Modulation of a brain-behavior relationship in verbal working memory by rTMS.

We investigated whether the brain-behavior relationship (BBR) between regional cerebral blood flow (rCBF) as measured by positron emission tomography (PET) and individual accuracy in verbal working memory (WM) can be modulated by repetitive transcranial magnetic stimulation (rTMS) of the left or right middle frontal gyrus (MFG). Fourteen right-handed male subjects received a 30-s rTMS train (4 Hz, 110% motor threshold) to the left or right MFG during a 2-back WM task using letters as stimuli. Simultaneously an rCBF PET tracer was injected and whole-brain functional images were acquired. A hypothesis-driven region-of-interest-analysis of the left and right MFG BBR as well as an explorative whole-brain analysis correlating the individual accuracy with rCBF was carried out. Without rTMS we found a negative BBR in the left but no significant BBR in the right MFG. This negative BBR is best explained by an increased effort of volunteers with an inferior task performance. Left-sided rTMS led to a shift of the BBR towards the superior frontal gyrus (SFG) and to a positive BBR in anterior parts of the left SFG. With rTMS of the right MFG the BBR was posterior and inferior in the left inferior frontal gyrus. Beyond the cognitive subtraction approach this correlation analysis provides information on how the prefrontal cortex is involved based on individual performance in working memory. The results are discussed along the idea of a short-term plasticity in an active neuronal network that reacts to an rTMS-induced temporary disruption of two different network modules.