Continuous theta-burst stimulation over the right dorsolateral prefrontal cortex disrupts fear memory reconsolidation in humans

Abstract

Continuous theta-burst stimulation (cTBS), a non-invasive brain stimulation technique, can induce long-lasting changes in synaptic plasticity, vital for memory reconsolidation. For this study, a total of 170 participants completed four experiments by a randomized controlled design. Succeeding fear conditioning, the subjects received cTBS over the right dorsolateral prefrontal cortex (dlPFC) or vertex (control) with or without exposure to the conditioned stimulus to reactivate the original fear memory, and then underwent fear response tests. Compared with cTBS over the vertex and without memory reactivation, only cTBS over the right dlPFC after reactivation decreased the fear response for both recent and remote fear memories. This procedure was effective only during the reconsolidation window. The disruptive effect of cTBS over the right dlPFC on fear memory reconsolidation was delay-dependent. These findings demonstrate that cTBS time-dependently and delay-dependently prevents the return of fear and may have clinical potential for treating fear-related disorders.

Medial prefrontal cortex stimulation abolishes implicit reactions to threats and prevents the return of fear

“…The authors observed that the stimulated groups failed to discriminate between threatening and safe stimuli (with an increase in autonomic responses to these last ones), and inferred that the perturbation of either left or right dlPFC during the reconsolidation time window was causally associated with a reduction of implicit defensive responses. A more recent study 59 adopted the continuous theta-burst stimulation (cTBS) over the right dlPFC during the reconsolidation window and successfully decreased the defensive responses for both recent and remote threat memories. In our study, by directly comparing the effects of the 1Hz-rTMS protocol over the mPFC and the left dlPFC, we found a stronger attenuation of implicit defensive responses to the threatening cue in subjects that were stimulated over the mPFC, suggesting that targeting this brain site might represent a more promising approach for therapeutic applications.…”

“…For the main statistics, i.e. one-way ANOVA with three groups, with the following input parameters: α equal to 0.05, power (1-β) equal to 0.80, and a hypothesized effect size (ηp 2 ) equal to 0.14, the estimated sample size resulted in n = 21 per experimental group, which was larger than those adopted in previous TMS studies 17,59 . Since all variables passed the D'Agostino-Pearson omnibus normality test, parametric statistics were adopted in each experiment.…”

A critical perspective on updating drug memories through the integration of memory editing and brain stimulation

“…For instance, continuous theta-burst stimulation over the right dlPFC delivered during the reconsolidation window of conditioned exposure of recent and remote fear memories decreases the fear response. It prevents recurrence (89). This approach has strong clinical prospects, especially when incorporated within a comprehensive clinical framework, like combining NIBS and psychotherapy in SUD (9,77).…”

“…At last, further research is needed to elucidate the role of brain networks, including the dlPFC and insula, in modifying these types of memories and how different NIBS techniques may aid in reconsolidating appetite memories (88,89). While further research is needed, using a combination of these approaches has the potential to change outdated memories and decrease compulsive behaviors.…”

“…The study showed that high-frequency rTMS applied over the ventromedial PFC can improve exposure therapy response for acrophobia symptoms (91). In another recent study, continuous theta-burst stimulation (cTBS) applied over the right dlPFC after CS exposure effectively reduces fear response and prevents its return (89). The fear response was reduced when cTBS was delivered only during the reconsolidation window and was effective for both recent and remote fear memories.…”