# Cortical Connectivity Response to Hyperventilation in Focal Epilepsy: A Stereo-EEG Study
## 5 Discussion  
This is the first study to investigate HV using SEEG intracranial electrodes, offering novel insights into the impact of such a maneuver on the cortical brain signals. The results denote how HV shares similar characteristics in terms of energy ratio and phase entropy to N-REM sleep, and the same occurs for the awake status and ictal transition, where the latter includes the 20 s preceding and following the seizure onset. Specifically, \(ER\) and \(H(\theta)\) are higher when the patient is conscious and during the ictal transition; in contrast, N-REM and HV present slower electrical activities, characterized by lower energy in high-frequency bands and more regular signal patterns. Interestingly, HV presents a reduced \(ER\) than awake status and, thus, seems to mitigate the rise in fast oscillations: this is in apparent contradiction to the scope of such an activation maneuver. The low effectiveness of the energy ratio and the phase entropy in discerning HV from the N-REM status may be explained by the fact that such metrics do capture the interdependency between different cortical sites but analyze each signal as an independent element. More insights into HV are obtained by looking at the PTE, which, instead, enables full discrimination between all the SEEG groups. Particularly, the PTE algorithm captures the characteristics of intrasignal relationships across multiple frequency bands. This is very beneficial for analyzing epileptiform activities, which, notably, are not confined to specific frequency ranges but affect both fast and slow oscillations [28]. Our results show that HV increases the PTE, even more strongly than N-REM, while ictal transition behaves in the opposite fashion. This is in agreement with past studies that proved that the epileptogenic network presents reduced connectivity during the early ictal phase while being characterized by higher synchronization during seizure propagation. The ictal connectivity pattern may be explained by observing that the epileptogenic area adopts  
Figure 2: Comparison between the median and interquartile range of the analyzed metrics for the different groups of SEEG epochs; the top of each bar denotes the expected values, while the black vertical lines denote the confidence intervals. a pathological behavior and, thus, results in being desynchronized by the rest of the network [29]. At first glance, our study denotes that HV is on the opposite side with respect to ictal transition, both in terms of the cortical connectivity and energy ratio, making its role in triggering seizures questionable. These findings are in line with other clinical studies on adults with focal epilepsy, suggesting that HV rarely triggers either clinical seizures or increases epileptiform discharges [10]. The connectivity increase during HV may be related to the specific characteristics of slow oscillations, which has been identified as a primary driver of interictal activity during N-REM sleep [30; 31; 32]. The cortical hypersynchronization has also been called into question to explain the IED diffusion that usually is observed in both N-REM sleep and HV, in opposite fashion with respect to the REM phase in which the IEDs becomes more focused [32; 33]. The fact that HV replicates the N-REM patterns explains the effectiveness of this activation maneuver in generalized epilepsy, such as absence epilepsy, where IED exploits the burst-firing mode of the wide-projecting corticothalamic system as is well documented during N-REM sleep [30]. The fact that cortical brain regions during HV replicate the conditions observed during the N-REM status has been hypothesized by some previous studies but, to our knowledge, was never shown via intracranial EEG recordings. This may steer against the current clinical practices, which recommend the use ofHV as an activation maneuver for both generalized and focal epilepsy.