Cerebellum to motor cortex paired associative stimulation induces bidirectional STDP-like plasticity in human motor cortex

Department of Neurology, Goethe-University Frankfurt/Main, Germany
Frontiers in Human Neuroscience (Impact Factor: 3.63). 09/2012; 6(260):260. DOI: 10.3389/fnhum.2012.00260
Source: PubMed


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 PAS(2 ms)), 6 ms (CB→M1 PAS(6 ms)) or 10 ms (CB→M1 PAS(10 ms)) or randomly alternating intervals of 2 and 10 ms (CB→M1 PAS(Control)). 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 PAS(2 ms) resulted in MEP potentiation, CB→M1 PAS(6 ms) and CB→M1 PAS(10 ms) in MEP depression, and CB→M1 PAS(Control) 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.

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Available from: Ming-Kuei Lu, Jan 12, 2016
    • "For instance, low-frequency cerebellar stimulation, presumably to inhibitory Purkinje cells, has enhanced the activation of primary motor cortical excitatory circuits with consecutive excitability increases (Oliveri et al. 2005; Fierro et al. 2007). Excitability gains have also resulted from paired-associative stimulation over the cerebellum and the motor cortex (Lu et al. 2012). Accordingly, cerebellar stroke patients showed reduced motor cortical excitability (Liepert et al. 2004). "
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    ABSTRACT: Functional imaging studies have argued that interactions between cortical motor areas and the cerebellum are relevant for motor output and recovery processes after stroke. However, the impact of the underlying structural connections is poorly understood. To investigate this, diffusion-weighted brain imaging was conducted in 26 well-characterized chronic stroke patients (aged 63 ± 1.9 years, 18 males) with supratentorial ischemic lesions and 26 healthy participants. Probabilistic tractography was used to reconstruct reciprocal cortico-cerebellar tracts and to relate their microstructural integrity to residual motor functioning applying linear regression modeling. The main finding was a significant association between cortico-cerebellar structural connectivity and residual motor function, independent from the level of damage to the cortico-spinal tract. Specifically, white matter integrity of the cerebellar outflow tract, the dentato-thalamo-cortical tract, was positively related to both general motor output and fine motor skills. Additionally, the integrity of the descending cortico-ponto-cerebellar tract contributed to rather fine motor skills. A comparable structure-function relationship was not evident in the controls. The present study provides first tract-related structural data demonstrating a critical importance of distinct cortico-cerebellar connections for motor output after stroke.
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    • "The coil was rotated to induce a current flow within SMA from anterior-to-posterior (Arai et al., 2011). To stimulate the cerebellum, the double cone coil was placed over the midpoint between the inion and the mastoid process ipsilateral to the recording site (Ugawa et al., 1995; Lu et al., 2012). The coil was oriented to induce an upward current in the cerebellum (Ugawa et al., 1995). "

    Full-text · Article · Feb 2015 · Clinical Neurophysiology
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    • "However, there is no conclusive evidence that CBI interactions could be directly related to other mechanisms of cortical plasticity or other interconnected inhibitory circuits. For instance, other investigations in healthy controls showed that bidirectional change of CBI after anodal (CBI increase) vs. cathodal TDCS (CBI decrease) of the lateral cerebellum [51], or a reduction of CBI after 1 Hz rTMS or continuous theta-burst stimulation [28] can be seen without changes in MEP amplitude, suggesting hat the modifications of M1 excitability (indexed by MEP amplitude) and CBI are often dissociated [54]. Moreover we observed a reversal of the CBI toward facilitation at ISI ¼ 10 ms. "
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