Variability in sensory processing and evoked potentials in Rett syndrome

Area of Science:

• Neuroscience
• Genetics
• Developmental Biology

Background:

• Rett syndrome (RTT) is a rare neurodevelopmental disorder linked to MECP2 gene variants.
• Key RTT features include cognitive, motor, and autonomic impairments, with atypical sensory processing being a core yet poorly understood aspect.
• Sensory processing in RTT presents with co-occurring hypo- and hyper-responsivity, and evoked potentials (EPs) show delayed responses, but underlying mechanisms are unclear.

Purpose of the Study:

• To investigate the role of neural response timing variability in RTT's atypical sensory processing.
• To assess inter-trial phase coherence (ITPC) as a potential functional biomarker for sensory impairments in RTT.
• To explore the relationship between ITPC, EP amplitudes, and caregiver-reported sensory responsivity in individuals with RTT.

Main Methods:

• Caregiver-reported sensory responsivity was characterized in 32 individuals with RTT and 28 controls.
• Evoked potentials (EPs) were recorded during passive visual and auditory stimulation.
• Inter-trial phase coherence (ITPC) was computed to quantify neural response consistency across trials.

Main Results:

• Both hypo- and hyper-responsivity were elevated and positively correlated in individuals with RTT.
• ITPC was significantly reduced in RTT across visual and auditory modalities, correlating with reduced EP amplitudes.
• Reduced visual ITPC was associated with increased visual responsivity and greater behavioral symptom severity in RTT.

Conclusions:

• Increased neural response timing variability, as measured by ITPC, may underlie reduced EPs and atypical sensory responsivity in RTT.
• ITPC shows promise as a functional biomarker for sensory processing variability in RTT.
• Decreased temporal precision of neural activity could unify the understanding of sensory dysfunction in RTT and other neurodevelopmental disorders.