Deep transcranial magnetic stimulation for adolescents with treatment-resistant depression: Behavioral and neural correlates of clinical improvement

Background: Affective bias toward negativity is associated with depression and may represent a promising treatment target. Stimulating the dorsolateral prefrontal cortex (dlPFC) with deep Transcranial Magnetic Stimulation (dTMS) could lead to shifts in affective bias. The current study examined behavioral and neural correlates of affective bias in the context of dTMS in adolescents with treatment-resistant depression (TRD). Methods: Adolescents completed a Word-Face Stroop (WFS) task during an fMRI scan before and after 30 sessions of dTMS targeting the left dlPFC. In the task, participants were shown words superimposed on faces in either a "congruent" (both word and face were positive or both negative) or an "incongruent" fashion; in both cases, participants identified whether the words were positive or negative. We examined pre-post intervention neural and behavioral WFS changes and their correlations with clinical improvement. Results: Usable pre- and post-intervention WFS data were available for 10 adolescents with TRD (Age, years: M = 16.3, SD = 1.09) for behavioral data; 9 for neuroimaging data. After treatment, although changes in behavioral performance did not suggest improved affective bias, amygdala activation decreased during the negative word/ happy face condition, which correlated with clinical improvement. Overall, clinical improvement correlated with decreased neural activation during congruent conditions. Limitations: Major limitations include the small sample size, lack of a sham control group, and unknown psychometric properties. Conclusions: Preliminary findings suggesting improving neural efficiency and normalizing affective bias in those with the most clinical improvement highlight the potential importance of targeting affective bias in treating adolescents with TRD.