Beyond the Pill: a startup reimagines mental health

Ronja Schrimpf

Startup Stories

Digital therapeutics for mental health treatment go beyond the pill improving standard of care. While treatment for mental illness typically focuses on a combination of medications and therapy, there is no one-size-fits-all solution for treating mental illness. That is why GrayMatters Health is developing a beyond the pill digital therapeutics for mental disorders through volitional regulation of brain process to improve the efficiency of said treatments. In an interview with 5-HT, co-founder and CEO Oded Kraft tells us how GrayMatters Health aims to redefine mental health using process-based framework for precise neuromodulation.

The GrayMatters Health Team around co-founders Shai Attia (r. l.), Rani Cohen (f. l.) and Oded Kraft (f. r.)

Seeking higher efficacy solutions for the treatment of mental disorders

The Israel based startup GrayMatters Health was founded 5 years ago.

Rani Cohen, one of my co-founders, was on a journey to seek for elevated solutions for treating mental disorders,” CEO, Oded Kraft recalls their early stages. “Cohen met with Prof. Talma Hendler, from TASMC (Tel Aviv Sourasky Medical Center) and TAU (Tel Aviv University) who was investigating the connection between the activity of different brain regions and the emotion regulation. Studies have shown that a hyperactive amygdala is associated with the presence of certain mental disorders. Through rigorous research for over a decade, Prof. Hendler developed a method to downregulate the amygdala activity non-invasively and improve clinical outcome for patients with different disorder. The result of the research was a machine learning computational model that reproduces the fMRI signal of the amygdala using EEG, in real time. It opened the way to develop an EEG neurofeedback device that enables amygdala downregulation using EEG. The model is called EFP (Electrical Finger Print).”

Oded Kraft, co-founder and CEO of GrayMatters Health

Revisiting the Role of the Amygdala

The Amygdala is a region of the brain involved in numerous behavioral and psychological tasks. Located in the sub-cortical level, just in front of the hippocampus the amygdala is the center of emotion regulation and fight-or-flight reaction in the brain. Linking sensory stimuli to psychological and physiological processes, the amygdala is creating the basis for emotional responses.

“Results have shown that if you could train a person to downregulate the activity of the amygdala using a form of biofeedback of activity focusing in the brain you could lead to clinical improvement,” Oded explains. “This is what we all desire, to help people. Right now, we are focusing on post-traumatic stress disorder (PTSD) population.”

Oded Kraft, co-founder and CEO of GrayMatters Health

Amygdala downregulation could be beneficial for many mental disorders, and after speaking with numerous healthcare providers and KOLs, we decided to focus on PTSD, which affects over 250M people around the globe. One of the main reasons was that PTSD lacks adequate therapy. The other was that research shows that lowering amygdala activity alleviates PTSD symptoms,” Oded says, explaining GrayMatters Helath´s focus on treating PTSD.

Patient with EEG cap during a session

Teaching patients to lower their amygdala activity level

GrayMatters’ product that uses the EFP is called Prism for PTSD. Prism therapy consists of 15 sessions each lasting 30 minutes. The sessions take place twice a week over a time span of 8 weeks. During each session the patient comes in and sits down in front of a screen where the EEG cap is placed on their head measuring the electrical activity on the scalp. Prism then reads the EEG signals and uses the EFP to calculate the fMRI-surrogate signal of the amygdala, which is used to set the activity level of the interactive interface, say of a busy and noisy waiting room with agitated avatars. In order to properly regulate their network activity, patients seek and find a mental strategy that will make them successful in controlling the interactive interface. In essence, patients learn how to regulate brain networks by receiving real time feedback from the interactive user interface.

“As a result of this training, the patient acquires a new skill of lowering their own amygdala activity level,” Oded elaborates. “Clinical studies with more than 400 people have shown that people can learn how to control this signal and downregulate the amygdala activity on their own after those sessions. 90 percent of the individuals who participate in the studies have been able to do this by themselves, Oded says, “The remaining 10 percent are provided with some guidance from the therapist.”

Unique approach to improve standard of care

The standard of care is one of the most important constructs in medicine. Within the field of mental health, the standard of care is usually pharmacotherapy and psychotherapy. GrayMatters Health aims to work together with the traditional methods to improve clinical outcomes. “Our mission is not to replace standard of care, rather to augment and enhance it. Our studies have shown that adding our therapeutic approach on top of standard treatment, improves efficiency in a safe manner.” Oded emphasizes, “The approach by itself is unique. The fact that we offer mechanism-based approach where we start from the amygdala causing a kind of cascade of actions in the body is unique and promising. Our approach is simple. The effort required by the patient is very minimal. The patient will go through 15 sessions and get into the habit of lowering their amygdala activity on their own. Which is really empowering for the patients to heal themselves.”

Taking further steps and venturing into the German market

GrayMatters wants to expand its portfolio beyond PTSD and treat a variety of mental disorders in the near future. “Our next steps are completing the clinical studies, generating meaningful data and gaining regulatory clearances. We intend to venture into the German market. With its broad ecosystem in the healthcare sector 5-HT is very valuable to us“ Oded emphasizes his excitement about the partnership with 5-HT Digital Hub Chemistry & Health.


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