Dose-response curve of associative plasticity in human motor cortex and interactions with motor practice

Abstract

Associative plasticity is hypothesized to be an important neurophysiological correlate of memory formation and learning with potentials for applications in neurorehabilitation and for the development of new electrophysiological measures to study disorders of cortical plasticity. We hypothesized that the magnitude of the paired associative stimulation (PAS)-induced long-term potentiation (LTP)-like effect depends on the number of pairs in the PAS protocol. We also hypothesized that homeostatic interaction of PAS with subsequent motor learning is related to the magnitude of the PAS-induced LTP-like effect. We studied 10 healthy subjects. In experiment 1a, subjects received 90 (PAS90), 180 (PAS180), or 270 (PAS270) pairs of stimuli, followed by a dynamic motor practice (DMP) 1 h after the end of the PAS protocols. In experiment 1b, the DMP preceded the PAS protocol. In experiment 2, the time course of PAS270 was studied. We found that PAS270 resulted in greater increase in motor evoked potential (MEP) amplitude compared with protocols with fewer pairs of stimuli. Moreover, the interaction between PAS protocols with motor learning differed depending on the number of stimulus pairs used to induce PAS. While DMP alone increased MEP amplitudes, DMP during the LTP-like effects induced by PAS270 led to a long-term depression (LTD)-like effect (homeostatic interaction). This homeostatic interaction did not occur after PAS90 and PAS180. In conclusion, we found a dose-dependent effect of the number of stimulus pairs used in the PAS protocol on cortical plasticity. Homeostatic interaction between PAS and DMP was observed only after PAS270.

The associative brain at work: Evidence from paired associative stimulation studies in humans

“…At the systems level of the human M1, practice of fastest possible thumb abductions resulted in learning, defined by an increase in maximum peak acceleration of the practiced movements, and prevented subsequent PAS25-induced MEP increase in a thumb muscle but enhanced subsequent PAS10-induced MEP decrease (Ziemann et al, 2004). These findings in accord with the BCM theory of homeostatic metaplasticity were subsequently confirmed by others (Avanzino et al, 2015, Elahi et al, 2014, Rosenkranz et al, 2007.…”

“…In summary, these findings could open up the opportunity to enhance learning processes by priming with PAS, for instance during motor rehabilitation of stroke patients. However, more evidence is needed, as others could not confirm a significant interaction between PAS and subsequent motor skill learning (Elahi et al, 2014).…”

Deleterious Effects of a Low Amount of Ethanol on LTP-Like Plasticity in Human Cortex

“…PAS LTP -induced LTP-like plasticity shares common mechanisms with motor skill learning (Elahi et al, 2013;Jung and Ziemann, 2009;Kang et al, 2011;Rosenkranz et al, 2007;Stefan et al, 2006;Ziemann et al, 2004) and acute EtOH ingestion has deleterious effects on memory formation and learning (Lister et al, 1991;Lowy, 1970;Mattila et al, 1998). Therefore, the present findings suggest a negative impact of EtOH on memory formation and learning at doses as low as reached by a single drink, but this will need to be tested in further experiments.…”

“…This LTP-like increase in MEP amplitude shows tight similarities to cellular LTP because it is associative, input specific, and blocked by dextromethorphan, a non-competitive NMDAR antagonist (Stefan et al, 2002;Stefan et al, 2000;Wolters et al, 2003). Furthermore, PAS LTP -induced LTP-like plasticity interacts homeostatically with prior or subsequent motor learning (Elahi et al, 2013;Jung and Ziemann, 2009;Kang et al, 2011;Rosenkranz et al, 2007;Stefan et al, 2006;Ziemann et al, 2004), indicating its mechanistic importance in learning processes.…”

Research Priorities in Limb and Task-Specific Dystonias

“…In addition, there is also variability in the PAS paradigms resulting in differing times between median nerve stimulation and TMS (e.g., 21.5 vs. 25 ms) (91). Other factors including the repetition rate, the stimulus strength and the number of paired stimuli delivered, the state of muscle activity, the time of the day, attention to the stimuli, and genetic factors, all are important factors in measurements of plasticity (92). Another form of LTP-like cortical plasticity induced by intermittent theta burst stimulation, which does not involve sensory input, showed abnormal plasticity but was decreased rather than increased in focal hand dystonia (93).…”