TY - JOUR T1 - Indirect frontocingulate structural connectivity predicts clinical response to accelerated rTMS in major depressive disorder JF - Journal of Psychiatry and Neuroscience JO - J Psychiatry Neurosci SP - 243 LP - 252 DO - 10.1503/jpn.190088 VL - 45 IS - 4 AU - Deborah C.W. Klooster AU - Iris N. Vos AU - Karen Caeyenberghs AU - Alexander Leemans AU - Szabolcs David AU - René M.H. Besseling AU - Albert P. Aldenkamp AU - Chris Baeken Y1 - 2020/07/01 UR - http://jpn.ca/content/45/4/243.abstract N2 - Background: Repetitive transcranial magnetic stimulation (rTMS) is an established treatment for major depressive disorder (MDD), but its clinical efficacy remains rather modest. One reason for this could be that the propagation of rTMS effects via structural connections from the stimulated area to deeper brain structures (such as the cingulate cortices) is suboptimal.Methods: We investigated whether structural connectivity — derived from diffusion MRI data — could serve as a biomarker to predict treatment response. We hypothesized that stronger structural connections between the patient-specific stimulation position in the left dorsolateral prefrontal cortex (dlPFC) and the cingulate cortices would predict better clinical outcomes. We applied accelerated intermittent theta burst stimulation (aiTBS) to the left dlPFC in 40 patients with MDD. We correlated baseline structural connectivity, quantified using various metrics (fractional anisotropy, mean diffusivity, tract density, tract volume and number of tracts), with changes in depression severity scores after aiTBS.Results: Exploratory results (p < 0.05) showed that structural connectivity between the patient-specific stimulation site and the caudal and posterior parts of the cingulate cortex had predictive potential for clinical response to aiTBS.Limitations We used the diffusion tensor to perform tractography. A main limitation was that multiple fibre directions within voxels could not be resolved, which might have led to missing connections in some patients.Conclusion: Stronger structural frontocingular connections may be of essence to optimally benefit from left dlPFC rTMS treatment in MDD. Even though the results are promising, further investigation with larger numbers of patients, more advanced tractography algorithms and classic daily rTMS treatment paradigms is warranted.Clinical trial registration http://clinicaltrials.gov/show/NCT01832805 ER -