At Neuroservices-Alliance, we lead the way in studying fear relapse after treatment, a critical area of research for PTSD and anxiety disorders. Our expert, Dr. Cyril Herry, has developed advanced behavioral models that closely replicate human exposure therapy in animals. These models provide valuable insights into fear recovery and are instrumental in developing more effective therapeutic strategies.
We start with classical fear conditioning. In this process, a conditioned stimulus (CS), such as a sound or light, is paired with a mild shock (unconditioned stimulus, US) in a controlled context. This pairing leads to increased fear responses. To simulate exposure therapy, we then conduct extinction. During this phase, the CS is presented without the shock in a different context, resulting in a gradual decrease in fear reactions.
The above illustration demonstrates the overall process of fear conditioning, extinction, and retrieval.
▪️ The top panel shows how the conditioned stimulus (CS) and unconditioned stimulus (US) are paired during the conditioning phase, leading to a robust fear reaction, depicted in the bottom left graph.
▪️ During extinction, the CS is presented without the US in a different context, causing a gradual reduction in the fear response, as shown in the middle graph.
▪️ However, after a delay, when the CS is presented again during retrieval, a partial recovery of the fear response is observed in some subjects, as shown in the rightmost graph.
The above illustration focuses on our findings in mice.
▪️ Panel A shows the fear response measured by freezing behavior in response to the CS+. As expected, mice exhibit high levels of freezing after fear conditioning (Day 2: Post-FC), which gradually decrease during extinction (Day 3: Ext.). However, after a 10-day delay, some mice show a significant recovery of freezing behavior when the CS+ is presented again (Day 10: Ret.).
▪️ Panel B further analyzes the rebound in fear response by categorizing the mice into low and high fear recovery groups. The histogram shows the distribution of mice based on their rebound percentages, highlighting that some animals display a strong recovery of fear, while others do not.
▪️ Panel C compares the extinction curves of these two groups, demonstrating that while both groups extinguish similarly, they diverge significantly during the retrieval phase, with high fear recovery mice showing a marked return of fear responses.
The above illustration extends these findings to healthy human subjects.
▪️ Panel A shows the skin conductance response (SCR) amplitude, which is an index of fear response. Similar to the findings in mice, the SCR amplitude is used to categorize individuals into low and high fear recovery groups based on their response during the retrieval phase (D2: Retrieval). The histogram on the left shows that some individuals exhibit low fear recovery, while others show high fear recovery.
▪️ Panel B presents the SCR amplitude across different phases of the experiment—neutral, conditioning, extinction, and retrieval. During the conditioning phase, the SCR amplitude increases, indicating a learned fear response. This response diminishes during extinction. However, during retrieval, a significant difference emerges between the low and high fear recovery groups, with the high fear recovery group showing a pronounced return of the fear response.
These models are invaluable for researchers, as they offer a robust framework for understanding the mechanisms behind fear relapse. They are crucial for developing new therapeutic approaches to prevent relapse in PTSD and anxiety disorder patients.
