MRC Social, Genetic, and Developmental Psychiatry Centre Institute of Psychiatry, King’s College London, UK Neural Correlates of Face and Eye Gaze Processing Differentiate Children with Autism Spectrum Disorder (ASD) and/or Attention Deficit Hyperactivity Disorder (ADHD) C. Tye1, E. Mercure2, P. Asherson1, K. L. Ashwood1, B. Azadi1, M.H. Johnson3, P. Bolton1 & G. McLoughlin1 1Institute of Psychiatry, King’s College London, UK. 2Institute of Cognitive Neuroscience, University College London, UK. 3Centre for Brain and Cognitive Development, Birkbeck College, UK. Email: charlotte.tye@kcl.ac.uk . Background Task Results 2 Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are common childhood-onset disorders1 with high rates of clinical and behavioural overlap2. The ability to process faces and gaze is considered fundamental to typical development and social interaction, impairments in which are characteristic of both ASD and ADHD.2 The P1 and N170 event-related potential (ERP) components are elicited by faces, and modulated by face inversion and changes in gaze direction.3 Individuals with ASD consistently display altered neural responses to faces, including reduced modulation by face inversion and gaze direction.4,5 There is limited research on neural markers of basic face processing in ADHD and ASD+ADHD. Colour images of 3 female faces with direct or averted gaze presented in upright or inverted orientation. Trials began with cartoon images used to stimulate the child’s participation and attention to task, monitored by video recording. N170 component: face detection and structural encoding Left hemisphere Right hemisphere N170 amplitude (μV) A flanker version of the cued continuous performance task Preparatory processing occurs during the cue Motor inhibition occurs at non-target stimuli TRIAL 1 TRIAL 2 N170 800- 1200ms 500ms 500ms 800-1200ms Fig 4: N170 at P7 and P8 across all stimuli (TD, ASD, ADHD, ASD+ADHD) Reduced right hemisphere lateralisation on N170 amplitude in children with ASD (ASD/ASD+ADHD) [F (1,85) 10.50 p=.002]. 80 trials of each of the 4 conditions “How many flags did you see?” Aims Fig.1: Face and gaze processing task i. To identify shared or distinct neural markers of face processing in children with ASD and ADHD, indexed by P1 and N170 ERP responses to face inversion and gaze direction. ii. To investigate whether children with ASD+ADHD demonstrate different impairments to the single diagnosis groups. Results Reduced effect of gaze direction on N170 amplitude in children with ASD (ASD/ASD+ADHD) [F (1,86) 4.01 p=.048] P1 component: visual processing Sample Reduced effect of face inversion on P1 latency in children with ADHD (ADHD/ASD+ADHD) [F (1,86) 5.35, p=.023] Cases were recruited from outpatient child and adolescent mental health clinics and parent support groups. Diagnosis was ascertained using standard diagnostic interviews (ADOS, ADI-R, PACS). This ensures minimal misspecification in group allocation. Typically developing (TD) controls were recruited from local schools. Fig 5: N170 amplitude at Pz to direct and averted gaze by ASD symptoms Conclusions Children with ADHD demonstrate abnormalities in response to face inversion, while children with ASD demonstrate impairments in gaze processing. ASD and ADHD do not share dysfunction in face processing, suggesting they can be dissociated at the neural level using ERPs. Children with comorbid ASD+ADHD present as a hybrid condition with the unique deficits of both disorders. This holds implications in assessment, diagnosis and treatment of these complex cases, and warrants systematic assessment of comorbid conditions when investigating underlying mechanisms. TD (n=26) ASD (n=19) ADHD (n=18) ASD+ (n=29) ANOVA Age 10.56 11.69 10.48 10.53 p=0.093 WASI IQ 120.04 115.68 104.11* 109.72* p=0.002 Fig 2: P1 latency across O1 and O2 to upright and inverted faces by ADHD symptoms * = significantly different from TD (p<.05) EEG recording and processing Altered modulation by gaze direction on P1 latency in children with ASD (ASD/ASD+ADHD) [F (1,86) 5.54, p=.021] Montages: 10-20 montages with additional EOG sites to FCz recording reference at 500 Hz sampling rate. Downsampled to 256 Hz, re-referenced to average, filtered offline with 0.1 to 30 Hz, 24 dB/oct Butterworth filters, artifacts exceeding 200μV peak-to-peak rejected. Averages contain at least 55 sweeps. P1 was maximal positive peak in 100- 200ms latency window at O1 and O2. N170 was maximal negative peak in 150-290ms latency window at P7, P8 and Pz. Age was a significant covariate in analysis of the N170 component. References American Psychiatric Association (2000) Diagnostic and Statistical Manual of Mental Disorders (4th edn), Washington, DC. Rommelse, N. et al. (2011). Neuroscience and Biobehavioural Reviews, 35(6), 1363-1396 Bentin, S. et al. (1996). Journal of Cognitive Neuroscience, 8, 551-565. McPartland, J. et al. (2004).. Journal of Child Psychology & Psychiatry, 45(7), 1235-1245. Senju, A. et al. (2005). Neuropsychologia, 43(9), 1297-1306. We would like to thank all of the participants. The first author was funded by a MRC PhD Studentship. The Specificity of Electrophysiology in Neurodevelopmental Disorders study (SEND) was made possible by time and support given by Sally Cartwright, Sarah Lewis and Stuart Newman. Fig 3: P1 latency across O1 and O2 to direct and averted gaze by ASD symptoms