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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

Fear-potentiated startle magnitudes for CS+ and CS− trials for active (A) and placebo (B) group and the difference score (C) accordingly. In all experimental phases mean responses and standard errors of the mean (SEM) are depicted. Asterisks indicate significant differences (*p < 0.05, ***p < 0.001). (C) illustrates CS+ and CS− trials as difference scores to indicate that groups did not differ in their conditioned response during the acquisition phase [independent t-contrast: t(43) = 1.47, p > 0.05].
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Figure 2: Fear-potentiated startle magnitudes for CS+ and CS− trials for active (A) and placebo (B) group and the difference score (C) accordingly. In all experimental phases mean responses and standard errors of the mean (SEM) are depicted. Asterisks indicate significant differences (*p < 0.05, ***p < 0.001). (C) illustrates CS+ and CS− trials as difference scores to indicate that groups did not differ in their conditioned response during the acquisition phase [independent t-contrast: t(43) = 1.47, p > 0.05].

Mentions: As expected, t-tests revealed significant differences between CS+ and CS− trials during acquisition within both groups (p < 0.001), but revealed sustained CS+/CS− discrimination for sham only, i.e., higher FPS responses for CS+ than for CS− for both extinction learning [t(23) = 2.3, p = 0.031] and extinction recall [t(23) = 2.44, p = 0.023; Figure 2]. CR for both groups in time course are provided in Figure 3. In order to statistically analyze these group differences during the experimental phases we continued to separate each extinction session into an early and a late phase consisting of 10 trials each for which we used the CS+/CS− differences. A one-way ANOVA examining the effects of phase (acquisition, early extinction learning day 1, late extinction learning day 1, early extinction recall day 2, late extinction recall day 2) on FPS magnitudes revealed a trend-wise significant main effect of phase for the active group [F(2.3, 46.7) = 2.98, p = 0.054]. This is composed of a negative linear trend [F(1, 20) = 4.19, p = 0.054]: FPS responses decreased proportionately through all phases while the sham group neither showed a significant main effect of phase (p > 0.79) nor significant trends. Figure 4 shows the time course of the difference scores (CS+ minus CS−) throughout the five phases.


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)

Fear-potentiated startle magnitudes for CS+ and CS− trials for active (A) and placebo (B) group and the difference score (C) accordingly. In all experimental phases mean responses and standard errors of the mean (SEM) are depicted. Asterisks indicate significant differences (*p < 0.05, ***p < 0.001). (C) illustrates CS+ and CS− trials as difference scores to indicate that groups did not differ in their conditioned response during the acquisition phase [independent t-contrast: t(43) = 1.47, p > 0.05].
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Fear-potentiated startle magnitudes for CS+ and CS− trials for active (A) and placebo (B) group and the difference score (C) accordingly. In all experimental phases mean responses and standard errors of the mean (SEM) are depicted. Asterisks indicate significant differences (*p < 0.05, ***p < 0.001). (C) illustrates CS+ and CS− trials as difference scores to indicate that groups did not differ in their conditioned response during the acquisition phase [independent t-contrast: t(43) = 1.47, p > 0.05].
Mentions: As expected, t-tests revealed significant differences between CS+ and CS− trials during acquisition within both groups (p < 0.001), but revealed sustained CS+/CS− discrimination for sham only, i.e., higher FPS responses for CS+ than for CS− for both extinction learning [t(23) = 2.3, p = 0.031] and extinction recall [t(23) = 2.44, p = 0.023; Figure 2]. CR for both groups in time course are provided in Figure 3. In order to statistically analyze these group differences during the experimental phases we continued to separate each extinction session into an early and a late phase consisting of 10 trials each for which we used the CS+/CS− differences. A one-way ANOVA examining the effects of phase (acquisition, early extinction learning day 1, late extinction learning day 1, early extinction recall day 2, late extinction recall day 2) on FPS magnitudes revealed a trend-wise significant main effect of phase for the active group [F(2.3, 46.7) = 2.98, p = 0.054]. This is composed of a negative linear trend [F(1, 20) = 4.19, p = 0.054]: FPS responses decreased proportionately through all phases while the sham group neither showed a significant main effect of phase (p > 0.79) nor significant trends. Figure 4 shows the time course of the difference scores (CS+ minus CS−) throughout the five phases.

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