RT Journal Article SR Electronic T1 Human periventricular nodular heterotopia shows several interictal epileptic patterns, associated with hyperexcitability of neuronal firing JF bioRxiv FD Cold Spring Harbor Laboratory SP 816173 DO 10.1101/816173 A1 Valerio Frazzini A1 Stephen Whitmarsh A1 Katia Lehongre A1 Pierre Yger A1 Jean-Didier Lemarechal A1 Bertrand Matching A1 Claude Adam A1 Dominique Hasboun A1 Virginie Lambrecq A1 Vincent Navarro YR 2022 UL http://biorxiv.org/content/early/2022/05/05/816173.abstract AB Periventricular nodular heterotopia (PNH) is a malformation of cortical development that frequently causes drug-resistant epilepsy. The epileptogenicity of ectopic neurons in PNH as well as their role in generating interictal and ictal activity is still a matter of debate. We report the first in vivo microelectrode recording of heterotopic neurons in humans. Highly consistent interictal patterns (IPs) were identified within the nodules: 1) Periodic Discharges PLUS Fast activity (PD+F), Sporadic discharges PLUS Fast activity (SD+F), and 3) epileptic spikes (ES). Neuronal firing rates were significantly modulated during all IPs, suggesting that multiple IPs were generated by the same local neuronal populations. Furthermore, firing rates closely followed IP morphologies. Among the different IPs, SD+FA pattern was found only in the three nodules that were actively involved in seizure generation, but was never observed in the nodule that did not take part in ictal discharges. On the contrary, PD+F and ES were identified in all nodules. Units that were modulated during the IPs were also found to participate in seizures, increasing their firing rate at seizure onset and maintaining an elevated rate during the seizures. Together, nodules in PNH are highly epileptogenic, and show several IPs that provide promising pathognomonic signatures of PNH. Furthermore, our results show that PNH nodules may well initiate seizures.HighlightsFirst in vivo microelectrode description of local epileptic activities in human PNHRecordings revealed multiple microscopic epileptic interictal patternsFiring rates of all detected units were significantly modulated during all interictal patternsSeizures recruited the same units that are involved in interictal activityCompeting Interest StatementThe authors have declared no competing interest.