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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

Experimental design. Flashes indicate startle stimuli during CS presentations as primary measure of the conditioned response.
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Figure 1: Experimental design. Flashes indicate startle stimuli during CS presentations as primary measure of the conditioned response.

Mentions: The paradigm consisted of four phases divided into familiarization, fear acquisition and extinction learning on day 1 and a test for extinction recall on day 2 (see Figure 1). Two male neutral faces served as conditioned stimuli (CS; Tottenham et al., 2009) and an aversive scream of 95 dB served as unconditioned stimulus (UCS; IADS, Bradley and Lang, 1999). Volunteers were first familiarized with both CS by presenting each face eight times without the UCS. During the following fear acquisition phase consisting of 32 CS presentations one neutral face (CS+) was randomly followed by the UCS in 50% of trials whereas the other face (CS−) never preceded the UCS. Both extinction phases (day 1 and 2) consisted of 40 trials in total (20 CS+, 20 CS−) without UCS presentations. CS stimuli were presented for 6000 ms duration separated by jittered inter trial intervals (ITI) of 5000–8000 ms displaying a fixation cross. The UCS lasted 1380 ms and followed CS+ offset after a jittered temporal gap of 0–1000 ms (Guhn et al., 2012). The assignment of CS+ and CS− was counterbalanced across subjects and stimuli were presented in a pseudo-randomized order such that maximally three similar faces followed each other. Presentation® version 12.2 software (Neurobehavioral Systems, Inc., Albany, CA, USA) was used for presenting the paradigm.


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)

Experimental design. Flashes indicate startle stimuli during CS presentations as primary measure of the conditioned response.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Experimental design. Flashes indicate startle stimuli during CS presentations as primary measure of the conditioned response.
Mentions: The paradigm consisted of four phases divided into familiarization, fear acquisition and extinction learning on day 1 and a test for extinction recall on day 2 (see Figure 1). Two male neutral faces served as conditioned stimuli (CS; Tottenham et al., 2009) and an aversive scream of 95 dB served as unconditioned stimulus (UCS; IADS, Bradley and Lang, 1999). Volunteers were first familiarized with both CS by presenting each face eight times without the UCS. During the following fear acquisition phase consisting of 32 CS presentations one neutral face (CS+) was randomly followed by the UCS in 50% of trials whereas the other face (CS−) never preceded the UCS. Both extinction phases (day 1 and 2) consisted of 40 trials in total (20 CS+, 20 CS−) without UCS presentations. CS stimuli were presented for 6000 ms duration separated by jittered inter trial intervals (ITI) of 5000–8000 ms displaying a fixation cross. The UCS lasted 1380 ms and followed CS+ offset after a jittered temporal gap of 0–1000 ms (Guhn et al., 2012). The assignment of CS+ and CS− was counterbalanced across subjects and stimuli were presented in a pseudo-randomized order such that maximally three similar faces followed each other. Presentation® version 12.2 software (Neurobehavioral Systems, Inc., Albany, CA, USA) was used for presenting the paradigm.

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