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Direct electrical stimulation (DES) is considered to be the gold standard for mapping cortical function. A careful mapping of the eloquent cortex is key to successful resective or ablative surgeries, with a minimal postoperative deficit, for treatment of drug‐resistant epilepsy. There is accumulating evidence suggesting that not only local, but also remote activations play an equally important role in evoking clinical effects. By introducing a new intracranial stimulation paradigm and signal analysis methodology allowing to disambiguate EEG responses from stimulation artifacts we highlight the spatial extent of the networks associated with clinical effects. Our study includes 26 patients that underwent stereoelectroencephalographic investigations for drug‐resistant epilepsy, having 337 depth electrodes with 4,351 contacts sampling most brain structures. The routine high‐frequency electrical stimulation protocol for eloquent cortex mapping was altered in a subtle way, by alternating the polarity of the biphasic pulses in a train, causing the splitting the spectral lines of the artifactual components, exposing the underlying tissue response. By performing a frequency‐domain analysis of the EEG responses during DES we were able to capture remote activations and highlight the effect's network. By using standard intersubject averaging and a fine granularity HCP‐MMP parcellation, we were able to create local and distant connectivity maps for 614 stimulations evoking specific clinical effects. The clinical value of such maps is not only for a better understanding of the extent of the effects' networks guiding the invasive exploration, but also for understanding the spatial patterns of seizure propagation given the timeline of the seizure semiology. [ABSTRACT FROM AUTHOR]

• Local and distant connections are differently modulated by sleep. • Clear interhemispheric difference in epileptogenic areas' connectivity during sleep. • Different patterns of information flow during sleep in physiologic versus pathologic structures. Sleep is an active process with an important role in memory. Epilepsy patients often display a disturbed sleep architecture, with consequences on cognition. We aimed to investigate the effect of sleep on cortical networks' organization. We analyzed cortico-cortical evoked responses elicited by single pulse electrical stimulation (SPES) using intracranial depth electrodes in 25 patients with drug-resistant focal epilepsy explored using stereo-EEG. We applied the SPES protocol during wakefulness and NREM – N2 sleep. We analyzed 31,710 significant responses elicited by 799 stimulations covering most brain structures, epileptogenic or non-epileptogenic. We analyzed effective connectivity between structures using a graph-theory approach. Sleep increases excitability in the brain, regardless of epileptogenicity. Local and distant connections are differently modulated by sleep, depending on the tissue epileptogenicity. In non-epileptogenic areas, frontal lobe connectivity is enhanced during sleep. There is increased connectivity between the hippocampus and temporal neocortex, while perisylvian structures are disconnected from the temporal lobe. In epileptogenic areas, we found a clear interhemispheric difference, with decreased connectivity in the right hemisphere during sleep. Sleep modulates brain excitability and reconfigures functional brain networks, depending on tissue epileptogenicity. We found specific patterns of information flow during sleep in physiologic and pathologic structures, with possible implications for cognition. [ABSTRACT FROM AUTHOR]

The cingulate cortex is part of the limbic system. Its function and connectivity are organized in a rostro-caudal and ventral-dorsal manner which was addressed by various other studies using rather coarse cortical parcellations. In this study, we aim at describing its function and connectivity using invasive recordings from patients explored for focal drug-resistant epilepsy. We included patients that underwent stereo-electroencephalographic recordings using intracranial electrodes in the University Emergency Hospital Bucharest between 2012 and 2019. We reviewed all high frequency stimulations (50 ​Hz) performed for functional mapping of the cingulate cortex. We used two methods to characterize brain connectivity. Effective connectivity was inferred based on the analysis of cortico-cortical potentials (CCEPs) evoked by single pulse electrical stimulation (SPES) (15 ​s inter-pulse interval). Functional connectivity was estimated using the non-linear regression method applied to 60 ​s spontaneous electrical brain signal intervals. The effective (stimulation-evoked) and functional (non-evoked) connectivity analyses highlight brain networks in a different way. While non-evoked connectivity evidences areas having related activity, often in close proximity to each other, evoked connectivity highlights spatially extended networks. To highlight in a comprehensive way the cingulate cortex's network, we have performed a bi-modal connectivity analysis that combines the resting-state broadband h 2 non-linear correlation with cortico-cortical evoked potentials. We co-registered the patient's anatomy with the fsaverage FreeSurfer template to perform the automatic labeling based on HCP-MMP parcellation. At a group level, connectivity was estimated by averaging responses over stimulated/recorded or recorded sites in each pair of parcels. Finally, for multiple regions that evoked a clinical response during high frequency stimulation, we combined the connectivity of individual pairs using maximum intensity projection. Connectivity was assessed by applying SPES on 2094 contact pairs and recording CCEPs on 3580 contacts out of 8582 contacts of 660 electrodes implanted in 47 patients. Clinical responses elicited by high frequency stimulations in 107 sites (pairs of contacts) located in the cingulate cortex were divided in 10 groups: affective, motor behavior, motor elementary, versive, speech, vestibular, autonomic, somatosensory, visual and changes in body perception. Anterior cingulate cortex was shown to be connected to the mesial temporal, orbitofrontal and prefrontal cortex. In the middle cingulate cortex, we located affective, motor behavior in the anterior region, and elementary motor and somatosensory in the posterior part. This region is connected to the prefrontal, premotor and primary motor network. Finally, the posterior cingulate was shown to be connected with the visual areas, mesial and lateral parietal and temporal cortex. Image 1 • Multi-modal (effective, functional) connectivity evidences cingulate cortex network. • Connectivity maps for cingulate subregions highlight a rostro-caudal organization. • High-frequency stimulation of 107 sites elicited clinical responses. • Bi-modal connectivity maps for regions evoking specific clinical effects are created. [ABSTRACT FROM AUTHOR]