Cerebellar neuronal activity correlates with spike and wave EEG patterns in the rat

Kandel, Adam; Buzsáki, György

doi:10.1016/0920-1211(93)90033-4

Cited by 65 publications

(45 citation statements)

References 24 publications

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“…GSWDs appeared simultaneously in bilateral primary motor (M1) and sensory cortices (S1) at 7.6 ± 0.6Hz with an average duration of 3.6 ± 1.4 seconds (n = 17 mice). The GSWD frequency and appearance were comparable to earlier reports of awake tg and other rodent models of absence epilepsy 30, 32, 34, 45. During these GSWDs, action potential firing of a subset of CN neurons was phase‐locked to GSWDs.…”

Section: Resultssupporting

confidence: 85%

Cerebellar output controls generalized spike‐and‐wave discharge occurrence

Kros

Rooda

Spanke

et al. 2015

Annals of Neurology

123

138

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ObjectiveDisrupting thalamocortical activity patterns has proven to be a promising approach to stop generalized spike‐and‐wave discharges (GSWDs) characteristic of absence seizures. Here, we investigated to what extent modulation of neuronal firing in cerebellar nuclei (CN), which are anatomically in an advantageous position to disrupt cortical oscillations through their innervation of a wide variety of thalamic nuclei, is effective in controlling absence seizures.MethodsTwo unrelated mouse models of generalized absence seizures were used: the natural mutant tottering, which is characterized by a missense mutation in Cacna1a, and inbred C3H/HeOuJ. While simultaneously recording single CN neuron activity and electrocorticogram in awake animals, we investigated to what extent pharmacologically increased or decreased CN neuron activity could modulate GSWD occurrence as well as short‐lasting, on‐demand CN stimulation could disrupt epileptic seizures.ResultsWe found that a subset of CN neurons show phase‐locked oscillatory firing during GSWDs and that manipulating this activity modulates GSWD occurrence. Inhibiting CN neuron action potential firing by local application of the γ‐aminobutyric acid type A (GABA‐A) agonist muscimol increased GSWD occurrence up to 37‐fold, whereas increasing the frequency and regularity of CN neuron firing with the use of GABA‐A antagonist gabazine decimated its occurrence. A single short‐lasting (30–300 milliseconds) optogenetic stimulation of CN neuron activity abruptly stopped GSWDs, even when applied unilaterally. Using a closed‐loop system, GSWDs were detected and stopped within 500 milliseconds.InterpretationCN neurons are potent modulators of pathological oscillations in thalamocortical network activity during absence seizures, and their potential therapeutic benefit for controlling other types of generalized epilepsies should be evaluated. Ann Neurol 2015;77:1027–1049

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Section: Resultssupporting

confidence: 85%

Cerebellar output controls generalized spike‐and‐wave discharge occurrence

Kros

Rooda

Spanke

et al. 2015

Annals of Neurology

123

138

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“…However, when synchrony is imposed on the cerebellar cortex from outside, large-amplitude local field potential (LFP) signals can emerge from cerebellar circuits (Kandel and Buzsáki, 1993;Buzsáki et al, 2012). In addition, the distance between voxels located in the cerebellum and the closest EEG electrodes is between 1−7 cm, which is similar to the distance between voxels in the occipital cortex and EEG sensors and not as deep as many other subcortical structures.…”

Section: Discussionmentioning

confidence: 77%

Upregulation of cortico-cerebellar functional connectivity after motor learning

et al. 2016

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Interactions between the cerebellum and primary motor cortex are crucial for the acquisition of new motor skills. Recent neuroimaging studies indicate that learning motor skills is associated with subsequent modulation of resting-state functional connectivity in the cerebellar and cerebral cortices. The neuronal processes underlying the motor-learning induced plasticity are not well understood. Here, we investigate changes in functional connectivity in source-reconstructed electroencephalography (EEG) following the performance of a single session of a dynamic force task in twenty young adults. Source activity was reconstructed in 112 regions of interest (ROIs) and the functional connectivity between all ROIs was estimated using imaginary part of the coherence. Significant changes in resting-state connectivity were assessed using partial least squares (PLS). We found that subjects adapted their motor performance during the training session and showed improved accuracy but with slower movement times. A number of connections were significantly upregulated after motor training, principally involving connections within the cerebellum and between the cerebellum and motor cortex. Increased connectivity was confined to specific frequency ranges in the mu and beta bands. Post-hoc analysis of the phase spectra of these cerebellar and corticocerebellar connections revealed an increased phase-lag between motor cortical and cerebellar activity following motor practice. These findings show a reorganization of intrinsic corticocerebellar connectivity related to motor adaption and demonstrate the potential of EEG connectivity analysis in source-space to reveal the neuronal processes that underpin neural plasticity.

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“…Cerebellar ictal hyperperfusion has been observed in patients with partial seizures, contralateral to the seizure focus (15), and it is therefore not so surprising to see bilateral involvement during bilateral discharges. Intense involvement of the cerebellum during spike-and-wave discharges has been observed in an experimental model, independently of movement, with the suggestion that cerebellar neurons may contribute to spike-and-wave rhythmicity (16). The role of the cerebellum during generalized seizures or discharges has been reviewed by Norden and Blumenfeld (17), but they do not propose a specific hypothesis regarding its function during seizures.…”

Section: Discussionmentioning

confidence: 99%

Generalized epileptic discharges show thalamocortical activation and suspension of the default state of the brain

Gotman

Grova

Bagshaw

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

538

491

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Our objective was to evaluate the brain regions showing increased and decreased metabolism in patients at the time of generalized bursts of epileptic discharges in order to understand their mechanism of generation and effect on brain function. By recording the electroencephalogram during the functional MRI, changes in the blood oxygenation level-dependent signal were obtained in response to epileptic discharges observed in the electroencephalogram of 15 patients with idiopathic generalized epilepsy. A group analysis was performed to determine the regions of positive (activation) and negative (deactivation) blood oxygenation leveldependent responses that were common to the patients. Activations were found bilaterally and symmetrically in the thalamus, mesial midfrontal region, insulae, and midline and bilateral cerebellum and on the borders of the lateral ventricles. Deactivations were bilateral and symmetrical in the anterior frontal and parietal regions and in the posterior cingulate gyri and were seen in the left posterior temporal region. Activations in thalamus and midfrontal regions confirm known involvement of these regions in the generation or spread of generalized epileptic discharges. Involvement of the insulae in generalized discharges had not previously been described. Cerebellar activation is not believed to reflect the generation of discharges. Deactivations in frontal and parietal regions remarkably followed the pattern of the default state of brain function. Thalamocortical activation and suspension of the default state may combine to cause the actual state of reduced responsiveness observed in patients during spike-and-wave discharges. This brief lapse of responsiveness may therefore not result only from the epileptic discharge but also from its effect on normal brain function.absence ͉ epilepsy ͉ thalamus T he electroencephalogram (EEG) of patients with epilepsy presents paroxysmal discharges that depend on the type of epilepsy. In epilepsy that has been termed ''idiopathic generalized'' according to the Commission on Classification and Terminology of the International League Against Epilepsy (1), the most common type of discharge is the 2-to 3-Hz spike-and-wave burst, which occurs simultaneously over wide cortical regions, most often with an anterior predominance. The origin of this discharge and of the absence seizures that often accompany spike-and-wave bursts when they last several seconds has been a subject of investigation and controversy for many years (see ref.2 for a review), particularly with respect to the involvement of subcortical structures. The recently developed method of combined EEG and functional magnetic resonance imaging (fMRI) (EEG͞fMRI) allows the investigation of the brain regions, cortical and subcortical, that are involved in metabolic changes as a result of epileptic discharges seen in the scalp EEG. In our recent publication (3), we described for each individual the patterns of increases and decreases in blood oxygenation leveldependent (BOLD) signal resulting from bu...

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Cerebellar neuronal activity correlates with spike and wave EEG patterns in the rat

Cited by 65 publications

References 24 publications

Cerebellar output controls generalized spike‐and‐wave discharge occurrence

Cerebellar output controls generalized spike‐and‐wave discharge occurrence

Upregulation of cortico-cerebellar functional connectivity after motor learning

Generalized epileptic discharges show thalamocortical activation and suspension of the default state of the brain

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