Previous resting state functional magnetic resonance imaging (RS-fMRI) studies suggested that repetitive transcranial magnetic stimulation (rTMS) can modulate local activity in distant areas via functional connectivity (FC). A brain region has more than one connection with the superficial cortical areas. The current study proposed a multi-target focused rTMS protocol for indirectly stimulating a deep region, and to investigate 1) whether FC strength between stimulation targets (right middle frontal gyrus [rMFG] and right inferior parietal lobule [rIPL]) and effective region (dorsal anterior cingulate cortex [dACC]) can predict local activity changes of dACC and 2) whether multiple stimulation targets can focus on the dACC via FC. A total of 24 healthy participants received rTMS with two stimulation targets, both showing strong FC with the dACC. There were four rTMS conditions (>1 week apart, 10 Hz, 1800 pulses for each): rMFG-target, rIPL-target, Double-targets (900 pulses for each target), and Sham. The results failed to validate the multi-target focused rTMS hypothesis. But rMFG-target significantly decreased the local activity in the dACC. In addition, stronger dACC-rMFG FC was associated with a greater local activity change in the dACC. Future studies should use stronger FC to focus stimulation effects on the deep region.

BackgroundCrohn’s disease (CD) is characterized by repetitive phases of remission and exacerbation, the quality of life of patients with CD is strongly influenced by disease activity, as patients in the active phase experience significantly worse symptoms. To investigate the underlying mechanism of how the course of CD is exacerbated based on the bi-directionality of the brain-gut axis (BGA), we conducted a multi-modality neuroimaging study that combined resting-state functional magnetic resonance imaging (rs-fMRI) with proton magnetic resonance spectroscopy (MRS) to detect abnormalities in the anterior cingulate cortex (ACC).Materials and MethodsClinical scales including Visual Analog Scale (VAS) and Hospital Anxiety and Depression Scale (HADS) were used to evaluate the degree of abdominal pain and mood state of participants. We made a comparison between CD patients in the active phase, the remission phase and healthy controls (HCs), not only employed the innovative wavelet-transform to analyze the amplitude of low frequency fluctuation (ALFF) but also compared the sensitivity of wavelet-transform and the traditional fast Fourier transform (FFT). Brain metabolites such as glutamate (Glu), myo-inositol (mIns) and gamma-aminobutyric acid (GABA) were also detected. Then correlation analysis was made to see whether changes in the ACC correlated with CD’s clinical symptoms.ResultsCD patients in the active phase showed higher VAS scores (p = 0.025), the scores of anxiety and depression were also higher (all p < 0.05). Wavelet-transform is slightly more sensitive in the current research. Patients in the active phase exhibited higher ALFF in the left ACC and the left superior frontal gyrus, medial (SFGmed). Patients in the active phase showed increased Glu levels in the ACC than patients in the remission phase or HCs (p = 0.039 and 0.034 respectively) and lower levels of mIns than HCs (p = 0.036). There was a positive correlation between mWavelet-ALFF values of the ACC and HADS-depression scores in CD patients (r = 0.462, p = 0.006). Besides, concentrations of Glu positively correlated with mWavelet-ALFF in the ACC in all participants (r = 0.367, p = 0.006).ConclusionAbnormal spontaneous activity and metabolic levels in the ACC were detected in CD patients in the active phase along with severer abdominal pain and worse mood state, these may contribute to the exacerbation of CD. Therefore, the ACC might be a potential neural alternative for managing the exacerbation of CD.

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