Behavioral impulsivity is associated with pupillary alterations and hyperactivity in CDKL5 mutant mice

Area of Science:

• Neuroscience
• Genetics
• Developmental Biology

Background:

• Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is a severe X-linked neurodevelopmental condition.
• CDD presents with early-onset seizures, intellectual disability, and motor/social impairments, lacking effective treatments.
• Mouse models suggest autism-like phenotypes and arousal system dysregulation, indicating potential translational biomarkers.

Purpose of the Study:

• To assess cognitive, motor, and arousal system functions in CDD mouse models.
• To evaluate the potential of behavioral and pupillometry data as biomarkers for CDD.
• To test artificial intelligence models for classifying CDD genotype based on phenotype.

Main Methods:

• Operant conditioning chambers were used to test cognitive and motor abilities in CDD mice.
• Pupillometry and locomotor activity recording assessed arousal system integrity.
• Machine learning models analyzed behavioral and physiological data for genotype classification.

Main Results:

• CDD mice exhibited impulsivity, reduced cognitive flexibility, and perseverative behaviors.
• Pupillometry showed smaller pupil size and impaired response to stimuli in CDD mice, alongside hyperlocomotion.
• Machine learning confirmed behavioral and pupillometry parameters as strong CDD predictors.

Conclusions:

• CDD mouse models display significant cognitive, motor, and arousal deficits.
• Pupil size monitoring is proposed as a promising, easily measurable biomarker for CDD.
• AI analysis of behavioral and physiological data aids in CDD prediction.