Abstracts

Rationale: Generalized spike wave discharges (GSW) are the electroencephalographic hallmark of idiopathic generalized epilepsy (IGE) and are also seen in secondarily generalized epilepsy (SGE). The pathophysiological substrate of GSW remains enigmatic and the debate between subcortical (the “centroencephalic hypothesis”) and cortical origins remains open [1]. The findings of a number of studies indicate that the prefrontal cortex (BA10 and BA32) may be involved in the generation of GSW [2]. In this work we analysed fMRI data using dynamic causal modelling (DCM) to investigate the effective connectivity between thalamus and frontal cortex in patients with GSW. Methods: We selected EEG-fMRI data from 8 patients (4 IGE and 4 SGE) with frequent GSW discharges which had shown significant GSW-correlated haemodynamic signal changes (activation or deactivation) in the thalamus, the frontal cortex (medial frontal gyrus-BA10) and precuneus in previous GSW-correlated analyses [3] Using DCM we assessed the effective connectivity, i.e. which region drives another region. Neuronal activity was modelled using the known inputs (GSW) and outputs (haemodynamic responses measured with fMRI). Two DCM pairs (four models) per patient were constructed (using ROIs derived from statistical parametric maps resulted from GLM analysis) each comprising two structurally connected regions (5 mm diameter spheres): a) thalamus and BA10: changes in the states of BA10 depend on the activity of the thalamus or vice versa; b) thalamus and precuneus: changes in the states of precuneus depend on the activity of the thalamus or vice versa. For each model, this dependency was parameterized considering GSW both as driving and modulatory effects. For each model, we computed its likelihood. Results: No consistent evidence in favour of any directional thalamus and BA10 modulation was found in 6 out of 8 patients (4 SGE and 2 IGE). In the other 2 patients (IGE) we found strong evidence for the model in which BA10 activity was driven by the thalamus. In 6 patients (3 IGE and 3 SGE), there was strong evidence for the model in which thalamic activity depended on the precuneal state but not vice versa. In the remaining two cases no consistent evidence in favour of any directional model was found. Conclusions: Given the tested models, our findings suggest that during sustained GSW there is no unidirectional connectivity between the thalamus and the frontal cortex but that thalamic activity is driven by the state of the precuneus. These data support the established hypothesis that both thalamus and cortex are equally involved during GSW in a reverberating cortico-subcortical loop. Moreover our findings suggest this thalamo-cortical activity is influenced by the precuneus, a key region related to vigilance and consciousness. References [1] H Meeren et al. Arch Neurol, 2005, vol 62; 371-376. [2] MD Holmes et al. Epilepsia 2004, 45(12):1568-1579. [3] K Hamandi et al. Neuroimage 31 (2006); 1700-1710.