Frontal Cortex Stimulation Modulates Attentional Circuits and Increases Anxiety-Potentiated Startle in Anxious Depression.

In 30 seconds

This double-blinded, parallel randomized trial examined acute effects of transcranial direct current stimulation (tDCS) in 141 adults with major depressive disorder and elevated anxiety. Participants received active or sham stimulation targeting the bilateral dorsolateral prefrontal cortex while completing attention and threat tasks. Active tDCS improved task accuracy (Cohen’s d = 0.52) and reaction times (Cohen’s d = 0.58), with increased activation in frontal and other attentional regions under high attentional load. However, it also heightened anxiety-potentiated startle and amygdala responses in specified task conditions, and did not reduce threat sensitivity.

Key findings

• Active tDCS improved task accuracy (Cohen’s d = 0.52) and reaction times (Cohen’s d = 0.58).
• Under high attentional load, active stimulation increased bilateral inferior frontal, mid-cingulate, and parietal activation (η p 2 = 0.44-0.78).
• Active tDCS increased anxiety-potentiated startle responses (partial η 2 = 0.07) and amygdala response under low attentional load (η 2 = 0.02).
• Anxiety ratings also increased with active stimulation (partial η p 2 = 0.001); the hypothesized reduction in threat sensitivity was not observed.

Why it matters

The findings show that acute stimulation can improve performance on an attention task while simultaneously increasing physiological and neural responses associated with threat. This divergence cautions against treating improved executive-task measures as evidence that threat sensitivity has improved, and highlights the importance of assessing multiple outcomes when evaluating neuromodulation in anxious depression.

What to keep in mind

The study assessed acute effects of a single 30-minute session, so it does not establish longer-term clinical effects or treatment outcomes.