Predicting Modulation in Corticomotor Excitability and in Transcallosal Inhibition in Response to Anodal Transcranial Direct Current Stimulation

Abstract

Introduction: Responses to neuromodulatory protocols based either on transcranial direct current stimulation (tDCS) or transcranial magnetic stimulation (TMS) are known to be highly variable between individuals. In this study, we examined whether variability of responses to anodal tDCS (a-tDCS) could be predicted from individual differences in the ability to recruit early or late indirect waves (I-waves), as reflected in latency differences of motor evoked potentials (MEPs) evoked by TMS of different coil orientation.Methods: Participants (n = 20) first underwent TMS to measure latency of MEPs elicited at different coil orientations (i.e., PA, posterior-anterior; AP, anterior-posterior; LM, latero-medial). Then, participants underwent a-tDCS (20 min @ 2 mA) targeting the primary motor cortex of the contralateral preferred hand (right, n = 18). Individual responses to a-tDCS were determined by monitoring changes in MEP amplitude at rest and in the duration of the contralateral silent period (cSP) and ipsilateral silent period (iSP) during contraction; the latter providing an index of the latency and duration of transcallosal inhibition (LTI and DTI).Results: Consistent with previous reports, individual responses to a-tDCS were highly variable when expressed in terms of changes in MEP amplitude or in cSP duration with ~50% of the participants showing either little or no modulation. In contrast, individual variations in measures of transcallosal inhibition were less variable, allowing detection of significant after-effects. The reduced LTI and prolonged DTI observed post-tDCS were indicative of an enhanced excitability of the transcallosal pathway in the stimulated hemisphere. In terms of predictions, AP-LM latency differences proved to be good predictors of responses to a-tDCS when considering MEP modulation.Conclusion: The present results corroborate the predictive value of latency differences derived from TMS to determine who is likely to express “canonical” responses to a-tDCS in terms of MEP modulation. The results also provide novel suggestive evidencethat a-tDCS can modulate the excitability of the transcallosal pathway of the stimulated hemisphere.

Comparison of repeated transcranial stimulation and transcranial direct-current stimulation on primary motor cortex excitability and inhibition: A pilot study

“…Pioneer tDCS study claimed the impossibility to modulate the cortical excitability of the opposite M1 via transcallosal pathways (Lang, Nitsche, Paulus, Rothwell, & Lemon, 2004). However, the increase of current intensities and protocol durations may bring this possibility as recent research reported contralateral effects of tDCS (Davidson, Bolic, & Tremblay, 2016;Muthalib et al, 2016a;Tazoe, Endoh, Kitamura, & Ogata, 2014;Teo et al, 2015). These studies show the direct impact of tDCS of one M1 on the opposite M1 most likely via transcallosal pathways.…”

Tuning noninvasive brain stimulation with MRI to cope with intersubject variability

“…Accordingly, the existing criteria for the definition of LTP at the synapse, more specifically persistence, input specificity, associativity, and cooperativity, could be employed as a starting point to justify the choice of terminology on the network level while also entailing separate analyses of network stimulation effects. Finding a bridge between local plasticity processes observed at the cellular level and the global network behaviour might provide researchers with crucial hints as to the underlying neurophysiological factors for the observed high interindividual variability [17][18][19], which impedes the efficacy and reliability of common tDCS paradigms [20,21 && ].…”

Measures to Predict The Individual Variability of Corticospinal Responses Following Transcranial Direct Current Stimulation

“…In particular, Wiethoff et al ( 2014 ) suggested that people who showed a facilitatory response to a-tDCS are more likely to recruit early I-waves or direct waves (D-waves) compared to tDCS non-responders or those that do not respond in a “canonical” manner. Later studies have further demonstrated the relationship between early I-wave recruitment and a-tDCS response (McCambridge et al, 2015 ; Davidson et al, 2016 ), with McCambridge et al ( 2015 ) finding the relationship only existing in the distal muscles of the upper limb (i.e., extensor carpi radialis (ECR)), not those of the proximal upper limb (i.e., biceps brachii). These studies used MEP latency differences, between different coil orientations, as a surrogate measure of I-wave recruitment (Wiethoff et al, 2014 ; McCambridge et al, 2015 ; Davidson et al, 2016 ).While it is unclear as to why such a relationship exists between early I-wave recruitment and a-tDCS response, one reason could be that a-tDCS depolarizes the cell bodies of pyramidal neurons for which early I-wave inputs are targeted (Wiethoff et al, 2014 ).…”

“…Later studies have further demonstrated the relationship between early I-wave recruitment and a-tDCS response (McCambridge et al, 2015 ; Davidson et al, 2016 ), with McCambridge et al ( 2015 ) finding the relationship only existing in the distal muscles of the upper limb (i.e., extensor carpi radialis (ECR)), not those of the proximal upper limb (i.e., biceps brachii). These studies used MEP latency differences, between different coil orientations, as a surrogate measure of I-wave recruitment (Wiethoff et al, 2014 ; McCambridge et al, 2015 ; Davidson et al, 2016 ).While it is unclear as to why such a relationship exists between early I-wave recruitment and a-tDCS response, one reason could be that a-tDCS depolarizes the cell bodies of pyramidal neurons for which early I-wave inputs are targeted (Wiethoff et al, 2014 ). Studies of patients implanted with high cervical epidural electrodes for pain suggested a-tDCS preferentially modulates cortical circuits generating D- and early I-wave activity (Lang et al, 2011 ; Di Lazzaro et al, 2013 ).…”