Biological Clues to a Mysterious Treatment: EMDR Therapy

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Since 2019, highly important articles on the neurobiology of EMDR have been published in many journals, including Nature and Lancet. Beyond its groundbreaking benefits in treatment and in helping people experiencing psychological distress find healing, EMDR also appears set to become a very important method for shedding light on unresolved questions in neuroscience. In this post, we wanted to translate and share an article about one of these important recent publications. Containing important scientific evidence on the underlying mechanisms, this article will also provide a foundation for entirely new ideas within the EMDR community….

 

 Biological Clues to a Mysterious Treatment

We live in stressful times. Epidemiological studies indicate an increase in “classic” stress-related conditions such as major depression, post-traumatic stress disorder, and anxiety disorders, as well as conditions triggered by stress, such as addiction. Fortunately, modern neuroscience is developing new strategies to decipher how the brain copes with stress, which may ultimately enable us to overcome it. In their article published in Nature, Baek and colleagues provide an example of how powerful these strategies can be. In this example, a combination of cutting-edge neuroscience techniques and creative behavioral analysis is tested in mice.

The gradual effects of chronic stress (such as that caused by living in a war zone) are fundamentally different from those of a major traumatic experience (such as driving over an explosive device). Acute, intense stressors and specific environmental cues can become linked in memory, allowing us to recall the original trauma and remain alert to potential future dangers. In post-traumatic stress disorder, however, these cues become powerful and pervasive triggers of anxiety.

Herein lies a therapeutic opportunity. Exposure to reminders of trauma without experiencing the harm caused by the trauma (for example, in the safe setting of a therapist’s office) allows a new type of memory (“extinction memory”) to form, alleviating anxiety. Although this approach, known as “extinction” therapy, is a mainstay of PTSD treatment, it is not successful for every patient, and its effects are known to weaken over time. Researchers are therefore seeking ways to strengthen the extinction process, for example by using drugs that facilitate the formation and consolidation of extinction memories.

The study by Baek and colleagues focuses on a psychological treatment called Eye Movement Desensitization and Reprocessing (EMDR). During EMDR treatment, patients are asked to recall the trauma while being shown visual stimuli that elicit repetitive eye movements (a process also known as bilateral stimulation). Although several major mental health organizations recommend EMDR for the treatment of PTSD, some studies suggest that its outcomes are not substantially different from those obtained through direct exposure to trauma reminders without simultaneous bilateral stimulation. The psychological processes involved in EMDR remain mysterious, and the neurobiological mechanisms underlying this treatment are still largely unresolved.

In their study, Baek and colleagues used mice that had developed a fear response (freezing) after hearing a tone while receiving electric shocks to their feet. (Figure 1a). They then played the tone to the mice without administering electric shocks and exposed the animals to an array of LED lights that illuminated from left to right and right to left, enabling them to form extinction memories. (Figure 1b). This approach aimed to mimic bilateral stimulation, although it was difficult to determine how the mice directed their gaze and attention toward the LED stimulus (unlike bilateral stimulation practices in humans). Interestingly, combining extinction with bilateral stimulation produced a clear and sustained reduction in fear behavior in the mice.

 

Figure 1 | An approach to reducing trauma-related fear responses. a, Baek and colleagues exposed mice to a specific tone and an unpleasant electric shock to their feet, establishing a memory association between the two stimuli and causing the mice to display fear behavior when they heard the tone. b, Using their experimental setup, they then repeatedly played the same tone to the mice while exposing them to LED lights designed to elicit specific eye movements. These mice showed a reduced fear response to the tone compared with mice exposed only to the lights or only to the tone. c, In the brains of mice exposed to both the lights and the tone simultaneously, excitatory neural connections (blue arrows) between the superior colliculus and the mediodorsal thalamus, and between the mediodorsal thalamus and the BLA, were strengthened. This led to the inhibition of fear-encoding neurons in the BLA (red arrows). As a result, output to the brain regions that generate fear decreased, and the fear response to the trauma reminder was reduced.

The researchers observed that combining extinction and bilateral stimulation procedures increased activity in the superior colliculus, a brain region that processes visual information and directs attention (Figure 1c). This process was also found to activate the mediodorsal thalamus, a region that receives neuronal projections from the superior colliculus. The level of activation in these two regions also predicted the degree of reduction in fear behavior resulting from combined extinction and bilateral stimulation. When the researchers genetically disrupted mediodorsal thalamic neurons to prevent them from firing, however, fear behavior did not decrease.

An optogenetic approach was then used. Laser light was delivered to neurons through a fiber-optic cable to silence neuronal signaling between the superior colliculus and the mediodorsal thalamus. Communication between these two regions was found to be necessary for the reduction in fear behavior produced by extinction and bilateral stimulation.

How did strengthening the connection between brain regions known for their roles in sensory processing reduce fear behavior? Baek and colleagues observed that extinction and bilateral stimulation dampened the excitability of neurons in the BLA (basolateral amygdala), a region that calibrates fear responses and whose neurons fire during fear behavior in mice. They then demonstrated a functional, two-step inhibitory connection between the mediodorsal thalamus and BLA neurons. When these BLA neurons were optogenetically silenced, the fear-reducing effects of extinction and bilateral stimulation also disappeared. Taken together, these findings suggested a model in which extinction and bilateral stimulation work together to recruit a neuronal pathway connecting the superior colliculus and the mediodorsal thalamus. This model reduces the BLA-driven fear response to a trauma-reminding cue.

Although based on a simplified model, the findings of Baek and colleagues provide a detailed account of one of the key neural circuits underlying the fear-reducing effects of extinction and bilateral stimulation. Nevertheless, unanswered questions remain. Memory extinction requires exposure to bilateral visual stimuli, so it is necessary to establish exactly how a mouse moving freely around the experimental chamber perceives these stimuli. Future studies could position the mouse’s head relative to the LEDs to ensure that the animal’s gaze is directed toward the alternately flashing lights.

A broader question concerns how bilateral stimulation, and EMDR itself, facilitate memory extinction and reduce fear behavior. According to one interpretation, the visual stimuli also act as distractors: by diverting attention away from fear-eliciting cues, they inhibit anxiety and enable extinction memories to be encoded. However, this still does not explain why randomly flashing LED lights failed to inhibit fear behavior. The distraction account is also inconsistent with the prevailing view: the general understanding is that directing more attention toward a fear-provoking stimulus strengthens memory extinction by reinforcing the association between the trauma-reminding situation and safety.

Baek and colleagues propose that bilateral stimulation shifts the balance between competing brain circuits, recruiting a neural pathway that promotes fear extinction and overrides the pathway that maintains fear. Whether or not their proposed model is correct, this study offers a neurobiologically plausible explanation for the behavioral effects of bilateral stimulation and perhaps even EMDR. Moreover, it provides a foundation for future research into this mysterious behavioral therapy. Given the growing need to offer effective treatment options to people with trauma-related disorders, this is indeed an important development.

There has been ongoing debate about whether the technology-driven revolution in neuroscience will lead to breakthroughs in the treatment of psychiatric disorders. The difficulty of fulfilling this promise becomes clear when we consider, in particular, the challenges of modeling psychiatric disorders and the psychotherapies used to treat them in the laboratory. Key features of trauma-related disorders, such as learned fear and fear extinction, can be observed even in simple organisms, making it possible to map their neural underpinnings in detail. Trauma-related disorders therefore also offer a major opportunity for therapeutic research. Ideas such as those put forward by Baek and colleagues inspire hope for groundbreaking advances in the diagnosis, treatment, and ultimately prevention of these devastating disorders.

 

Source

https://www.nature.com/articles/d41586-019-00294-8?fbclid=IwAR1vet_7DrLLdVGm5uIp7vRF9AxXloMAuhqCso0vp3V2kNicGLQk99aN13U#ref-CR5

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