The role of the basal ganglia in the control of seizure

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Abstract

<p class="first" id="P1">Epilepsy is a network disorder and each type of seizure involves distinct cortical and subcortical network, differently implicated in the control and propagation of the ictal activity. The role of the basal ganglia has been revealed in several cases of focal and generalized seizures. Here, we review the data that shows the implication of the basal ganglia in absence, temporal lobe, and neocortical seizure in animal models (rodent, cat, and non-human primate) and in human. Based on these results and the advancement of deep brain stimulation for Parkinson’s disease, basal ganglia neuromodulation has been tested with some success that can be equally seen as promising or disappointing. The effect of deep brain stimulation can be considered promising with a 76% in seizures reduction in temporal lobe epilepsy patients, but also disappointing, since only few patients have become seizure free and the anti-epileptic effects have been highly variable among patients. This variability could probably be explained by the heterogeneity among the patients included in these clinical studies. To illustrate the importance of specific network identification, electrophysiological activity of the putamen and caudate nucleus has been recorded during penicillin-induced pre-frontal and motor seizures in one monkey. While an increase of the firing rate was found in putamen and caudate nucleus during pre-frontal seizures, only the activity of the putamen cells was increased during motor seizures. These preliminary results demonstrate the implication of the basal ganglia in two types of neocortical seizures and the necessity of studying the network in order to identify the important nodes implicated in the propagation and control of each type of seizure. </p>

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Functional neuroanatomy of the basal ganglia.

Natasha Luquin, Jose Obeso, José Lanciego (2012)

The "basal ganglia" refers to a group of subcortical nuclei responsible primarily for motor control, as well as other roles such as motor learning, executive functions and behaviors, and emotions. Proposed more than two decades ago, the classical basal ganglia model shows how information flows through the basal ganglia back to the cortex through two pathways with opposing effects for the proper execution of movement. Although much of the model has remained, the model has been modified and amplified with the emergence of new data. Furthermore, parallel circuits subserve the other functions of the basal ganglia engaging associative and limbic territories. Disruption of the basal ganglia network forms the basis for several movement disorders. This article provides a comprehensive account of basal ganglia functional anatomy and chemistry and the major pathophysiological changes underlying disorders of movement. We try to answer three key questions related to the basal ganglia, as follows: What are the basal ganglia? What are they made of? How do they work? Some insight on the canonical basal ganglia model is provided, together with a selection of paradoxes and some views over the horizon in the field.

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Critical review of current animal models of seizures and epilepsy used in the discovery and development of new antiepileptic drugs.

Wolfgang Löscher (2011)

Animal models for seizures and epilepsy have played a fundamental role in advancing our understanding of basic mechanisms underlying ictogenesis and epileptogenesis and have been instrumental in the discovery and preclinical development of novel antiepileptic drugs (AEDs). However, there is growing concern that the efficacy of drug treatment of epilepsy has not substantially improved with the introduction of new AEDs, which, at least in part, may be due to the fact that the same simple screening models, i.e., the maximal electroshock seizure (MES) and s.c. pentylenetetrazole (PTZ) seizure tests, have been used as gatekeepers in AED discovery for >6 decades. It has been argued that these old models may identify only drugs that share characteristics with existing drugs, and are unlikely to have an effect on refractory epilepsies. Indeed, accumulating evidence with several novel AEDs, including levetiracetan, has shown that the MES and PTZ models do not identify all potential AEDs but instead may fail to discover compounds that have great potential efficacy but work through mechanisms not tested by these models. Awareness of the limitations of acute seizure models comes at a critical crossroad. Clearly, preclinical strategies of AED discovery and development need a conceptual shift that is moving away from using models that identify therapies for the symptomatic treatment of epilepsy to those that may be useful for identifying therapies that are more effective in the refractory population and that may ultimately lead to an effective cure in susceptible individuals by interfering with the processes underlying epilepsy. To realize this goal, the molecular mechanisms of the next generation of therapies must necessarily evolve to include targets that contribute to epileptogenesis and pharmacoresistance in relevant epilepsy models. Copyright © 2011 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

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Basal ganglia functional connectivity based on a meta-analysis of 126 positron emission tomography and functional magnetic resonance imaging publications.

Ronald Postuma, Alain Dagher (2006)

The striatum receives projections from the entire cerebral cortex. Different, but not mutually exclusive, models of corticostriatal connectivity have been proposed, including connectivity based on proximity, parallel loops, and a model of a tripartite division of the striatum into motor, associative, and limbic areas. All these models were largely based on studies of anatomic connectivity in nonhuman mammals and lesion studies in animals and humans. Functional neuroimaging has the potential to discern patterns of functional connectivity in humans in vivo. We analyzed the functional connectivity between the cortex and the striatum in a meta-analysis of 126 published functional neuroimaging studies. We mapped the peak activations listed in each publication into stereotaxic space and used standard functional imaging statistical methods to determine which cortical areas were most likely to coactivate with different parts of the striatum. The patterns of functional connectivity between the cortex and the different striatal nuclei are broadly consistent with the predictions of the parallel loop model. The rostrocaudal and dorsoventral patterns of corticostriatal functional connectivity are consistent with the tripartite division of the striatum into motor, associative, and limbic zones.