Abstract
While repetitive transcranial magnetic stimulation (rTMS) is widely used to treat psychiatric disorders, innovations are needed to improve its efficacy. An important limitation is that while psychiatric disorders are associated with fronto-limbic dysregulation, rTMS does not have sufficient depth penetration to modulate affected subcortical structures. Recent advances in task-related functional connectivity provide a means to better link superficial and deeper cortical sources with the possibility of increasing fronto-limbic modulation to induce stronger therapeutic effects. The objective of this pilot study was to test whether task-related, connectivity-based rTMS could modulate amygdala activation through its connectivity with the medial prefrontal cortex (mPFC). fMRI was collected to identify a node in the mPFC showing the strongest connectivity with the amygdala, as defined by psychophysiological interaction analysis. To promote Hebbian-like plasticity, and potentially stronger modulation, 5 Hz rTMS was applied while participants viewed frightening video-clips that engaged the fronto-limbic network. Significant increases in both the mPFC and amygdala were found for active rTMS compared to sham, offering promising preliminary evidence that functional connectivity-based targeting may provide a useful approach to treat network dysregulation. Further research is needed to better understand connectivity influences on rTMS effects to leverage this information to improve therapeutic applications.
Highlights
Repetitive transcranial magnetic stimulation is a non-invasive brain stimulation approach that uses rapidly changing magnetic fields to modulate neuronal activity underneath a stimulating coil. repetitive transcranial magnetic stimulation (rTMS) is approved by the U.S Food and Drug Administration as a therapy for treatment-resistant depression and obsessive compulsive disorders and has been proposed as a potential treatment for patients with posttraumatic stress disorders (PTSD)
This approach has been used successfully to modulate hippocampus [21], insula [22,23] and amygdala [24]. Such studies have demonstrated that “connectivity-based” rTMS may provide a promising approach to modulate deep brain regions, which is highly relevant when using rTMS as a treatment for psychiatric disorders that are hypothesized to primarily stem from fronto-limbic dysfunction. We explore these possibilities by implementing task-related functional connectivity-based rTMS to test for blood oxygen level dependent (BOLD) and connectivity changes due to stimulation
Stimulation was found with stronger connectivity after Active compared to Sham rTMS (Figure 6B) and a significant interaction between Timing and Stimulation (Figure 6C). To better understand these effects, t-tests were performed on each visit separately. These analyses demonstrated that the connectivity pattern was reversed during th1e0 soef c1-4 ond visit, by switching from a negative connectivity between the right amygdala and the whole brain, during the first visit (Figure 7A) to a positive connectivity on the second visit (vFiisgitu(rFeig7Bu)r.eW7Bh)e. nWchoemnpcaorminpgatrhinegeftfheectesffoefctAscotfivAecatinvde SahnadmShraTmMSrTiMn VS iisnitV2i,sit 2w, aitswobassoebrsveerdvtehdaththaet stehecsheanchgeasnwgeesrewdeure tdouienctoreianscerdeafusendctfiounaclticoonnanleccotinvniteyctfirvoimtyAfrcotmiveArTctMivSe troTtMheS sttoimthuelastiemdulelaftemdPleFfCt m(FPigFuCre(F7iCgu).re 7C)
Summary
Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation approach that uses rapidly changing magnetic fields to modulate neuronal activity underneath a stimulating coil. rTMS is approved by the U.S Food and Drug Administration as a therapy for treatment-resistant depression and obsessive compulsive disorders and has been proposed as a potential treatment for patients with posttraumatic stress disorders (PTSD). As reported in a recent comprehensive review [1], 13 studies have been published that attempt to test rTMS effects on PTSD symptoms and/or pathophysiology. These studies demonstrate significant, but modest PTSD symptom improvements from rTMS treatment. In a systematic review of 33 studies with baseline and post-rTMS measures of fMRI resting-state functional connectivity, it has been found that rTMS can induce significant changes in brain connectivity that spread both within and between functional brain networks, and produce a diverse pattern of connectivity increases and decreases within these networks [20]
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