Deficient Homeostatic Regulation of Practice-Dependent Plasticity in Writer’s Cramp

Abstract

Homeostatic metaplasticity is important to maintain overall synaptic weight in neuronal networks. Previous work suggested that homeostatic metaplasticity in motor cortex is impaired in writer's cramp, the most common form of task-specific focal dystonia, when explored by the interactions between 2 successive plasticity inducing transcranial brain stimulation protocols (Quartarone Rizzo V, Bagnato S, Morgante F, Sant'angelo A, Romano M, Crupi D, Girlanda P, Rothwell JC, Siebner HR. 2005. Homeostatic-like plasticity of the primary motor hand area is impaired in focal hand dystonia. Brain. 128:1943Brain. 128: --1950. To which extent deficient homeostatic metaplasticity applies also to the behavioral level of practicedependent plasticity is unknown. Here, we examined the interactions of 3 paired associative transcranial magnetic stimulation protocols (motor cortical excitability-enhancing paired associative stimulation (PAS) 25ms , excitability-depressing PAS 10ms , and control PAS 100ms ) with subsequent practice-dependent plasticity. Ten patients with writer's cramp and 10 healthy controls practiced rapid thumb abductions for 30 min. Practice-dependent plasticity was quantified by the increase in peak acceleration of the trained movement. The healthy controls but not the writer's cramp patients showed homeostatic suppression of practice-dependent plasticity after PAS 25ms when compared with practice-dependent plasticity after PAS 10ms and PAS 100ms . The lack of the PAS 25ms -induced suppression of practice-dependent plasticity in writer's cramp correlated with clinical severity of the focal hand dystonia. Findings support the notion that deficient homeostatic metaplasticity of practicedependent plasticity plays a significant role in the pathophysiology of writer's cramp.

Neuromodulatory Neurotransmitters Influence LTP-Like Plasticity in Human Cortex: A Pharmaco-TMS Study

“…In summary, these findings provide convergent evidence that the PAS-induced long-term increase in MEP amplitude can be taken as a model of LTP-like plasticity at the systems level of human motor cortex (Cooke and Bliss, 2006;Ziemann et al, 2008;Müller-Dahlhaus et al, 2010). This is supported further by the significant interactions of PAS with LTP-dependent processes such as motor learning Stefan et al, 2006;Rosenkranz et al, 2007;Jung and Ziemann, 2009;Kang et al, 2011).…”

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

“…While the healthy control group showed a homeostatic enhancement of learning-dependent plasticity following an excitability-reducing prime and a homeostatic suppression of learning-dependent plasticity following an excitability-increasing prime, the writer's cramp patients did not show any modulation of learning-dependent plasticity and the lack of homeostatic modulation was correlated with the clinical severity of the dystonia [128]. These results suggest that focal hand dystonia is associated with a dysfunctional homeostatic regulation of plasticity, which might set the frame for aberrant sensorimotor plasticity.…”

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.…”

“…After a second screening step, nine subjects were retained and enrolled into this study that exhibited a significant PAS LTP -induced increase in MEP amplitudeX1.2 (ratio of MEP amplitude post-PAS/pre-PAS) (Heidegger et al, 2010;Korchounov and Ziemann, 2011). Therefore, this selection excluded subjects with a long-term depression-like MEP decrease or no MEP change following PAS LTP (Müller-Dahlhaus et al, 2008), as the explicit aim of this study was to study drug effects on LTP-like plasticity, a process with significant relation to motor learning (Jung and Ziemann, 2009;Kang et al, 2011;Rosenkranz et al, 2007;Ziemann et al, 2004), rather than exploring drug effects on a great variety of magnitudes and directions of PAS LTP -induced plasticity in the general population.…”