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Abstract

Semantic cognition is central to communication and our understanding of the world. It is usually well preserved in healthy aging. However, semantic control processes, which guide semantic access and retrieval, decline with age. On the neural level, the network of semantic control is multidimensional, consisting of domain-specific control, such as the retrieval of less salient conceptual features, and domain-general control, which supports general selection and inhibition mechanisms. The present neuroimaging study explored the potential of intermittent theta-burst stimulation (iTBS) to enhance semantic cognition in a group of healthy middle-aged to older adults (n = 30; mean age: 61.6, SD: 7.64, range: 45–74 years). We applied effective and sham iTBS to the pre-supplementary motor area (pre-SMA), an area of semantic but also domain-general control, and assessed the effect of stimulation using a semantic judgement and a tone judgement task as control task during functional magnetic resonance imaging. Results showed stronger activation after effective relative to sham stimulation only for the semantic task. We found increased activation in bilateral visual networks, right middle temporal gyrus, and left superior parietal and temporal lobes, but no changes at the stimulation site. Surprisingly, increased activation was indicative of poorer semantic performance. Using generalized psychophysiological interaction analysis, we explored functional connectivity between the stimulation site and upregulated clusters. Stronger connectivity between the pre-SMA and a cluster in the dorsal attention network after effective iTBS was associated with faster performance in the most demanding semantic condition. Overall, our findings indicate differential effects of iTBS on activation and connectivity. Further, we show that iTBS modulates networks in a task-dependent manner and generates effects at regions distal to the stimulation site. Finally, stimulating the pre-SMA was associated with more efficient but not better performance, which was reflected in connectivity increases, confirming its role in semantic control processes.