Single unit-derived connectivity networks in tuberous sclerosis complex reveal propensity for network hypersynchrony driven by tuber-tuber interactions

Network hypersynchrony is emerging as an important system-level mechanism underlying seizures, as well as cognitive and behavioural impairments, in children with structural brain abnormalities. We investigated patterns of single neuron action potential behaviour in 206 neurons recorded from tubers, transmantle tails of tubers and normal looking cortex in 3 children with tuberous sclerosis. The patterns of neuronal firing, on a neuron-by-neuron (autocorrelation) basis did not reveal any differences as a function of anatomy. However, at the level of functional networks (cross-correlation), there is a much larger propensity towards hypersynchrony of tuber-tuber neurons that in neurons from any other anatomical site. This suggests that tubers are the primary drivers of adverse outcomes in children with tuberous sclerosis. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This project was funded by a GOSH Childrens Charity Surgeon Scientist Fellowship (awarded to AC) and supported by the NIHR Great Ormond Street Biomedical Research Centre. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This prospective study was approved by the London-Brent Research Ethics Committee on behalf of the UK Health Research Authority (IRAS ID 255823). In line with UK law, the parents of all included patients provided informed consent for study participation. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Code used for this study is available at and data (the single unit spike trains after spike sorting, subsequent filters and networks) are available at .