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Medial prefrontal cortex stimulation modulates the processing of conditioned fear.

Guhn A, Dresler T, Andreatta M, Müller LD, Hahn T, Tupak SV, Polak T, Deckert J, Herrmann MJ - Front Behav Neurosci (2014)

Bottom Line: In rats, high-frequency electrical mPFC stimulation has been shown to improve extinction by means of a reduction of amygdala activity.However, so far it is unclear whether stimulation of homologues regions in humans might have similar beneficial effects.Consistent with the hypothesis of a modulated processing of conditioned fear after high-frequency rTMS, the active group showed a reduced CS+/CS- discrimination during extinction learning as evident in FPS as well as in SCR and arousal ratings.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg Würzburg, Germany.

ABSTRACT
The extinction of conditioned fear depends on an efficient interplay between the amygdala and the medial prefrontal cortex (mPFC). In rats, high-frequency electrical mPFC stimulation has been shown to improve extinction by means of a reduction of amygdala activity. However, so far it is unclear whether stimulation of homologues regions in humans might have similar beneficial effects. Healthy volunteers received one session of either active or sham repetitive transcranial magnetic stimulation (rTMS) covering the mPFC while undergoing a 2-day fear conditioning and extinction paradigm. Repetitive TMS was applied offline after fear acquisition in which one of two faces (CS+ but not CS-) was associated with an aversive scream (UCS). Immediate extinction learning (day 1) and extinction recall (day 2) were conducted without UCS delivery. Conditioned responses (CR) were assessed in a multimodal approach using fear-potentiated startle (FPS), skin conductance responses (SCR), functional near-infrared spectroscopy (fNIRS), and self-report scales. Consistent with the hypothesis of a modulated processing of conditioned fear after high-frequency rTMS, the active group showed a reduced CS+/CS- discrimination during extinction learning as evident in FPS as well as in SCR and arousal ratings. FPS responses to CS+ further showed a linear decrement throughout both extinction sessions. This study describes the first experimental approach of influencing conditioned fear by using rTMS and can thus be a basis for future studies investigating a complementation of mPFC stimulation to cognitive behavioral therapy (CBT).

No MeSH data available.


Related in: MedlinePlus

For reasons of visualization arousal difference scores (CS+ minus CS−) were depicted (M + SEM) during familiarization, acquisition, extinction learning, and extinction recall for the active (n = 32) and the sham group (n = 30). Groups significantly differed during extinction learning (*p < 0.05), i.e., sham showed higher arousal for CS+ than CS− trials.
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Figure 6: For reasons of visualization arousal difference scores (CS+ minus CS−) were depicted (M + SEM) during familiarization, acquisition, extinction learning, and extinction recall for the active (n = 32) and the sham group (n = 30). Groups significantly differed during extinction learning (*p < 0.05), i.e., sham showed higher arousal for CS+ than CS− trials.

Mentions: In order to account for rTMS induced group differences we conducted a three-way ANOVA examining effects of stimulus by phase with only two levels (extinction learning, extinction recall) between groups. We found a significant stimulus × phase × group interaction for arousal [F(1, 60) = 4.33, p = 0.042]. The active group (n = 32) discriminated significantly less between CS+ and CS− while the sham group (n = 30) persisted to evaluate CS+ as more arousing than CS− [t(53.8) = −2.01, p = 0.043] resembling the FPS and SCR results (Figure 6). Valence ratings revealed no group differences. The three-fold interaction did not reach statistical significance (p > 0.2) for the whole sample (N = 85), including conditioners and non-conditioners.


Medial prefrontal cortex stimulation modulates the processing of conditioned fear.

Guhn A, Dresler T, Andreatta M, Müller LD, Hahn T, Tupak SV, Polak T, Deckert J, Herrmann MJ - Front Behav Neurosci (2014)

For reasons of visualization arousal difference scores (CS+ minus CS−) were depicted (M + SEM) during familiarization, acquisition, extinction learning, and extinction recall for the active (n = 32) and the sham group (n = 30). Groups significantly differed during extinction learning (*p < 0.05), i.e., sham showed higher arousal for CS+ than CS− trials.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3927128&req=5

Figure 6: For reasons of visualization arousal difference scores (CS+ minus CS−) were depicted (M + SEM) during familiarization, acquisition, extinction learning, and extinction recall for the active (n = 32) and the sham group (n = 30). Groups significantly differed during extinction learning (*p < 0.05), i.e., sham showed higher arousal for CS+ than CS− trials.
Mentions: In order to account for rTMS induced group differences we conducted a three-way ANOVA examining effects of stimulus by phase with only two levels (extinction learning, extinction recall) between groups. We found a significant stimulus × phase × group interaction for arousal [F(1, 60) = 4.33, p = 0.042]. The active group (n = 32) discriminated significantly less between CS+ and CS− while the sham group (n = 30) persisted to evaluate CS+ as more arousing than CS− [t(53.8) = −2.01, p = 0.043] resembling the FPS and SCR results (Figure 6). Valence ratings revealed no group differences. The three-fold interaction did not reach statistical significance (p > 0.2) for the whole sample (N = 85), including conditioners and non-conditioners.

Bottom Line: In rats, high-frequency electrical mPFC stimulation has been shown to improve extinction by means of a reduction of amygdala activity.However, so far it is unclear whether stimulation of homologues regions in humans might have similar beneficial effects.Consistent with the hypothesis of a modulated processing of conditioned fear after high-frequency rTMS, the active group showed a reduced CS+/CS- discrimination during extinction learning as evident in FPS as well as in SCR and arousal ratings.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg Würzburg, Germany.

ABSTRACT
The extinction of conditioned fear depends on an efficient interplay between the amygdala and the medial prefrontal cortex (mPFC). In rats, high-frequency electrical mPFC stimulation has been shown to improve extinction by means of a reduction of amygdala activity. However, so far it is unclear whether stimulation of homologues regions in humans might have similar beneficial effects. Healthy volunteers received one session of either active or sham repetitive transcranial magnetic stimulation (rTMS) covering the mPFC while undergoing a 2-day fear conditioning and extinction paradigm. Repetitive TMS was applied offline after fear acquisition in which one of two faces (CS+ but not CS-) was associated with an aversive scream (UCS). Immediate extinction learning (day 1) and extinction recall (day 2) were conducted without UCS delivery. Conditioned responses (CR) were assessed in a multimodal approach using fear-potentiated startle (FPS), skin conductance responses (SCR), functional near-infrared spectroscopy (fNIRS), and self-report scales. Consistent with the hypothesis of a modulated processing of conditioned fear after high-frequency rTMS, the active group showed a reduced CS+/CS- discrimination during extinction learning as evident in FPS as well as in SCR and arousal ratings. FPS responses to CS+ further showed a linear decrement throughout both extinction sessions. This study describes the first experimental approach of influencing conditioned fear by using rTMS and can thus be a basis for future studies investigating a complementation of mPFC stimulation to cognitive behavioral therapy (CBT).

No MeSH data available.


Related in: MedlinePlus