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.Julia B. Pitcher, Alysha M. Riley, Sebastian H. Doeltgen, Lisa Kurylowicz, John C. Rothwell, Suzanne M. McAllister, Ashleigh E. Smith, Angela Clow, David J. Kennaway, and Michael C. Riddin

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; cTBS₃₀₀) 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 cTBS₃₀₀ applied at intensities of 60%, 65% or 70% of resting motor threshold (RMT). In addition, the effect of cTBS₃₀₀ applied at 60% RMT on low level SICI (20% test MEP suppression) was examined. Results: Low-intensity cTBS₃₀₀ facilitated MEP amplitude when applied at 70% RMT, and inhibited MEP amplitude when applied at 65% RMT. In contrast, none of the cTBS₃₀₀ protocols had significant effects on moderate or low levels of SICI. Conclusions: The effects of cTBS₃₀₀ on MEP generating motor networks are highly sensitive to stimulation intensity. Low-intensity cTBS₃₀₀ 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.Sebastian H. Doeltgen, Michael C. Riddin

Emerging modalities in dysphagia rehabilitation: neuromuscular electrical stimulation

AIM: The aim of this review article is to advise the New Zealand medical community about the application of neuromuscular electrical stimulation (NMES) as a treatment for pharyngeal swallowing impairment (dysphagia). NMES in this field of rehabilitation medicine has quickly emerged as a widely used method overseas but has been accompanied by significant controversy. METHODS: Basic information is provided about the physiologic background of electrical stimulation. The literature reviewed in this manuscript was derived through a computer-assisted search using the biomedical database Medline to identify all relevant articles published until from the initiation of the databases up to January 2007. The reviewers used the following search strategy: [(deglutition disorders OR dysphagia) AND (neuromuscular electrical stimulation OR NMES)]. In addition, the technique of reference tracing was used and very recently published studies known to the authors but not yet included in the database systems were included. SUMMARY: This review elucidates not only the substantive potential benefit of this treatment, but also potential key concerns for patient safety and long term outcome. The discussion within the clinical and research communities, especially around the commercially available VitalStim™ stimulator, is objectively explained.Maggie-Lee Huckabee and Sebastian Doeltge

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: 9 A.M. and 4 P.M. of the same day, and 9 A.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.Sebastian H. Doeltgen and Michael C. Riddin

Simultaneous application of slow-oscillation transcranial direct current stimulation and theta burst stimulation prolongs continuous theta burst stimulation-induced suppression of corticomotor excitability in humans

The objective of this study was to assess whether the simultaneous application of slow-oscillation transcranial direct current stimulation enhances the neuroplastic response to transcranial magnetic theta burst stimulation. Motor evoked potential amplitude was assessed at baseline and at regular intervals up to 60 min following continuous theta burst stimulation, slow-oscillation transcranial direct current stimulation, and the simultaneous application of these paradigms. In addition, the electroencephalographic power spectra of slow and fast delta, and theta frequency bands recorded over the motor cortex were analyzed prior to and up to 5 min following each intervention. There was longer-lasting motor evoked potential suppression following the simultaneous application of continuous theta burst stimulation and slow-oscillation transcranial direct current stimulation compared with when continuous theta burst stimulation was applied alone. Slow-oscillation transcranial direct current stimulation applied alone did not modulate the motor evoked potential amplitude. No significant changes in spectral power were observed following slow-oscillation transcranial direct current stimulation. Simultaneous application of continuous theta burst stimulation and slow-oscillation transcranial direct current stimulation may provide an approach to prolong the induction of neuroplastic changes in motor cortical circuits by repetitive transcranial magnetic brain stimulation.Sebastian H. Doeltgen, Suzanne M. McAllister and Michael C. Riddin

Pharyngeal pressure generation during tongue-hold swallows across age groups

PurposeTo compare the effects of the tongue-hold swallowing maneuver on pharyngeal pressure generation in healthy young and elderly research volunteers.MethodSixty-eight healthy research volunteers (young, n = 34, mean age = 26.8 years, SD = 5.5; elderly, n = 34, mean age = 72.6 years, SD = 4.8; sex equally represented) performed 5 noneffortful saliva swallows and 5 tongue-hold swallows each. Amplitude and duration of pharyngeal pressure were investigated during both swallowing conditions with solid-state pharyngeal manometry at the level of the oropharynx, hypopharynx, and upper esophageal sphincter (UES).ResultsAt both pharyngeal levels, tongue-hold swallows produced lower peak pressure compared with saliva swallows. During tongue-hold swallows, UES relaxation pressure was increased in the elders, whereas the younger group displayed a trend toward reduced relaxation pressure. Elderly individuals produced pressure longer during control swallows in the oropharynx and hypopharynx than young individuals.ConclusionsThe tongue-hold maneuver affects oropharyngeal and hypopharyngeal pressure in the young and elders in similar ways, whereas effects on UES peak relaxation pressure differ between age groups. Reduced pharyngeal peak pressure and increased UES relaxation pressure underscore the notion that tongue-hold swallows should not be performed when bolus is present. Long-term training effects remain to be investigated.Sebastian H. Doeltgen, Phoebe Macrae, Maggie-Lee Huckabe

Effect of submental electrical stimulation on pharyngeal pressure generation

Purpose: The aim of this study was to investigate the effects of swallowing-triggered neuromuscular electrical stimulation (NMES) of the submental musculature on pharyngeal pressure generation in healthy research participants during stimulation and up to 60 min thereafter. Methods: Twenty healthy research participants [mean age = 23.7 years (SD = 3.8), 10 females] performed 60 noneffortful saliva swallows at a rate of approximately one every 30 s. Each swallow triggered a 4-s block of submental NMES, which consisted of 200-ls2 stimuli applied at a rate of 80 Hz and an intensity of 75% of the individual’s pain threshold utilising a treatment protocol identified to increase motor evoked potentials to the submental muscle group (Doeltgen et al., in review). Pharyngeal pressures during both non-effortful and effortful saliva swallows were measured at baseline, during stimulation and at 5, 30, and 60 min post-stimulation in the oropharynx, hypopharynx and, upper esophageal sphincter (UES). Results: Effortful swallows produced greater pharyngeal pressure (p = 0.001), and lower UES relaxation pressure (p = 0.021), than noneffortful swallows. Pharyngeal and UES pressures during stimulated and nonstimulated noneffortful swallows did not differ (p[0.05). At 30 and 60 min post stimulation, noneffortful swallows were completed with lower pressures at all sensors (p = 0.025), whereas effortful swallows were not affected by stimulation (p[0.05). Conclusion: Swallowing-triggered submental NMES has no immediate effects on pharyngeal pressure generation, whereas at 30 and 60 min post stimulation, decreased pressure in the oro- and hypopharynx poses a potential risk for compromising airway protection and bolus flow. Decreased UES relaxation pressure may facilitate bolus transit at this level of the pharynx.Doeltgen, Sebastian, Heck, F. and Huckabee, M. L

Effects of submental neuromuscular electrical stimulation on pharyngeal pressure generation

Heck FM, Doeltgen SH, Huckabee M-L. 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.Frauke M. Heck, Sebastian H. Doeltgen, Maggie-Lee Huckabe