Prefrontal Cortex Stimulation Enhances Fear Extinction Memory in Humans

Raij, Tommi; Nummenmaa, Aapo; Marin, Marie‐France; Porter, Daria; Furtak, Sharon C.; Setsompop, Kawin; Milad, Mohammed R.

doi:10.1016/j.biopsych.2017.10.022

Cited by 109 publications

(97 citation statements)

References 70 publications

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“…Modulated VS activity and VS‐amygdala connectivity may have also contributed to the influence on subjective emotional experience. Considered key structures in a core limbic system, both VS and amygdala are reliably activated in studies of negative and positive emotion, although their specific role in emotional experience is not yet clear . Complementing extensive findings linking VS and (more prominently) amygdala activation to negative affect , our results suggest that increased VS activation and decreased VS‐amygdala connectivity are associated with an attenuated negative emotional experience.…”

Section: Discussionsupporting

confidence: 71%

Modulating Emotional Experience Using Electrical Stimulation of the Medial-Prefrontal Cortex: A Preliminary tDCS-fMRI Study

Abend

Sar-el

Gonen

et al. 2019

Neuromodulation: Technology at the Neural Interface

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Section: Discussionsupporting

confidence: 71%

Modulating Emotional Experience Using Electrical Stimulation of the Medial-Prefrontal Cortex: A Preliminary tDCS-fMRI Study

Abend

Sar-el

Gonen

et al. 2019

Neuromodulation: Technology at the Neural Interface

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“…Noninvasive brain stimulation can be achieved by, for example, transcranial magnetic stimulation (TMS). And indeed, vmPFC stimulation by TMS has been shown to enhance fear extinction memory in healthy humans 79 . Moreover, a recent meta-analysis investigated the effect of dorsolateral PFC TMS in patients suffering from anxiety disorders, with the general finding that TMS seems to have an overall positive therapeutic effect and can be well tolerated by patients 80 .…”

Section: Discussionmentioning

confidence: 99%

Chronic inhibition of GABA synthesis in the infralimbic cortex facilitates conditioned safety memory and reduces contextual fear

Kreutzmann

Fendt

2020

Transl Psychiatry

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Accurate discrimination between danger and safety cues is essential for survival. Recent findings in humans indicate that patients suffering from anxiety disorders cannot reliably use safety cues in order to inhibit fear responses. However, the neuroanatomical pathways of conditioned safety are still unclear. Aim of the present study was to investigate whether chronic inhibition of GABA synthesis in the infralimbic (IL) cortex, a critical region for fear inhibition, would lead to enhanced conditioned safety memory. Male Sprague Dawley rats were equipped with osmotic mini-pumps attached to an infusion cannula aimed at the IL. Mini-pumps were either filled with the glutamate decarboxylase (GAD) inhibitor L-allylglycine (L-AG) or the inactive enantiomer D-allylglycine (D-AG). Previous studies demonstrated that chronic infusions of LAG lead to lower GABA levels and overall enhanced neural activity. The effect of IL disinhibition on conditioned safety was investigated utilizing the acoustic startle response. Chronic disinhibition of the IL facilitated conditioned safety memory, along with reduced contextual fear and lower corticosterone levels. The present findings suggest that the IL is a key brain region for conditioned safety memory. Because anxiety disorder patients are often not capable to use safety cues to inhibit unnecessary fear responses, the present findings are of clinical relevance and could potentially contribute to therapy optimization.

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“…Further investigation revealed the effects of Guhn's stimulation protocol for the improvement of exposure therapy of acrophobic patients (Herrmann et al, 2017 ). Raij et al ( 2017 ) tried a temporally specific rTMS of the prefrontal cortex according to a prior study, which showed, that stimulation of the infralimbic cortex of rats—the equivalent to the human vmPFC—only improves extinction when it is applied 100 ms after the stimulus onset (Milad et al, 2004 ). Raij et al ( 2017 ) used an incomplete extinction paradigm with just four trials and could achieve an improvement of extinction recall on the next day.…”

Section: Introductionmentioning

confidence: 99%

“…Raij et al ( 2017 ) tried a temporally specific rTMS of the prefrontal cortex according to a prior study, which showed, that stimulation of the infralimbic cortex of rats—the equivalent to the human vmPFC—only improves extinction when it is applied 100 ms after the stimulus onset (Milad et al, 2004 ). Raij et al ( 2017 ) used an incomplete extinction paradigm with just four trials and could achieve an improvement of extinction recall on the next day. They made no measurements during extinction learning, thus, rTMS could have affected extinction recall or the four trials of early extinction learning equally.…”

Section: Introductionmentioning

confidence: 99%

Augmentation of Fear Extinction by Transcranial Direct Current Stimulation (tDCS)

Dittert

Hüttner

Polak

et al. 2018

Front. Behav. Neurosci.

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Although posttraumatic stress disorder (PTSD; DSM-V 309.82) and anxiety disorders (DSM-V 300.xx) are widely spread mental disorders, the effectiveness of their therapy is still unsatisfying. Non-invasive brain-stimulation techniques like transcranial direct current stimulation (tDCS) might be an option to improve extinction learning, which is a main functional factor of exposure-based therapy for anxiety disorders. To examine this hypothesis, we used a fear conditioning paradigm with female faces as conditioned stimuli (CS) and a 95-dB female scream as unconditioned stimulus (UCS). We aimed to perform a tDCS of the ventromedial prefrontal cortex (vmPFC), which is mainly involved in the control of extinction-processes. Therefore, we applied two 4 × 4 cm electrodes approximately at the EEG-positions F7 and F8 and used a direct current of 1.5 mA. The 20-min stimulation was started during a 10-min break between acquisition and extinction and went on overall extinction-trials. The healthy participants were randomly assigned in two double-blinded process into two sham stimulation and two verum stimulation groups with opposite current flow directions. To measure the fear reactions, we used skin conductance responses (SCR) and subjective ratings. We performed a generalized estimating equations model for the SCR to assess the impact of tDCS and current flow direction on extinction processes for all subjects that showed a successful conditioning (N = 84). The results indicate that tDCS accelerates early extinction processes with a significantly faster loss of CS+/CS– discrimination. The discrimination loss was driven by a significant decrease in reaction toward the CS+ as well as an increase in reaction toward the CS– in the tDCS verum groups, whereas the sham groups showed no significant reaction changes during this period. Therefore, we assume that tDCS of the vmPFC can be used to enhance early extinction processes successfully. But before it should be tested in a clinical context further investigation is needed to assess the reason for the reaction increase on CS–. If this negative side effect can be avoided, tDCS may be a tool to improve exposure-based anxiety therapies.

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Prefrontal Cortex Stimulation Enhances Fear Extinction Memory in Humans

Abstract: The results showed that spatiotemporally focused TMS may enhance extinction learning and/or consolidation of extinction memory and suggested novel cortical areas and large-scale networks for targeting in future studies.

Cited by 109 publications

References 70 publications

Modulating Emotional Experience Using Electrical Stimulation of the Medial-Prefrontal Cortex: A Preliminary tDCS-fMRI Study

Modulating Emotional Experience Using Electrical Stimulation of the Medial-Prefrontal Cortex: A Preliminary tDCS-fMRI Study

Chronic inhibition of GABA synthesis in the infralimbic cortex facilitates conditioned safety memory and reduces contextual fear

Augmentation of Fear Extinction by Transcranial Direct Current Stimulation (tDCS)

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