Huge thank you to first author Gongjun Ji for leading this study, to @foxmdphd.bsky.social for his invaluable mentorship at @braincircuits.bsky.social, and all collaborators for their support and generous sharing of their data:

We then combined the networks of brain abnormalities in IGE with the CM DBS data and identified a convergent IGE network, which could represent a brain stimulation target to better control generalized seizures.

The thalamic peak in our IGE network even converged on the same MNI coordinate as a recently identified DBS sweet-spot for IGE, potentially suggesting an optimal DBS target based on connectivity of brain abnormalities in IGE.

We collected all published and unpublished IGE cases we could get our hands on (thank you collaborators!) and we found the leads nicely aligned with the peak in the IGE network. Patients had a median response rate of 90% (!), supporting the CM as an off label DBS target for generalized seizures.

My take: generalized seizures may 'hijack' (parts of) the SCAN resulting in the electroclinical expression of generalized seizures along intrinsic human brain networks leading to convulsions of the whole body or myoclonic jerks as well as loss of consciousness or absences.

YES! The IGE network beautifully aligned with the inter-effector regions and SCAN which is an evolutionary preserved integrated action and executive control system to coordinate gross movements, control muscle groups, posture, and internal physiology.

This IGE network encompassed the regions identified in the ENIGMA study and was further validated by data from EEG-fMRI studies that show BOLD activation at the time of the generalized spike-wave in the positive functional connections of the IGE network.

We therefore computed the network connections of these brain abnormalities using the human connectome and identified an 'IGE network' involving the SMA, perirolandic cortex, thalamus, piriform cortex, frontal poles, superior temporal gyrus, precuneus, and cerebellum.

We therefore collected all published coordinates of voxel-wise brain abnormalities associated with IGE and plotted them here:

We believed these brain abnormalities could give us crucial clues about where the generalized seizure starts or travels to in the brain. Think of pebbles that track a path the generalized seizure prefers to travel along...

Patients with idiopathic generalized epilepsy (IGE) typically present with generalized spike wave discharges with 'normal' brain MRI, leaving the neuroanatomical basis of IGE unclear.