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.

1 Follower
15 Reads
    • "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). "
    [Show abstract] [Hide abstract]
    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.
    Cerebral Cortex 10/2015; DOI:10.1093/cercor/bhv251 · 8.67 Impact Factor
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Dystonia is generally regarded as a disorder of the basal ganglia and their efferent connections to the thalamus and brainstem, but an important role of cerebellar-thalamo-cortical (CTC) circuits in the pathophysiology of dystonia has been invoked. Here in a sham controlled trial, we tested the effects of two-weeks of cerebellar continuous theta burst stimulation (cTBS) in a sample of cervical dystonia (CD) patients. Clinical evaluations were performed by administering the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). We used TMS to measure the inhibitory connectivity between the cerebellum and the contralateral motor cortex (cerebellar brain inhibition [CBI]), and the excitability of the contralateral primary motor cortex assessing intracortical inhibition (SICI), intracortical facilitation (ICF) and cortical silent period (CSP). Paired associative stimulation (PAS) was tested to evaluate the level and the topographical specificity of cortical plasticity, which is abnormally enhanced and non-focal in CD patients. Two weeks of cerebellar stimulation resulted in a small but significant clinical improvement as measured by the TWSTRS of approximately 15%. Cerebellar stimulation modified the CBI circuits and reduced the heterotopic PAS potentiation, leading to a normal pattern of topographic specific induced plasticity. These data provide novel evidence CTC circuits could be a potential target to partially control some dystonic symptoms in patients with cervical dystonia.
    Brain Stimulation 05/2014; 7(4). DOI:10.1016/j.brs.2014.05.002 · 4.40 Impact Factor
  • Source
    • "Stimulation of these descending tracts may provide an explanation to the observation that stimulation of the ipsilesional M1 improved better motor function than inhibition of the contralesional M1 [58]. Recently, Ziemann et al (2013) have also reported in healthy subjects an increased excitability of M1 when they targeted in a paired-associative stimulation protocol the cerebellum with the primary motor cortex [60]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Motor outcome after stroke is associated with reorganisation of cortical networks and corticospinal tract (CST) integrity. However, the relationships between motor severity, CST damage, and functional brain connectivity are not well understood. Here, the main objective was to study the effect of CST damage on the relationship between functional motor network connectivity and hand motor function in two groups of stroke patients: the severely (n=8) and the mildly impaired (n=14). Twenty-two carotid stroke patients with motor deficits were studied with magnetic resonance imaging (MRI) at 3 weeks, at 3 and 6 months. Healthy subjects (n=28) were scanned once. The CST injury was assessed by fractional anisotropy values. Functional connectivity was studied from a whole-hand grip task fMRI in a cortical and cerebellar motor network. Functional connectivity indexes were computed between these regions at each time point. The relationship between hand motor strength, ipsilesional CST damage and functional connectivity from the primary motor cortex (M1) was investigated using global and partial correlations. In mildly impaired patients, cortico-cortical connectivity was disturbed at three weeks but returned to a normal pattern after 3 months. Cortico-cerebellar connectivity was still decreased at 6 months. In severely impaired patients, the cortico-cortical connectivity tended to return to a normal pattern, but the cortico-cerebellar connectivity was totally abolished during the follow-up. In the entire group of patients, the hand motor strength was correlated to the ipsilesional functional connectivity from M1. Partial correlations revealed that these associations were not anymore significant when the impact of CST damage was removed, except for the ipsilesional M1-contralateral cerebellum connectivity. Functional brain connectivity changes can be observed, even in severely impaired patients with no recovery. Upper limb function is mainly explained by the CST damage and by the ipsilesional cortico-cerebellar connectivity.
    PLoS ONE 09/2013; 8(9):e73164. DOI:10.1371/journal.pone.0073164 · 3.23 Impact Factor
Show more

Similar Publications

Preview (2 Sources)

15 Reads
Available from