Abstract
The cerebellum is crucially important for motor control and adaptation. Recent non-invasive brain stimulation studies have indicated the possibility to alter the excitability of the cerebellum and its projections to the contralateral motor cortex, with behavioral consequences on motor control and adaptation. Here we sought to induce bidirectional spike-timing dependent plasticity (STDP)-like modifications of motor cortex (M1) excitability by application of paired associative stimulation (PAS) in healthy subjects. Conditioning stimulation over the right lateral cerebellum (CB) preceded focal transcranial magnetic stimulation (TMS) of the left M1 hand area at an interstimulus interval of 2 ms (CB→M1 PAS2 ms), 6 ms (CB→M1 PAS6 ms) or 10 ms (CB→M1 PAS10 ms) or randomly alternating intervals of 2 and 10 ms (CB→M1 PASControl). Effects of PAS on M1 excitability were assessed by the motor-evoked potential (MEP) amplitude, short-interval intracortical inhibition (SICI), intracortical facilitation (ICF) and cerebellar-motor cortex inhibition (CBI) in the first dorsal interosseous muscle of the right hand. CB→M1 PAS2 ms resulted in MEP potentiation, CB→M1 PAS6 ms and CB→M1 PAS10 ms in MEP depression, and CB→M1 PASControl in no change. The MEP changes lasted for 30–60 min after PAS. SICI and CBI decreased non-specifically after all PAS protocols, while ICF remained unaltered. The physiological mechanisms underlying these MEP changes are carefully discussed. Findings support the notion of bidirectional STDP-like plasticity in M1 mediated by associative stimulation of the cerebello-dentato-thalamo-cortical pathway and M1. Future studies may investigate the behavioral significance of this plasticity.
Highlights
The cerebellum is essentially important for control of posture and movement (Brooks and Thach, 1981) and for specific motor learning processes, in particular motor adaptation (Shmuelof and Krakauer, 2011)
This study demonstrates, to the best of our knowledge for the first time, bidirectional long-term (> 30 min) spike-timing dependent plasticity (STDP)-like plasticity of motor-evoked potential (MEP) amplitude induced by associative stimulation of the cerebello-dentato-thalamo-M1 pathway and the corticospinal output network in M1: CB→M1 PAS2 ms resulted in an increase in corticospinal excitability indexed by MEP amplitude, while CB→M1 PAS6 ms and CB→M1 PAS10 ms resulted in a MEP decrease, and CB→M1 PASControl in no change
The data extend previous studies showing bidirectional STDPlike plasticity in M1 when focal transcranial magnetic stimulation (TMS) of the M1HAND was paired with conditioning stimulation of a peripheral nerve (Stefan et al, 2000; Wolters et al, 2003) or with another TMS pulse applied to the ipsilateral ventral premotor cortex (Buch et al, 2011), suggesting that STDP-like plasticity in human M1 is a generally operating principle for various afferent inputs
Summary
The cerebellum is essentially important for control of posture and movement (Brooks and Thach, 1981) and for specific motor learning processes, in particular motor adaptation (Shmuelof and Krakauer, 2011). Paired associative stimulation (PAS) is a well explored stimulation technique that allows induction of bidirectional spike-timing dependent plasticity (STDP)-like plasticity (for reviews, Ziemann et al, 2008; Müller-Dahlhaus et al, 2010). Bidirectional STDP-like plasticity has so far been demonstrated for repeated pairing of TMS of M1 with afferent inputs into M1 from peripheral nerves (Stefan et al, 2000, 2002; Wolters et al, 2003; Ziemann et al, 2004; Müller et al, 2007) and from the ipsilateral ventral premotor cortex (Buch et al, 2011)
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