Dynamic reconfiguration of aperiodic brain activity supports cognitive functioning in epilepsy: a neural fingerprint identification

Background Temporal lobe epilepsy (TLE) is characterized by alterations of brain dynamic at large scale associated with altered cognitive functioning. Interindividual variability of brain activity is a source of heterogeneity in this disorder. Here, we aimed at analyzing dynamical reconfiguration of brain activity, using the neural fingerprint approach, to delineate subject-specific characteristics and their cognitive correlates in TLE. Methods We collected 10 minutes of resting state electroencephalography (128 channels), free from epileptiform activity, from 68 TLE patients and 34 healthy controls. The functional network was defined by the spatio-temporal spreading, across cortical regions, of aperiodic bursts of activations (neuronal avalanches). This metric allowed encapsulating brain reconfiguration patterns into the avalanche transition matrix (ATM). We used a neural fingerprint approach to differentiate across controls and patients diagnosis, linking altered brain dynamic with cognitive outcome. Findings Patients’ brain dynamics were more stereotyped as compared to controls. The neural fingerprint using ATMs differentiated, in a data-driven fashion, patients with respect to healthy controls, being sensitive not only to the pathology but also to the subtype (unilateral vs. bilateral TLE). Notably, in unilateral TLE patients, a better memory performance was associated with a larger similarity of the brain dynamic configuration with controls. Interpretation TLE is characterized by reduced variability and more stereotyped brain dynamics, implicating widespread alterations across the brain. These alterations correlate with cognitive function in patients with unilateral TLE. This study underscores the utility of brain fingerprinting in elucidating disease-specific brain dynamics, offering novel metrics for personalized patient care. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Fundings: European Union “NextGenerationEU”, (Investimento 3.1.M4. C2), project IR0000011, EBRAINS-Italy of PNRR. Funds for biomedical research of the Italian Ministry of Health: Ricerca Corrente 2024. ### 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: Ethics committee "Comitato Etico Area Nord Veneto" waived ethical approval for this work (number protocol: 0001878/24). 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 The data that support the findings of this study are available on request to the corresponding author. The raw data are not publicly available due to privacy or ethical restrictions.