Authors' reply to the commentary on "Establishing norms for error-related brain activity during the arrow Flanker task among young adults".

In their commentary on our article, "Establishing norms for error-related brain activity during the arrow Flanker task among young adults" (Imburgio et al., 2020), Clayson and colleagues (2021) voiced their concerns about our development of norms for an event-related potential measure of error monitoring, the error-related negativity (ERN). The central flaw in their commentary is the idea that because we don't know all the factors that can affect the ERN, it should not be normed. We respond to this idea, while also reiterating points made in our original manuscript: a) at present, the reported norms are not intended to be used for individual clinical assessment and b) our norms should be considered specific to the procedures (i.e., recording and processing parameters) and task used (i.e., arrow Flanker). Contrary to Clayson and colleagues' claims, we believe that information about the distribution of the ERN (i.e., our norms) in a large sample representative of those used in much of the ERN literature (i.e., unselected young adults) will be useful to the field and that this information stands to increase, not decrease, understanding of the ERN.

Establishing norms for error-related brain activity during the arrow Flanker task among young adults.

Psychological assessments typically rely on self-report and behavioral measures. Augmenting these with neurophysiological measures of the construct in question may increase the accuracy and predictive power of these assessments. Moreover, thinking about neurophysiological measures from an assessment perspective may facilitate under-utilized research approaches (e.g., brain-based recruitment of participants). However, the lack of normative data for most neurophysiological measures has prevented the comparison of individual responses to the general population, precluding these approaches. The current work examines the distributions of two event-related potentials (ERPs) commonly used in individual differences research: the error-related negativity (ERN) and error positivity (Pe). Across three lab sites, 800 unselected participants between the ages of 18 and 30 performed the arrow version of a Flanker task while EEG was recorded. Percentile scores and distributions for ERPs on error trials, correct trials, and the difference (ΔERN, ΔPe; error minus correct) at Fz, Cz and Pz are reported. The 25th, 50th, and 75th percentile values for the ΔERN at Cz were -2.37 â€‹µV, -5.41 â€‹µV, and -8.65 â€‹µV, respectively. The same values for ΔPe at Cz were 7.51 â€‹µV, 11.18 â€‹µV, and 15.55 â€‹µV. Females displayed significantly larger ΔPe magnitudes and smaller ΔERN magnitudes than males. Additionally, normative data for behavioral performance (accuracy, post-error slowing, and reaction time) on the Flanker task is reported. Results provide a means by which ERN and Pe amplitudes of young adults elicited by the arrow Flanker task can be benchmarked, facilitating the classification of neural responses as 'large,' 'medium,' or 'small'. The ability to classify responses in this manner is a necessary step towards expanded use of these measures in assessment and research settings. These norms may not apply to ERPs elicited by other tasks, and future work should establish similar norms using other tasks.

Striatal-frontal network activation during voluntary task selection under conditions of monetary reward.

During voluntary task selection, a number of internal and external biases may guide such a choice. However, it is not well understood how reward influences task selection when multiple options are possible. To address this issue, we examined brain activation in a voluntary task-switching paradigm while participants underwent fMRI (n = 19). To reinforce the overall goal to choose the tasks randomly, participants were told of a large bonus that they would receive at the end of the experiment for making random task choices. We also examined how occasional, random rewards influenced both task performance and brain activation. We hypothesized that these transient rewards would increase the value of the just-performed task, and therefore bias participants to choose to repeat the same task on the subsequent trial. Contrary to expectations, transient reward had no consistent behavioral effect on subsequent task choice. Nevertheless, the receipt of such rewards did influence activation in brain regions associated with reward processing as well as those associated with goal-directed control. In addition, reward on a prior trial was found to influence activation during task choice on a subsequent trial, with greater activation in a number of executive function regions compared with no-reward trials. We posit that both the random presentation of transient rewards and the overall task bonus for random task choices together reinforced the goal to choose the tasks randomly, which in turn influenced activation in both reward-related regions and those regions involved in abstract goal processing.

Correction to: Striatal-frontal network activation during voluntary task selection under conditions of monetary reward.

Conflict of interest statement: Although co-author Marie T. Banich is the Editor-in-Chief of Cognitive, Affective, and Behavioral Neuroscience, Stan Floresco served as the action editor for this manuscript.

Component processes underlying voluntary task selection: Separable contributions of task-set inertia and reconfiguration.

Most theories describing the cognitive processes underlying task switching allow for contributions of active task-set reconfiguration and task set inertia. Manipulations of the Cue-to-Stimulus-Interval (CSI) are generally thought to influence task set reconfiguration, while Response-to-Cue (RCI) manipulations are thought to influence task set inertia. Together, these intervals compose the Response-to-Stimulus (RSI) interval. However, these theories do not adequately account for voluntary task switching, because a participant can theoretically prepare for an upcoming trial at any point. We used drift diffusion models to examine the contributions of reconfiguration and task set inertia to performance in single- and double-registrant-registrant voluntary task switching. In both paradigms, RSI length moderated nondecision time, suggesting both switch-specific and general preparation prior to cue presentation. In only the double-registrant registrant paradigm, RSI length additionally moderated task set inertia and CSI length affected general (but not switch-specific) preparation. The effects of cue timing (CSI length) depended upon required response to the cue. Future work should attempt to corroborate our findings regarding switch-specific and general preparation effects of interval lengths using EEG.

Preliminary effects of prefrontal tDCS on dopamine-mediated behavior and psychophysiology.

The ability to manipulate dopamine in vivo through non-invasive, reversible mechanisms has the potential to impact clinical, translational, and basic research. Recent PET studies have demonstrated increased dopamine release in the striatum after bifrontal transcranial direct current stimulation (tDCS). We sought to extend this work by examining whether bifrontal tDCS could demonstrate an effect on behavioral and physiological correlates of subcortical dopamine activity. We conducted a preliminary between-subjects study (n = 30) with active and sham tDCS and used spontaneous eye blink rate (EBR), facial attractiveness ratings, and greyscales orienting bias as indirect proxies for dopamine functioning. The initial design and analyses were pre-registered (https://osf.io/gmnpc). Stimulation did not significantly affect any of the three measures, though effect sizes were often moderately large and were all in the predicted directions. Additional exploratory analyses suggested that stimulation's effect on EBR might depend on pre-stimulation dopamine levels. Our results suggest that larger samples than those that are standard in tDCS literature should be used to assess the effect of tDCS on dopamine using indirect measures. Further, exploratory results add to a growing body of work demonstrating the importance of accounting for individual differences in tDCS response.

Adolescents at clinical high risk for psychosis show qualitatively altered patterns of activation during rule learning.

BACKGROUND: The ability to flexibly apply rules to novel situations is a critical aspect of adaptive human behavior. While executive function deficits are known to appear early in the course of psychosis, it is unclear which specific facets are affected. Identifying whether rule learning is impacted at the early stages of psychosis is necessary for truly understanding the etiology of psychosis and may be critical for designing novel treatments. Therefore, we examined rule learning in healthy adolescents and those meeting criteria for clinical high risk (CHR) for psychosis. METHODS: 24 control and 22 CHR adolescents underwent rapid, high-resolution fMRI while performing a paradigm which required them to apply novel or practiced task rules. RESULTS: Previous work has suggested that practiced rules rely on rostrolateral prefrontal cortex (RLPFC) during rule encoding and dorsolateral prefrontal cortex (DLPFC) during task performance, while novel rules show the opposite pattern. We failed to replicate this finding, with greater activity for novel rules during performance. Comparing the HC and CHR group, there were no statistically significant effects, but an effect size analysis found that the CHR group showed less activation during encoding and greater activation during performance. This suggests the CHR group may use less efficient reactive control to retrieve task rules at the time of task performance, rather than proactively during rule encoding. CONCLUSIONS: These findings suggest that flexibility is qualitatively altered in the clinical high risk state, however, more data is needed to determine whether these deficits predict disease progression.

Cognitive reappraisal in an unpredictable world: Prior context matters.

Cognitive reappraisal is a higher order emotion regulation strategy, the effects of which can be measured using the late positive potential (LPP), an event-related potential that is larger for emotional versus neutral stimuli. Whereas the lab provides a relatively predictable and calm environment in which to engage in reappraisal, outside of the lab, individuals may need to enact reappraisal in unpredictable and anxiety-provoking environments. In prior work, unpredictable auditory tones have been shown to increase threat-processing and induce anxiety. Here, forty-seven participants performed a reappraisal task while being exposed in a blockwise fashion to a "Random Tone" sequence or silence ("No Tone"), to determine the effects of an unpredictable auditory stimulus on the reappraisal of negative pictures. In addition, exploratory analyses assessed whether starting block (i.e., beginning the task in a Random Tone versus No Tone block) would moderate effects. Results showed that during an early time window, reappraisal LPPs were smallest for participants who started in a No Tone block and who performed reappraisal in a No Tone block. Therefore, reappraisal may be optimally performed when conditions are predictable/calm, by participants whose initial learning context was also predictable/calm. In addition, larger LPPs for negative versus neutral images were only observed throughout the later portion of picture presentation for participants who began in a Random Tone block, suggesting that unpredictability may increase sustained attention towards aversive stimuli. The results fit within a growing body of work aimed at understanding contextual and individual differences in emotion regulation.

Single session high definition transcranial direct current stimulation to the cerebellum does not impact higher cognitive function.

The prefrontal cortex is central to higher order cognitive function. However, the cerebellum, generally thought to be involved in motor control and learning, has also been implicated in higher order cognition. Recent work using transcranial direct current stimulation (tDCS) provides some support for right cerebellar involvement in higher order cognition, though the results are mixed, and often contradictory. Here, we used cathodal high definition tDCS (HD-tDCS) over the right cerebellum to assess the impact of HD-tDCS on modulating cognitive performance. We predicted that stimulation would result in performance decreases, which would suggest that optimal cerebellar function is necessary for cognitive performance, much like the prefrontal cortex. That is, it is not simply a structure that lends support to complete difficult tasks. While the expected cognitive behavioral effects were present, we did not find effects of stimulation. This has broad implications for cerebellar tDCS research, particularly for those who are interested in using HD-tDCS as a way of examining cerebellar function. Further implications, limitations, and future directions are discussed with particular emphasis on why null findings might be critical in developing a clear picture of the effects of tDCS on the cerebellum.

Effects of prefrontal tDCS on executive function: Methodological considerations revealed by meta-analysis.

A meta-analysis of studies using single-session transcranial direct current stimulation (tDCS) to target the dorsolateral prefrontal cortex (DLPFC) was undertaken to examine the effect of stimulation on executive function (EF) in healthy samples. 27 studies were included in analyses, yielding 71 effect sizes. The most relevant measure for each task was determined a priori and used to calculate Hedge's g. Methodological characteristics of each study were examined individually as potential moderators of effect size. Stimulation effects on three domains of EF (inhibition of prepotent responses, mental set shifting, and information updating and monitoring) were analyzed separately. In line with previous work, the current study found no significant effect of anodal unilateral tDCS, cathodal unilateral tDCS, or bilateral tDCS on EF. Further moderator and subgroup analyses were only carried out for anodal unilateral montages due to the small number of studies using other montages. Subgroup analyses revealed a significant effect of anodal unilateral tDCS on updating tasks, but not on inhibition or set-shifting tasks. Cathode location significantly moderated the effect of anodal unilateral tDCS. Extracranial cathodes yielded a significant effect on EF while cranial cathodes yielded no effect. Anode size also significantly moderated effect of anodal unilateral tDCS, with smaller anodes being more effective than larger anodes. In summary, anodal DLPFC stimulation is more effective at improving updating ability than inhibition and set-shifting ability, but anodal stimulation can significantly improve general executive function when extracranial cathodes or small anodes are used. Future meta-analyses may examine how stimulation's effects on specific behavioral tasks, rather than broader domains, might be affected by methodological moderators.