Longitudinal processing speed impairments in males with autism and the effects of white matter microstructure
Introduction
The ability to process implicit social cues and filter essential signals from a complex array of stimuli requires fast-paced integration of a large number of sensory inputs. Therefore, processing speed, or the speed at which we are able to perceive and react to stimuli in the environment, is a fundamental cognitive ability. Clinically, individuals with autism spectrum disorder (ASD) often demonstrate the need for increased time to process information and perform tasks, which appears to contribute to functioning in daily life. Research studies also have found evidence of slower processing speeds across the lifespan in individuals with ASD. On standardized Wechsler tests of intelligence, lower processing speed index scores have been reported in children, (Mayes and Calhoun, 2003, Mayes and Calhoun, 2008, Oliveras-Rentas et al., 2012, Wechsler, 2003) adolescents, and adults with ASD (Spek, Schatorjé, Scholte, & van Berckelaer-Onnes, 2009). These slower processing speeds were associated with more severe ASD communication symptoms in high-functioning children with ASD (Oliveras-Rentas et al., 2012) and were found to be predictive of educational achievements in math, reading, and writing (Assouline, Foley Nicpon, & Dockery, 2011). These observations and results suggest that slower processing speed may be a common difficulty experienced by individuals with ASD and may relate to core ASD features, as well as educational and occupational prospects.
Although processing speed difficulties have been consistently reported in persons with ASD, little is known regarding how processing speed develops and changes with age in this population. In individuals with typical development, cross-sectional and longitudinal studies suggest rapid increases in processing speed during the first year of life (Rose, Feldman, & Jankowski, 2002), followed by continued increases through childhood and adolescence (Kail, 2007, Kail and Ferrer, 2007). Although very little is known about typical processing speed changes in middle age, processing speed appears to decline and may be related to other age-related declines in cognitive functions in older-adult populations (Salthouse, 1996, Salthouse and Ferrer-Caja, 2003, Sliwinski and Buschke, 1999, Sternäng et al., 2008, Zimprich and Kurtz, 2013). In both typically developing and patient populations, age-appropriate development of processing speed may be a critical predictor of a number of important cognitive and outcome measures. For example, processing speed may be a key predictor of general intelligence in typically developing adolescents (Coyle, Pillow, Snyder, & Kochunov, 2011), and in individuals with schizophrenia, processing speed may predict vocational outcome and social function (Sánchez et al., 2009). Therefore, understanding the longitudinal development of processing speed in persons with ASD may be a key element to better understanding and accommodating the needs of persons with ASD throughout the lifespan.
A better understanding of processing speed development in ASD may also elucidate underlying neural substrates contributing to the etiology of ASD. DTI studies in individuals with typical development suggest that processing speed may be associated with the white matter microstructure of a number of white matter tracts across the brain, including the bilateral anterior corona radiata, bilateral superior fronto-occipital fasciculus, bilateral superior longitudinal fasciculus, bilateral internal capsule, bilateral posterior cingulum, right inferior fronto-occipital fasciculus, and bilateral posterior corona radiata (Bendlin et al., 2010). In individuals with traumatic brain injury, processing speed was related to white matter microstructure of the superior longitudinal fasciculus (Turken et al., 2008), ventral striatum (Shah et al., 2012), as well as the corpus callosum and centrum semiovale (Kourtidou et al., 2012). Further, decreases in white matter integrity of the corpus callosum were related to decreases in processing speed in children with multiple sclerosis (Bethune et al., 2011) and in children and adults with ASD (Alexander et al., 2007). These results provide converging evidence across distinct samples and methodologies that the white matter microstructure of a number of tracts is likely involved in processing speed.
Because of the number of tracts likely involved, it is possible that a metric of whole-brain white matter microstructure may predict processing speed more accurately than the white matter microstructure of any individual tract. Indeed, in older individuals with typical development, a measure of higher radial diffusivity (RD) across all lobes of the brain was found to be associated with executive function and processing speed measures (Jacobs et al., 2013). Furthermore, two studies have found that a composite white matter integrity factor (i.e., a combination of FA, RD, MD, and axial diffusivity (AD) across eight major tracts, or an aggregation of the white matter integrity of healthy looking white matter tracts) was more predictive of processing speed than when the individual tracts were treated as single predictors (Penke et al., 2010, Venkatraman et al., 2011). Given that white matter microstructure atypicalities have been commonly reported in ASD (see Travers et al., 2012 for a review), investigating white matter microstructure as a predictor of processing speed is essential to better understand the links between the behavioral and the neural manifestations of ASD.
To examine the intersection among possible processing speed differences in ASD, age-related development of processing speed, and white matter contributions to processing speed, the present study longitudinally examined age-related processing speed changes in 81 individuals with ASD and 56 age-matched individuals with typical development from childhood to mid-adulthood (6–39 years old). Additional analyses examined whether whole-brain white matter FA, MD, RD, and AD predicted processing speed in a subset of participants who underwent multiple DTI scans.
Section snippets
Design
As part of a 13-year longitudinal study, the current study employed an accelerated longitudinal design (i.e., cohort-sequential design) (Harezlak et al., 2005, Nesselroade and Baltes, 1979), which simultaneously measured individual longitudinal changes in processing speed across multiple age cohorts. Data were collected at four separate time points: Pre-Time 1 (henceforth called Time 0), Time 1, Time 2, and Time 3. Processing speed data were collected at Time 0, Time 1, and Time 3. DTI scans
Longitudinal group differences in processing speed index (PSI)
We tested for group differences in PSI scores and their longitudinal trajectories. PSI scores for each participant are presented in Fig. 2. A linear mixed-effects model analysis controlling for full scale IQ suggested slower processing speed in individuals with ASD, such that the group with ASD averaged 12 points lower on PSI scores than typically developing peers (see Table 2). These significant group differences were not accompanied by significant age-related changes in PSI from six to 39
Discussion
Using an accelerated longitudinal design, the present study examined group differences and age-related changes in processing speed in individuals with ASD compared to individuals with typical development from childhood into adulthood. The results yielded three important findings: (1) A significant processing speed standard score deficit in ASD that tends to be sustained from childhood to adulthood, (2) a significant and robust processing speed raw score deficit in the ASD group in the adult but
Acknowledgements
This work was supported by the National Institute of Mental Health [RO1 MH080826 to JEL, ALA, NL, EDB; and RO1 MH084795 to JEL, NL], the Eunice Kennedy Shriver National Institute of Child Health and Human Development [T32 HD07489 to BGT, and P30 HD003352 to the Waisman Center], the Hartwell Foundation [to BGT], and the Poelman Foundation [to EDB]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental
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