Effects of repetitive transcranial magnetic stimulation combined with cognitive training on resting-state brain activity in Alzheimer's disease.

OBJECTIVES

Repetitive transcranial magnetic stimulation (rTMS) is a promising tool to modulate brain plasticity, but the neural basis has been little addressed. The purpose was to investigate the effects of rTMS on resting-state brain activity in patients with Alzheimer's disease (AD).

METHODS

Seventeen patients with mild or moderate AD were enrolled and randomly divided into one of the two intervention groups: (1) real rTMS combined with cognitive training (real group, = 9); (2) sham rTMS with cognitive training (sham group, = 8). 10 Hz rTMS was used to stimulate the left dorsolateral prefrontal cortex and then the left lateral temporal lobe for 20 min each day for 4 weeks. Each patient underwent neuropsychological assessment and resting-state functional magnetic resonance imaging (rsfMRI) before and after treatment. The fractional amplitude of low frequency fluctuation (fALFF) of rsfMRI data in real group were: (1) compared to sham; (2) correlated with rTMS-induced cognitive alterations.

RESULTS

Significantly increased fALFF in right cerebellum/declive, left lingual/cuneus and left cingulate gyrus, as well as decreased fALFF in left middle frontal gyrus were found after 10 Hz rTMS, but not after sham stimulation. Using these suprathreshold regions, we found that rTMS increased functional connectivity between the right cerebellum/declive and left precentral/postcentral gyrus. The fALFF increase in left lingual/cuneus and right cerebellum/declive was associated with significant improvement in cognitive function.

CONCLUSIONS

rTMS combined with cognitive training induced increased low frequency fluctuation neural oscillations and functional connectivity in brain regions subserving cognition, suggesting a possible neuronal mechanism of the beneficial effects of rTMS.