Belanger, C. | bioRxiv Science

bioRxiv2024

Information-based rhythmic transcranial magnetic stimulation accelerates learning during auditory working memory training.

Rhythmic transcranial magnetic stimulation (rhTMS) has been shown to enhance auditory working memory manipulation, specifically by boosting theta oscillatory power in the dorsal auditory pathway during task performance. It remains unclear whether these enhancements i) persist beyond the period of stimulation, ii) if they can accelerate learning and iii) if they would accumulate over several days of stimulation. In the present study, we investigated the lasting behavioural and electrophysiological effects of applying rhTMS over the left intraparietal sulcus (IPS) throughout the course of seven sessions of cognitive training on an auditory working memory task. Fourteen neurologically healthy participants took part in the training protocol with an auditory working memory task while being stimulated with either theta (5Hz) rhTMS or sham TMS. Electroencephalography (EEG) was recorded before, throughout five training sessions and after the end of training to assess to effects of rhTMS on behavioural performance and on oscillatory entrainment of the dorsal auditory network. We show that this combined approach enhances theta oscillatory activity within the fronto-parietal network and causes improvements in auditory working memory performance. We show that compared to individuals who received sham stimulation, cognitive training can be accelerated when combined with optimized rhTMS, and that task performance benefits can outlast the training period by up to 3 days. Furthermore, we show that there is increased theta oscillatory power within the recruited dorsal auditory network during training, and that sustained EEG changes can be observed up to 3 days following stimulation. The present study improves our understanding of the causal dynamic interactions supporting auditory working memory. Our results constitute an important proof of concept for the potential translational impact of non-invasive brain stimulation protocols and provide preliminary data for developing optimized rhTMS and training protocols that could be implemented in clinical populations.

neuroscience↗

bioRxiv2022

FAM172A controls the nuclear import and alternative splicing function of AGO2

The poorly characterized protein FAM172A is mutated in some individuals affected by a disorder of neural crest development called CHARGE syndrome. We also know that FAM172A can interact with the main CHARGE syndrome-associated protein CHD7 and the small RNA-binding protein AGO2 at the chromatin-spliceosome interface. Focusing on this intriguing FAM172A-AGO2 interaction, we now report that FAM172A is one of the long sought-after regulator of AGO2 nuclear import. This FAM172A function relies on its nuclear localization signal, being enhanced by CK2-mediated phosphorylation and abrogated by a CHARGE syndrome-associated missense mutation. Accordingly, Fam172a and Ago2 genetically interact in mice, and neural crest-specific depletion of Ago2 is sufficient to phenocopy CHARGE syndrome without impacting post-transcriptional gene silencing. Rapamycin-mediated rescue suggests that observed morphological anomalies are instead due to alternative splicing defects. This work thus demonstrates that non-canonical nuclear functions of AGO2 and associated regulatory mechanisms may be clinically relevant.

developmental biology↗