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  • Previous work examining the link between the COMT


    Previous work examining the link between the COMT gene and ISV is limited and has produced contradicting results. The Val allele was linked with higher ISV of RTs following target trials in a continuous performance task (Stefanis et al., 2005) and with higher ISV of RT and P3b latencies of unfamiliar faces compared to familiar faces in a face-recognition task (Rostami et al., 2017). Contrastingly, the Met allele was associated with higher ISV of anti-saccade latency (Haraldsson et al., 2010). While each of these studies is highly suggestive of a link between COMT and ISV in various cognitive tasks, they Isoxsuprine hydrochloride all confined the measurement of variability to RTSD, a sensitive but non-specific global measure of ISV. Given that variability of biological systems rarely exhibits absolute stochastic or strictly periodic patterns (Billman, 2011) but rather combines elements of both types of processes (Auffray, Imbeaud, Roux-rouquie, & Hood, 2003), RTSD likely represents the amalgamation of various types of ISV (e.g. (non-)linear, (non-)periodic). In this regard, the use of distributional (e.g. ex-Gaussian, see below) and time-series (e.g. frequency-spectral measures to capture periodicity of RTs) measures may characterize and unmask potentially unique neural sources of variability; and thus collectively reflect different “facets” of ISV. The ex-Gaussian model describes the shape of individual RT distributions with mu and sigma describing the mean and standard deviation of a Gaussian RT component, respectively, and tau, describing the mean and standard deviation of the ex-Gaussian RT component. Ex-Gaussian tau is proposed to reflect lapses of attention (Leth-Steensen, King Elbaz, Douglas, Elbaz, & Douglas, 2000) which are considered to emerge due to poor suppression of the default mode network (DMN) in ADHD (Fassbender et al., 2009). Using Fast Fourier Transform (FFT) based filtering techniques on distributional measures, we have shown that tau is rather exclusively characterised by ultra-slow quasi-periodic RT fluctuations in ADHD children (Feige et al., 2013); a spectral signature that corresponds directly with that of electrophysiological fluctuations linked with the DMN (Ko, Poliakov, Sorensen, Ojemann, & Darvas, 2011). A replication of this finding in a larger healthy sample would further support the interpretation of elevated tau as recurrent lapses of attention due to DMN interference (Sonuga-Barke & Castellanos, 2007). With regard to the Gaussian potion of RT distributions, the consensus on a psychological interpretation is less clear that for tau. Yet, as the Gaussian mean, mu, has been linked with rather “basic” internal processes such as neural transmission or sensory and motor processes (see review by Matzke & Wagenmakers, 2009); sigma may index neural noise. Based on previous COMT studies in which Val allele carriers appropriately deactivated DMN-related regions (Ettinger et al., 2008, Stokes et al., 2011) and had increased prefrontal “noise” while performing various cognitive tasks (Egan et al., 2001, Winterer et al., 2006, Winterer et al., 2006), it is plausible that ISV for these carriers is characterized by generally lower tau and elevated sigma. Yet, results may vary largely depending on task requirements. Based on the tonic-phasic theory, variations in levels of DA via COMT may be beneficial or detrimental for performance depending on the cognitive demands of the task at hand (Bilder, Volavka, Lachman, & Grace, 2004). The Met allele, associated with high tonic DA transmission and cortical D1 stimulation, is linked with higher cognitive stability. Conversely, the Val allele, linked with high phasic Isoxsuprine hydrochloride DA transmission and subcortical D2 stimulation, is related with higher cognitive flexibility. The critical association between DA and cognitive demands may underlie the contradiction in previous COMT studies on ISV (Haraldsson et al., 2010, Rostami et al., 2017, Stefanis et al., 2005). As such, a more detailed examination of the demands of working memory (WM) and response-switching and their interactions with COMT on ISV facets is warranted.