The Dynamic Interaction between Procedural Learning and Resting-State Functional Connectivity in Self-Limited Focal...

The functional brain networks related to procedural learning (PL) have never been explored in children with self-limited focal epilepsies of childhood (SeLFE), despite their role in the development of various sequence-related sensorimotor, language, and cognitive abilities that are impaired in this clinical population. Our study fills this gap by investigating PL and its interaction with the rapid reorganisation of resting-state functional connectivity (rsFC) in SeLFE. A serial reaction time task, preceded and followed by resting-state magnetoencephalography (MEG) recordings, was used to assess PL in 10 children with SeLFE and 28 age-, sex- and IQ-matched typically developing (TD) children. Pre- to post-learning rsFC changes were estimated using band-limited power envelope correlation, after regressing interictal epileptic discharges (IEDs) in SeLFE patients. rsFC maps were compared between groups and correlated with PL and IED frequency. Compared to TD peers, children with SeLFE showed atypical pre- to post-learning rsFC changes within widespread antero-posterior brain networks in theta, alpha and low beta bands, as well as reduced PL performance negatively correlated with sleep IED frequency. This MEG study is the first to demonstrate reduced PL abilities combined with atypical post-learning reorganisation of rsFC in children with SeLFE compared to TD peers. These results suggest that the pathophysiology of SeLFE, including the chronic repetition of IEDs during sleep across development, have a detrimental impact on the acquisition of PL brain-behaviour processes in these patients.