Residual muscle weakness in the affected upper limb (UL) has a significant negative
impact on the performance of activities of daily living (ADL) of individuals with a
stroke. Studies report that the degree of UL weakness is strongly correlated to the level
of functioning in ADL, thus affecting the overall level of independence post-stroke.
Motor recovery post-stroke is mainly associated with the central nervous system's ability
to reorganize, or neuroplasticity. Neuroplasticity can be assessed with non-invasive
transcranial magnetic stimulation (TMS). TMS allows for assessing the excitability of the
descending corticospinal pathway, the main motor pathway controlling movements of the
limbs and trunk. The amplitude of TMS-elicited motor evoked potentials (MEP) gives a
direct measure of the excitability of corticospinal neurons and studies have shown that
MEP amplitudes can be used to probe neuroplastic changes associated with motor recovery
and are good predictors of an individual response to exercise post-stroke. In a recent
study on UL exercises in chronic stroke survivors, baseline MEP amplitudes were used to
estimate participants' potential for recovery and to tailor the intensity of the UL
training program accordingly. By stratifying them based on their MEP amplitudes, all
participants, regardless of their level of post-stroke recovery, showed significant
improvements in UL function following their tailored training program. Collectively,
these results suggest that assessing MEP amplitude can provide an efficient way to
evaluate neuroplasticity as well as to assist in staging and tailoring individuals'
training intervention to optimize post-stroke recovery.
To enhance neuroplasticity, training exercises are critical to rehabilitation post-stroke
since they allow for improvement in UL motor function and strength as well as promote
brain plasticity, leading to increased use of the UL in ADLs. To capitalize on the
benefit of strength training at promoting motor recovery and neuroplasticity,
non-invasive brain neurostimulation (NIBS) modalities are increasingly studied as an
adjunct therapy in stroke rehabilitation. To date, transcranial direct current
stimulation (tDCS) is the most studied NIBS, but a great variability in response to tDCS
is noted, with more than 50% of individuals not responding as expected. This
heterogeneity across studies in tDCS response could be explained by the absence of a
consensus on optimal stimulation parameters, the influence of individual brain anatomical
characteristics on the response to tDCS and the presence of an electric current shunting
through the skull. Thus, to counteract the impact of inter-individual anatomical
variability and electrical current shunting by the skull, recent studies are now
investigating cranial nerve stimulation as an adjunct therapy in stroke when paired with
rehabilitation. An emerging NIBS therapeutic device, stimulating two major cranial
nerves, the trigeminal and glossopharyngeal nerves, by tongue stimulation, is making its
way into neurological rehabilitation, that is cranial nerve non-invasive neuromodulation
(CN-NINM). By applying electrodes directly to the tongue, CN-NINM allows the generation
of a direct flow of neural impulses that travel to the cranial nerve nuclei of the
brainstem and then to the motor cortex to induce targeted neuroplastic changes when
combined with rehabilitation treatments. Following various neurological injuries and
combined with many interventions, CN-NINM results in improved functional performance such
as walking and balance. Neuroplasticity changes have also been observed such as an
increase in the brain beta activation measured with electroencephalography and increased
activation in the primary motor cortex area. Post-stroke, only one study has compared the
impact of CN-NINM combined with a 2-week balance and gait training program (experimental
group) to a 2-week balance and gait training program alone (control group) on functional
performance, as assessed with the Mini-Best test, in individuals in the subacute stage of
a stroke. Based on Mini-Best test score, an improvement in balance in the experimental
group compared with the control group was noted (p=0.032). Although promising, CN-NINM
has not been studied to improve UL function, despite the negative impact of UL impairment
on post-stroke functional performance. Also, to lay the foundation for the applicability
of this NIBS in stroke, understanding the neurophysiological effects of CN-NINM by
evaluating neuroplasticity changes is crucial.
Objective: The main objective is to assess the impact of CN-NINM combined with a tailored
UL strength training program on improvement in UL function and brain excitability in
individuals at the chronic stage of a stroke. The secondary objective is to assess the
presence of a relationship between UL functional gain and change in brain excitability
for the study sample.
Methods: In this multicentered stratified randomized controlled trial, 74 participants
will be recruited and stratified according to the baseline amplitude of their TMS-induced
MEP responses into three strata of training intensity: 1) low-intensity (MEP 20-49μV); 2)
moderate-intensity (MEP 50-120uV) and 3) high-intensity (MEP>120uV). . Within each
stratum, participants will be randomized into the experimental group (real CN-NINM + UL
strength training) or the control group (sham CN-NINM + UL strength training).
Sociodemographic and stroke-related variables (e.g., age, time since stroke) will be
collected to confirm participant eligibility. Prior to and at the end of the
intervention, participants will undergo a clinical evaluation of their affected UL as
well as a neurophysiological brain evaluation with TMS. The intervention will consist of
a 4-week UL strength training program (3X/week, 60-minute duration) combined to a
20-minute CN-NINM application. For the experimental group, the intensity of the stimulus
will be set by each participant to a comfortable level of sensation, similar to the
sensation in the mouth of a soft drink. For the control group, participants will wear the
device such as the experimental group, but the intensity will be controlled by the
trainer and set to a non-perceivable stimulus.