Brain Activity Alterations Cause Hearing Problems in Fragile X Syndrome, Mouse Study Finds
Mice that lack the gene responsible for fragile X syndrome have similar changes in brain activity in the auditory cortex as those reported in humans.
The study with that finding, “Translation-relevant EEG phenotypes in a mouse model of Fragile X Syndrome,” was published in the journal of Neurobiology of Disease.
Fragile X syndrome is caused by genetic mutations affecting the FMR1 gene; consequently, it reduces the levels of its encoded fragile X mental retardation protein (FMRP). Due to FMRP’s important role in brain cells’ function, the disease is characterized by altered brainwave activity that translates into several neurological symptoms. These include anxiety, repetitive behaviors, social communication deficits, delayed language development, and abnormal sensory processing.
University of California researchers now have shown the underlying mechanisms involved in auditory impairment in fragile X, and that a mouse lacking the FMR1 gene can be a good model to further understand the human disease.
Previous studies have shown that human patients and mice lacking the FMR1 gene (knockout) have similar hearing deficits and hypersensitivity.
In humans, this can be explained partly by altered brainwave activity: fragile X patients were found to have increased brain activity at a resting state compared to healthy volunteers. This suggested they had higher background activity (so-called “network noise”) that could contribute for the hypersensitivity and interfere with their stimuli-processing capacity.
To understand if such neurological mechanisms could explain hearing impairment in FMR1 knockout mice, researchers analyzed mice brainwaves using electroencephalography (EEG) — a noninvasive monitoring method — to record electrical activity of the brain.
Similar to the human findings, mice lacking the FMR1 gene had increased brainwave activity in the auditory and frontal cortex in a resting state when compared to control animals. Also, when animals were exposed to auditory stimuli similar to those used in human studies, their brains were unable to properly interpret sound data and showed a delayed response.
“These deficits suggest a form of enhanced ‘resting state noise’ that interferes with the ability of the circuit to mount a synchronized response to sensory input, predicting specific sensory and cognitive deficits in Fragile X syndrome,” researchers wrote.
Collectively, these results demonstrate that EEG alterations in the auditory and frontal cortex may represent a biomarker for fragile X syndrome, improving the understanding of auditory deficits in this population.
