hyomandibular (submental) muscles are primary targets for the clinical application of NMES to improve disordered swallowing, but the optimal NMES parameters for this application are unknown. Objective. To determine the influence of NMES parameters on the excitability of corticobulbar projections to the submental musculature. Methods. Transcranial magnetic stimulation (TMS) was used in event-related protocols, triggered by either volitional contraction of the submental muscles or pharyngeal swallowing, to assess corticobulbar excitability prior to, immediately following, and 30, 60, and 90 minutes post-NMES in 25 healthy volunteers. In the first 2 experiments, 4 stimulus frequencies (5, 20, 40, and 80 Hz) and 3 NMES dosages, manipulated through stimulus train durations or number of repetitions, were evaluated. The optimal excitatory NMES triggered by volitional swallowing (event-related NMES) was then replicated in a new sample and contrasted with non-event-related NMES (either discrete events or continuously for 1 hour). Results. It was found that 80Hz NMES increased motor-evoked potential (MEP) amplitude at 30 minutes and 60 minutes poststimulation only after 60 repetitions of 4-s event-related NMES trains. Non-event-related and continuous NMES did not affect MEP amplitudes. No changes in MEP onset latencies were observed. Conclusions. Changes in corticobulbar excitability induced by NMES of the submental muscle group are frequency and dose dependent and only occur after NMES triggered by volitional swallowing. Underlying neural mechanisms are discussed.

Test–retest reliability of motor evoked potentials (MEPs) at the submental muscle group during volitional swallowing

Motor evoked potentials (MEPs) recorded from pharyngeal and anterior hyo-mandibular (submental) muscles at rest have been used to evaluate treatment effects on neural pathways underlying swallowing. This study documents a novel methodological approach of recording reliable intra- and inter-session MEPs at the submental muscle group during task-related volitional swallowing. MEPs were elicited by single-pulse transcranial magnetic stimulation (TMS), triggered by a custom-made system when a pre-set level of surface electromyographic activity in the target muscles was breached. Fifteen MEPs were recorded during each of four sessions. Intraclass correlation coefficients (ICCs) were used to assess test-retest reliability within and across sessions for blocks of 3, 5, 10 and 15 trials. Highly reliable intra-session reliability was achieved, maximal for blocks of five trials (0.915). Inter-session reliability varied between 0.474 (three trials per block) and 0.909 (10 trials per block). Surface electromyography-triggered TMS allows reliable measurement of MEP amplitude at the submental muscle group within and across sessions when muscles are pre-activated during volitional swallowing. This methodology will be useful for future investigations on the effects of pathology and modulation of swallowing neural pathways.

Swallowing Neurorehabilitation: From the Research Laboratory to Routine Clinical Application

The recent application of neurostimulation techniques to enhance the understanding of swallowing neural plasticity has expanded the focus of rehabilitation research from manipulation of swallowing biomechanics to manipulation of underlying neural systems. Neuromodulatory strategies that promote the brains ability to reorganize its neural connections have been shown to hold promising potential to aid the recovery of impaired swallowing function. These techniques include those applied to the brain through the intact skull, such as transcranial magnetic stimulation or transcranial direct current stimulation, or those applied to the sensorimotor system in the periphery, such as neuromuscular electrical stimulation. Recent research has demonstrated that each of these techniques, either by themselves or in combination with these and other treatments, can, under certain circumstances, modify the excitability of motor representations of muscles involved in swallowing. In some studies, experimentally induced plastic changes have been shown to have functional relevance for swallowing biomechanics. However, the transition of novel, neuromodulatory brain stimulation techniques from the research laboratory to routine clinical practice is accompanied by a number of ethical, organizational, and clinical implications that impact professions concerned with the treatment of swallowing rehabilitation. In this article, we provide a brief overview of the neuromodulatory strategies that may hold potential to aid the recovery of swallowing function, and raise a number of issues that we believe the clinical professions involved in the rehabilitation of swallowing disorders must confront as these novel brain stimulation techniques emerge into clinical practice.

Behavioural exposure and sleep do not modify corticospinal and intracortical excitability in the human motor system

OBJECTIVE Behavioural exposure and sleep may bidirectionally modify the excitability of cortical networks including those in the motor cortex. Here we tested whether the excitability of intracortical inhibitory and excitatory networks within the primary motor cortex exhibited changes suggestive of a time of day influence. METHODS Short-interval intracortical inhibition (SICI) and facilitation (ICF), and input-output curves (IO curves) were investigated using transcranial magnetic stimulation (TMS). Recordings were made from the resting right first dorsal interosseous (FDI) muscle in 10 healthy subjects on three occasions: 9A.M. and 4P.M. of the same day, and 9A.M. of the following day. RESULTS There was no significant change in any of the measures across the three assessments. CONCLUSIONS These findings provide evidence that time of day does not significantly influence corticospinal and intracortical excitability in the primary motor cortex. SIGNIFICANCE These results provide no support for the hypothesis that synapses within the motor cortex undergo potentiation due to daytime use and behavioural experiences. Additionally, these findings provide evidence that measurement of motor cortical excitability is not systematically biased by time-of-day dependent variability and thus does not pose a confound in studies assessing corticospinal excitability longitudinally.

Effects of Submental Neuromuscular Electrical Stimulation on Pharyngeal Pressure Generation

OBJECTIVE To investigate the immediate and late effects of submental event-related neuromuscular electrical stimulation (NMES) on pharyngeal pressure generation during noneffortful and effortful saliva swallows. DESIGN Before-after trial. SETTING Swallowing rehabilitation research laboratory. PARTICIPANTS Sex-matched (N=20) healthy research volunteers. INTERVENTIONS Participants received 80Hz NMES of 4-second duration to floor of mouth muscles that was time-locked to 60 volitional saliva swallows. MAIN OUTCOME MEASURES Manometry measures of peak pressures and duration of pressure events in the oropharynx, hypopharynx, and the upper esophageal sphincter (UES) were derived during execution of noneffortful and effortful saliva swallows. Measures were taken at baseline, during stimulation, and at 5-, 30-, and 60-minutes poststimulation. RESULTS Baseline pharyngeal and UES pressures did not differ between stimulated and nonstimulated swallows. At 5- and 30-minutes poststimulation, peak pressure decreased at the hypopharyngeal and at the UES sensor during noneffortful swallows. The effect lasted up to an hour only in the hypopharynx. No changes in duration of pressure events were observed. CONCLUSIONS Using this treatment paradigm, decreased peak amplitude in the hypopharynx up to an hour after treatment indicates a potential risk of decreased bolus flow associated with NMES. On the other hand, decreased UES relaxation pressure may facilitate bolus transit into the esophagus.

A comparison of two methods for estimating 50% of the maximal motor evoked potential

OBJECTIVES Two commonly-used methods for setting stimulus intensities in transcranial magnetic brain stimulation studies were compared to determine which best approximated a motor evoked potential (MEP) of 50% of the maximal MEP amplitude (SI50); a suprathreshold intensity relative to resting motor threshold (rMT) or adjusting the intensity to evoke an MEP amplitude of 1mV. METHODS Corticomotor stimulus-response curves and rMT for the right first dorsal interosseous (FDI) muscle of 176 subjects (aged 10-74 years) were retrospectively analysed. RESULTS Regardless of subject age or sex, SI50 occurred at 127.5 ± 11.3% rMT. Except in young children, MEPs of 1 mV were significantly smaller than those evoked at SI50. CONCLUSIONS In the inactive FDI muscle, a stimulus intensity of 127-128% rMT consistently gives the best approximation of SI50 in most subjects, except perhaps young children. SIGNIFICANCE Setting TMS stimulus intensities relative to rMT provides a less variable inter-subject comparator, with respect to individual differences in corticomotor input-output characteristics, than adjusting the stimulator output to give an absolute MEP magnitude.

Intra‐ and inter‐rater reliability for analysis of hyoid displacement measured with sonography

Anterior hyoid displacement is essential for efficient swallowing and is usually investigated with videofluoroscopy. Ultrasound offers a less expensive and noninvasive method of investigation. The present study investigated the viability of a novel method of quantifying hyoid displacement from sonograms using an anatomic reference point, through an evaluation of inter‐ and intra‐rater reliability.