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Introduction: Fear extinction is a fundamental component of exposure-based therapies for anxiety-related disorders. The renewal of fear in a different context after extinction highlights the importance of contextual factors. In this study, we aimed to investigate the causal role of the left inferior frontal gyrus (LiFG) in the context-dependency of fear extinction learning via administration of transcranial direct current stimulation (tDCS) over this area. Methods: 180 healthy subjects were assigned to 9 groups: 3 tDCS conditions (anodal, cathodal, and sham) × 3 context combinations (AAA, ABA, and ABB). The fear conditioning/extinction task was conducted over three consecutive days: acquisition, extinction learning, and extinction recall. tDCS (2 mA, 10min) was administered during the extinction learning phase over the LiFG via a 4-electrode montage. Skin conductance response (SCR) data and self-report assessments were collected. Results: During the extinction learning phase, groups with excitability-enhancing anodal tDCS showed a significantly higher fear response to the threat cues compared to cathodal and sham stimulation conditions, irrespective of contextual factors. This effect was stable until the extinction recall phase. Additionally, excitability-reducing cathodal tDCS caused a significant decrease of the response difference between the threat and safety cues during the extinction recall phase. The self-report assessments showed no significant differences between the conditions throughout the experiment. Conclusion: Independent of the context, excitability enhancement of the LiFG did impair fear extinction, and led to preservation of fear memory. In contrast, excitability reduction of this area enhanced fear extinction retention. These findings imply that the LiFG plays a role in the fear extinction network, which seems to be however context-independent.

Background: Neural oscillations in the cerebral cortex are associated with a range of cognitive processes and neuropsychiatric disorders. However, non-invasively modulating oscillatory activity remains technically challenging, due to limited strength, duration, or non-synchronization of stimulation waveforms with endogenous rhythms. Objective: We hypothesized that applying controllable phase-synchronized repetitive transcranial magnetic stimulation pulses (rTMS) with alternating currents (tACS) may induce and stabilize neuro-oscillatory resting-state activity at targeted frequencies. Methods: Using a novel circuit to precisely synchronize rTMS pulses with phase of tACS, we empirically tested whether combined, 10-Hz prefrontal bilateral stimulation could induce and stabilize 10-Hz oscillations in the bilateral prefrontal cortex (PFC). 25 healthy participants took part in a repeated-measures design. Whole-brain resting-state EEG in eyes-open (EO) and eyes-closed (EC) was recorded before (baseline), immediately (1-min), and 15- and 30-min after stimulation. Bilateral, phase-synchronized rTMS aligned to the positive tACS peak was compared with rTMS at tACS trough, with bilateral tACS or rTMS on its own, and to sham. Results: 10-Hz resting-state PFC power increased significantly with peak-synchronized rTMS + tACS (EO: 44.64%, EC: 46.30%, p