Neural Mechanisms of Sensory Processing Anomalies

Neurodevelopmental disorders, such as attention-deficit-hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), have been associated with a high prevalence of sensory processing anomalies. With the update of the diagnostic manuals International Classification of Diseases eleventh revision (ICD-11) and Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V), more emphasis has been given to the sensory symptoms of both these disorders. The demand of reliable and valid quantitative measurements of sensory processing anomalies are therefore increasing as such metrics has the potential to assist clinical decision-making e.g., in (differential) diagnostics and treatment response evaluation and prediction. The present observational study focuses on auditory and tactile processing. Hearing and touch are two of the most frequency reported modalities in which individuals with ASD experience sensory anomalies. In addition, adequate auditory and tactile processing are presumed fundamental in the emergence of various social and cognitive functions such as the development of language. Elucidating the sensory symptoms by means of psychophysics, neuroimaging, and quantitative measures of peripheral sensory organs could elucidate the underlying (neuro)physiology of sensory anomalies in ASD and ADHD.

The present project aims to elucidate the physiological substrates of abnormal sensory processing by conducting a battery of tests in children with ASD, ADHD, and neurotypical children. First, a series of questionnaires will be administered to acquire a (clinical) description of the participants (Wechsler Intelligence Scale for Children, Fifth Edition (WISC-V); Autism Quotient (AQ, child version); Childhood Behavioral Checklist (CBCL 6-16); ADHD-Ration Scale (ADHD-RS); Autism Diagnostic Observation Schedule, 2nd edition (ADOS-2); Use of pharmacotherapy). A standardized caregiver-reported sensory profile questionnaire will serve as the primary outcome (Sensory Profile 2, Child version). Second, transiently evoked otoacoustic emissions will be measured in order to account for peripheral mechanisms of hearing as well as their contralateral suppression to measure efferent auditory system functioning. Third, a psychophysic task will be conducted for the purpose of estimating the just-noticeable difference to auditory loudness and vibrotactile displacement intensities followed by a subjective categorical loudness scale experiment. Finally, two electroencephalographic experiments will be performed: a frequency tagging paradigm with interspersed pitch oddballs and a classical sensory gating paradigm using vibrotactile stimuli and auditory clicks.

• Discrimination Acuity test (Behavioral): Estimating the just-noticeable difference of auditory loudness and vibrotactile displacement to fit a psychometric function for each modality with parameters: threshold, slope, sensitivity, and response criterion.
• Transiently Evoked Otoacoustic Emission (Diagnostic test): Examination of integrity of outer hair cells in the inner ear; with and without contralateral suppression.
• Questionnaires (Other): Caregiver questionnaires send to parents online to acquire demographic information Autism Quotient (AQ), Child Behavior Checklist (CBCL6-16), Sensory Profile 2 (SP-2).
• Wechsler Intelligence Scale for Children, Fifth Edition (WISC-V) (Behavioral): Estimates intelligence quotient
• Clinical tests of ASD (Diagnostic test): Autism Diagnostic Observation Schedule, 2nd edition (ADOS-2)
• Electroencephalography (EEG) with auditory or vibrotactile stimuli (Other): Two paradigms will be used: an auditory frequency tagging paradigm with interspersed pitch oddballs and a classical sensory gating paradigm with either vibrotactile stimuli or auditory clicks.
• Clinical tests of ADHD (Diagnostic test): ADHD-Rating Scale (ADHD-RS)

Primary outcomes

• Sensory Profile 2 [8 minutes, answered within 1 month of the experimental session]: Caregiver questionnaire to assess sensory anomalies

Secondary outcomes

• Wechsler Intelligence Scale for Children, Fifth Edition (WISC-V) [1 hour 15 minutes, conducted within 1 year of the experimental session]: General intelligence quotient
• Autism Quotient (AQ, child version) [8 minutes, answered within 1 month of the experimental session]: Questionnaire addressing autistic traits
• Childhood Behavioral Checklist (CBCL 6-16) [15 minutes, answered within 1 month of the experimental session]: Questionnaire addressing various behaviors relevant to DSM-V
• ADHD-Ration Scale (ADHD-RS) [15 minutes, conducted within 1 year of the experimental session]: Questionnaire addressing behaviors related to severity of ADHD symptoms
• Autism Diagnostic Observation Schedule, 2nd edition (ADOS-2) [1 hour, conducted within 1 year of the experimental session]: Questionnaire addressing behaviors related to severity of ASD symptoms
• Use of pharmacotherapy [At time of experimental session]: Use of pharmacotherapy
• Transiently Evoked Otoacoustic Emission (TEOAE) [2 minutes, during experimental session]: Cochlear energy produced during the processing of a click sound using Titan (Interacoustics A/S, Denmark) measured in decibel (dB) above the noise floor (i.e., signal-to-noise ratio).
• Contralateral suppression of TEOAE [2 minutes, during experimental session]: The suppression effect on the TEOAE during binaural stimulation. Here, constant contralateral broadband pink noise is applied simultaneous to a ipsilateral TEOAE measurement. Thus, the measurement is similar to a TEOAE but here the outcome measure is the difference score (i.e., suppression effect) of with/without contralateral stimulation.
• Categorical Loudness Scale [5 minutes, during experimental session]: Identifying quiet threshold, loudness discomfort level, and a grading of sound intensities between (quiet threshold, soft, comfortable, loud, loudness discomfort level).
• Auditory Loudness Discrimination Acuity [5 minutes, during experimental session]: The just-noticeable difference (JND) from a reference tone intensity (65 decibel sound pressure level (dBSPL), 250 ms, 1000 Hz at interval one) to a test tone (amplitude increase between 0-15 dBSPL at interval two). The unit of JND is the change in dBSLP relative to the reference tone (ΔdBSLP).
• Vibrotactile Displacement Discrimination Acuity [5 minutes, during experimental session]: The just-noticeable difference (JND) from a reference displacement intensity (160 µm, 250 ms, 230 Hz at interval one) to a test tone (amplitude increase between 0-640 µm at interval two). The unit of JND is the change in µm relative to the reference displacement (Δµm).
• Electroencephalography, sensory gating paradigm with auditory and vibrotactile stimulation [30 minutes, during experimental session]: Gating/suppression of components in the event-related potential (ERP), beta-band power, and inter-trial phase coherence during stimulation.
• Electroencephalography, frequency tagging with pitch oddball (two conditions) [7 minutes, during experimental session]: Difference scores for half semi-tone oddball and four semi-tone oddball in pitch deviation. 1. Frequency domain amplitude for the standard and oddball (1.6 and 8 Hz) 2. Narrow-band filtered EEG amplitudes (1-17 Hz)

Sex: All, ages: 8 Years to 15 Years

Inclusion Criteria:

* Clinically diagnosed with either ADHD, ASD, or no diagnosis (typical development)
* Between 8-15 years old

Exclusion Criteria:

* Familiar history of schizophrenia and depression.
* Epilepsy, cerebral palsy, traumatic brain injury
* Musculoskeletal illnesses
* Hearing or visual impairment that cannot be corrected
* Lack of ability to cooperate
* Parents cannot read Danish