Abstract

Motor sequence learning (MSL) is supported by dynamical interactions between hippocampal and striatal networks that are thought to be orchestrated by the prefrontal cortex. In the present study, we tested whether individually-tailored theta-burst stimulation of the dorsolateral prefrontal cortex (DLPFC) prior to MSL can modulate multivoxel response patterns in the stimulated cortical area, the hippocampus and the striatum. Response patterns were assessed with multivoxel correlation structure analyses of functional magnetic resonance imaging data acquired during task practice and during resting-state scans before and after learning/stimulation. Results revealed that, across stimulation conditions, MSL induced greater modulation of task-related DLPFC multivoxel patterns than random practice. A similar learning-related modulatory effect was observed on sensorimotor putamen patterns under inhibitory stimulation. Furthermore, MSL as well as inhibitory stimulation affected (posterior) hippocampal multivoxel patterns at post-intervention rest. Exploratory analyses showed that MSL-related brain patterns in the posterior hippocampus persisted into post-learning rest preferentially after inhibitory stimulation. These results collectively show that prefrontal stimulation can alter multivoxel brain patterns in deep brain regions that are critical for the MSL process. They also suggest that stimulation influenced early offline consolidation processes as evidenced by a stimulation-induced modulation of the reinstatement of task pattern into post-learning wakeful rest.

Highlights

  • Motor sequence learning (MSL) is supported by dynamical interactions between hippocampal and striatal networks that are thought to be orchestrated by the prefrontal cortex

  • Cortico-striatal and cortico-hippocampal networks have received particular attention and research has shown that the interaction between these systems - thought to be mediated by the dorsolateral prefrontal cortex (DLPFC) - is critical for the learning and retention of motor s­ equences[4,6,7]

  • We examined the effect of task and stimulation conditions on the task- and resting-state-related multivoxel patterns in four regions of interest (ROIs: DLPFC, hippocampus, associative putamen and sensorimotor putamen)

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Summary

Material and methods

The research presented in this manuscript is part of a larger experimental protocol (see Supplemental Fig. S1 for the full design). RS fMRI data were acquired during the baseline session as well as during the four experimental sessions preTBS and post-task with an ascending gradient EPI pulse sequence for T2*-weighted images (TR/TE = 1000/33 ms; multiband factor 3; flip angle = 80°; 42 transverse slices; interslice gap = 0.5 mm; voxel size = 2.15 × 2.14 × 3 ­mm[3]; FoV = 240 × 240 × 146.5 ­mm[3]; matrix = 112 × 110; 300 dynamic scans). Task-related fMRI data were acquired in each experimental session with an ascending gradient EPI pulse sequence for T2*-weighted images (TR/TE = 2000/29.8 ms; multiband factor 2; flip angle = 90°; 54 transverse slices; interslice gap = 0.2 mm; voxel size = 2.5 × 2.5 × 2.5 ­mm[3]; FoV = 210 × 210 × 145.6 ­mm[3]; matrix = 84 × 82; 345.09 ± 22.37 dynamical scans). Results surviving false-discovery-rate ­(FDR61) correction for multiple comparisons are indicated with an asterisk in the corresponding tables

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