The Role of Thalamus Versus Cortex in Epilepsy: Evidence from Human Ictal Centromedian Recordings in Patients Assessed for Deep Brain Stimulation

Abstract

In human generalized seizures, the thalamus may become involved early or late in the seizure but, once it becomes involved, it leads the cortex. In contrast, in human frontal seizures the thalamus gets involved late in the seizure and, once it becomes involved, it lags behind the cortex. In addition, the centromedian nucleus of the thalamus is capable of autonomous epileptogenesis as suggested by the presence of independent focal unilateral epileptiform discharges restricted to thalamic structures. The thalamus may also be responsible for maintaining the rhythmicity of ictal discharges.

Cortex leads the thalamic centromedian nucleus in generalized epileptic discharges in Lennox‐Gastaut syndrome

“…Conversely, a study of three patients (two with generalized epilepsy and one with frontal epilepsy) determined that thalamic onset tended to lag cortical onset during generalized seizures in two patients; however, once the thalamus became involved, there was an increase in discharge rhythmicity consistent with a belated but then leading synchronizing role of the thalamus 26 . Additionally, there was evidence of a thalamic lag in seizures arising from the frontal lobe, 26 in keeping with our observations of GPFA, a discharge type that tends to show maximal amplitude over frontal and frontocentral scalp areas 27 . Variability in these previous studies’ findings likely reflects heterogeneity in the epilepsy syndromes/seizure types studied, as well as small sample sizes.…”

“…In another study of four children with LGS, scalp and CM onsets were deemed to occur simultaneously during generalized tonic, tonic‐clonic, and atypical absence seizures; however, the CM showed an earlier onset during myoclonic seizures only 2 . Conversely, a study of three patients (two with generalized epilepsy and one with frontal epilepsy) determined that thalamic onset tended to lag cortical onset during generalized seizures in two patients; however, once the thalamus became involved, there was an increase in discharge rhythmicity consistent with a belated but then leading synchronizing role of the thalamus 26 . Additionally, there was evidence of a thalamic lag in seizures arising from the frontal lobe, 26 in keeping with our observations of GPFA, a discharge type that tends to show maximal amplitude over frontal and frontocentral scalp areas 27 .…”

Low frequency centromedian thalamic nuclei deep brain stimulation for the treatment of super refractory status epilepticus: A case report and a review of the literature

“…One potential hypothesis for the apparent benefit of CMN lowfrequency stimulation is that CMN thalamic nuclei are functionally connected with the fronto-parietal structures of the cortex [9] and this could cause highly-synchronized brain activity, facilitating inhibitory mechanisms which could be involved in the termination of focal seizures during srSE [10]. Continuous low-frequency stimulation of these nuclei may disrupt seizure generation in connected cortical epileptogenic regions, reducing number and/or severity of focal seizures.…”

Novel test strategies for in vitro seizure liability assessment

“…Rodent primary cortical cultures contain most of the components of the in vivo cortex, including GABA-ergic and glutamatergic neurotransmitter systems as well as supportive astrocytes. Moreover, cortical neurons are involved in seizures [ 64 ] and thus play a crucial role in in vitro seizure liability assessment. While many different cell types from different animals can be grown on MEAs, rat primary cortical cultures have become the current gold standard [ 5 ].…”