Cerebellar modulation of human associative plasticity

• Published in: The Journal of physiology 2012-05, Vol.590 (10), p.2365-2374
• Main Authors: Hamada, Masashi, Strigaro, Gionata, Murase, Nagako, Sadnicka, Anna, Galea, Joseph M., Edwards, Mark J., Rothwell, John C.
• Format: Article
• Language: English
• Subjects: Adult; Cerebellum - physiology; Cross-Over Studies; Electric Stimulation; Evoked Potentials, Motor; Evoked Potentials, Somatosensory; Female; Humans; Long-Term Potentiation; Male; Middle Aged; Motor Cortex - physiology; Neuronal Plasticity - physiology; Neuroscience: Development/Plasticity/Repair; Transcranial Magnetic Stimulation; Young Adult
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.2012.230540

Key point  •  Increases in the strength of synaptic connections in the motor cortex (long term potentiation) can be induced in humans by repetitively pairing peripheral nerve stimuli and motor cortex transcranial magnetic stimuli given 21–25 ms apart – paired associative stimulation (PAS). •  This ‘associative plasticity’ effect has been assumed to relate to synchronicity between sensory input and motor output, with a similar mechanism proposed to underlie effects at all interstimulus intervals. •  Here we show that modulation of cerebellar activity using transcranial direct current stimulation can abolish associative plasticity in the motor cortex, but only for sensory/motor stimuli paired at 25 ms, not at 21.5 ms. •  The results indicate that human associative plasticity can be affected by cerebellar activity and that at least two different mechanisms are involved in the effects previously reported in studies using PAS at different inter‐stimulus intervals.   Paired associative stimulation (PAS) is a method commonly used in human studies of motor cortex synaptic plasticity. It involves repeated pairs of electrical stimuli to the median nerve and transcranial magnetic stimulation (TMS) of the motor cortex. If the interval between peripheral and TMS stimulation is around 21–25 ms, corticospinal excitability is increased for the following 30–60 min via a long term potentiation (LTP)‐like effect within the primary motor cortex. Previous work has shown that PAS depends on the present and previous levels of activity in cortex, and that it can be modified by motor learning or attention. Here we show that simultaneous transcranial direct current stimulation (TDCS; 2 mA) over the cerebellum can abolish the PAS effect entirely. Surprisingly, the effect is seen when the PAS interval is 25 ms but not when it is 21.5 ms. There are two implications from this work. First, the cerebellum influences PAS effects in motor cortex; second, LTP‐like effects of PAS have at least two different mechanisms. The results are relevant for interpretation of pathological changes that have been reported in response to PAS in people with movement disorders and to changes in healthy individuals following exercise or other interventions.