Low-Frequency TMS Results in Condition-Related Dynamic Activation Changes of Stimulated and Contralateral Inferior Parietal Lobule

Abstract

Non-invasive brain stimulation is a promising approach to study the causal relationship between brain function and behavior. However, it is difficult to interpret behavioral null results as dynamic brain network changes have the potential to prevent stimulation from affecting behavior, ultimately compensating for the stimulation. The present study investigated local and remote changes in brain activity via functional magnetic resonance imaging (fMRI) after offline disruption of the inferior parietal lobule (IPL) or the vertex in human participants via 1 Hz repetitive transcranial magnetic stimulation (rTMS). Since the IPL acts as a multimodal hub of several networks, we implemented two experimental conditions in order to robustly engage task-positive networks, such as the fronto-parietal control network (on-task condition) and the default mode network (off-task condition). The condition-dependent neural after-effects following rTMS applied to the IPL were dynamic in affecting post-rTMS BOLD activity depending on the exact time-window. More specifically, we found that 1 Hz rTMS applied to the right IPL led to a delayed activity increase in both, the stimulated and the contralateral IPL, as well as in other brain regions of a task-positive network. This was markedly more pronounced in the on-task condition suggesting a condition-related delayed upregulation. Thus together, our results revealed a dynamic compensatory reorganization including upregulation and intra-network compensation which may explain mixed findings after low-frequency offline TMS.

Keywords: default mode network; fronto-parietal control network; functional magnetic resonance imaging; functional reorganization; inferior parietal lobe; intra-network compensation; offline TMS.

FIGURE 1

(A) Experimental procedure (B) task fMRI consisting of external attention condition (Simon task) and internal attention condition.

FIGURE 2

Activation changes over time: Brain regions showing increasing condition-unspecific activity over time after rTMS administered to the right AG compared to vertex. (A) For visualization purposes all images are thresholded at voxel level p = 0.001 uncorrected with red color denoting suprathreshold activation. The ROI centered on the stimulation site in right angular gyrus is indicated by the yellow circle. (B) Left and right AG peak coordinates for interaction of stimulation and time. AG: angular gyrus. SEM: standard error of the mean ^∗ denotes p < 0.05, ^∗∗ denotes p < 0.01 ^∗∗∗ denotes p < 0.005.

FIGURE 3

Condition-related activation changes over time. (A) Brain regions showing increasing condition-related activity over time after 1 Hz rTMS applied to the right AG compared to vertex. Yellow circle denotes left and right angular gyrus ROIs (12 mm). For visualization purposes all images are thresholded at voxel level p = 0.001 uncorrected. (B) Interaction of stimulation × time × condition displayed at the left and right AG peak coordinates. (C) Interaction of stimulation × time × condition, displayed at preSMA and MFG peaks as identified for showing a compatibility effect. AG: angular gyrus. MFG: middle frontal gyrus. PreSMA: pre-supplementary motor area. SEM: standard error of the mean. ^∗ denotes p < 0.05, ^∗∗ denotes p < 0.01, ^∗∗∗ denotes p < 0.005.