*Article* **Structure-Function Coupling Reveals Seizure Onset Connectivity Patterns**

**Christina Maher 1,2,\*, Arkiev D'Souza 2,3, Michael Barnett 2,4,5, Omid Kavehei 1, Chenyu Wang 2,3,5 and Armin Nikpour 4,6**

	- <sup>5</sup> Sydney Neuroimaging Analysis Centre, Camperdown, NSW 2050, Australia
	- <sup>6</sup> Central Clinical School, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2050, Australia
	- **\*** Correspondence: christina.maher@sydney.edu.au; Tel.: +61-02-9114-4187

**Abstract:** The implications of combining structural and functional connectivity to quantify the most active brain regions in seizure onset remain unclear. This study tested a new model that may facilitate the incorporation of diffusion MRI (dMRI) in clinical practice. We obtained structural connectomes from dMRI and functional connectomes from electroencephalography (EEG) to assess whether high structure-function coupling corresponded with the seizure onset region. We mapped individual electrodes to their nearest cortical region to allow for a one-to-one comparison between the structural and functional connectomes. A seizure laterality score and expected onset zone were defined. The patients with well-lateralised seizures revealed high structure-function coupling consistent with the seizure onset zone. However, a lower seizure lateralisation score translated to reduced alignment between the high structure-function coupling regions and the seizure onset zone. We illustrate that dMRI, in combination with EEG, can improve the identification of the seizure onset zone. Our model may be valuable in enhancing ultra-long-term monitoring by indicating optimal, individualised electrode placement.

**Keywords:** focal epilepsy; diffusion imaging; electroencephalography; structure-function coupling; seizure onset; structural connectivity; functional connectivity
