Multi-Target Focused RTMS:Modulating The Dorsal Anterior Cingulate Cortex

IntroductionRepetitive transcranial magnetic stimulation(r TMS)is a non-invasive neuromodulation technique.The magnetic field of figure-8 coil TMS can only reach a depth of 2-4 cm from the scalp and cannot directly stimulate the deep brain area.In 2014,Wang et al.found that r TMS on the lateral parietal cortex modulated the activity of hippocampus network via functional connectivity(FC),thereby improving the performance of the memory task.But such studies used only a single cortical target to modulate a deep region of the brain.In fact,any deep brain region can functionally link to multiple superficial cortices.Therefore,we hypothesized that stimulating multiple cortical targets can induce a focused effect on the same deep brain region through the related functional network.We name this hypothesis as "multi-target focused r TMS"(MTF-r TMS).The dorsal anterior cingulate cortex(d ACC)is a key node of the cingulofrontal-parietal(CFP)cognitive/attention network,and also a widely reported abnormal brain region for attention deficit hyperactivity disorder(ADHD).In the present study,two superficial cortices,i.e.,the frontal and parietal cortex of the CFP network were employed as r TMS stimulation targets and the local activity of the d ACC as an index of modulation effect of r TMS to verify the hypothesis of “MTF-r TMS”.Material and MethodsThere were 2 experiments in the current research.The purpose of Experiment-1 was to verify deep brain effective region and stimulation targets at the group level.The results of Experiment-1 were used to guide individual precise localization of the effective region and stimulation targets in Experiment-2.Experiment-1 included 7 participants.The effective region(d ACC)was defined in the activation in the d ACC by using Eriksen flanker task at the group level.The activation peak was taken as a seed,and then seed-based FC was performed.The right middle frontal gyrus(r MFG)and the right inferior parietal lobule(r IPL)showed significant FC with the d ACC.The r MFG and r IPL were defined as masks of stimulation targets,which were used to guide the definition of stimulation targets(frontal targets and parietal targets in subsequent Experiment-2)at the individual level.In the Experiment-2,twenty-four healthy young participants were enrolled.First,Eriksen flanker task functional magnetic resonance imaging was used to determine the individualize peak activation in the d ACC,which was defined as a seed for the whole-brain FC.The FC peak voxel in the r MFG and r IPL was taken as a stimulation target,respectively.Each subject underwent four 10 Hz r TMS sessions,i.e.,the r MFG-target,r IPL-target,Double-targets,and Sham.For the r MFG-target and r IPL-target conditions,1800 r TMS pulses were delivered to the individual stimulation target in the r MFG and r IPL separately.For the Double-targets condition,900 pulses were delivered to each of the r MFG and the r IPL,with the counterbalanced order across participants.The r TMS pulses in the Sham condition were the same as those in the Double-targets condition,but not a real stimulation.Resting-state f MRI(RSf MRI)was scanned before and after r TMS.One target was stimulated for one visit.The interval of two visits was at least one week.We compared the local brain activity in the effective region(d ACC)via mean percent low-frequency amplitude(m Per AF)and mean regional homogeneity(m Re Ho)in a spherical region of interest in each of the effective region(i.e.,d ACC)and the two stimulation targets(i.e.,r MFG and r IPL).The FC between the effective region and stimulation targets were also calculated.We were first interested in the change of local activity and FC.Thus,one-way repeated ANOVA was performed among the four conditions.And then,we compared simple effects.ResultsOne-way ANOVA did not find significant differences in any ROIs(d ACC,r MFG,and r IPL)among the four conditions(r MFG-target,r IPL-target,Doubletargets,and Sham)for either the local activity change nor the FC change.However,paired t-tests(post-r TMS vs.pre-r TMS)found that local brain activity in the effective region(d ACC)significantly decreased in m Per AF(t =-2.124,p = 0.045)and m Re Ho(t =-3.389,p = 0.003)after the r MFG-target stimualtion.FC change between effective region and stimulation targets(i.e.FC d ACC-r MFG and FC d ACC-r IPL)did not find any significant difference among means(F = 0.602,p = 0.612).In the case of r MFG-target,the pre-r TMS FC of d ACC-r MFG significantly predict the local brain activity change(m Per AF r =-0.452,p = 0.026;m Re Ho r =-0.438,p = 0.003)in the effective region.ConclusionsAlthough this current study failed to prove the MTF-r TMS hypothesis,we found that the r MFG-target condition modulated the local activity of the effective region(i.e.,the d ACC).Moreover,the FC between the superficial(r MFG)stimulation target and the deep effective region(d ACC)can predict the changes of the local activity.To further to testify the MTF-r TMS hypothesis,future studies should use other parameters,e.g.,another stimulation target together with r MFG,or difference stimulation frequencies.If the MTF-r TMS hypothesis is proved,it will be helpful to r TMS treatment of various brain disorders.