Cerebellar modulation of human associative plasticity

Hamada, Masayuki; Strigaro, Gionata; Murase, Nagako; Sadnicka, Anna; Galea, Joseph M.; Edwards, Mark J.; Rothwell, John C.

doi:10.1113/jphysiol.2012.230540

Cited by 135 publications

(168 citation statements)

References 39 publications

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“…We cannot tell with certainty if any of these two receptor subtypes was more likely to mediate the observed EtOH effects on LTP-like plasticity. However, it was recently shown that increasing cerebellar excitability by anodal transcranial direct current stimulation or intermittent theta-burst stimulation abolished PAS-induced LTP-like plasticity (Hamada et al, 2012;Popa et al, 2013), but this suppressive effect was seen only with PAS 25ms (ie with the interval between the electrical stimulus to the median nerve and TMS of the contralateral M1 equaling 25 ms) and not with PAS 21.5ms (Hamada et al, 2012). The mean PAS interstimulus interval in our study was 21.9 ms.…”

Section: Drug Effects On Pas Ltp -Induced Ltp-like Increase Of Mep Iomentioning

confidence: 43%

Deleterious Effects of a Low Amount of Ethanol on LTP-Like Plasticity in Human Cortex

Lücke

Heidegger

Röhner

et al. 2014

Neuropsychopharmacol

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Ingesting ethanol (EtOH) at low doses during social drinking is a common human behavior for its facilitating effects on social interactions. However, low-dose EtOH may have also detrimental effects that so far are underexplored. Here we sought to test the effects of lowdose EtOH on long-term potentiation (LTP)-like plasticity in human motor cortex. Previous cellular experiments showed that low-dose EtOH potentiates extrasynaptic GABAAR and reduces NMDAR-mediated currents, processes that would limit the expression of LTP. Paired associative transcranial magnetic stimulation (PAS LTP ) was employed in nine healthy subjects for induction of LTP-like plasticity, indexed by a long-term increase in motor-evoked potential input-output curves. Synaptic a1-GABAAR function was measured by saccadic peak velocity (SPV). Very low doses of EtOH (resulting in blood concentrations of o5 mM) suppressed LTP-like plasticity but did not affect SPV when compared with a placebo condition. In contrast, 1 mg of alprazolam, a classical benzodiazepine, or 10 mg of zolpidem, a non-benzodiazepine hypnotic, decreased SPV but did not significantly affect LTP-like plasticity when compared with placebo. This double dissociation of low-dose EtOH vs alprazolam/zolpidem effects is best explained by the putatively high affinity of EtOH but not alprazolam/zolpidem to extrasynaptic GABAARs and to NMDARs. Findings suggest that enhancement of extrasynaptic GABAARmediated tonic inhibition and/or reduction of NMDAR-mediated neurotransmission by EtOH blocks LTP-like plasticity in human cortex at very low doses that are easily reached during social drinking. Therefore, low-dose EtOH may jeopardize LTP-dependent processes, such as learning and memory formation.

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Section: Drug Effects On Pas Ltp -Induced Ltp-like Increase Of Mep Iomentioning

confidence: 43%

Deleterious Effects of a Low Amount of Ethanol on LTP-Like Plasticity in Human Cortex

Lücke

Heidegger

Röhner

et al. 2014

Neuropsychopharmacol

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“…In recent work, we have demonstrated that cerebellar suppression in healthy subjects by transcranial direct current stimulation impairs subsequent motor cortical facilitation by PAS. 26 We therefore speculate that the absent PAS response in tremulous neuropathy patients may reflect cerebellar dysfunction that is also responsible for their impaired EBCC.…”

Section: Figure 2 Short Afferent Inhibition In the 3 Groupsmentioning

confidence: 99%

Cerebellar learning distinguishes inflammatory neuropathy with and without tremor

et al. 2013

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Objectives: This study aims to investigate if patients with inflammatory neuropathies and tremor have evidence of dysfunction in the cerebellum and interactions in sensorimotor cortex compared to nontremulous patients and healthy controls.Methods: A prospective data collection study investigating patients with inflammatory neuropathy and tremor, patients with inflammatory neuropathy without tremor, and healthy controls on a test of cerebellar associative learning (eyeblink classical conditioning), a test of sensorimotor integration (short afferent inhibition), and a test of associative plasticity (paired associative stimulation). We also recorded tremor in the arms using accelerometry and surface EMG. Results:We found impaired responses to eyeblink classical conditioning and paired associative stimulation in patients with neuropathy and tremor compared with neuropathy patients without tremor and healthy controls. Short afferent inhibition was normal in all groups.Conclusions: Our data strongly suggest impairment of cerebellar function is linked to the production of tremor in patients with inflammatory neuropathy. Neurology â 2013;80:1867-1873 GLOSSARY ADM 5 abductor digiti minimi; ANOVA 5 analysis of variance; APB 5 abductor pollicis brevis; CIDP 5 chronic inflammatory demyelinating polyradiculoneuropathy; CR 5 conditioned blink responses; EBCC 5 eyeblink classical conditioning; FDI 5 first dorsal interossei; IgMPN 5 immunoglobulin M paraproteinaemic neuropathy; MEP 5 motor evoked potential; MMNCB 5 multifocal motor neuropathy with conduction block; MRC 5 Medical Research Council; ONLS 5 Overall Neuropathy Limitation Scale; PAS 5 paired associative stimulation; PF 5 peak tremor frequency; SAI 5 short afferent inhibition; TMS 5 transcranial magnetic stimulation; TP 5 total power of the spectra between 1 and 30 Hz used as surrogate measure of tremor amplitude; US 5 unconditioned stimulus; WE 5 wrist extensor muscles.Inflammatory mediated neuropathies are common and potentially treatable.1 Tremor occurs with immunoglobulin M paraproteinaemic neuropathy (IgMPN) 2-4 and less commonly in other inflammatory neuropathies.5 It has been suggested that temporally distorted peripheral inputs reach a normally functioning central processor, such as the cerebellum, which is misled into producing a delayed second agonist burst and tremor. [6][7][8] The involvement of the cerebellum in neuropathic tremor is supported by functional imaging abnormalities.9 There does not seem to be a straightforward relationship between the development of tremor and conduction velocity.10 Further, no relationship seems to exist between tremor and the severity of neuropathy as assessed by proprioceptive loss, weakness, or fatigue.11,12 However, we have shown that although conduction velocity does not predict the presence of tremor, it is correlated with its severity for those in whom tremor is present. 5 This indicates a second mechanism may be necessary to produce tremor. Here we set out to explore aspects of CNS physiology in tremulous ...

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“…Dystonia might result from cerebellar dysfunction and not destruction, or from abnormal interactions of cerebellar and basal ganglia networks. These networks might interact anatomically at the level of the motor cortex or the striatum, as evidenced by histological tract tracing in animals, 85 animal models of dystonia, 84 and functionally in healthy human volunteers, in whom cortical excitability can be modulated after cerebellar interventions [86][87][88] or after cerebellar degeneration or infarction (S46). The cerebellum might contribute to the deficit in sensorimotor integration recorded in dystonia 89 because it processes proprioceptive information, alters somatosensory thresholds in the cortex, and has a key role in both temporal and spatial discrimination (S47).…”

Section: Dystoniamentioning

confidence: 99%

Imaging insights into basal ganglia function, Parkinson's disease, and dystonia

Stoessl¹,

Lehericy²,

Strafella³

2014

The Lancet

136

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Recent advances in structural and functional imaging have greatly improved our ability to assess normal functions of the basal ganglia, diagnose parkinsonian syndromes, understand the pathophysiology of parkinsonism and other movement disorders, and detect and monitor disease progression. Radionuclide imaging is the best way to detect and monitor dopamine deficiency, and will probably continue to be the best biomarker for assessment of the effects of disease-modifying therapies. However, advances in magnetic resonance enable the separation of patients with Parkinson's disease from healthy controls, and show great promise for differentiation between Parkinson's disease and other akinetic-rigid syndromes. Radionuclide imaging is useful to show the dopaminergic basis for both motor and behavioural complications of Parkinson's disease and its treatment, and alterations in non-dopaminergic systems. Both PET and MRI can be used to study patterns of functional connectivity in the brain, which is disrupted in Parkinson's disease and in association with its complications, and in other basal-ganglia disorders such as dystonia, in which an anatomical substrate is not otherwise apparent. Functional imaging is increasingly used to assess underlying pathological processes such as neuroinflammation and abnormal protein Correspondence to: Prof A J Stoessl,

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Cerebellar modulation of human associative plasticity

Cited by 135 publications

References 39 publications

Deleterious Effects of a Low Amount of Ethanol on LTP-Like Plasticity in Human Cortex

Deleterious Effects of a Low Amount of Ethanol on LTP-Like Plasticity in Human Cortex

Cerebellar learning distinguishes inflammatory neuropathy with and without tremor

Imaging insights into basal ganglia function, Parkinson's disease, and dystonia

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