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 Psychopharmacology, help to translate animal models of cognitive processes to humans.
“The overwhelming majority of animal experiments fail to translate to humans. One big issue is that the measures we use to assess things like drug response rely on very low-fidelity behavioral changes,” explained study author Jim Cavanagh, an associate professor at the University of New Mexico and director of the Cognitive Rhythms and Computation Lab.
“Rodents are so different from humans that we know this only offers weak evidence. So why not go right to the source and look at similar brain system responses? Well, the answer is that — it’s hard! But here we used a novel approach and theoretical perspective – taking findings from human brain activities that are well-associated with behaviors, 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 larger reward positivity signal reflects an enhanced brain response to reward. Previous research has indicated that abnormal reward positivity responses are associated with depression and other mental health conditions.
In their new double blind, randomized, placebo-controlled study, Cavanagh and his colleagues had 23 humans and 28 mice complete probabilistic learning tasks while using electroencephalography, or EEG, to record their brain activity. They found that the stimulant amphetamine boosted reward positivity responses in both humans and mice. The researchers observed “similar sensitivity of both species to increasing doses of d-amphetamine, demonstrating pharmacological predictive validity for this biomarker of reward sensitivity.”
“Previously separate fields of neuroscience are formally merging to better address major issues in brain health,” Cavanagh told PsyPost. “It’s hard work getting isolated fields to work together, but it’s worth the effort. We want to use animal models better, and directly apply those findings to inform individualized clinical outcomes in mental health treatment.”
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 caveats, speedbumps, and roadblocks. But we’re addressing them all rapidly. The major issue is that we need tasks where mice and humans perform them somewhat similarly. If this sounds hard — well, you’re right,” the researcher explained.
“We started with similar touch-screen interfaces in both species. Then moved to similar types of task complexities and demands. We’ve finally developed some techniques for reliably eliciting the same cognitive process in mice and humans and recording the outcome. Each of these desired outcomes took a lot of work to hone. But our ongoing work is already stronger than what we’ve just published, which shows how rapid this learning curve has been.”
The efforts could lead to important advancements in our understanding of the brain and new treatments for mental illnesses.
“This type of work takes a lot of time, effort, and funding. Collaboration between labs has been critical, and support from the NIMH has been essential. We are making great progress, however, and we have a lot of current studies ongoing and planned advancements in the near future,” Cavanagh said.
“Soon we’d like to see if antidepressants boost this reward biomarker signal in mice. This would provide a test of why antidepressants work, and this could hopefully inform what people certain antidepressants will work best for. This is a merging of ‘bench-to-bedside’ translation and personalized medicine – and the whole thing would be very inexpensive to apply in a clinical setting.”
The study, “Amphetamine alters an EEG marker of reward processing in humans and mice“, was 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.
