Causal Hierarchy within the Thalamo-Cortical Network in Spike and Wave Discharges

Abstract

BackgroundGeneralised spike wave (GSW) discharges are the electroencephalographic (EEG) hallmark of absence seizures, clinically characterised by a transitory interruption of ongoing activities and impaired consciousness, occurring during states of reduced awareness. Several theories have been proposed to explain the pathophysiology of GSW discharges and the role of thalamus and cortex as generators. In this work we extend the existing theories by hypothesizing a role for the precuneus, a brain region neglected in previous works on GSW generation but already known to be linked to consciousness and awareness. We analysed fMRI data using dynamic causal modelling (DCM) to investigate the effective connectivity between precuneus, thalamus and prefrontal cortex in patients with GSW discharges.Methodology and Principal FindingsWe analysed fMRI data from seven patients affected by Idiopathic Generalized Epilepsy (IGE) with frequent GSW discharges and significant GSW-correlated haemodynamic signal changes in the thalamus, the prefrontal cortex and the precuneus. Using DCM we assessed their effective connectivity, i.e. which region drives another region. Three dynamic causal models were constructed: GSW was modelled as autonomous input to the thalamus (model A), ventromedial prefrontal cortex (model B), and precuneus (model C). Bayesian model comparison revealed Model C (GSW as autonomous input to precuneus), to be the best in 5 patients while model A prevailed in two cases. At the group level model C dominated and at the population-level the p value of model C was ∼1.ConclusionOur results provide strong evidence that activity in the precuneus gates GSW discharges in the thalamo-(fronto) cortical network. This study is the first demonstration of a causal link between haemodynamic changes in the precuneus - an index of awareness - and the occurrence of pathological discharges in epilepsy.

Imaging haemodynamic changes related to seizures: Comparison of EEG-based general linear model, independent component analysis of fMRI and intracranial EEG

“…Cases #1, 2 and 5 had mesial neo-cortical seizures with rapid EEG propagation, and BOLD decreases in the thalamus or basal ganglia. This is in keeping with involvement of these structures in seizures Steriade et al, 1991;Vaudano et al, 2009). BOLD decreases were observed in relation to the late ictal phase in 3 cases, suggesting a cerebral perfusion/ metabolic demand mismatch resulting in sustained tissue hypoxia adjacent to the seizure focus despite, hyperoxygenation following the "initial dip" within the focus (Zhao et al, 2009).…”

Identifying Corticothalamic Network Epicenters in Patients with Idiopathic Generalized Epilepsy

“…32 Given that the default mode network-pulvinar network is associated with the default state of the human brain, 31 increased synchrony with thalamic nuclei in the interictal or preictal state may facilitate seizures. 33 In the temporal-thalamic network, the morphometric features of the posterior part of the middle temporal gyrus showed stronger correlation with those of the thalamus in patients with IGE than in controls. 6 Our results provide additional evidence for abnormalities in this network at the functional level.…”

Epilepsy‐related brain networks in ring chromosome 20 syndrome: An EEG‐fMRI study

“…35 These "paroxysmal" DMN negative hemodynamic responses may reflect disturbance of awareness or consciousness associated with absences. 36 If we consider that the pathologic slow-wave rhythm of patients with [r (20)] syndrome is a fluctuating state that is enduring, it is clear that its detrimental effects on the brain resting state are not short lived but protracted over time. Future studies should specifically address this hypothesis, correlating the patients' neuropsychological/behavioral performances with quantitative EEG measures of the 3-5 Hz slow wave rhythm.…”