Simultaneous tDCS-rTMS stimulation to regulate the language network and improve language ability in Landau–Kleffner syndrome

Landau–Kleffner syndrome (LKS) is a rare epileptic syndrome causing language regression. In this preliminary study, we investigated the effects of simultaneous transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (rTMS) on LKS patients and the underlying mechanism based on magnetoencephalography (MEG) network analysis. Three LKS patients were included, all receiving daily stimulation for 15 days in 3 weeks, with MEG data collected to determine stimulation target and measure functional connectivity through normalized phase transfer entropy (PTE). The primary clinical outcome was measured through the Peabody Picture Vocabulary Test. Two patients with clustered spike dipoles in the right inferior parietal lobe (IPL) showed profound clinical improvement after stimulation. PTE analysis showed increased dorsal pathway information flow, mainly in the left hemisphere, and increased ventral pathway information flow in both hemispheres. This study preliminarily showed that tDCS-rTMS was safe to undergo and likely to improve language function in LKS patients. Stimulating the right IPL not only affects the right hemisphere language network but also profoundly affects the left hemisphere network that participates in language perception, processing, and understanding. The dynamic balance of the language network connections was reconstructed, which may be associated with improved language function in LKS. Plain Language Summary: Due to the lack of effective long-term treatment options, we investigated the effects of transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (rTMS) on language function in Landau–Kleffner syndrome (LKS) patients and the possible therapeutic mechanism by magnetoencephalography network analysis. Three LKS patients were included. We found tDCS-rTMS improved language function without side effects in two of the patients whose stimulation target was the right inferior parietal lobe, possibly due to significantly enhanced information flow in bilateral language streams, indicating modulated language network connections. Thus, we preliminarily proved the safety and effectiveness of tDCS-rTMS and unveiled underlying network mechanisms.