# Structure-Function Coupling Reveals Seizure Onset Connectivity Patterns
## 4 Discussion  
In this study, we obtained structural and functional connectomes from nine patients to investigate whether our model could uncover the structure-function coupling during seizure onset. We also examined the pattern and congruence of the structure-function coupling with the expected seizure onset zone. The first key finding was that patients with well-lateralised seizures displayed high structural-functional congruence consistent with the expected seizure onset zone. The second key finding was that patients who were not well-lateralised had varying coupled electrodes that were not consistently in the onset zone. The results indicate that for well-lateralised patients, connectivity data derived from dMRI can be a valuable tool to augment routine EEG observations. However, the dMRI should be interpreted in the context of other routinely collected data from the patient. Our findings offer some compelling evidence for the use of dMRI in clinical practice. Firstly, in patients with high structure-function coupling in the expected onset zone, dMRI may provide additional support to the EEG observations. A recent work used intracranial EEG (iEEG) and dMRI to explore the relation between structure-function coupling and post-surgery seizure freedom [9]. The Authors showed that patients who achieved post-surgery seizure freedom had higher structure-function coupling pre-surgery. However, access to iEEG may not be feasible in the initial diagnosis stage. Additionally, the diagnostic yield of low-density scalp EEG (25 electrodes) has been suggested to be comparable to high-density EEG (256 electrodes) [44]. Taken together, our findings suggest that our model may be used  
Figure 2: Highly connected electrode pairs in structural and functional connectome. Each “head” shows a schematic of the electrode pairs for each of the nine patients (numbered 1–9 above each head). The “L” value represents each patient’s overall seizure lateralisation score based on their available recorded seizures. A score of zero represented poorly lateralised seizures, whilst highly lateralised seizures received a score of three. The patients’ seizures stratified them into three categories: patients 1–3 had high laterality, patients 4–6 had some seizures that were well lateralised, while others were not, and patients 7–9 had poor laterality in all seizures. The purple lines (and circled electrodes) represent the electrode pairs that displayed strong connectivity (z-scores > 2) in the structural (MRI) connectome. The orange lines (and circled electrodes) represent the electrode pairs that displayed strong connectivity (z-scores > 2) in the functional (EEG) connectome. Dotted lines in either colour represent a z-score of 1.8–2. The blue shading represents the most frequently observed seizure onset zone for a given patient, as observed from their ward EEG recordings. If a seizure did not have a specific onset region within the first 5 s, it was considered non-lateralised, even if it displayed late-lateralisation. Purple and orange circled electrodes in the blue shaded areas represent high structure-function coupling in the seizure onset zone. during the diagnosis stage to determine the suitability of surgery for newly-diagnosed patients. Notably, we provide evidence that high structure-function coupling was present for patients regardless of whether they had previously experienced an FBTC seizure. Our finding suggests that a history of infrequent FBTC seizures (present in Patients 1 and 3) does not preclude the patient from having well-lateralised structure-function coupling. Secondly, in the patients with poorly lateralised seizures, the structure-function coupling was more predominant in the ipsilateral hemisphere. However, the presence of structure-function coupling in the contralateral hemisphere was unsurprising, given their laterality score. In these patients, dMRI may provide additional information that can guide the placement of additional electrodes in longer ward recordings.