Behavioral and neural stability of attention bias to threat in healthy adolescents
Introduction
An emerging literature examines test–retest reliability of functional magnetic resonance imaging (fMRI) measures, which crucially informs understandings on the neural underpinnings of psychopathology (Sauder et al., 2013). Specifically, finding reliable neural correlates of specific behaviors vitally guides attempts to identify biomarkers, which may guide treatment and prevention research (Zuo and Xing, 2014). However, few such studies document temporal stability of functional connectivity or examine tasks that probe behaviors strongly linked to psychopathology. To address these gaps, the current study examines reliability of both activation and functional connectivity during the dot-probe task, which consistently elicits behavioral differences between patients with anxiety and healthy subjects.
An expanding literature uses the dot-probe task to assess attention allocation to threat. In this task (Fig 1), threat and neutral stimuli are presented simultaneously, followed by a probe. Individual differences in anxiety relate to differences in reaction-time (RT) on trials where the probe appears in the same, vs. different, spatial location as the threat. This RT-difference measure is referred to as an “attention bias”. Increased attention bias to threat in anxious relative to healthy children and adults is one of the most consistently observed associations in research on anxiety (for review see Bar-Haim et al., 2007) and provides a target for novel therapies (Beard, 2011, Hakamata et al., 2010, Linetzky et al., 2015).
Recent work demonstrates poor stability for at least some RT-based measures of attention bias (e.g., Brown et al., 2014), which could reflect limitations in particular RT-based measures (Salthouse and Hedden, 2002). For example, an RT-based measure of variability in attention bias across trials (Iacoviello et al., 2014, Naim et al., 2015) shows better stability than the standard RT-based attention bias measure (Price et al., 2015). However, even the most stable RT-based measure is likely to incompletely reflect particular neural function. This is because RT-based measures of attention bias reduce multiple, dissociable neuro-behavioral processes, such as attention orienting, response selection, and motor execution, to a single value. Some of these neuro-behavioral processes may be more stable than others, and RT-based measures could be unduly influenced by particularly unreliable processes. Such unreliable processes could vary across task administration, as opposed to other processes, which are expressed more stably. Brain-based measures may detect these more stable processes (Britton et al., 2013), which may quantify more stable underlying functions that sustain threat-processing patterns within an individual. Given widespread use of the dot-probe task in clinical research, finding reliable brain functions engaged by the task could advance attempts to adapt the task to create a biomarker in translational neuroscience research on anxiety.
To date, fMRI research using the dot-probe task yields generally consistent findings (Britton, 2012, Fani et al., 2012, Monk et al., 2006, Monk et al., 2008, Telzer et al., 2008). On this task, individual differences in anxiety relate to perturbed function in brain regions supporting emotional processing (e.g., amygdala) and attentional control (e.g., ventrolateral prefrontal cortex, vlPFC; dorsolateral prefrontal cortex, dlPFC). Considerable imaging research examines individuals between the ages of 10 and 17, which creates a particular need for reliability in subjects within this age range. Moreover, in these imaging studies, some findings emerge for contrasts comparing angry incongruent (different spatial location) and angry congruent (same spatial location) trials (i.e., the attention bias to threat contrast). These studies find that anxiety is associated with greater amygdala (Monk et al., 2008) and greater lateral PFC activation (e.g., Britton, 2012, Telzer et al., 2008). Other findings emerge when examining neural activation to any threatening facial expression, collapsing across congruency, compared to neutral facial expressions on the dot-probe task (Monk et al., 2006). Perhaps the most consistent finding in adults (Hardee et al., 2013) and youths (Monk et al., 2008) links individual differences in anxiety to negative coupling of frontal and amygdala regions (i.e., fronto-amygdala connectivity). This suggests dysfunctional recruitment of attentional control processes following threat exposure, as has been found on other attention-emotion tasks (Gold et al., 2014, McClure et al., 2007, Payer et al., 2012).
Such perturbed fronto-amygdala connectivity is associated with anxiety and threat processing beyond the dot-probe task (e.g., Sylvester et al., 2012, McClure et al., 2007); therefore, fronto-amygdala connectivity may represent a biomarker to be pursued in translational neuroscience research and in reliability studies. However, to date, no study examines test–retest reliability of task-based fronto-amygdala connectivity. Moreover, across various other task-based indices of activation, divergent reliability estimates emerge in youth (e.g., Koolschijn et al., 2011) and adults (e.g Sauder et al., 2013). For example, intraclass correlation coefficients (ICCs) for PFC activation vary widely across children and adolescents (e.g., ICCs: 0.07–0.62, Koolschijn et al., 2011; ICCs: 0.15–0.43, Ordaz et al., 2013; ICCs: 0.17–0.56, Van den Bulk et al., 2013) and adults (e.g., ICCs: 0.37–0.66, Koolschijn et al., 2011; ICCs: 0.15–0.55, Plichta et al., 2012) with few estimates falling in the “good” (ICCs of 0.6–0.74) or “excellent” (ICCs > 0.75) range (Cicchetti, 2001). Estimates of amygdala stability are also quite variable. Some studies report poor reliability (ICCs < .4) in samples of adults (Sauder et al., 2013) and youth (Van den Bulk et al., 2013), while other studies have reported good amygdala reliability (ICCs > 0.5) in adults (e.g., Manuck et al., 2007). Of note, the one stability study for the dot-probe task generated reasonable amygdala and PFC reliability in children and adolescents (ICCs: 0.73–0.83), but the study is limited by a small sample size (n = 12; Britton et al., 2013).
The current study examines reliability using the dot-probe task in healthy children and adolescents. There is a particular need for such research in youth. As noted above, considerable fMRI research uses the dot-probe task in this age group. Moreover, behavioral data in youth link attention bias to anxiety vulnerability (Pérez-Edgar et al., 2011, Shechner et al., 2012, White et al., in press), which creates a further need. Finally, in the few fMRI reliability studies conducted in children and adolescents, reliability estimates appear to be significantly lower in youth than adults (Koolschijn et al., 2011, Ordaz et al., 2013). Thus, understanding the reliability of neural activation associated with this behavioral vulnerability factor in child and adolescent populations is important. Of note, no prior studies examine reliability for task-specific functional connectivity, where between-group differences most consistently emerge in studies of anxiety. To address this issue, the current study reports a method for examining stability of connectivity and applies this method to the dot-probe task. Moreover, reliability work often compares task conditions to an implicit baseline (e.g., response to faces vs. fixation cross). To identify clinically-relevant targets, research is needed on contrasts typically used for group level analyses (e.g., threat incongruent trials vs. threat congruent trials, threat faces vs. neutral faces). The current study considers both such types of contrasts across a nine-week period. This interval between visits was chosen to parallel the frame when effects of treatment on brain function and dot-probe behavioral performance have been examined in anxious youth.
Section snippets
Participants
Thirty-nine healthy children and adolescents (18 female; M = 13.71 years, SD = 2.31, range: 10.25–17.42) completed the current study. Beyond these 39 individuals, an additional seven participants were enrolled but excluded due to technical issues during fMRI data acquisition (n = 2) or poor task performance (accuracy < 75%; n = 5). Participants were free of psychopathology as determined by a structured interview (K-SADS-PL; Kaufman et al., 1997). All participants had an IQ > 70 as assessed by the Wechsler
Reliability of anxiety and dot-probe behavioral reaction time measures
Means and standard deviations of anxiety scores and behavioral data from the dot-probe task are presented in Table 1. For task performance, participant's RTs on the task, collapsed across all conditions, were stable across time (ICC = 0.57). However, attention bias to threat scores (ICC = − 0.16) and threat distraction scores (ICC = − 0.12) showed poor test–retest reliability. ABV scores also showed low reliability, but did have a higher ICC values than the other behavioral measures (ICC = 0.36). It
Discussion
The current study examined test–retest reliability of brain regions engaged by the dot-probe task in healthy youth. Results suggest the potential utility of continuing to explore attention tasks as anxiety-related biomarkers. Specifically, the current findings demonstrate good test–retest reliability in key PFC regions highlighted in prior dot-probe research. The findings also revealed good stability in fronto-amygdala connectivity. In fact, more regions were found to be stable for the
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