Shaping the Effects of Associative Brain Stimulation by Contractions of the Opposite Limb

Abstract

There has been an explosion of interest in methods that may promote neural plasticity by indirectly stimulating tissue in damaged brains using transient magnetic fields or weak electrical currents. A major limitation of these approaches is that the induced variations in brain activity tend to be diffuse. Thus far it has proved extremely difficult to target pathways from the brain to specific muscles. This is a particular challenge for applications in rehabilitation. Stroke survivors often exhibit abnormal patterns of muscle activation, including diminished specificity and high levels of co-contraction. For the clinical relevance of brain stimulation to be enhanced, it is desirable that the effects can be restricted to pathways controlling muscles that are the specific targets of movement therapy. We have demonstrated previously that increases in the excitability of corticospinal projections to forearm muscles generated by paired associative stimulation (PAS), are modulated by contractions ipsilateral to the site of the cortical stimulus. The current aim was to determine whether in chronic stroke survivors, simultaneous contractions performed by the non-paretic limb increase the muscle specificity of changes in the excitability of projections to the impaired limb induced by PAS. Ten chronic stroke survivors, 13 age-equivalent and 27 younger healthy controls, completed two separate sessions/conditions. In one (PAS+CONT), isometric wrist flexion contractions of the non-impaired limb were made simultaneously with PAS. In the other (PAS), associative stimulation only was applied. In all groups, PAS alone gave rise to large increases in the excitability of projections to a wrist extensor muscle (extensor carpi radialis – ECR) that was not the target of stimulation. In marked contrast, for the stroke survivors, following combined PAS and flexion contractions of the non-impaired limb, there was no corresponding elevation in the excitability of corticospinal projections to the ECR of the paretic limb. A similar effect was present for the healthy young adults, but not expressed clearly for the age-equivalent controls. The implications of these findings with respect to the clinical deployment of non-invasive brain stimulation in movement rehabilitation are discussed.

Neuromuscular electrical stimulation‐promoted plasticity of the human brain

“…Foremost among these is the observation variants of PAS in which the timing of the contributory elements is not strictly confined, for example when extended trains of peripheral nerve stimuli are used (e.g. Ridding & Taylor, 2001;McNickle & Carson, 2015;Shulga et al 2016;Carson & Rankin, 2018;Tolmacheva et al 2019), produce elevations in CSE that are comparable to, if not greater than, those obtained when the ISI separating the peripheral and cortical events is precisely circumscribed. The associative nature of the effects are, however, emphasized by the fact that in these studies the NMES alone (typically at an intensity MT) does not bring about changes in CSE.…”

“…2013; McNickle & Carson, 2015; Shulga et al . 2016; Carson & Rankin, 2018; Tolmacheva et al . 2019), produce elevations in CSE that are comparable to, if not greater than, those obtained when the ISI separating the peripheral and cortical events is precisely circumscribed.…”

A Bayesian approach to analysing cortico-cortical associative stimulation induced increases in the excitability of corticospinal projections in humans

“…It has been noted previously for projections to forearm muscles that the magnitude of the increases in corticospinal excitability brought about by an associative protocol (in young adults) tends to increase over a period of time following the cessation of the intervention (e.g.,Carson et al 2013 ; McNickle and Carson 2015 ; Carson and Rankin 2018 ). This was also the case in the present study.…”

“…In particular, it has been observed that: (1) the polarity of the changes in corticospinal excitability induced by PAS are contingent upon the order in which stimulation is delivered to the (presumed) pre- and post-synaptic targets, and (2) that to be effective the ISIs must lie within a restricted (milliseconds) range (Wolters et al 2003 ). These observations notwithstanding, qualitatively equivalent outcomes (i.e., suggestive of associative plasticity) have been achieved using methods that deviate from the notional requirements for STDP—for example using stimulus pairs that cannot be defined in terms of a discrete ISI (e.g.,Ridding and Taylor 2001 ; Carson et al 2013 ; McNickle and Carson 2015 ; Shulga et al 2016 ; Carson and Rankin 2018 ; Tolmacheva et al 2019 ).…”

Contraction Phase and Force Differentially Change Motor Evoked Potential Recruitment Slope and Interhemispheric Inhibition in Young Versus Old

“…While we monitored other arm muscles, both to set the neuroanatomically relevant stimulation intensity range for our MEP recruitment and to monitor task performance, we did not design the study to measure corticospinal activity of our non-target muscles. Future studies should investigate the somatotopic specificity of corticospinal and interhemispheric interactions as they are clearly important for training and transfer ( Ruddy et al, 2017 ; Carson and Rankin, 2018 ; Chye et al, 2018 ). With the framework we have designed, future studies can interrogate multiple forms of unimanual and bimanual activity, and delve further into differences in force production, MEP recruitment, other circuits, and the influence of aging.…”