Metaplasticity and non-invasive brain stimulation: the search for new biomarkers and directions for therapeutic neuromodulation

Metaplasticity (plasticity of synaptic plasticity) is defined as a change in the direction or degree of synaptic plasticity in response to preceding neuronal activity. Recent advances in brain stimulation methods have enabled us to non-invasively examine cortical metaplasticity, including research in a clinical setting. According to current knowledge, non-invasive neuromodulation affects synaptic plasticity by inducing cortical processes that are similar to long-term potentiation and depression. Two stimulation blocks are usually used to assess metaplasticity priming and testing blocks. The technology of studying metaplasticity involves assessing the influence of priming on the testing protocol effect. Several dozen studies have examined the effects of different stimulation protocols in healthy persons. They found that priming can both enhance and weaken, or even change the direction of the testing protocol effect. The interaction between priming and testing stimulation depends on many factors: the direction of their effect, duration of the stimulation blocks, and the interval between them. Non-invasive brain stimulation can be used to assess aberrant metaplasticity in nervous system diseases, in order to develop new biomarkers. Metaplasticity disorders are found in focal hand dystonia, migraine with aura, multiple sclerosis, chronic disorders of consciousness, and age-related cognitive changes. The development of new, metaplasticity-based, optimized, combined stimulation protocols appears to be highly promising for use in therapeutic neuromodulation in clinical practice.