Decreased set-shifting performance, neural activity, and neural connectivity after inhibiting repetitive transcranial magnetic stimulation on the left dorsal prefrontal cortex

Sub-optimal functioning of the dorsal prefrontal cortex is associated with executive dysfunction, such as set-shifting deficits, in neurological and psychiatric disorders. We tested this hypothesis by investigating the effect of low-frequency 'inhibiting' off-line repetitive transcranial magnetic stimulation (rTMS) on the left dorsal pre-frontal cortex on behavioural performance, neural activity, and network connectivity during the performance of a set-shifting paradigm in healthy elderly (mean age 50+). Behaviourally, we found a group-by-session interaction for errors on set-shift trials, where the verum, compared with sham, group made trend-significantly more errors on the second session, but not on the first. In addition, the verum group, when compared with the sham group, displayed reduced task-related activity in the left temporal gyrus, and reduced task-related connectivity of the left PFC with the left postcentral gyrus and posterior insula. These results show that low-frequency off-line rTMS on the left dorsal PFC resulted in decreased task performance, task-related activity, and network connectivity, thus providing causal evidence for the importance of an optimally functioning PFC in set-shifting.