Investigation of multisensory processing and structural brain differences in Autism Spectrum Disorder

This thesis is an investigation of structural brain abnormalities, as well as multisensory and unisensory processing deficits in autistic traits and Autism Spectrum Disorder (ASD). To achieve this, structural and functional magnetic resonance imaging (fMRI) and psychophysical techniques were employed. ASD is a neurodevelopmental condition which is characterised by the social communication and interaction deficits, as well as repetitive patterns of behaviour, interests and activities. These traits are thought to be present in a typical population. The Autism Spectrum Quotient questionnaire (AQ) was developed to assess the prevalence of autistic traits in the general population. Von dem Hagen et al. (2011) revealed a link between AQ with white matter (WM) and grey matter (GM) volume (using voxel-based-morphometry). However, their findings revealed no difference in GM in areas associated with social cognition. Cortical thickness (CT) measurements are known to be a more direct measure of cortical morphology than GM volume. Therefore, Chapter 2 investigated the relationship between AQ scores and CT in the same sample of participants. This study showed that AQ scores correlated with CT in the left temporo-occipital junction, left posterior cingulate, right precentral gyrus and bilateral precentral sulcus, in a typical population. These areas were previously associated with structural and functional differences in ASD. Thus the findings suggest, to some extent, autistic traits are reflected in brain structure - in the general population. The ability to integrate auditory and visual information is crucial to everyday life, and results are mixed regarding how ASD influences audiovisual integration. To investigate this question, Chapter 3 examined the Temporal Integration Window (TIW), which indicates how precisely sight and sound need to be temporally aligned so that a unitary audiovisual event can be perceived. 26 adult males with ASD and 26 age and IQ-matched typically developed males were presented with flash-beep (BF), point-light drummer, and face-voice (FV) displays with varying degrees of asynchrony and asked to make Synchrony Judgements (SJ) and Temporal Order Judgements (TOJ). Analysis of the data included fitting Gaussian functions as well as using an Independent Channels Model (ICM) to fit the data (Garcia-Perez & Alcala-Quintana, 2012). Gaussian curve fitting for SJs showed that the ASD group had a wider TIW, but for TOJ no group effect was found. The ICM supported these results and model parameters indicated that the wider TIW for SJs in the ASD group was not due to sensory processing at the unisensory level, but rather due to decreased temporal resolution at a decisional level of combining sensory information. Furthermore, when performing TOJ, the ICM revealed a smaller Point of Subjective Simultaneity (PSS; closer to physical synchrony) in the ASD group than in the TD group. Finding that audiovisual temporal processing is different in ASD encouraged us to investigate the neural correlates of multisensory as well as unisensory processing using functional magnetic resonance imaging fMRI. Therefore, Chapter 4 investigated audiovisual, auditory and visual processing in ASD of simple BF displays and complex, social FV displays. During a block design experiment, we measured the BOLD signal when 13 adults with ASD and 13 typically developed (TD) age-sex- and IQ- matched adults were presented with audiovisual, audio and visual information of BF and FV displays. Our analyses revealed that processing of audiovisual as well as unisensory auditory and visual stimulus conditions in both the BF and FV displays was associated with reduced activation in ASD. Audiovisual, auditory and visual conditions of FV stimuli revealed reduced activation in ASD in regions of the frontal cortex, while BF stimuli revealed reduced activation the lingual gyri. The inferior parietal gyrus revealed an interaction between stimulus sensory condition of BF stimuli and group. Conjunction analyses revealed smaller regions of the superior temporal cortex (STC) in ASD to be audiovisual sensitive. Against our predictions, the STC did not reveal any activation differences, per se, between the two groups. However, a superior frontal area was shown to be sensitive to audiovisual face-voice stimuli in the TD group, but not in the ASD group. Overall this study indicated differences in brain activity for audiovisual, auditory and visual processing of social and non-social stimuli in individuals with ASD compared to TD individuals. These results contrast previous behavioural findings, suggesting different audiovisual integration, yet intact auditory and visual processing in ASD. Our behavioural findings revealed audiovisual temporal processing deficits in ASD during SJ tasks, therefore we investigated the neural correlates of SJ in ASD and TD controls. Similar to Chapter 4, we used fMRI in Chapter 5 to investigate audiovisual temporal processing in ASD in the same participants as recruited in Chapter 4. BOLD signals were measured while the ASD and TD participants were asked to make SJ on audiovisual displays of different levels of asynchrony: the participants’ PSS, audio leading visual information (audio first), visual leading audio information (visual first). Whereas no effect of group was found with BF displays, increased putamen activation was observed in ASD participants compared to TD participants when making SJs on FV displays. Investigating SJ on audiovisual displays in the bilateral superior temporal gyrus (STG), an area involved in audiovisual integration (see Chapter 4), we found no group differences or interaction between group and levels of audiovisual asynchrony. The investigation of different levels of asynchrony revealed a complex pattern of results indicating a network of areas more involved in processing PSS than audio first and visual first, as well as areas responding differently to audio first compared to video first. These activation differences between audio first and video first in different brain areas are constant with the view that audio leading and visual leading stimuli are processed differently.

Understanding and validating accelerometry as a measure of physical activity in children with intellectual disabilities

Background Physical activity in children with intellectual disabilities is a neglected area of study, which is most apparent in relation to physical activity measurement research. Although objective measures, specifically accelerometers, are widely used in research involving children with intellectual disabilities, existing research is based on measurement methods and data interpretation techniques generalised from typically developing children. However, due to physiological and biomechanical differences between these populations, questions have been raised in the existing literature on the validity of generalising data interpretation techniques from typically developing children to children with intellectual disabilities. Therefore, there is a need to conduct population-specific measurement research for children with intellectual disabilities and develop valid methods to interpret accelerometer data, which will increase our understanding of physical activity in this population. Methods Study 1: A systematic review was initially conducted to increase the knowledge base on how accelerometers were used within existing physical activity research involving children with intellectual disabilities and to identify important areas for future research. A systematic search strategy was used to identify relevant articles which used accelerometry-based monitors to quantify activity levels in ambulatory children with intellectual disabilities. Based on best practice guidelines, a novel form was developed to extract data based on 17 research components of accelerometer use. Accelerometer use in relation to best practice guidelines was calculated using percentage scores on a study-by-study and component-by-component basis. Study 2: To investigate the effect of data interpretation methods on the estimation of physical activity intensity in children with intellectual disabilities, a secondary data analysis was conducted. Nine existing sets of child-specific ActiGraph intensity cut points were applied to accelerometer data collected from 10 children with intellectual disabilities during an activity session. Four one-way repeated measures ANOVAs were used to examine differences in estimated time spent in sedentary, moderate, vigorous, and moderate to vigorous intensity activity. Post-hoc pairwise comparisons with Bonferroni adjustments were additionally used to identify where significant differences occurred. Study 3: The feasibility on a laboratory-based calibration protocol developed for typically developing children was investigated in children with intellectual disabilities. Specifically, the feasibility of activities, measurements, and recruitment was investigated. Five children with intellectual disabilities and five typically developing children participated in 14 treadmill-based and free-living activities. In addition, resting energy expenditure was measured and a treadmill-based graded exercise test was used to assess cardiorespiratory fitness. Breath-by-breath respiratory gas exchange and accelerometry were continually measured during all activities. Feasibility was assessed using observations, activity completion rates, and respiratory data. Study 4: Thirty-six children with intellectual disabilities participated in a semi-structured school-based physical activity session to calibrate accelerometry for the estimation of physical activity intensity. Participants wore a hip-mounted ActiGraph wGT3X+ accelerometer, with direct observation (SOFIT) used as the criterion measure. Receiver operating characteristic curve analyses were conducted to determine the optimal accelerometer cut points for sedentary, moderate, and vigorous intensity physical activity. Study 5: To cross-validate the calibrated cut points and compare classification accuracy with existing cut points developed in typically developing children, a sub-sample of 14 children with intellectual disabilities who participated in the school-based sessions, as described in Study 4, were included in this study. To examine the validity, classification agreement was investigated between the criterion measure of SOFIT and each set of cut points using sensitivity, specificity, total agreement, and Cohen’s kappa scores. Results Study 1: Ten full text articles were included in this review. The percentage of review criteria met ranged from 12%−47%. Various methods of accelerometer use were reported, with most use decisions not based on population-specific research. A lack of measurement research, specifically the calibration/validation of accelerometers for children with intellectual disabilities, is limiting the ability of researchers to make appropriate and valid accelerometer use decisions. Study 2: The choice of cut points had significant and clinically meaningful effects on the estimation of physical activity intensity and sedentary behaviour. For the 71-minute session, estimations for time spent in each intensity between cut points ranged from: sedentary = 9.50 (± 4.97) to 31.90 (± 6.77) minutes; moderate = 8.10 (± 4.07) to 40.40 (± 5.74) minutes; vigorous = 0.00 (± .00) to 17.40 (± 6.54) minutes; and moderate to vigorous = 8.80 (± 4.64) to 46.50 (± 6.02) minutes. Study 3: All typically developing participants and one participant with intellectual disabilities completed the protocol. No participant met the maximal criteria for the graded exercise test or attained a steady state during the resting measurements. Limitations were identified with the usability of respiratory gas exchange equipment and the validity of measurements. The school-based recruitment strategy was not effective, with a participation rate of 6%. Therefore, a laboratory-based calibration protocol was not feasible for children with intellectual disabilities. Study 4: The optimal vertical axis cut points (cpm) were ≤ 507 (sedentary), 1008−2300 (moderate), and ≥ 2301 (vigorous). Sensitivity scores ranged from 81−88%, specificity 81−85%, and AUC .87−.94. The optimal vector magnitude cut points (cpm) were ≤ 1863 (sedentary), ≥ 2610 (moderate) and ≥ 4215 (vigorous). Sensitivity scores ranged from 80−86%, specificity 77−82%, and AUC .86−.92. Therefore, the vertical axis cut points provide a higher level of accuracy in comparison to the vector magnitude cut points. Study 5: Substantial to excellent classification agreement was found for the calibrated cut points. The calibrated sedentary cut point (ĸ =.66) provided comparable classification agreement with existing cut points (ĸ =.55−.67). However, the existing moderate and vigorous cut points demonstrated low sensitivity (0.33−33.33% and 1.33−53.00%, respectively) and disproportionately high specificity (75.44−.98.12% and 94.61−100.00%, respectively), indicating that cut points developed in typically developing children are too high to accurately classify physical activity intensity in children with intellectual disabilities. Conclusions The studies reported in this thesis are the first to calibrate and validate accelerometry for the estimation of physical activity intensity in children with intellectual disabilities. In comparison with typically developing children, children with intellectual disabilities require lower cut points for the classification of moderate and vigorous intensity activity. Therefore, generalising existing cut points to children with intellectual disabilities will underestimate physical activity and introduce systematic measurement error, which could be a contributing factor to the low levels of physical activity reported for children with intellectual disabilities in previous research.

Glasgow Psychosis Screening tool for use in adults with Intellectual Disabilities (GPS-ID): development and psychometric properties

Background: Prevalence of psychosis is known to be higher in adults with intellectual disabilities (ID) than in the general adult population. However, there have been no attempts to develop a psychosis screening tool specifically for the adult ID population. The present study describes the development and preliminary evaluation of a new measure, the Glasgow Psychosis Screening tool for use in Adults with Intellectual Disabilities (GPS-ID). Method: An item pool was generated following: 1) focus groups with adults with ID and psychosis, and their carers and/or workers; 2) expert input from clinicians. A draft scale was compiled and refined following expert feedback. The new scale, along with the Psychotic Symptom Rating Scales was administered to 20 adults with ID (10 with and 10 without psychosis) and their relative or carers. Results: The GPS-ID total score, self-report subscale and informant rating-subscale differentiated psychosis and non-psychosis groups. The tool had good internal consistency (Cronbach’s α=0.91), and a cut-off score ≥4 yielded high sensitivity (90%) and specificity (100%). The method of tool development supports face and content validity. Criterion validity was not supported. Conclusions: Preliminary investigation of the tool’s psychometric properties is positive, although further investigation is required. The tool is accessible to adults with mild to moderate ID and can be completed in 15-30 minutes. The GPS-ID is not a diagnostic tool, therefore any adult exceeding the cut-off score of ≥4 should receive further assessment.