Efficacy of Connectivity-Based Targeting in TMS for Adolescents with Treatment-Resistant Depression

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Background. Thirteen percent of 12- to 17-year-old adolescents suffer from depression, but only half respond to antidepressants and psychotherapy. Recent studies have successfully employed repetitive Transcranial Magnetic Stimulation (rTMS) to treat depression. However, there is a need to precisely determine the rTMS site of stimulation. A recent study in adults with depression (Fox et al., 2012) proposes that using the connectivity between the dorsolateral prefrontal cortex (DLPFC) and subgenual cingulate to define the site of stimulation for rTMS results in increased clinical efficacy. To date, no studies have investigated this phenomenon in the pediatric population. Methodology. Functional magnetic resonance imaging (fMRI) scans of 37 adolescents with treatment-resistant depression (TRD) and 18 controls were analysed. TRD individuals underwent 15 consecutive rTMS sessions and were assessed for depression before and after treatment by the Hamilton Depression Rating Scale (Ham-D). We calculated the DLPFC-Subgenual connectivity for the seven different rTMS targeting approaches described in Fox et al. (2012). Then, we measured the DLPFC-Subgenual connectivity from the individual stimulation sites and explored any correlation with clinical efficacy. Results. Contrary to Fox et al. (2012), four and three targeting approaches presented a positive correlation for the TRD and control groups respectively. Moreover, more positive values of DLPFC-Subgenual connectivity were significantly associated with a higher decrease in Ham-D scores (p = 0.025, one-tailed). Limitations. We used coordinates for the targeting approaches and subgenual cingulate that had been originally defined in adults. Furthermore, small changes in the noise reduction procedure causes great divergence in the outcomes. Conclusions. Since adolescents showed a distinctive and stronger functional connectivity between DLPFC and the subgenual cingulate, depression treatments have to be directly adjusted to pediatric population. Additionally, higher DLPFC-Subgenual positive connectivity predicted a higher clinical efficacy. This suggests that future work should consider defining the stimulation site at the DLPFC location with the strongest positive connectivity with the subgenual cingulate. However, the novelty of this research and the differences in outcomes with the literature in adult population indicates that reanalysing this association is necessary.
Depression, resting-state functional MRI, DLPFC, rTMS, DLPFC-Subgenual connectivity
Tapia Palacio, C. (2021). Efficacy of Connectivity-Based Targeting in TMS for Adolescents with Treatment-Resistant Depression (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.