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The basal ganglia and the epilepsies
Willian Lazarini-Lopes1, Logan Perry1,2, Patrick A Forcelli2
1Department of Pharmacology and Physiology, Georgetown University, Washington, DC, USA.
Abstract:
The basal ganglia are an evolutionarily conserved neural circuit best known for the selection and sequencing of voluntary movement. Increasing evidence, however, indicates that these structures also play an important role in regulating pathological brain states, including seizures. Early pharmacological and lesion studies demonstrated that manipulation of basal ganglia output nuclei, particularly the substantia nigra pars reticulata, profoundly alters seizure susceptibility across multiple experimental models. Subsequent work expanded this view, revealing that several basal ganglia structures, including the striatum, subthalamic nucleus, globus pallidus, and superior colliculus, participate in a distributed network capable of modulating seizure initiation, propagation, and generalization. Modern systems neuroscience approaches have begun to define the specific cell types and projection-defined pathways through which these effects are mediated. Together, these findings support the concept that the basal ganglia function as a "seizure-gating" network that interacts with thalamocortical and brainstem arousal systems to regulate cortical synchronization. Understanding how these circuits influence seizure dynamics may enable new therapeutic strategies that strengthen endogenous seizure-suppressing networks rather than targeting the seizure focus alone. PLAIN LANGUAGE SUMMARY: The basal ganglia are a group of deep brain structures best known for helping to start and stop movements. Over the past 40 years, research has shown that they also act as a brake on seizures. Studies across species demonstrate that "turning off" one of the main output structures of the basal ganglia, the substantia nigra pars reticulata, can stop many types of seizures. This review presents the "wiring diagram" of this brain circuit, including the effects of "turning on" and "turning off" individual brain regions and their connections on seizure initiation, propagation, and termination.
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