Neural dynamics shed light on how the brain adapts to and suppresses fearful memories

Over the course of their lives, humans can sometimes acquire fear responses to specific stimuli, animals, objects or situations, typically following adverse experiences or traumatic events. Understanding the brain processes associated with the extinction of these learned fearful responses could guide the development of more effective therapeutic strategies to treat phobias or other anxiety disorders.

Researchers at Ruhr University Bochum, Paris Brain Institute—Institut du Cerveau, ICM, INSERM, CNRS, APHP, Pitié-Salpêtrière Hospital and other institutes recently carried out a study investigating what happens in the brain when humans and other animals are learning to suppress fearful memories associated with specific stimuli and create new ones.

Their findings, published in Nature Human Behavior, suggest that this process of fear extinction is supported by stable and context-specific neural representations that are concurrently produced by a network of brain regions, including the amygdala and hippocampus.

“Extinction learning is a fundamental ability that is needed to adapt to a changing environment,” Nikolai Axmacher, senior author of the paper, told Medical Xpress. “For example, one may have learned through bad experience that some electrical devices (e.g., a toaster) may be dangerous in case of malfunction and thus may be hesitant to use them in the future.

“However, one could then find out that in a different environment, toasters are in fact safe. This is called extinction learning. Now, one striking aspect of extinction learning is that the original fear memory is not entirely gone—when coming back to the original environment, or when moving to a completely new place, one may think that toasters could be dangerous again.”

Earlier studies have consistently shown that extinction learning (i.e., the process through which a person’s emotional responses to a feared stimulus become less intense) is highly dependent on the context in which they encounter the stimulus. However, the exact neural mechanisms involved in this process had not yet been fully elucidated.

Axmacher and his colleagues set out to fill this gap in the literature by conducting a series of experiments involving human participants. They specifically looked at how specific cues (e.g., pictures of objects) and contexts (e.g., videos of a given environment) are represented in the brains of different individuals.

In addition, they tried to determine whether context representations were more “specific” while a fear was becoming extinct than while people were learning to fear a particular stimulus. If this were the case, the neutral trace associated with one context would become more distinguishable from the trace of another context.

“One particular challenge when analyzing these questions in humans is that the brain areas that are putatively relevant are very small and deep in the brain, and thus difficult to investigate,” said Axmacher.

“We thus opted for a relatively uncommon method: we conducted recordings from thin electrodes implanted in the brain. This is not possible in healthy participants, but there are certain epilepsy patients in whom such electrodes are implanted anyway for clinical reasons (to test where their epilepsy comes from). These patients are of great value for addressing fundamental questions in cognitive neuroscience, and our labs have longstanding expertise in analyzing such data.”

In their experiments, Axmacher and his colleagues showed participants who had electrodes implanted in their brains as part of their epilepsy treatment images of specific electric devices, including a toaster, a hair dryer, a fan and a washing machine. Some of these images were immediately followed by an aversive stimulus (i.e., the image of a person who looked fearful and a screaming sound).

“Each of these pictures was shown in the background of a particular context,” explained Axmacher. “During the experiment, some devices that were initially ‘dangerous’ became safe (i.e., they were not followed by the aversive stimulus any longer) to test extinction learning. We recorded brain activity from intracranial electrodes in several brain regions that we expected to be relevant for this process. Through the analysis of this data, we investigated how representations of the devices and the contexts were formed (and extinguished) in these areas.”

When the researchers analyzed the data they collected, they uncovered specific neural patterns that occurred when people were learning to associate specific objects with a sense of safety, as opposed to a threat. Firstly, they found that responses in the amygdala, a brain region that is known to play a part in fear responses and the signaling of threats, were surprisingly associated with the safety of a given stimulus.

“Second, we indeed found that the neural representations of individual contexts were more specific during extinction than they were during acquisition,” said Axmacher. “This effect occurred in a brain region called the prefrontal cortex, which is important for adaptive control of behavior, suggesting that these context representations may have been deliberatively modified by the patients. Finally, we observed that this effect influenced whether the patients would afterwards be fearful of the extinguished stimuli in a new experimental environment.”

Axmacher and his colleagues observed that if neural representations of the extinction contexts presented to participants differed greatly from each other, their extinction learning did not generalize to a new environment. This essentially means that participants might no longer perceive an object (e.g., a toaster) as threatening in one context, but still thought it was in another context. This phenomenon, also referred to as ‘return of fear,’ thus appeared to be influenced by neural representations of contexts.

The team’s findings could soon inspire similar studies focusing on the neural underpinnings of fear learning and extinction. Meanwhile, Axmacher and his colleagues plan to adapt their experiment to ensure that it is more aligned with everyday situations and settings.

“Our approach of ‘extinction learning in the wild’ assumes that in the real world, contingencies (i.e., whether something is dangerous or not) may change back and forth between contexts,” added Axmacher.

“It would be relevant to investigate this phenomenon using technologies like Virtual Reality, which allow us to create immersive and engaging experiences in which naturalistic contexts can be created and manipulated. This leads to an exciting hypothesis: If—as our current results suggest—extinction learning leads to novel memory traces that suppress rather than replace the previously formed memories, does this mean that multiple changes lead to a hierarchy of mutually inhibiting memory traces?”

© 2025 Science X Network

Over the course of their lives, humans can sometimes acquire fear responses to specific stimuli, animals, objects or situations, typically following adverse experiences or traumatic events. Understanding the brain processes associated with the extinction of these learned fearful responses could guide the development of more effective therapeutic strategies to treat phobias or other anxiety disorders.

Researchers at Ruhr University Bochum, Paris Brain Institute—Institut du Cerveau, ICM, INSERM, CNRS, APHP, Pitié-Salpêtrière Hospital and other institutes recently carried out a study investigating what happens in the brain when humans and other animals are learning to suppress fearful memories associated with specific stimuli and create new ones.

Their findings, published in Nature Human Behavior, suggest that this process of fear extinction is supported by stable and context-specific neural representations that are concurrently produced by a network of brain regions, including the amygdala and hippocampus.

“Extinction learning is a fundamental ability that is needed to adapt to a changing environment,” Nikolai Axmacher, senior author of the paper, told Medical Xpress. “For example, one may have learned through bad experience that some electrical devices (e.g., a toaster) may be dangerous in case of malfunction and thus may be hesitant to use them in the future.

“However, one could then find out that in a different environment, toasters are in fact safe. This is called extinction learning. Now, one striking aspect of extinction learning is that the original fear memory is not entirely gone—when coming back to the original environment, or when moving to a completely new place, one may think that toasters could be dangerous again.”

Earlier studies have consistently shown that extinction learning (i.e., the process through which a person’s emotional responses to a feared stimulus become less intense) is highly dependent on the context in which they encounter the stimulus. However, the exact neural mechanisms involved in this process had not yet been fully elucidated.

Axmacher and his colleagues set out to fill this gap in the literature by conducting a series of experiments involving human participants. They specifically looked at how specific cues (e.g., pictures of objects) and contexts (e.g., videos of a given environment) are represented in the brains of different individuals.

In addition, they tried to determine whether context representations were more “specific” while a fear was becoming extinct than while people were learning to fear a particular stimulus. If this were the case, the neutral trace associated with one context would become more distinguishable from the trace of another context.

“One particular challenge when analyzing these questions in humans is that the brain areas that are putatively relevant are very small and deep in the brain, and thus difficult to investigate,” said Axmacher.

“We thus opted for a relatively uncommon method: we conducted recordings from thin electrodes implanted in the brain. This is not possible in healthy participants, but there are certain epilepsy patients in whom such electrodes are implanted anyway for clinical reasons (to test where their epilepsy comes from). These patients are of great value for addressing fundamental questions in cognitive neuroscience, and our labs have longstanding expertise in analyzing such data.”

In their experiments, Axmacher and his colleagues showed participants who had electrodes implanted in their brains as part of their epilepsy treatment images of specific electric devices, including a toaster, a hair dryer, a fan and a washing machine. Some of these images were immediately followed by an aversive stimulus (i.e., the image of a person who looked fearful and a screaming sound).

“Each of these pictures was shown in the background of a particular context,” explained Axmacher. “During the experiment, some devices that were initially ‘dangerous’ became safe (i.e., they were not followed by the aversive stimulus any longer) to test extinction learning. We recorded brain activity from intracranial electrodes in several brain regions that we expected to be relevant for this process. Through the analysis of this data, we investigated how representations of the devices and the contexts were formed (and extinguished) in these areas.”

When the researchers analyzed the data they collected, they uncovered specific neural patterns that occurred when people were learning to associate specific objects with a sense of safety, as opposed to a threat. Firstly, they found that responses in the amygdala, a brain region that is known to play a part in fear responses and the signaling of threats, were surprisingly associated with the safety of a given stimulus.

“Second, we indeed found that the neural representations of individual contexts were more specific during extinction than they were during acquisition,” said Axmacher. “This effect occurred in a brain region called the prefrontal cortex, which is important for adaptive control of behavior, suggesting that these context representations may have been deliberatively modified by the patients. Finally, we observed that this effect influenced whether the patients would afterwards be fearful of the extinguished stimuli in a new experimental environment.”

Axmacher and his colleagues observed that if neural representations of the extinction contexts presented to participants differed greatly from each other, their extinction learning did not generalize to a new environment. This essentially means that participants might no longer perceive an object (e.g., a toaster) as threatening in one context, but still thought it was in another context. This phenomenon, also referred to as ‘return of fear,’ thus appeared to be influenced by neural representations of contexts.

The team’s findings could soon inspire similar studies focusing on the neural underpinnings of fear learning and extinction. Meanwhile, Axmacher and his colleagues plan to adapt their experiment to ensure that it is more aligned with everyday situations and settings.

“Our approach of ‘extinction learning in the wild’ assumes that in the real world, contingencies (i.e., whether something is dangerous or not) may change back and forth between contexts,” added Axmacher.

“It would be relevant to investigate this phenomenon using technologies like Virtual Reality, which allow us to create immersive and engaging experiences in which naturalistic contexts can be created and manipulated. This leads to an exciting hypothesis: If—as our current results suggest—extinction learning leads to novel memory traces that suppress rather than replace the previously formed memories, does this mean that multiple changes lead to a hierarchy of mutually inhibiting memory traces?”

© 2025 Science X Network