A groundbreaking study has revealed a fascinating connection between brain waves in humans and mice, offering a potential breakthrough in our understanding of neurological conditions like autism spectrum disorders. This research, led by a team of dedicated scientists, has identified a unique biomarker in fragile X syndrome, the most common inherited form of autism.
The study, published in Nature Communications, was conducted by researchers from MIT, in collaboration with experts across the United States and the United Kingdom. By measuring brain waves in human boys and men, both with and without fragile X syndrome, and comparing them to similarly aged male mice with and without the genetic alteration that models the disorder, the team made some remarkable discoveries.
Using a novel analytical approach, postdoc Sara Kornfeld-Sylla uncovered specific patterns of differences in low-frequency brain waves between typical and fragile X brains, shared across species and age groups. These findings provide an objective and non-invasive way to assess treatment efficacy in both humans and mice, which has been a significant challenge in the past.
"This research bridges the gap between human and mouse models," Kornfeld-Sylla explains. "By identifying the connection between brain wave activity in fragile X humans and the mouse model, we've uncovered a cross-species biomarker. The collaboration and the exciting results make this paper stand out."
Mark Bear, a faculty member at The Picower Institute for Learning and Memory, emphasizes the importance of this discovery: "Having a direct comparison of brain waves can greatly enhance our treatment studies. We can now ask questions about the effects of drug treatments and map physiological changes to behavioral measures."
The researchers measured EEG over the occipital lobe in humans and on the surface of the visual cortex in mice. By analyzing the power across the frequency spectrum, they replicated previous findings of altered low-frequency brain waves in adult humans with fragile X and provided new insights into these disruptions in children with the syndrome.
Kornfeld-Sylla's innovative approach involved isolating periodic fluctuations in power, disregarding the traditional frequency bands, and comparing the periodic power spectra of humans and mice directly. This revealed significant, similar patterns in a different low-frequency band between the two species (theta vs. alpha).
The biomarker is characterized by a peak in the power of low-frequency waves, which is shifted to a slower frequency in fragile X cases compared to neurotypical cases. In boys and juvenile mice with fragile X, the peak is also shifted, but the most notable difference is a reduction in power.
Further experiments delved into the neural activity underlying these measurements. By manipulating the activity of inhibitory neurons, the researchers found that somatostatin-expressing interneurons specifically affected the lower-frequency subpeak, which is associated with the newly discovered biomarker in fragile X model mice.
The study also explored the effects of the drug arbaclofen, which enhances GABA activity and has shown promise in treating fragile X syndrome. Even a single low dose of arbaclofen made a significant difference in neurotypical mice, while fragile X mice required a higher dose. However, after administration, there was a notable increase in the power of the key subpeak, indicating a reduction in the deficit seen in juvenile mice.
"This proof of concept demonstrates that drug treatments can have an acute impact on this phenotype, bringing it closer to the wild-type," Bear says. "It shows we have sensitive readouts for drug treatments."
Kornfeld-Sylla adds that low-frequency (alpha) brain wave differences are a common feature in various brain disorders, suggesting that the biomarker identified in this study could have broader implications for translational neuroscience research.
The study was supported by various organizations, including the National Institutes of Health, the FRAXA Foundation, and the Autism Science Foundation.
This exciting research opens up new avenues for understanding and treating neurological conditions, offering hope and potential for those affected by fragile X syndrome and other related disorders.
