Facilitatory stimulation of the pre-SMA enhances semantic cognition via remote network effects on task-based activity and connectivity

BackgroundThe continuous decline of executive abilities with age is mirrored by increased neural activity of domain-general networks during task processing. So far, it remains unclear how much domain-general networks contribute to domain-specific processes such as language when cognitive demands increase. The current neuroimaging study explored the potential of intermittent theta-burst stimulation (iTBS) over a domain-general hub to enhance executive and semantic processing in healthy middle-aged to older adults. MethodsWe implemented a cross-over within-subject study design with three task-based neuroimaging sessions per participant. Using an individualized stimulation approach, we stimulated each participant once with effective and once with sham iTBS over the pre-supplementary motor area (pre-SMA), a region of domain-general control. Subsequently, task-specific stimulation effects were assessed in functional MRI using a semantic and a non-verbal executive task with varying cognitive demand. ResultsEffective stimulation increased activation relative to sham stimulation only during semantic processing in visual and dorsal attention networks. Further, iTBS induced increased functional connectivity in task-specific networks for semantic and executive conditions with high cognitive load. Notably, stimulation-induced changes in activation and connectivity related differently to behavior: While increased activation of the parietal dorsal attention network was linked to poorer semantic performance, its enhanced coupling with the pre-SMA was associated with more efficient semantic processing. ConclusionsiTBS modulates networks in a task-dependent manner and generates effects at regions remote to the stimulation site. These neural changes are linked to more efficient semantic processing, which underlines the general potential of network stimulation approaches in cognitive aging.