Defining Clusters of Young Autistic and Typically-Developing Children Based on Loudness-Dependent Auditory Electrophysiological Responses

Abstract

Background: Autistic individuals exhibit atypical patterns of sensory processing that are known to be related to quality of life, but which are also highly heterogeneous. Previous investigations of this heterogeneity have ordinarily used questionnaires and have rarely investigated sensory processing in Typical Development (TD) alongside Autism Spectrum Development (ASD). Methods: The present study used hierarchical clustering in a large sample to identify subgroups of young autistic and typically-developing children based the normalized global field power (GFP) of their event-related potentials (ERPs) to auditory stimuli of four different loudness intensities (50, 60, 70, 80 dB SPL): that is, based on an index of the relative strengths of their neural responses across these loudness conditions. Results: Four clusters of participants were defined. Normalized GFP responses to sounds of different intensities differed strongly across clusters. There was considerable overlap in cluster assignments of autistic and typically-developing participants, but autistic participants were more likely to display a pattern of relatively linear increases in response strength accompanied by a disproportionately strong response to 70 dB stimuli. Autistic participants displaying this pattern trended towards obtaining higher scores on assessments of cognitive abilities. There was also a trend for typically-developing participants to disproportionately fall into a cluster characterized by disproportionately/nonlinearly strong 60 dB responses. Greater auditory distractibility was reported among autistic participants in a cluster characterized by disproportionately strong responses to the loudest (80 dB) sounds, and furthermore, relatively strong responses to loud sounds were correlated with both auditory distractibility and noise distress. This appears to provide evidence of coinciding behavioural and neural sensory atypicalities. Limitations : Replication may be needed to verify exploratory results. This analysis may ignore some variability related to classical ERP latencies and topographies. The sensory questionnaire employed was not specifically designed for use in autism. Variability in sensory responses unrelated to loudness is ignored, leaving much room for additional research. Conclusions: Taken together, these data demonstrate the broader benefits of using electrophysiology to explore individual differences. They illuminate different neural response patterns and suggest relationships between sensory neural responses and sensory behaviours, cognitive abilities, and autism diagnostic status.

Candidate diagnostic biomarkers for neurodevelopmental disorders in children and adolescents: a systematic review

“…It is hoped that in the future the biomarker research in youth with neurodevelopmental disorders will benefit from larger samples, consistent methods, concerted efforts focusing on replication, building on recent consortia and other promising ongoing efforts 82,83 . This research should follow the lead of biomarker research in adults with severe mental disorders 84,85 and of other areas of medicine 86,87 , that can inform appropriate assessment techniques.…”

“…Of note, previous studies indicate that neurophysiological pro files are highly heterogeneous in children with neurodevelop mental disorders, particularly with ADHD 77 and ASD 78 , meaning that the lack of replication on these measures may not be solely attributable to methodological limitations of original studies (e.g., unrepresentative and underpowered samples). This is demon strated by studies identifying datadriven subgroups of patients characterized by different EEG profiles, which appear associated with various clinical characteristics 79 and different rates of treat ment response 80,81 .…”

A Multidimensional Investigation of Sensory Processing in Autism: Parent- and Self-Report Questionnaires, Psychophysical Thresholds, and Event-Related Potentials in the Auditory and Somatosensory Modalities

“…Although the review did not formally metaanalyze group differences in Tb latencies, it also notes that prior studies examining Tb latencies reported substantial delays in the ASD group (45). Interestingly, prior research also suggests that there is considerable heterogeneity in auditory responses within both ASD and TD individuals (54)(55)(56). Furthermore, although the neurophysiological literature regarding somatosensory responses in ASD is not as well-developed as that investigating auditory responses, a few prior studies have documented that ERPs and ERFs to somatosensory stimuli in ASD might be delayed (57) or reduced in amplitude (58,59) relative to TD.…”

“…Some prior studies have examined, in ASD, the convergence between questionnaire reports of sensory processing and ERP/ERF responses to auditory stimuli. For example, larger early neural responses to sounds could be related to reports of auditory distractibility or sensory sensitivity (55,67), and weaker later auditory responses might trend towards being associated with reports of hyporesponsiveness (68). Prior research has also explored associations between reported sensory behaviours and auditory mismatch/P3 responses (69,70) as well as ERP indices of auditory habituation (71).…”

“…It appears intuitively reasonable to imagine that subjective experiences of hyper-or hyporesponsivity to stimuli (as reported in questionnaires) should be related to neural hyper-and hypo-responsiveness, especially when brain responses are recorded in a context comparable to the complex, uncontrolled contexts in which atypical sensory experiences occur in real life. In this sense, it is not surprising to observe associations between ERPs and sensory questionnaire scores when ERPs are recorded in passive paradigms while background stimuli compete for attention (as in (55,68)). However, convergence between sensory questionnaire scores and amplitudes of ERPs has also been found when recorded while participants complete active tasks, requiring maintenance of particular attentional sets, in controlled, low-stimulation environments (e.g., (67)).…”