New research helps pinpoint a cognitive biomarker found in both humans and rodents

Scientists have identified a pattern of brain activity that appears to be an electrophysiological marker of sensitivity to reward in both mice and humans. The findings, published in Psychopharmacologyhelp translate animal models of cognitive processes to humans.

“The vast majority of animal testing cannot be translated to humans. A big problem is that the measures we use to assess things like drug response rely on behavioral changes with very low confidence,” explains study author Jim Cavanagh, an associate professor at the University of New Mexico and director of the University of New Mexico. Cognitive Rhythms and Computation Lab.

“Rodents are so different from humans that we know this provides only weak evidence. So why not go straight to the source and look at similar responses from the brain system? Well, the answer is that – it’s hard! But here we used a novel approach and a theoretical perspective – taking findings of human brain activities that are well associated with behavior, seeing if these are present in mice, and then seeing if these similar biomarkers respond in a similar way to things like drug challenge. .”

The researchers were particularly interested in a pattern of electrical brain activity known as reward positivity, which is seen in response to receiving a reward. A greater reward positivity signal reflects an improved brain response to reward. Previous research has shown that abnormal positive responses to rewards are associated with depression and other mental illnesses.

In their new double-blind, randomized, placebo-controlled study, Cavanagh and colleagues had 23 people and 28 mice perform probabilistic learning tasks while using electroencephalography, or EEG, to record their brain activity. They found that the stimulant amphetamine increased positive responses to rewards in both humans and mice. The researchers observed “comparable sensitivity of both species to increasing doses of d-amphetamine, demonstrating pharmacological predictive validity for this biomarker of reward sensitivity.”

“Formerly separate areas of neuroscience are formally merging to better address important brain health issues,” Cavanagh told PsyPost. “It’s hard work to make isolated fields work together, but it’s worth it. We want to make better use of animal models and directly apply those findings to inform individualized clinical outcomes in mental health.”

Cavanagh also noted that developing behavioral tasks that can be performed by both humans and mice is not an easy undertaking.

“There are so many warnings, speed bumps and roadblocks. But we tackle them all quickly. The main problem is that we need tasks where mice and humans perform them somewhat in the same way. If this sounds difficult, then you’re right,” explained the researcher.

“We started with similar touchscreen interfaces in both species. Then moved on to similar types of task complexity and demands. We finally developed some techniques to reliably elicit the same cognitive process in mice and humans and record the outcome. Each of these desired results took a lot of work to fine-tune, but our ongoing work is already stronger than what we just published, showing how fast this learning curve has been.”

The efforts could lead to important advances in our understanding of the brain and new treatments for mental illness.

“This kind of work takes a lot of time, effort and money. Collaboration between laboratories was critical and support from the NIMH was essential. However, we are making great progress and we have many ongoing studies and improvements planned in the near future,” said Cavanagh.

“Soon we want to see if antidepressants amplify this reward biomarker signal in mice. This would be a test of why antidepressants work, and this could hopefully inform which people certain antidepressants work best for. This is an amalgamation of couch-to-bed translation and personalized medicine – and the whole thing would be very cheap to use in a clinical setting.”

The study, “Amphetamine alters an EEG marker of reward processing in humans and mice,” is authored by James F. Cavanagh, Sarah L. Olguin, Jo A. Talledo, Juliana E. Kotz, Benjamin Z. Roberts, John A. Nungaray , Joyce Sprock, David Gregg, Savita G. Bhakta, Gregory A. Light, Neal R. Swerdlow, Jared W. Young, and Jonathan L. Brigman.