Engineering Brain Circuits to Improve Mental Flexibility

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Alik Widge, MD, PhD

Assistant Professor of Psychiatry at the University of Minnesota

2017 One Mind / Janssen Rising Star Translational Research Award in Memory of Jeffrey S. Nye M.D., Ph.D. Award winner

Rigid, inflexible behavior is a core impairment that cuts across mental illnesses, from the intrusive thoughts of obsessive-compulsive disorder (OCD) to the automatic negative assumptions of depression to escalating drug-seeking even in the face of negative consequences of addiction.

One Mind Rising Star Awardee, Alik Widge, MD, PhD, aims to identify brain circuits involved in flexible decision-making, then identify ways to enhance them with electrical brain stimulation. Ultimately, he hopes to develop a brain stimulation treatment thatcould improve flexibility for a wide range of clinical disorders, such as schizophrenia, depression, addiction, post-traumatic stress, and autism.

During his initial research, Dr. Widge and his team studied a group of patients who received experimental brain stimulation for depression and OCD. By stimulating brain circuits between two regions of the brain, the prefrontal cortex and the striatum, patients performed better on a laboratory test of mental flexibility. However, the simulation also produced broad changes throughout the prefrontal cortex, rather than specifically targeting circuits that are important in creating the improved flexibility. Currently clinical brain stimulators are not precise enough to identify and target these circuits.

With the funding from One Mind, Alik and his team are addressing the need for greater precision by using an animal model to study the flexibility effect. Results to date have shown that similar to the clinical studies this rodent brain stimulation model improves mental flexibility. In the near future, they plan to apply optogenetics, an advanced tool for brain circuit manipulation, to change the activity of specific sub-circuits within these connections. This will let Dr. Widge and his team identify which parts of this prefrontal-striatal pathway are most critical for improving flexibility, knowledge that we can turn back into treatments for humans.

One Mind acknowledges their productivity to date towards the goal of developing a targeted therapy to increase mental flexibility. We also thank Janssen Research and Development and our donors for enabling us to provide this Rising Star Award to this remarkable scientist.

To learn more about Dr. Widge’s research, please watch the presentation he gave at our 2017 Music Festival for Brain Health (shown below) as well as the August 2018 Brain Waves interview he participated in.