# Multi-Graph Assessment of Temporal and Extratemporal Lobe Epilepsy in Resting-State fMRI
## 4 Discussion
### Key Region Mapping  
Regarding specific brain areas from the analysis of the hub regions SFG, SPG, PCUN, MOG, SOG, ParaCG, Calcarine, and ITG were identified in Pearson correlation and MI graphs. The significance of these regions is corroborated by various studies [62; 63; 64; 65]. The review of [PERSON] and [PERSON] designates the PCUN, SFG, and SPG regions as both structural and functional hubs [64]. In line with this review, [PERSON] et al. [65] suggested that bilateral PCUN, SFG and SPG are part of a set of regions that are strongly connected to each other and they observed that TLE patients show decreased functional connectivity especially between ROIs that belong to rich-club. On the other hand, bilateral CUN presented low probability values of being a hub in TLE and ETLE patients, while it is identified as a hub in most control subjects. This is supported by other studies indicating that surgery in children with epilepsy improved significantly the nodal efficiency of cuneus [23; 66]. Also, the study of [PERSON] et al. [67] reports a progressive cortical thinning in the left CUN, observed in patients with left temporal lobe and right frontal lobe epilepies.Furthermore, in the Pearson graphs an alteration in the hubs of the occipital lobe was observed in the bilateral SOC and IOG, demonstrating low hub probability in both TLE and ETLE groups while in healthy controls this probability was high. Previous studies have also found decreased regional homogeneity in TLE patients compared to controls in these regions (SOG, IOG, and CUN), suggesting that abnormalities in brain regions which act as central nodes could deter efficient communication and integration of information across different parts of the brain [68]. On the contrary, in the MI graphs, ANG was identified as a hub region for all ETLE patients and 64% of the TLE patients but displayed less than 50% probability of being a hub region in the control group. Similar to this outcome, previous studies report increased nodal parameters, such as betweenness and degree centrality, in the ANG of patients with temporal lobe and juvenile mycolonic epilepseis compared to controls [69; 70]. Since the angular gyrus is part of the inferior parietal cluster of the default mode network (DMN), the increased connectivity of this region may lead to the spread of the seizure within the DMN and can be the reason for cognitive difficulties observed in patients with TLE [71; 72; 73]. Regarding the causal relationship between ROIs, the Granger causality graphs in the control group identified the left parahippocampal gyrus and the left STG polar as hubs. However, those regions show lower hub probability in both TLE and ETLE epilepsy groups. In the study by [PERSON] et al. [67] the left STG presents progressive atrophy in patients with left TLE and they provide evidence of increased progressive atrophy of the parahippocampal gyrus in the TLE compared to patients with frontal lobe epilepsy. In our study, the significance of parahippocampal gyrus is also highlighted in the patient groups but only in the right hemisphere. Since the majority of the patients have left hemisphere lateralized epilepsy (68.2% of total patients), this could imply a disturbance of this region ipsilateral to the seizure onset. Moreover, in the directed Granger causality graphs, the subcortical regions were significant across all groups, while the amygdala and the pallidum were the most prominent. This is corroborated by recent studies indicating the subcortical areas of pallidum, putamen, and thalamus as brain connector hubs, suggesting their multiple roles in the efficient information flow of the healthy brain [63; 74]. The subcortical regions play a key role in seizure propagation, especially the thalamus [75; 76]. There is evidence supporting that reduction in the grey matter of thalamus and hippocampus may be related to the severity of epilepsy [77].