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Using Clustering to Examine Inter-individual Variability in Topography of Auditory Event-Related Potentials in Autism and Typical Development

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Abstract

Although prior studies have compared sensory event-related potential (ERP) responses between groups of autistic and typically-developing participants, it is unclear how heterogeneity contributes to the results of these studies. The present study used examined individual differences in these responses. 130 autistic children and 81 typically-developing children, aged between 2 and 5 years, listened to tones at four identity levels while 61-channel electroencephalography was recorded. Hierarchical clustering was used to group participants based on rescaled ERP topographies between 51 and 350 ms. The hierarchical clustering analysis revealed substantial heterogeneity. Some of the seven clusters defined in this analysis were characterized by prolonged fronto-central positivities and/or weak or absent N2 negativities. However, many other participants fell into clusters in which N2 responses were present at varying latencies. Atypical response morphologies such as absent N2 responses and/or prolonged positive-going responses found in some autistic participants may account for prior research findings of attenuated N2 amplitudes in autism. However, there was also considerable overlap between groups, with participants of both groups appearing in all clusters. These results emphasize the utility of using clustering to explore individual differences in brain responses, which can expand on and clarify the results of analyses of group mean differences.

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Data Availability

The data generated in the present study are not publicly available, but are available from the corresponding author on reasonable request.

Notes

  1. We use identity-first language (e.g., “autistic person”) in preference to person-first language (e.g., “person with autism”) in deference to prior research indicating that this is preferred by many, albeit not all, autistic people (Bury et al. 2020; Kenny et al. 2016), and out of a desire to avoid stigmatizing language (Gernsbacher 2017). Furthermore, given many autistic people’s aversion to the term “disorder” (Bury et al. 2020), the general unpopularity of the terms “disorder” and “condition” among autistics (Kenny et al. 2016), and the desirability of excluding subjective value judgements from scientific terminology, we have chosen to use the neutral phrase “autism spectrum development” instead.

  2. Typically referred to as “attention deficit hyperactivity disorder.”.

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Acknowledgements

We wish to gratefully acknowledge all of the children and families who generously devoted considerable time and effort to participating in this large study, which included many other components besides ERP data collection. We warmly acknowledge the MIND Institute APP implementation and assessment team for their neuropsychological screening work and for coordinating the logistics of ERP appointments with participants’ families. We thank all of the research assistants and junior specialists for their help with EEG data collection and processing (including Sarah Abedi, Margarita Beransky, Costanza Columbi, Sam Cheyette, Sharon Corina, Tucker Fisher, Sevan K. Harootonian, David Horton, Ryan Hubbard, Anne Kalomiris, Sarabeth Maciey, Lindsey Marcelino, Joshua Martin, Saloni Mathur, Thomas McLennan, Tracy Riggins, and Ashley Stark). We also thank Manish Saggar and Iman Mohammadrezazadeh for software development, and Yukari Takarae for scientific support. We thank Dr. Tal Kenet, of the Harvard Medical School Department of Pediatric Neurology, who provided the stimuli used in this study.

Funding

This work was supported by the UC Davis MIND Institute, by the Robert Shoes Fund, by Scott & Jennifer Fearon, by the UC Davis Deans’ Distinguished Graduate Fellowship, by the NIH (1R01 MH089626-01), the Swiss National Science Foundation (Grant Number P2LAP3_164911), the NIMH (U24MH081810), and by an Autism Center of Excellence Grant awarded by the NICHD (P50 HD093079).

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Contributions

CDS and SMR were responsible for designing the electrophysiological experiment that forms the basis of the present analysis. RDM-M processed many of the electrophysiological data included in the present manuscript. All authors contributed to planning the statistical analyses described in the present study, which were performed by PD. XW provided code that was employed in the clustering analysis. PD drafted the manuscript of the present study, which was read, edited, and approved by all authors.

Corresponding author

Correspondence to Patrick Dwyer.

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Conflict of interest

None of the authors have potential conflicts of interest to be disclosed.

Ethical Approval

This study was approved by the UC Davis Institutional Review Board Clinical Committee A (ID 220915-57). All procedures were in accordance with the 1964 Declaration of Helsinki and its later amendments.

Informed Consent

Caregivers of participants provided informed consent to study participation.

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Handling Editor: Christoph M. Michel.

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Dwyer, P., Wang, X., De Meo-Monteil, R. et al. Using Clustering to Examine Inter-individual Variability in Topography of Auditory Event-Related Potentials in Autism and Typical Development. Brain Topogr 34, 681–697 (2021). https://doi.org/10.1007/s10548-021-00863-z

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