Early differences in auditory processing in infants with Neurofibromatosis Type 1

• In Event: Poster Session 07
  In Poster Session: PS 07 Topic - Perceptual, Sensory, Motor

Abstract

Neurofibromatosis Type 1 is a genetic disorder that results from a mutation of the NF1 gene on chromosome 17. The NF1 gene produces the neurofibromin protein that is responsible for regulating cell growth. Whilst NF1 presents with a number of physical symptoms, the condition has also been associated with neurodevelopmental disorders. For example, individuals with NF1 are five times more likely to receive an Autism Spectrum Disorder (ASD) diagnosis (Bilder et al., 2016) than the general population. Thus, prospective longitudinal studies of infants with NF1 may provide translational insights into the mechanisms that underpin symptom emergence.

Here, we assessed neural habituation to repeated auditory stimulation in a group of infants with NF1 tested at 5 and 10 months. Habituation is a particularly important function as it is necessary to determine the level of processing that occurs for incoming sensory information. Research has demonstrated atypical habituation patterns in neurodevelopmental disorders such as Fragile X Syndrome and ASD (Ethridge et al., 2016; Guiraud et al., 2011; Gomot et al., 2006) and more recently in infants with later ASD (Kolesnik et al., 2018). If individuals cannot reduce the sensory response to repeated incoming stimuli (i.e., habituate), this may underpin core symptoms of ASD such as sensory hypersensitivity.

25 infants with NF1 and 52 age-matched typically developing (TD) infants were assessed longitudinally at 5- and 10 months of age. Infants listened to 150 repetitions of trains of tones; a single ‘train’ was made up of three consecutive ‘Standards’, a /u/ vowel sound administered at 500Hz before a final ‘deviant’ sound. Each tone was presented for 100ms, with a 5ms rise and fall time and the inter-stimulus interval was jittered ~500ms. Neural activity was recorded over the whole scalp using a high density EEG array.

Examining the mean amplitude of the auditory evoked potential in the first 500ms after stimulus onset, analyses showed that the TD group showed decreasing effects of repetition between 5 and 10 months (mean diff = -1.37µV, df = 2496, p < .001, CI = -2.09µV to -.64µV); whereas responses in the NF1 group did not change (mean diff = .48µV, df = 2429, p = .67, CI = -.83µV to 1.79µV; Figure 1). This pattern at the group level held for change detection abilities, with the TD group demonstrating greater differentiation of the Standards and Deviant Pitch (mean diff = 2.09µV, df = 2421, p < .001, CI = 1.37µV -2.81µV), but the NF1 group not (mean diff = -.8µV, df = 2420, p = .21, CI = -2.06µV -.46µV; Figure 2). Autocorrelation analyses also demonstrate that the NF1 group are slower to differentiate between auditory stimuli compared to the TD group.

Our findings show that infants with NF1 demonstrate developmental delays in the emergence of neural repetition and change detection to auditory stimuli. Further analyses will examine how individual differences relate to later diagnostic outcome. We discuss the potential cascading effects of these early differences with respect to how infants process, and engage with, the world around them.

Group Authors

STAARS Team, EDEN Team

Authors

• Jannath Begum Ali, Centre for Brain and Cognitive Development
  Presenting Author

• Anna Kolesnik, Centre for Brain and Cognitive Development
  Non-Presenting Author

• Isabel Quiroz, Birkbeck, University of London
  Non-Presenting Author

• Luke Mason, Birkbeck, University of London
  Non-Presenting Author

• Shruti Garg, University of Manchester
  Non-Presenting Author

• Jonathan Green, University of Manchester
  Non-Presenting Author

• Mark H. Johnson, University of Cambridge
  Non-Presenting Author

• Emily J.H. Jones, Birkbeck, University of London
  Non-Presenting Author