Lower white matter microstructure in the superior longitudinal fasciculus is associated with increased response time variability in adults with attention-deficit/hyperactivity disorder

Abstract

IntroductionAttention-deficit/hyperactivity disorder (ADHD) is characterized by a pervasive pattern of age-inappropriate inattentive behaviour and/or impulsiveness and hyperactivity. Although ADHD is often viewed as a childhood disorder, it also affects 2.5% of adults, 1 which has profound negative implications for the patients themselves, their social environment and society. The pathophysiology of ADHD is still poorly understood owing in part to its substantial clinical and etiological heterogeneity. Increased response time variability (RTV) is one of the most common characteristics of patients with ADHD. Response time variability is the moment-to-moment fluctuation of performance in neuropsychological response time experiments and has been found to be increased in patients with ADHD across a number of different experimental paradigms, including sustained attention, flanker interference and working memory tasks (for reviews see the studies by Tamm and colleagues 3 and Kofler and colleagues 4 ). Recent studies suggest that increased performance variability in patients with ADHD might be a neurocognitive marker and may serve as a potential endophenotype for this disorder. 5,6 In addition to capturing RTV through standard deviation (SD) of response time (RT), other quantitative measures of RTV have also been reported. The exponentially modified Gaussian (ex-Gaussian) method, for example, provides quantification of the shapes of Background: Response time variability (RTV) is consistently increased in patients with attention-deficit/hyperactivity disorder (ADHD). A right-hemispheric frontoparietal attention network model has been implicated in these patients. The 3 main connecting fibre tracts in this network, the superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF) and the cingulum bundle (CB), show microstructural abnormalities in patients with ADHD. We hypothesized that the microstructural integrity of the 3 white matter tracts of this network are associated with ADHD and RTV. Methods: We examined RTV in adults with ADHD by modelling the reaction time distribution as an exponentially modified Gaussian (ex-Gaussian) function with the parameters μ, σ and τ, the latter of which has been attributed to lapses of attention. We assessed adults with ADHD and healthy controls using a sustained attention task. Diffusion tensor imaging-derived fractional anisotropy (FA) values were determined to quantify bilateral microstructural integrity of the tracts of interest. Results: We included 100 adults with ADHD and 96 controls in our study. Increased τ was associated with ADHD diagnosis and was linked to symptoms of inattention. An inverse correlation of τ with mean FA was seen in the right SLF of patients with ADHD, but no direct association between the mean FA of the 6 regions of interest with ADHD could be observed. Limitations: Regions of interest were defined a priori based on the attentional network model for ADHD and thus we might have missed effects in other networks. Conclusion: This stud...

Cognitive heterogeneity in adult attention deficit/hyperactivity disorder: A systematic analysis of neuropsychological measurements

“…Rather, RTV is thought to reflect lapses in attention that produce a skewed reaction time distribution with a large tail (Leth-Steensen et al, 2000). More thorough investigation of RTV used ex-Gaussian modeling and showed that increased RTV is partly due to overly slow responses (Feige et al 2013; Gmehlin et al, 2013; Wolfers et al, 2015). These slow responses are reflected by the ex-Gaussian parameter tau , which represents the exponential component of the reaction time distribution.…”

“…These slow responses are reflected by the ex-Gaussian parameter tau , which represents the exponential component of the reaction time distribution. Recently, we showed that the tau parameter was associated with the microstructural integrity of the right superior longitudinal fasciculus, a white matter tract implicated in both attention and ADHD (Wolfers et al, 2015). Taken together, such findings suggest a neurobiological basis for within-subject variability in ADHD.…”

Individual differences in children’s global motion sensitivity correlate with TBSS-based measures of the superior longitudinal fasciculus

“…It is also correlated with response time variability in attention-deficit hyperactivity disorder (Wolfers et al, 2015). However in Williams Syndrome, fractional anisotropy of the superior longitudinal fasciculus is increased relative to controls, and high fractional anisotropy is associated with poor visuospatial performance (Hoeft et al, 2007).…”

Annual Research Review: Enduring neurobiological effects of childhood abuse and neglect

“…The previously mentioned arcuate fasciculus, which interconnects Wernicke's and Broca's areas, is also considered to be part of this pathway. Reduced FA in the superior longitudinal fasciculus has been observed in children and adults with ADHD (Hamilton et al., ; Wolfers et al., ), bipolar disorder (Benedetti et al., ; Frazier et al., ), major depression (Lai & Wu, ) and schizophrenia (Clark et al., ; Melicher et al., ).…”

“…The previously mentioned arcuate fasciculus, which interconnects Wernicke's and Broca's areas, is also considered to be part of this pathway. Reduced FA in the superior longitudinal fasciculus has been observed in children and adults with ADHD (Hamilton et al, 2008;Wolfers et al, 2015), bipolar disorder (Benedetti et al, 2011;Frazier et al, 2007), major depression (Lai & Wu, 2014) and schizophrenia (Clark et al, 2012;Melicher et al, 2015). Sun et al (2015) recently reported that first episode individuals with schizophrenia can be clustered into two groups: one with pervasive white matter deficits and another with deficits limited specifically to the superior longitudinal fasciculus.…”