Electrical stimulation to a specific region of the brain can block the return of fear responses, study finds

An experimental study on university students explored whether electrical stimulation to the ventromedial prefrontal cortex region of the brain can prevent a person’s fear response to cues associated with unpleasant stimuli from returning after the person has learned to not react with fear to those stimuli. Results showed that the electrical stimulation of this brain region prevented the participants from being startled upon seeing the experimental cues and it also abolished the involuntary components of the fear response. The study was published in Translational Psychiatry.

In order to survive, living beings need to be able to recognize things that they should fear and those they should not. They need to be able to react defensively in the face of cues that have been previously associated with a threat, before the threat itself has appeared. This process of learning which cues are associated with a threat and which are not is scientifically called “the fear memory recall.”

As conditions change, organisms need also to be able to learn to not react defensively or to tune down their defensive reactions when cues are no longer associated with a threat. This is referred to as fear extinction.

Studies have found that fear extinction memories inhibit the previously learned fear memories, thus preventing them from initiating a defensive response. However, fear extinction memories seem to be much more fragile that fear memories and this might lead to the onset of maladaptive defensive responses, particularly after fear-inducing events have been experienced again.

Research on animals has shown that the basolateral complex of the amygdala region of the brain is critical for fear extinction memory, but that these memories seem to be consolidated in the region of the brain called ventromedial prefrontal cortex. It is possible that facilitating the activity of this region of the brain might help better consolidate these fear extinction memories. One way to do that is through stimulation of the brain using electricity through a technique called anodal transcranial direct current stimulation (tDCS).

“Currently, the most efficient treatment for anxiety, stressor or trauma-related mental disorders involves an exposure of patients to their individual fear cues — for example, a dog in the case of a dog phobic individual,” explained study author Christoph Szeska of the University of Potsdam.

“Researchers have long been investigating what might drive the fear reducing effects of this strategy and have come to the conclusion that one critical element is a memory process that we refer to as fear extinction: learning and recalling, that a fear cue is not signaling any danger (anymore). Unfortunately, patients with anxiety, stressor- and trauma-related disorders have difficulties in fear extinction, which in turn hampers responding to treatment.”

“Fortunately, however, we know the brain areas underlying fear extinction quite well and therefore wanted to investigate whether a non-invasive electrical stimulation of these areas might improve the long-term reduction of fear,” Szeska said. “This might open up new avenues for improving treatment of mental disorders.”

To study whether anodal transcranial direct current stimulation of the ventromedial prefrontal cortex region of the brain can indeed better consolidate fear extinction memories, Szeska and his colleagues conducted an experimental study on a group of 40 students from the University of Greifswald. Students were divided into two groups – one that would receive tDSC electrical stimulation to their brains and one that would not.

This was a sham-controlled double-blind experiment, meaning that the group that does not received the electrical stimulation to the brain would also have tDSC electrodes attached to their heads and go through the exact same procedure as the first group, with the only difference being that there will be no electrical stimulation. They would not know that there was no electrical stimulation.

The researchers used electric shocks to the non-dominant hands of participants as the adverse stimulation, meant to incite the fear reaction. The strength of the electric shock was calibrated on the first day to be “unpleasant, but not painful.” They also used so-called acoustic startle probes to elicit startle responses in students. Startle responses were recorded using small electrodes recording the activity of the eye muscles underneath the left eye.

The researchers recorded the skin conductance response using electrodes attached to the palm of participants’ hand and electrodes were also used to record participants’ heart rate. They asked participants to provide ratings on a 11-point scale on how much they expect an electrical shock at certain points.

The experiment was carried out during two days. On the first day, participants learned to associate receiving an electrical shock with the projection of one of the two pictures, but not with the other. Sessions in which both pictures were presented but no electrical shocks were given followed. This was done in order to form a fear extinction memory – that participants learn not to react with fear and startling to the picture that used to be associated with electric shock.

On the second day, electrical brain stimulation (tDSC) was applied on one group and the other group went through the sham stimulation procedure (tDSC electrodes attached, the same procedure applied, but without electricity). After that, electric shocks were given to both groups. These were followed by a new session of picture projections (but without shocks) and researchers wanted to know whether participants will react again with fear and startling reactions to the picture that used to be associated with electric shocks, now that shocks have been reintroduced.

The results showed that participants did learn to associate one picture with shocks and showed stronger fear and startle reactions when it was exposed compared to the other picture. The fear extinction session was also successful for the most part. On day two, all fear indices started at an elevated level. Participants reported that they more expect to receive a shock after being shown a picture that was associated with shocks the day before, but their physiological reactions did not differ between the two pictures throughout the first session.

In the last session, after tDSC electrical stimulation of the ventromedial prefrontal cortex, both groups reported expecting electric shock after the picture that was associated with it the day before. However, startle response and physiological fear responses were abolished in the group that underwent electrical stimulation of the brain and this did not happen in the sham stimulation group.

“Typically, fear extinction memory consolidation and recall is rather fragile, as fear responses usually rise again after unpleasant events have been re-experienced,” Szeska told PsyPost. “For example, even after patients got rid of their fear of dogs, they might experience a resurgence of this fear if they get bitten again.”

“In the current study, we showed that a non-invasive electrical stimulation of the ventromedial prefrontal cortex – a critical relay, that mediates the consolidation and recall of fear extinction memory – can block such return of fear. Such a stimulation might therefore be considered as a novel strategy to prevent relapses after successful exposure treatments of mental disorders.”

The study shed light on important brain mechanisms for regulating defensive reactions. However, it should be noted that the study was done in a highly controlled experimental setting and reactions in natural situations might be different. Also, electric shocks applied were unpleasant but not painful and not really dangerous. It is possible that reactions to truly dangerous situations are different.

“Although we showed, that a non-invasive stimulation of the ventromedial prefrontal cortex can prevent the return of fear, there are at least two major questions that still need to be addressed in order to consider this technique as a tool for relapse prevention,” Szeska said. “First, optimal stimulation parameters (frequency, amperage, timing etc.) that lead to the strongest fear reducing effects need to be identified. Second, we need clinical studies that examine, whether this type of brain stimulation may in fact prevent the return of pathological fear.”

The paper “Stimulation of the ventromedial prefrontal cortex blocks the return of subcortically mediated fear responses” was authored by Christoph Szeska, Hannah Pünjer, Steffen Riemann, Marcus Meinzer, and Alfons O. Hamm.