Causal evidence supporting functional dissociation of verbal and spatial working memory in the human dorsolateral prefrontal cortex.

The human dorsolateral prefrontal cortex (dlPFC) is crucial for monitoring and manipulating information in working memory, but whether such contributions are domain-specific remains unsettled. Neuroimaging studies have shown bilateral dlPFC activity associated with working memory independent of the stimulus domain, but the causality of this relationship cannot be inferred. Repetitive transcranial magnetic stimulation (rTMS) has the potential to test whether the left and right dlPFC contribute equally to verbal and spatial domains; however, this is the first study to investigate the interaction of task domain and hemisphere using offline rTMS to temporarily modulate dlPFC activity. In separate sessions, 20 healthy right-handed adults received 1 Hz rTMS to the left dlPFC and right dlPFC, plus the vertex as a control site. The working memory performance was assessed pre-rTMS and post-rTMS using both verbal-'letter' and spatial-'location' versions of the 3-back task. The response times were faster post-rTMS, independent of the task domain or stimulation condition, indicating the influence of practice or other nonspecific effects. For accuracy, rTMS of the right dlPFC, but not the left dlPFC or vertex, led to a transient dissociation, reducing spatial, but increasing verbal accuracy. A post-hoc correlation analysis found no relationship between these changes, indicating that the substrates underlying the verbal and spatial domains are functionally independent. Collapsing across time, there was a trend towards a double dissociation, suggesting a potential laterality in the functional organisation of verbal and spatial working memory. At a minimum, these findings provide human evidence for domain-specific contributions of the dlPFC to working memory and reinforce the potential of rTMS to ameliorate cognition.