Low intensity rTMS in adolescent mice affects visuomotor behaviour with no impact on visual topography

Abstract

Background

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique used as a therapeutic and experimental tool. It is FDA-approved for treating major depressive disorder in adults and has an excellent safety profile. rTMS is less well characterised in children but was recently approved as an augmentative treatment in adolescents (15–21 years). However, the adolescent brain is still undergoing structural and functional changes and the effect of rTMS on neurodevelopment is not understood.

Objective

In the present study we used a mouse model to assess the impact of low intensity (perifocal) rTMS (LI-rTMS) in the developing brain on visual system organisation and associated behavioural outcomes.

Methods

We used miniature coils to deliver LI-rTMS to the primary visual cortex (V1) in mice aged 28 days (∼12 human years), every day for two weeks (biomimetic high frequency stimulation, 10 min). We measured anatomical organisation of the corticocollicular and geniculocortical visual pathways, visuomotor behaviour, as well as V1 expression of markers of inhibition, excitation and inflammation (astrocytes and microglia) in LI-rTMS and sham treated groups.

Results

LI-rTMS did not alter the organisation of visual pathways, excitatory/inhibitory balance or cause overt inflammation in the brain but did result in a mild deficit in visuomotor behaviour. Our results suggest that LI-rTMS delivered during development may have network-wide effects impacting sensorimotor integration.

Conclusion

While we cannot rule out that changes in functional connectivity might be transient and/or beneficial in a disease context, our findings highlight that more clinical and preclinical studies are needed to validate the safety and mechanism of action of rTMS for children and adolescents.