Is reaction time variability in ADHD mainly at low frequencies

Excess intra-individual variability in reaction times (hereafter: RT variability) is a prominent feature of cognitive performance for children with Attention Deficit Hyperactivity Disorder (ADHD), as well as other disorders. Effect sizes (ESs) seem large (Willcutt, Doyle, Nigg, Faraone, & Pennington, 2005) and neurobiological theories have emerged. RT variability may reflect integrity of key brain networks, pre-frontal cortex functioning, white matter integrity, and/or efficiency of dopamine neuromodulation (for review see MacDonald, Li, & Backman, 2009). The most well-developed neurobiological account in ADHD is the default-mode interference hypothesis, which suggests that RT variability reflects difficulty suppressing activity in neural networks typically associated with rest (Castellanos, Kelly, & Milham, 2009; Sonuga-Barke & Castellanos, 2007). The “default” network seems to show coherent oscillation at low frequencies (i.e. those <0.1 Hz, but strongest at <0.08 Hz, Cordes et al., 2001), which are roughly similar to the low-frequency patterns studied in ADHD RT variability data. This theory therefore proposes that low-frequency patterns (i.e. <0.10 Hz) will uniquely account for RT variability in ADHD. However, this prediction remains largely untested. Consensus is lacking as to defining frequency bands in the RT data. Approaches have included: 1) features of the task employed (Johnson et al., 2008; Johnson et al., 2007a; Johnson et al., 2007b); 2) theory about physiologically important frequency divisions (Di Martino et al., 2008; Vaurio, Simmonds, & Mostofsky, 2009); or 3) data-driven approaches based on where variability best differentiates groups (Castellanos et al., 2005; Helps, Broyd, Bitsakou, & Sonuga-Barke, 2011). Figure 1 provides a visual depiction of the frequency bands under discussion, as well as the frequencies examined in prior studies. Early work using a data-driven approach identified group differences in a band centered around 0.05 Hz, which corresponds to a cycle about once every 20 seconds (Castellanos, et al., 2005, study not shown in Figure 1 because no comparison band was used). Studies using theoretically-driven frequency bands have found group differences in a range from 0.027–0.073 Hz (or every 13–37 seconds), called the “Slow-4” band (see Figure 1). Studies using task-driven approaches have similarly identified differences at frequencies less than 0.077 Hz. All of the definitions of “low” frequency have thereby emphasized the frequencies below 0.08 Hz. Figure 1 shows the “low” and comparison frequency bands used in studies of RT variability in ADHD. The ranges of the physiological “Slow-4,” “Slow-3,” and “Slow-2” bands are indicated along the bottom ... However, some studies also report ADHD-control group differences in faster frequencies using each of the preceding methods for defining bands (Helps, et al., 2011; Johnson, et al., 2008; Johnson, et al., 2007b; Vaurio, et al., 2009, all depicted on Figure 1 as well), suggesting that children with ADHD are more variable at a range of frequencies. These results seem to suggest a lack of specificity that would fail to support the basic hypothesis of frequency-domain-specific alterations in ADHD RT variability. However, the diagnosis × frequency interaction effect required to determine the relative strength of group differences was reported in only one study (the interaction was not significant, but the study’s power was low, Geurts et al., 2008). Thus, the relative strength of ADHD-related group differences at different frequencies is unclear.