Dynamic Functional Connectivity Within the Fronto-Limbic Network Induced by Intermittent Theta-Burst Stimulation: A Pilot Study

Abstract

PurposeThe utility of transcranial magnetic stimulation (TMS) has been growing rapidly in both neurocognitive studies and clinical applications in decades. However, it remains unclear how the responses of the stimulated site and the site-related functional network to the external TMS manipulation dynamically change over time.MethodsA multi-session combining TMS-fMRI experiment was conducted to explore the spatiotemporal effects of TMS within the fronto-limbic network. Ten healthy volunteers were modulated by intermittent theta-burst stimulation (iTBS) at a precise site within the left dorsolateral prefrontal cortex (DLPFC, MNI coordinate [-44 36 20]), navigated by individual structural MRI image. Three-session resting-state fMRI images were acquired before iTBS (TP1), immediately after iTBS (TP2), and 15 min after iTBS (TP3) for each participant. Seventy-four regions of interests (ROIs) within the fronto-limbic network were chosen including the bilateral superior frontal gyrus (SFG), middle frontal gyrus (MidFG), inferior frontal gyrus (IFG), orbital gyrus (OrG), cingulate gyrus (CG), and subcortical nuclei (hippocampus and amygdala). Regional fractional amplitude of low-frequency fluctuation (fALFF) and ROI-to-ROI functional connectivity (FC) were compared among TP1, TP2, and TP3.ResultsThe immediate iTBS effect was observed at the stimulated site. FC between the left dorsolateral SFG and left dorsal IFG and between the left rostral IFG and right MidFG increased at TP2 as compared to at TP1 (all FDR-p < 0.05), while FC within the left OrG decreased. The relatively long-term iTBS effect transmitted with decreased FC between the left IFG and right amygdala, increased FC between the left MidFG and left OrG, and decreased FC between bilateral IFG and OrG at TP3 than at TP1 (all FDR-p < 0.05). Meanwhile, mean fALFF values over the left SFG, MidFG, ventral CG, and IFG were significantly increased at TP3 as compared to those at TP2 (all p < 0.05 with Bonferroni correction).ConclusionBy combining TMS and fMRI, it becomes possible to track the spatiotemporal dynamics of TMS after-effects within the fronto-limbic network. Our findings suggested that the iTBS effect dynamically changed over time from the local neural activation at the stimulated site to its connected remote regions within the fronto-limbic network.

Hippocampal and striatal responses during motor learning are modulated by prefrontal cortex stimulation

“…This is partly in line with the available literature as there is, to our knowledge, no report of prefrontal-stimulation induced modulation of hippocampal activity [but see ( Kim et al, 2018 ; Hermiller et al, 2020 ; Thakral et al, 2020 ) for parietal-stimulation-induced modulation of hippocampal activity] and only a few observations of activity changes in the striatum ( Ott et al, 2011 ; van Holstein et al, 2018 ). This stands in contrast with extensive evidence of prefrontal-stimulation-induced modulation of functional connectivity, in particular between the cortical target and deeper brain regions ( van der Werf et al, 2010 ; Bilek et al, 2013 ; Esslinger et al, 2014 ; Alkhasli et al, 2019 ; Shang et al, 2019 ; Tang et al, 2019 ). Together with these earlier observations, our results suggest that prefrontal stimulation can modulate connectivity patterns of the target and deeper brain regions without inducing changes in activity levels.…”

Hippocampal and striatal responses during motor learning are modulated by prefrontal cortex stimulation

“…Previous research investigating the effect of DLPFC stimulation on brain activity at rest or during task-practice has reported significant effects on the brain responses in the stimulated area itself as well as in widespread networks including various cortical areas (motor, frontal, parietal, cingulate, temporal, insula), the cerebellum and deep regions including the striatum and the hippocampus (Esslinger et al, 2014;Gratton, Lee, Nomura, & D'Esposito, 2014;Hanlon et al, 2013Hanlon et al, , 2016Rounis et al, 2006;Shang et al, 2019;Tang et al, 2019;van der Werf et al, 2010;Xue et al, 2017). Our results indicate that facilitatory iTBS, as compared to inhibitory cTBS, applied prior to motor sequence learning, as compared to random, induced greater task-related activity in the cerebellum and the parietal cortex as well as in frontal areas nonoverlapping with the TBS target.…”

Clinical Response of Major Depressive Disorder Patients With Suicidal Ideation to Individual Target-Transcranial Magnetic Stimulation

“…Only a few treatment options are available for suicidal ideation (e.g., lithium, Emission Computed Tomography) and are only partially effective (6). Individual target-transcranial magnetic stimulation (IT-TMS) represents an original tool that opens new avenues in the treatment of mental disorders, especially MDD (7). However, the clinical responses and neural networks of patients with MDD and SI are unclear.…”