Response to beeps may measure juvenile Batten disease progression
Higher MMN means brain can distinguish sound's length from previous one
Measuring how unconscious brain signals respond to different sounds may help track neurocognitive decline in people with juvenile Batten disease, a new study suggests.
The study, “Assessing the integrity of auditory sensory memory processing in CLN3 disease (Juvenile Neuronal Ceroid Lipofuscinosis (Batten disease)): an auditory evoked potential study of the duration-evoked mismatch negativity (MMN),” was published in the Journal of Neurodevelopmental Disorders.
Juvenile Batten disease, or CLN3 disease, is marked by symptoms that first appear in childhood and worsen over time as the disease progresses. There is not an objective biological measure or biomarker that’s been proven to be reliable for tracking disease progression. Such biomarkers are essential for tracking the disease in clinics and for testing potential treatments’ effectiveness.
Here, researchers tested whether a neurological measure called the duration-evoked mismatch negativity, or MMN, could be used to track CLN3 disease progression. MMN is measured via electroencephalography (EEG), where electrodes on the scalp can detect brain activity. In a MMN measurement, a person listens to a series of beeps, where some are slightly longer than others, to see how the brain responds differently to ones of different lengths, which reflects its ability to retain information. A higher MMN means the brain is better able to tell when a new beep is not the same length as a previous beep.
Importantly, the brain activity measured for MMN is subconscious and doesn’t require any active involvement from the person being assessed. The measure is particularly well suited in Batten disease, where patients often struggle to communicate and engage in complex assessments, the researchers said.
Measuring MMN to assess neurocognitive decline
MMN was measured in 21 people with CLN3 disease and 41 typically developing control subjects of similar ages. Measuring MMN took about an hour and the participants watched a muted movie of their choice while the measurements took place.
When beeps were played relatively close together, MMN measurements were more or less comparable between CLN3 disease patients and the controls. But when the beeps were spaced out, Batten patients had markedly lower MMNs.
MMNs also varied by age. In the controls, the measurement was generally higher in older participants, which the researchers said is reflective of the brain growing and maturing as a person grows up. But in Batten disease, MMN tended to be lower in older patients, likely reflecting disease progression.
“We found that age significantly predicted neurophysiological correlates of sensory memory in CLN3 disease – that is, that the MMN showed a progressive reduction in amplitude with increasing age (i.e., disease progression), exactly opposite to what was observed in [typically developing] control participants,” wrote the researchers, who said future studies must validate the results and assess how changes in MMN are associated with symptom progression.
They called their work “a good first step in exploring and developing objective neural markers of pathology (biomarkers) that can be easily carried out noninvasively throughout the progressive stages of CLN3 disease.” The scientists are working to apply the results toward a mouse model of CLN3 disease that can be used for testing possible treatments.
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