An Experimental Therapeutics Approach to the Development of a Novel Computerized Treatment Targeting Error-Related Brain Activity in Young Children.

In the current study, we utilize an experimental medicine approach to examine the extent to which a single-session, computerized intervention impacts a transdiagnostic neural marker of risk (i.e., the error-related negativity [ERN]) in 70 children between the ages of 6 and 9 years. The ERN is a deflection in the event-related potential occurring after an individual makes a mistake on a lab-based task and has been shown to be transdiagnostically associated with a variety of anxiety disorders (e.g., social anxiety, generalized anxiety), obsessive-compulsive disorder, and depressive disorders in over 60 studies to date. Building on these findings, work has been done to link an increased ERN to negative reactions to, and avoidance of, making mistakes (i.e., error sensitivity). In the current study, we capitalize on this previous work by examining the extent to which a single-session, computerized intervention may engage the target of "error sensitivity" (measured by the ERN, as well as self-report of error sensitivity). We examine the convergence of multiple measures of the construct of "error sensitivity" (i.e., child self-report, parent report on child, and child electroencephalogram [EEG]). We also examine relationships between these three measures of "error sensitivity" and child anxiety symptoms. Overall, results suggested that treatment condition predicted changes in self-reported error sensitivity but not changes in ERN. Based on the lack of previous work in this area, we view this study as a novel, preliminary, first step toward using an experimental medicine approach to examine our ability to engage the target of the ERN (i.e., error sensitivity) early in development.

COVID-related fear maintains controlling parenting behaviors during the pandemic.

The direct threat posed by the 2019 novel coronavirus (COVID-19), uncertainty surrounding best safety practices, and secondary consequences of the virus have led to widespread stress and declining mental health across communities and individuals. These stresses may impact parenting behaviors, potentially leading to negative consequences for children. Controlling parenting behaviors increase in the face of perceived environmental threat and are associated with adverse mental health outcomes for children; however, determinants of parenting behaviors have not been investigated during the COVID-19 pandemic. The current study prospectively evaluated parenting behaviors during the pandemic (N=87). Results indicated that all negative affect emotions investigated were positively associated with controlling parenting behaviors. However, only COVID-related fear predicted changes in controlling parenting behaviors across timepoints. Specifically, although controlling parenting behaviors decreased in the overall sample from time 1 to time 2, higher COVID-related fear scores at time 1 predicted maintenance of high levels of controlling parenting behaviors at time 2. Additionally, this effect was specific to controlling, as opposed to more adaptive, parenting behaviors. Future studies should investigate the association between parents' COVID-related fear, controlling parenting behaviors, and adverse mental health outcomes for children in the context of the COVID-19 pandemic.

Controlling parenting and perfectionism is associated with an increased error-related negativity (ERN) in young adults.

A substantial amount of research focuses on the error-related negativity (ERN)-a negative deflection in the event-related potential waveform that occurs when individuals commit errors on lab-based tasks. The ERN has been link to concurrent and prospective risk for psychopathology and is thought to index sensitivity or reactivity to errors. The ERN can be potentiated in the lab with punishment and has been shown to be increased among offspring of harsh or controlling parents. A separate line of work has demonstrated that the ERN is increased among individuals high in perfectionism. In the current study, we integrate these separate lines of work by examining parenting styles, perfectionism and the ERN in a sample of young adults. Results suggest that the ERN is increased among offspring of controlling parents (both maternal and paternal). Additionally, the ERN is increased among individuals who report being high in perfectionism-specifically, the concerns over mistake and the personal standard perfectionism subscales of the Frost Multidimensional Perfectionism Scale. Moreover, results supported a mediation model wherein the indirect pathway from controlling parenting style to perfectionism (personal standard subscale) was mediated by the ERN-for paternal parenting.

A brief, computerized intervention targeting error sensitivity reduces the error-related negativity.

Research has identified the neural response to errors (the error-related negativity; ERN) as a marker of current anxiety, as well as risk for future anxiety. Previous work found that traditional cognitive behavioral therapy approaches do not impact the ERN. However, none of these approaches directly target the psychological constructs linked to an increased ERN (e.g., error sensitivity). In the current study, we examine the extent to which a brief, computerized intervention ("Treating the ERN"; i.e., TERN) might impact the ERN by reducing error sensitivity. Results suggest that TERN reduced the ERN and that the impact of the intervention was larger amongst individuals with an increased baseline ERN. This study is an important first step in the development of a novel intervention approach that directly targets error sensitivity, and thereby the ERN.

Insomnia symptoms predict the development of post-traumatic stress symptoms following an experimental trauma.

Insomnia symptoms prior to traumatic event exposure predict the development of post-traumatic stress symptoms. However, potential mechanisms underlying the association between insomnia and risk for post-traumatic stress disorder symptoms have not been prospectively tested. The current study used the trauma film paradigm to test whether insomnia symptoms prior to analogue trauma exposure predict subsequent analogue post-traumatic stress disorder symptoms, and potential mediators of this relationship, among an at-risk sample of 108 participants. Results indicated that, after covarying for negative affectivity, insomnia symptoms in the 2 weeks prior to analogue trauma exposure significantly predicted increased post-traumatic stress disorder symptoms 3 days and 1 week post-exposure. Moreover, distress immediately after exposure and post-traumatic avoidance mediated the association between insomnia symptoms and post-traumatic stress disorder symptoms 1 week after exposure. Effect sizes were small. The current study uses an analogue trauma and analogue post-traumatic stress disorder symptoms to model clinical symptoms, includes an additional intervention prior to analogue trauma, and lacks a control film. Findings suggest increased reactivity to trauma exposure and subsequent reminders, and attempts to suppress trauma memories may be mechanisms in the association between insomnia symptoms and risk for post-traumatic stress disorder symptoms.

The Presence of a Controlling Parent Is Related to an Increase in the Error-Related Negativity in 5-7 Year-Old Children.

Anxiety disorders often begin early in life and there is substantial interest in identifying neural markers that characterize developmental trajectories that result in anxiety. The error-related negativity (ERN) is elicited when people make errors on lab-based reaction-time tasks, is increased in anxious children, and can predict the onset of anxiety across development. In light of this, there is an increasing interest in identifying environmental factors that may shape the ERN in children. Previous work suggests that controlling parenting styles may relate to the ERN in offspring. However, no study had yet examined the specific mechanism whereby parenting style may impact the ERN in children. We propose that it may be children's repeated exposure to making mistakes in the context of their parents' reactions (i.e., verbal or non-verbal reactions, displays of parental control, etc.) that may lead to an increased ERN. We test this novel hypothesis by measuring the ERN in 94 children between the ages of 5-7 years old, while their parent observes them and then while an experimenter observes them complete a Go-No/Go task. Results suggest that the presence of parents characterized by high control potentiates the ERN in their children. Moreover, the relationship between controlling parenting styles and child anxiety disorder status was mediated by the parent presence potentiation of the ERN. These findings are important and novel insofar as they highlight the impact of an environmental factor (i.e., parenting) in shaping a neural marker of risk for anxiety in children (i.e., the ERN).

Correction to: Improvement in Cognitive Function as Measured by NeuroTrax in Patients with Relapsing Multiple Sclerosis Treated with Natalizumab: A 2-Year Retrospective Analysis.

An Online First version of this article was made available online at http://link.springer.com/journal/40263/onlineFirst/page/1 on 24 August 2018. An error was subsequently identified in the article, and the following correction should be noted.

Improvement in Cognitive Function as Measured by NeuroTrax in Patients with Relapsing Multiple Sclerosis Treated with Natalizumab: A 2-Year Retrospective Analysis.

BACKGROUND: Cognitive impairment affects many patients with multiple sclerosis (MS). NeuroTrax, a computerized cognitive screen that can be administered during routine clinical care, provides a consistent, validated, objective cognitive profile measure with a global cognitive score (GCS) and seven individual domain scores. Natalizumab is an efficacious therapy for relapsing MS, demonstrating reductions in disability worsening and MS disease activity measured by magnetic resonance imaging. OBJECTIVE: The aim of this study was to assess cognitive function as measured by NeuroTrax in MS patients treated with natalizumab for ≥ 2 years. METHODS: This retrospective observational study included adult MS patients in the United States who received 300 mg intravenous natalizumab every 4 weeks for ≥ 2 years. NeuroTrax data were evaluated at baseline and yearly thereafter. Changes in GCS and the seven individual cognitive domain scores from baseline to after 24 infusions of natalizumab were analyzed. RESULTS: In the study population at baseline (N = 52), 22 patients (42.3%) had disease duration of 0-5 years; 12 patients (23.1%) were treatment naive. GCS score improved significantly from baseline [mean 95.5, standard deviation (SD) 12.9] to year 2 (mean 98.9, SD 13.2; change from baseline 3.4; p = 0.003). After 2 years on natalizumab, 17 patients (32.7%) demonstrated clinically significant improvement (increase from baseline > 1 SD) in GCS. Results were similar regardless of whether patients had previously received MS therapy. CONCLUSIONS: Patients treated with natalizumab demonstrated significant improvement in cognitive function, measured by NeuroTrax GCS, over 2 years of treatment.

The Parent Sensitivity to Child Anxiety Index.

Anxiety sensitivity (AS) is the perception that anxiety symptoms and experiences have negative consequences, and has been identified as a risk factor for the development of anxiety disorders. AS has been measured in adults and in children, but to date, the construct of parent's sensitivity to their children's anxiety symptoms has not been identified, measured, or evaluated. The current study presents a novel measure of this construct, the Parent Sensitivity to Child Anxiety Index (PSCAI), and an initial evaluation of its psychometric properties. Factor analysis revealed a three-factor structure consisting of parents' concern for physical symptoms, concern of social evaluation, and fear of anxiety symptoms. The PSCAI demonstrated good internal consistency, and was positively correlated with relevant parental constructs such as parental accommodation, anxiety sensitivity, and trait anxiety. This new measurement system opens new avenues for researching the early development of anxiety disorders and the possibility for novel targeted interventions.

The impact of subjective cognitive fatigue and depression on cognitive function in patients with multiple sclerosis.

BACKGROUND: The association between subjective cognitive fatigue and objective cognitive dysfunction in patients with multiple sclerosis (PwMS) has been studied, with conflicting results. OBJECTIVE: To explore the impact of fatigue on cognitive function, while controlling for the influence of depression, disability, comorbidities, and psychotropic medications. METHODS: PwMS completed a computerized cognitive testing battery with age- and education-adjusted cognitive domain scores. Disability (Expanded Disability Status Scale (EDSS)), cognitive fatigue, and depression were concurrently evaluated. RESULTS: In all, 699 PwMS were included. Both cognitive fatigue and depression were significantly and negatively correlated with the same cognitive domains: information processing speed, executive function, attention, motor function, and memory (-0.15 ⩽ r ⩽ -0.14 for cognitive fatigue; -0.24 ⩽ r ⩽ -0.19 for depression). Multivariate analysis revealed significant but small independent correlations only between depression and neuropsychological test results, while cognitive fatigue had no independent correlation with objective cognitive function except for a trend toward impaired motor function in highly fatigued PwMS. Depression and cognitive fatigue accounted for no more than 6% of the variance in objective cognitive domain scores. CONCLUSION: Cognitive fatigue is not independently related to objective cognitive impairment. Depression may influence cognitive function of PwMS primarily when it is severe. Cognitive impairment in PwMS should not be ascribed to fatigue or mild depression.