[ARTICLE] Repetitive reaching training combined with transcranial Random Noise Stimulation in stroke survivors with chronic and severe arm paresis is feasible: a pilot, triple-blind, randomised case series – Full Text



Therapy that combines repetitive training with non-invasive brain stimulation is a potential avenue to enhance upper limb recovery after stroke. This study aimed to investigate the feasibility of transcranial Random Noise Stimulation (tRNS), timed to coincide with the generation of voluntary motor commands, during reaching training.


A triple-blind pilot RCT was completed. Four stroke survivors with chronic (6-months to 5-years) and severe arm paresis, not taking any medications that had the potential to alter cortical excitability, and no contraindications to tRNS or MRI were recruited. Participants were randomly allocated to 12 sessions of reaching training over 4-weeks with active or sham tRNS delivered over the lesioned hemisphere motor representation. tRNS was triggered to coincide with a voluntary movement attempt, ceasing after 5-s. At this point, peripheral nerve stimulation enabled full range reaching. To determine feasibility, we considered adverse events, training outcomes, clinical outcomes, corticospinal tract (CST) structural integrity, and reflections on training through in-depth interviews from each individual case.


Two participants received active and two sham tRNS. There were no adverse events. All training sessions were completed, repetitive practice performed and clinically relevant improvements across motor outcomes demonstrated. The amount of improvement varied across individuals and appeared to be independent of group allocation and CST integrity.


Reaching training that includes tRNS timed to coincide with generation of voluntary motor commands is feasible. Clinical improvements were possible even in the most severely affected individuals as evidenced by CST integrity.

Trial registration

This study was registered on the Australian and New Zealand Clinical Trials Registry (ANZCTR) http://www.ANZCTR.org.au/ACTRN12614000952640.aspx. Registration date 4 September 2014, first participant date 9 September 2014


It is estimated that 30% of stroke survivors have severe upper limb impairment [1], whereby the functional capacity of the paretic arm is diminished to the extent that it cannot be moved against gravity [2]. For these individuals, who do not have sufficient movement with which to work, the provision of effective therapy can be challenging. The associated consequences are poor prospects for recovery [3], limited rehabilitation opportunities [4], and ultimately reduced quality of life (QoL) [5]. Yet, if task-oriented practice can be made possible by some means, there exists the potential to promote motor recovery, and in turn make a significant positive impact upon individual QoL and alleviate burden of care. In seeking to achieve levels of task-oriented practice beyond those that are possible through traditional therapy alone, attention has therefore turned to enabling technologies, including “assistive” devices, and adjuvant methods such as peripheral nerve and brain stimulation.

Best evidence syntheses [67] suggest that goal-directed movements can be assisted by minimizing the mechanical degrees of freedom to be controlled, in combination with the augmentation of voluntary muscle activity via peripheral nerve stimulation of target muscles, or the use of mechanical actuators. To encourage positive changes in motor performance, the capacity to increase task difficulty through small, yet incremental progressions and provision of meaningful real-time visual and auditory feedback have also been highlighted [89]. The authors have previously sought to implement these principles, using the Sensorimotor Active Rehabilitation Training of the Arm (SMART Arm) device to promote functional recovery in severely impaired stroke survivors [8910]. It has been shown that 4-weeks (12-h) of community-based training of reaching in people greater than 6-months post stroke improved upper limb function (and increased reaching distance) [8], enhanced the specificity of muscle recruitment (elevated ratio of biceps to triceps activation during reaching) [11], and accentuated corticospinal reactivity (decreased motor evoked potential [MEP] onset latency) [12]. Of particular interest in the context of the current study is the observation that not all individuals achieved functional gains. In these cases, the intrinsic neurobiological reserve of the injured brain may have been insufficient for repetitive training alone to drive recovery of motor function.

A variety of non-invasive brain stimulation (NIBS) techniques are now being used with the aim of altering the excitability of brain networks that have the potential to be engaged during the execution of motor tasks. The most commonly applied NIBS techniques are transcranial-direct current stimulation (tDCS) and repetitive-transcranial magnetic stimulation (rTMS) [13]. In general, the application of these techniques is predicated on the assumption that by altering the state of circuits within (contralateral) primary motor cortex (M1) in a manner that produces sustained increases in the excitability of corticospinal projections to the impaired limb (or by decreasing the excitability of circuits in the M1 ipsilateral to the impaired limb), therapeutic gains will be realised. The fact that these approaches have limited efficacy in severely impaired stroke survivors notwithstanding [14], there exist other forms of therapeutic NIBS that are motivated by a different premise.

It is well established that in some circumstances, the addition of random interference or noise, enhances the detection of weak stimuli, or the information content of a signal (e.g., trains of action potentials) [15]. In light of this phenomenon, it has been proposed that the application of transcranial random noise stimulation (tRNS) may boost the adaptive potential of cortical tissue [16]. The present investigation is motivated by the conjecture that: if the delivery of random noise stimulation is timed to occur simultaneously with the generation of voluntary motor commands, it may serve to amplify functional adaptations invoked by the intrinsic neural activity.

Implemented through a triple-blind pilot randomised control design, the specific aim of this study was to establish the feasibility of delivering tRNS, timed to coincide with the generation of the voluntary motor commands, in the context of reaching movements performed by individuals with chronic and severe upper limb paresis after stroke. Recognising that the response to any therapeutic intervention is constrained by the state of pathways that can convey signals from the brain to the periphery, diffusion-weighted magnetic resonance imaging (DW-MRI) was performed to characterize the structural integrity of the descending corticospinal tract (CST) projections for each participant.

Continue —>  Repetitive reaching training combined with transcranial Random Noise Stimulation in stroke survivors with chronic and severe arm paresis is feasible: a pilot, triple-blind, randomised case series | Journal of NeuroEngineering and Rehabilitation | Full Text

Fig. 1 Representation of the training setup including horizontal reaching track, trunk restraint, visual feedback, transcranial random noise stimulation application, and electrical stimulation application to lateral head of triceps


Fig. 2 Corticospinal tract streamline reconstructions: the corticospinal tract is indicated for each of the four participants, displayed on coronal (x view) slices of T1 weighted anatomical scans with direction encoded fractional anisotropy (FA) colour maps superimposed. Images are shown in radiological format (ie. right on the image is the patient’s left side). The reconstructed streamlines for the corticospinal tract are also superimposed, and indicated by red circles. The posterior limb of the internal capsule (PLIC) within the corticospinal tract was the region of interest that was delineated manually for each scan, using anatomical landmarks. No tracts were detected in the PLIC region in the right hemisphere for P03, or the left hemisphere for P04


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