Reversal of plasticity-like effects in the human motor cortex

Abstract

A number of experiments in animals have shown that successful induction of plasticity can be abolished if an individually ineffective intervention is given shortly afterwards. Such effects are termed depotentiation/de-depression. These effects contrast with metaplasticity/homeostatic plasticity in which pretreatment of the system with one protocol modulates the response to a second plasticity-inducing protocol. Homeostatic plasticity maintains the balance of plasticity in the nervous system at a stable level whereas depotentiation/de-depression abolishes synaptic plasticity that has just occurred in order to prevent ongoing learning. In the present study, we developed novel protocols to explore the reversal of LTP-and LTD-like effects in healthy conscious humans based on the recently developed theta burst form of repetitive transcranial magnetic stimulation (TBS). The potentiation effect induced by intermittent TBS (iTBS) was completely erased by a short form of continuous TBS (cTBS150) given 1 min after iTBS, whereas the depressive effect of continuous TBS (cTBS) was successfully abolished by a short form of iTBS (iTBS150). The reversal was specific to the nature of the second protocol and was time dependent since it was less effective when the intervention was given 10 min after induction of plasticity. All these features are compatible with those of depotentiation and de-depression demonstrated in animal studies. The development of the present protocols would be helpful to study the physiology of the reversal of plasticity and learning and to probe the abnormal depotentiation/de-depression shown in animal models of neurological diseases (e.g. Parkinson's disease with dyskinesia, dystonia and Huntingon's disease).

Consensus Paper: Probing Homeostatic Plasticity of Human Cortex With Non-invasive Transcranial Brain Stimulation

“…There is ample evidence for depotentiation and de-depression in the animal literature, which implicates this form of metaplasticity as a factor in learning reversal and forgetting [103e105]. Metaplasticity patterns resembling de-potentiation and de-depression were observed in an experiment that combined iTBS and cTBS [106]: The normal LTP-like effect induced by facilitatory iTBS was abolished (de-potentiated), when a short train of inhibitory cTBS followed the iTBS protocol. Vice versa, the LTD-like effect normally induced by a cTBS protocol was abolished (de-depressed), if followed by a short train of facilitatory iTBS.…”

“…Only when given within a certain time window after an LTP-or LTD-inducing protocol are these effects visible. The early phases of LTP and LTD induction are more vulnerable to the effect of interfering stimuli than later phases, when synaptic changes in synaptic efficacy have been stabilized [106].…”

Preconditioning tDCS facilitates subsequent tDCS effect on skill acquisition in older adults

“…The standard cTBS protocol involves delivery of trains of three subthreshold stimuli at 50 Hz every 200 ms for 20 or 40 sec (for a total of 300 or 600 pulsescTBS300 or cTBS600, respectively), which elicit decreases in corticospinal excitability when applied over M1 (Huang et al 2005). Notably, a shorter duration of cTBS involving 150 pulses (cTBS150) -without itself inducing overt changes in corticospinal excitability -reverses the subsequent effect of cTBS300 from the expected LTP-like effects to LTD-like effects of cTBS300 (Huang et al 2010). …”

Behavioural and neurophysiological markers reveal differential sensitivity to homeostatic interactions between centrally and peripherally applied passive stimulation

“…Furthermore, the time window during which homeostatic plasticity can be demonstrated using this paradigm appears to be relatively short, as revealed by studies in which short priming interventions were used. In such cases, even a 5-or 10-min interval between interventions is sufficient to abolish homeostatic interaction (Huang et al, 2010;Iezzi et al, 2011).…”