Modulating spontaneous brain activity using repetitive transcranial magnetic stimulation

Abstract

Background: When no specific stimulus or task is presented, spontaneous fluctuations in brain activity occur. Brain regions showing such coherent fluctuations are thought to form organized networks known as 'resting-state' networks, a main representation of which is the default mode network. Spontaneous brain activity shows abnormalities in several neurological and psychiatric diseases that may reflect disturbances of ongoing thought processes. Information about the degree to which such spontaneous brain activity can be modulated may prove helpful in the development of treatment options. We investigated the effect of offline low-frequency rTMS on spontaneous neural activity, as measured with fMRI, using a sequential independent-component-analysis and regression approach to investigate local changes within the default mode network.

Results: We show that rTMS applied over the left dorsolateral prefrontal cortex results in distal changes of neural activity, relative to the site of stimulation, and that these changes depend on the patterns of brain network activity during 'resting-state'.

Conclusions: Whereas the proximal changes may reflect the off-line effect of direct stimulation of neural elements, the distal changes likely reflect modulation of functional connectivity.

Figure 1

Meaningful components from the independent component analysis across the 20 resting state acquisitions. The topmost component represents the DMN used for this analysis. Note that component D also represents the DMN, but slightly more posteriorly weighted.

Figure 2

Step-wise procedure and end result of the regression method. From the independent component representing the DMN, obtained with spatiotemporal group ICA (1), we used the subject-and-session specific timecourses (2) to reconstruct subject-specific 3D maps for the 10 subjects*2 sessions (3). As a verification, we calculated the group means of the sham and rTMS groups separately ('reconstructed IC4') and observed that the DMN-characteristic pattern of regional co-activations occurred in both groups, with an additional co-activation of the hippocampal and lateral temporal cortices after sham stimulation but not real stimulation (4). Upon formal testing, using groupwise within-subject component general linear modelling, the lateral temporal regions differed significantly between conditions, such that their activation was reduced after rTMS. The image is thresholded at z > 2.3, showing the extent of the reductions and subthreshold reductions in the bilateral hippocampus (5). The reverse contrast showed an increase in activation of the right caudate nucleus (not shown).