Hippocampal and striatal responses during motor learning are modulated by prefrontal cortex stimulation

While it is widely accepted that motor sequence learning (MSL) is supported by a prefrontal-mediated interaction between hippocampal and striatal networks, it remains unknown whether the functional responses of these networks can be modulated in humans with targeted experimental interventions. The present proof- of-concept study employed a comprehensive multimodal neuroimaging approach, including functional magnetic resonance (MR) imaging and MR spectroscopy, to investigate whether individually-tailored theta-burst stimulation of the dorsolateral prefrontal cortex can modulate responses in the hippocampus and striatum during motor learning. Our results indicate that stimulation influenced task-related connectivity patterns within hippocampo-frontal and striatal networks. Stimulation also altered the relationship between the levels of gamma-aminobutyric acid (GABA) in the stimulated prefrontal cortex and learning-related changes in both activity and connectivity in fronto-striato-hippocampal networks. This study provides the first experimental evidence that brain stimulation can alter motor learning-related functional responses in the striatum and hippocampus.