The role of subcortical structures in human epilepsy

Norden, Andrew D.; Blumenfeld, Hal

doi:10.1016/s1525-5050(02)00029-x

Cited by 311 publications

(248 citation statements)

References 151 publications

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“…This is consistent with the known extensive anatomic interconnectivity between the hippocampus and thalamus [35], and the significant role of the thalamus in seizure initiation, modulation, and propagation [16,36,37]. Here we found significant bilateral volume loss compared to the control group with greater ipsilateral than contralateral volume loss.…”

Section: Thalamussupporting

confidence: 90%

“…Selection of regions of interest (ROIs) was guided by previous findings indicating atrophy in these regions, and evidence that these structures are considered important in seizure initiation, modulation, and/or propagation [16]. Specifically, we used quantitative MRI to: 1) measure and compare MR volumes of the hippocampus, thalamus, corpus callosum, caudate, and putamen; (2) examine the association of age of onset, duration of epilepsy, number of antiepileptic drugs (AEDs), and lifetime number of secondarily generalized seizures with brain volume in these structures; and 3) provide a systematic presentation of the relative volume abnormality (effect size and percent difference) evident in these structures.…”

Section: Introductionmentioning

confidence: 99%

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MRI volume loss of subcortical structures in unilateral temporal lobe epilepsy

Pulsipher

Seidenberg

Morton

et al. 2007

Epilepsy & Behavior

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Few studies have examined the relative degree of brain volume loss in both the hippocampi and subcortical structures in unilateral temporal lobe epilepsy (TLE), and their association with clinical seizure correlates. In this study, quantitative MRI volumes were measured in the hippocampus, thalamus, caudate, putamen, and corpus callosum in 48 unilateral TLE patients (26 rights, and 22 lefts) and compared to 29 healthy controls. The ipsilateral hippocampus, corpus callosum, and bilateral thalami showed the greatest volume loss, reflected by large to moderate effect size differences compared to controls. Bilaterally, the putamen showed the next highest volume reduction. The contralateral hippocampus and bilateral caudate nuclei showed the least volume reduction, characterized by small effect sizes. Furthermore, clinical seizure characteristics (e.g, duration of epilepsy) showed different patterns of association with the volume reductions observed across these structures. Findings suggest that distinct neurodevelopmental features may play a role in the volume abnormality observed in these regions.

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Section: Thalamussupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

MRI volume loss of subcortical structures in unilateral temporal lobe epilepsy

Pulsipher

Seidenberg

Morton

et al. 2007

Epilepsy & Behavior

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“…CN neurons provide excitatory input to thalamic neurons4, 6, 23, 24, 25, 26, 27, 28, 29 and thereby potentially contribute to the excitation–inhibition balance that sets thalamic activity patterns. Excess tonic inhibition of thalamic activity has been linked to the occurrence of absence seizures,3, 7, 8 and therefore we hypothesized that a decrease in CN output in tg should increase the occurrence of GSWDs, whereas increased CN output should have the opposite effect.…”

Section: Resultsmentioning

confidence: 99%

“…CN axons that project to the thalamus have been shown to originate from glutamatergic neurons, which synapse predominantly perisomatically and evoke substantial excitatory responses 4, 6, 23, 24, 25, 26, 27, 28, 29. Upon CN injections with muscimol, we must in effect have substantially reduced the level of excitation of thalamic neurons and thereby disturbed the balance of inhibition and excitation in thalamocortical networks in favor of inhibition.…”

Section: Discussionmentioning

confidence: 99%

“…Given the considerable divergence of excitatory axonal projections from the CN to a wide range of motor, associative, and intralaminar thalamic nuclei,4, 6, 23, 24, 25, 26, 27, 28, 29 we considered this region an ideal candidate to effectively modulate thalamocortical oscillations. We hypothesized that altering the firing patterns of CN neurons should affect GSWD occurrence.…”

mentioning

confidence: 99%

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Cerebellar output controls generalized spike‐and‐wave discharge occurrence

Kros

Rooda

Spanke

et al. 2015

Annals of Neurology

121

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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