Resistant Against De-depression: LTD-Like Plasticity in the Human Motor Cortex Induced by Spaced cTBS

Abstract

The long-term depression (LTD)-like changes in human primary motor cortex (M1) excitability induced by continuous theta burst stimulation (cTBS) are subject to reversal (i.e., de-depression) following behavioral engagement of M1, limiting its therapeutic potential under behaviorally relevant conditions. Experiments in animals suggest that the repeated, spaced application of stimulation trains may consolidate synaptic plasticity, making it resistant to reversal by physiological activity. Although there is evidence that repeated cTBS prolongs LTD-like M1 neuroplasticity in humans, whether these effects are resistant to de-depression has not been tested. We investigated whether the neuroplastic effects of paired cTBS trains were resistant to de-depression by a sustained, submaximal voluntary contraction of the hand muscles. In the absence of cTBS, voluntary contraction had no effect on motor evoked potentials (MEPs) recorded from the right first dorsal interosseous muscle. While the LTD-like MEP depression induced by a single cTBS was abolished by subsequent voluntary contraction, paired cTBS induced MEP depression that was resistant to reversal. This MEP depression was also resistant to reversal when an experimental de-depression protocol was used instead of a voluntary contraction. Our findings suggest that repeated cTBS applications consolidate LTD-like M1 neuroplasticity, which may have important implications for the clinical application of cTBS.

Investigations of motor-cortex cortical plasticity following facilitatory and inhibitory transcranial theta-burst stimulation in schizophrenia: A proof-of-concept study

“…For both experimental setups, continuous TBS (cTBS), with each burst consisting of three stimuli with a repetition rate of 50 Hz for a duration of either 20 s (cTBS300, LTP-like plasticity) (Gentner et al, 2008) or 40 s (cTBS600, LTD-like plasticity) (Huang et al, 2005), was used. The condition intensity was set at 70% of the resting motor threshold (RMT) to avoid any influence of prior voluntary motor activation on cTBS-induced after-effects (Gentner et al, 2008;Goldsworthy et al, 2014;Huang et al, 2011a). Experimental sessions were performed either side of an interval of at least five days.…”

Increasing motor cortex plasticity with spaced paired associative stimulation at different intervals in older adults

“…This likely reflects activation of alternative synaptic mechanisms to those utilised during homoeostatic interactions, possibly involving group 1 metabotropic glutamate receptors (Abraham, ). A growing literature has used NIBS protocols to demonstrate both homeostatic (Siebner et al ., ; Muller et al ., ; Murakami et al ., ) and non‐homoeostatic (Goldsworthy et al ., , ) metaplasticity in humans, and to establish the utility of ‘priming’ stimulation for improving the response to training (Jung & Ziemann, ; Teo et al ., ; Fujiyama et al ., ).…”

The effect of stimulation interval on plasticity following repeated blocks of intermittent theta burst stimulation

“…In humans, two blocks of cTBS at 10-15 minute intervals results in a more reliable and longer lasting reduction in MEP amplitude [32] and impairment in behaviour [33] compared with a single block alone (however see [34]). Importantly, the plasticity following spaced cTBS is resistant to reversal by subsequent physiological activity, such as muscle contractions, suggesting consolidation of LTD-like plasticity [35].…”