Emotional processing and rTMS: does inhibitory theta burst stimulation affect the human startle reflex?

Abstract

Repetitive transcranial magnetic stimulation (rTMS) enables the local and non-invasive modulation of cortical activity and has proved to achieve antidepressant effects. To a lesser extent, rTMS is investigated as a treatment option for anxiety disorders. As the prefrontal cortex and the amygdala represent key components of human emotion regulation, we investigated how prefrontally applied rTMS affects the responsiveness of the subcortical amygdala during a fear-relevant study paradigm to examine potential cortico-limbic effects. Sham-controlled, randomised inhibitory rTMS (continuous theta burst stimulation, TBS) was applied to 102 healthy subjects (female = 54) over the right dorsolateral prefrontal cortex. Subsequently, the emotion-potentiated (unpleasant, neutral, and pleasant International Affective Picture System pictures) acoustic startle response was investigated. Subjective anxiety ratings (anxiety sensitivity, trait and state anxiety) were considered. Picture category affected the startle magnitude as expected for both TBS intervention groups (highest startle response for unpleasant, lowest for pleasant pictures). However, no modulatory effects of TBS on startle potentiation were discerned. No significant interaction effects of TBS intervention, subjective anxiety ratings, and gender were identified. Interestingly, startle habituation was influenced by TBS intervention on a trend-level, with verum TBS leading to an accelerated habituation. We found no evidence for the hypothesis that prefrontal inhibitory TBS affects the responsiveness of the amygdala during the presentation of emotionally relevant stimuli in healthy subjects. Instead, we found accelerated habituation under verum TBS on a statistical trend-level. Hence, some preliminary hints for modulatory effects of inhibitory TBS on basic learning mechanisms could be found.

Mechanistic link between right prefrontal cortical activity and anxious arousal revealed using transcranial magnetic stimulation in healthy subjects

“…This hypothesis, form the basis for left dlPFC-focused TMS treatments for depression that have been largely successful [37]. For instance, inhibitory continuous theta burst stimulation (cTBS) to the right dlPFC leads to accelerated habituation of the overall startle response during affective picture viewing [38], and cTBS to the left dlPFC attenuates positive affective startle modulation [39]. Similarly, high-frequency rTMS to the right dlPFC increases threatrelated attentional capture in those with high trait anxiety [40].…”

Repetitive transcranial magnetic stimulation for the treatment of anxiety disorders: A systematic review of the state-of-the-art

“…Ferrari 19,20,26; Machado et al 15 ; Vanderhasselt et al 23 ; Zwanzger et al 28 Baeken et al 24 ; Vanderhasselt et al 25 Anxiety/social phobia Pallanti et al 36 ; Balderson et al 45 Specific phobia Deppermann et al 29 ; Herrmann 30 Deppermann et al 33 ; Notzon et al 34 Anxious depression/ depression and anxiety Diefenbach et al 18 ; LaSalle-Ricci et al 21 Depression Deppermann et al 29 ; Fitzgerald et al 27 Depersonalization Jay et al 16 Parkinson, anxiety and depression Kormos 22 Automatic emotional reactions/ emotional processing Berger et al 31 ; De Raedt et al 38 Vennewald et al 32 suffering any other disease of the central nervous system, psychiatric or neurological, or cardiovascular; only the concomitance of some other disease was allowed…”