Lindsay D. Nelson

A construct-network approach to bridging diagnostic and physiological domains: application to assessment of externalizing psychopathology.

A crucial challenge in efforts to link psychological disorders to neural systems, with the aim of developing biologically informed conceptions of such disorders, is the problem of method variance (Campbell & Fiske, 1959). Since even measures of the same construct in differing domains correlate only moderately, it is unsurprising that large sample studies of diagnostic biomarkers yield only modest associations. To address this challenge, a construct-network approach is proposed in which psychometric operationalizations of key neurobehavioral constructs serve as anchors for identifying neural indicators of psychopathology-relevant dispositions, and as vehicles for bridging between domains of clinical problems and neurophysiology. An empirical illustration is provided for the construct of inhibition-disinhibition, which is of central relevance to problems entailing deficient impulse control. Findings demonstrate that: (1) a well-designed psychometric index of trait disinhibition effectively predicts externalizing problems of multiple types, (2) this psychometric measure of disinhibition shows reliable brain response correlates, and (3) psychometric and brain-response indicators can be combined to form a joint psychoneurometric factor that predicts effectively across clinical and physiological domains. As a methodology for bridging between clinical problems and neural systems, the construct-network approach provides a concrete means by which existing conceptions of psychological disorders can accommodate and be reshaped by neurobiological insights.

Externalizing Psychopathology and Gain-Loss Feedback in a Simulated Gambling Task: Dissociable Components of Brain Response Revealed by Time-Frequency Analysis

Externalizing is a broad construct that reflects propensity toward a variety of impulse control problems, including antisocial personality disorder and substance use disorders. Two event-related potential responses known to be reduced among individuals high in externalizing proneness are the P300, which reflects postperceptual processing of a stimulus, and the error-related negativity (ERN), which indexes performance monitoring based on endogenous representations. In the current study, the authors used a simulated gambling task to examine the relation between externalizing proneness and the feedback-related negativity (FRN), a brain response that indexes performance monitoring related to exogenous cues, which is thought to be highly related to the ERN. Time-frequency (TF) analysis was used to disentangle the FRN from the accompanying P300 response to feedback cues by parsing the overall feedback-locked potential into distinctive theta (4-7 Hz) and delta (<3 Hz) TF components. Whereas delta-P300 amplitude was reduced among individuals high in externalizing proneness, theta-FRN response was unrelated to externalizing. These findings suggest that in contrast with previously reported deficits in endogenously based performance monitoring (as indexed by the ERN), individuals prone to externalizing problems show intact monitoring of exogenous cues (as indexed by the FRN). The results also contribute to a growing body of evidence indicating that the P300 is attenuated across a broad range of task conditions in high-externalizing individuals.

Clarifying domains of internalizing psychopathology using neurophysiology.

Current initiatives such as the National Institute of Mental Healths Research Domain Criteria project aim to reorganize classification of mental disorders along neurobiological lines. Here, we describe how consideration of findings from psychiatric research employing two physiological measures with distinct neural substrates--the startle blink reflex and the error-related negativity (ERN)--can help to clarify relations among disorders entailing salient anxiety or depressive symptomatology. Specifically, findings across various studies and reviews reveal distinct patterns of association for both the startle blink reflex and the ERN with three key domains of psychopathology: (1) Fear (or phobic) disorders (distinguished by increased startle to unpleasant stimuli, but normal-range ERN). (2) Non-phobic anxiety disorders and negative affect (associated with increased ERN, increased startle across all types of emotional stimuli and increased baseline startle) and, more tentatively (3) Major depression (for which patterns of response for both startle and ERN appear to vary, as a function of severity and distinct symptomatology). Findings from this review point to distinct neurobiological indicators of key psychopathology domains that have been previously demarcated using personality and diagnostic data. Notably, these indicators exhibit more specificity in their relations with these three domains than has been seen in quantitative-dimensional models. Implications of these findings are discussed.

Operationalizing proneness to externalizing psychopathology as a multivariate psychophysiological phenotype.

The externalizing dimension is viewed as a broad dispositional factor underlying risk for numerous disinhibitory disorders. Prior work has documented deficits in event-related brain potential (ERP) responses in individuals prone to externalizing problems. Here, we constructed a direct physiological index of externalizing vulnerability from three ERP indicators and evaluated its validity in relation to criterion measures in two distinct domains: psychometric and physiological. The index was derived from three ERP measures that covaried in their relations with externalizing proneness-the error-related negativity and two variants of the P3. Scores on this ERP composite predicted psychometric criterion variables and accounted for externalizing-related variance in P3 response from a separate task. These findings illustrate how a diagnostic construct can be operationalized as a composite (multivariate) psychophysiological variable (phenotype).

Cerebral Blood Flow Alterations in Acute Sport-Related Concussion

Sport-related concussion (SRC) is a major health problem, affecting millions of athletes each year. While the clinical effects of SRC (e.g., symptoms and functional impairments) typically resolve within several days, increasing evidence suggests persistent neurophysiological abnormalities beyond the point of clinical recovery after injury. This study aimed to evaluate cerebral blood flow (CBF) changes in acute SRC, as measured using advanced arterial spin labeling (ASL) magnetic resonance imaging (MRI). We compared CBF maps assessed in 18 concussed football players (age, 17.8 ± 1.5 years) obtained within 24 h and at 8 days after injury with a control group of 19 matched non-concussed football players. While the control group did not show any changes in CBF between the two time-points, concussed athletes demonstrated a significant decrease in CBF at 8 days relative to within 24 h. Scores on the clinical symptom (Sport Concussion Assessment Tool 3, SCAT3) and cognitive measures (Standardized Assessment of Concussion [SAC]) demonstrated significant impairment (vs. pre-season baseline levels) at 24 h (SCAT, p < 0.0001; SAC, p < 0.01) but returned to baseline levels at 8 days. Two additional computerized neurocognitive tests, the Automated Neuropsychological Assessment Metrics and Immediate Post-Concussion and Cognitive Testing, showed a similar pattern of changes. These data support the hypothesis that physiological changes persist beyond the point of clinical recovery after SRC. Our results also indicate that advanced ASL MRI methods might be useful for detecting and tracking the longitudinal course of underlying neurophysiological recovery from concussion.

Preinjury somatization symptoms contribute to clinical recovery after sport-related concussion.

Objective: To determine the degree to which preinjury and acute postinjury psychosocial and injury-related variables predict symptom duration following sport-related concussion. Methods: A total of 2,055 high school and collegiate athletes completed preseason evaluations. Concussed athletes (n = 127) repeated assessments serially (<24 hours and days 8, 15, and 45) postinjury. Cox proportional hazard modeling was used to predict concussive symptom duration (in days). Predictors considered included demographic and history variables; baseline psychological, neurocognitive, and balance functioning; acute injury characteristics; and postinjury clinical measures. Results: Preinjury somatic symptom score (Brief Symptom Inventory–18 somatization scale) was the strongest premorbid predictor of symptom duration. Acute (24-hour) postconcussive symptom burden (Sport Concussion Assessment Tool–3 symptom severity) was the best injury-related predictor of recovery. These 2 predictors were moderately correlated (r = 0.51). Path analyses indicated that the relationship between preinjury somatization symptoms and symptom recovery was mediated by postinjury concussive symptoms. Conclusions: Preinjury somatization symptoms contribute to reported postconcussive symptom recovery via their influence on acute postconcussive symptoms. The findings highlight the relevance of premorbid psychological factors in postconcussive recovery, even in a healthy athlete sample relatively free of psychopathology or medical comorbidities. Future research should elucidate the neurobiopsychosocial mechanisms that explain the role of this individual difference variable in outcome following concussive injury.

Reliability and Validity of the Sport Concussion Assessment Tool–3 (SCAT3) in High School and Collegiate Athletes

Background: The Sport Concussion Assessment Tool–3 (SCAT3) facilitates sideline clinical assessments of concussed athletes. Yet, there is little published research on clinically relevant metrics for the SCAT3 as a whole. Purpose: We documented the psychometric properties of the major SCAT3 components (symptoms, cognition, balance) and derived clinical decision criteria (ie, reliable change score cutoffs and normative conversation tables) for clinicians to apply to cases with and without available preinjury baseline data. Study Design: Cohort study (diagnosis); Level of evidence, 2. Methods: High school and collegiate athletes (N = 2018) completed preseason baseline evaluations including the SCAT3. Re-evaluations of 166 injured athletes and 164 noninjured controls were performed within 24 hours of injury and at 8, 15, and 45 days after injury. Analyses focused on predictors of baseline performance, test-retest reliability, and sensitivity and specificity of the SCAT3 using either single postinjury cutoffs or reliable change index (RCI) criteria derived from this sample. Results: Athlete sex, level of competition, attention-deficit/hyperactivity disorder (ADHD), learning disability (LD), and estimated verbal intellectual ability (but not concussion history) were associated with baseline scores on ≥1 SCAT3 components (small to moderate effect sizes). Female sex, high school level of competition (vs college), and ADHD were associated with higher baseline symptom ratings (d = 0.25-0.32). Male sex, ADHD, and LD were associated with lower baseline Standardized Assessment of Concussion (SAC) scores (d = 0.28-0.68). Male sex, high school level of competition, ADHD, and LD were associated with poorer baseline Balance Error Scoring System (BESS) performance (d = 0.14-0.26). After injury, the symptom checklist manifested the largest effect size at the 24-hour assessment (d = 1.52), with group differences diminished but statistically significant at day 8 (d = 0.39) and nonsignificant at day 15. Effect sizes for the SAC and BESS were small to moderate at 24 hours (SAC: d = −0.36; modified BESS: d = 0.46; full BESS: d = 0.51) and became nonsignificant at day 8 (SAC) and day 15 (BESS). Receiver operating characteristic curve analyses demonstrated a stronger discrimination for symptoms (area under the curve [AUC] = 0.86) than cognitive and balance measures (AUCs = 0.58 and 0.62, respectively), with comparable discrimination of each SCAT3 component using postinjury scores alone versus baseline-adjusted scores (P = .71-.90). Normative conversion tables and RCI criteria were created to facilitate the use of the SCAT3 both with and without baseline test results. Conclusion: Individual predictors should be taken into account when interpreting the SCAT3. The normative conversion tables and RCIs presented can be used to help interpret concussed athletes’ performance both with and without baseline data, given the comparability of the 2 interpretative approaches.

Sport-Related Concussion Reporting and State Legislative Effects.

Objective:To investigate concussion rates and reporting frequencies in high school and collegiate athletes in 2013, compare results to those obtained from 1999 to 2002, and examine to what extent the 2012 Wisconsin state concussion law affected reporting in 2013. Design:Retrospective 2013 survey compared with prior survey. Setting:High schools and colleges in the Milwaukee, Wisconsin, area. Participants:Athletes (N = 784) from multiple sports were surveyed in 2013. Football players (N = 1532) from 1999 to 2002 completed the same measure. Main Outcome Measures:Both surveys assessed concussion history, concussion incidence during the current season, whether incident concussions were reported, who concussions were reported to, and reasons for not reporting. The 2013 survey also assessed awareness of the Wisconsin state law and its effect on reporting. Results:Rates of concussion in the surveyed season were comparable to previous findings from 1999 to 2002 (16.6% vs 15.3%, P = 0.558). Notably, athletes were significantly more likely to report their concussions in 2013 (70.6% vs 47.3% previously, P = 0.011). Among high school athletes surveyed, 59.5% were aware of the Wisconsin state law, with 55.1% stating it would make them more likely to report a concussion. Conclusions:Rates of concussion for 1 sport season have not changed significantly over the past 14 years. The percentage of concussions that are reported to someone has increased significantly. Awareness of the Wisconsin state law does not fully account for the increase in concussion reporting. Clinical Relevance:Given the finite amount of knowledge regarding the influence of concussion-related cultural and legal changes, these findings will help to inform clinicians of the current concussion milieu from the perspective of athletes. It will inform practitioners involved in concussion management to what extent athletes are aware of and report concussions.

Acute white matter changes following sport-related concussion: A serial diffusion tensor and diffusion kurtosis tensor imaging study

Recent neuroimaging studies have suggested that following sport‐related concussion (SRC) physiological brain alterations may persist after an athlete has shown full symptom recovery. Diffusion MRI is a versatile technique to study white matter injury following SRC, yet serial follow‐up studies in the very acute stages following SRC utilizing a comprehensive set of diffusion metrics are lacking. The aim of the current study was to characterize white matter changes within 24 hours of concussion in a group of high school and collegiate athletes, using Diffusion Tensor and Diffusion Kurtosis Tensor metrics. Participants were reassessed a week later. At 24 hours post‐injury, the concussed group reported significantly more concussion symptoms than a well‐matched control group and demonstrated poorer performance on a cognitive screening measure, yet these differences were nonsignificant at the 8‐day follow‐up. Similarly, within 24‐hours after injury, the concussed group exhibited a widespread decrease in mean diffusivity, increased axial kurtosis and, to a lesser extent, decreased axial and radial diffusivities compared with control subjects. At 8 days post injury, the differences in these diffusion metrics were even more widespread in the injured athletes, despite improvement of symptoms and cognitive performance. These MRI findings suggest that the athletes might not have reached full physiological recovery a week after the injury. These findings have significant implications for the management of SRC because allowing an athlete to return to play before the brain has fully recovered from injury may have negative consequences. Hum Brain Mapp 37:3821–3834, 2016.

Rates and Predictors of Invalid Baseline Test Performance in High School and Collegiate Athletes for 3 Computerized Neurocognitive Tests ANAM, Axon Sports, and ImPACT

Background: Preseason baseline testing using computerized neurocognitive tests (CNTs) is increasingly performed on athletes. Adequate effort is critical to establish valid estimates of ability, but many users do not evaluate performance validity, and the conditions that affect validity are not well understood across the available CNTs. Purpose: To examine the rates and predictors of invalid baseline performance for 3 popular CNTs: Automated Neuropsychological Assessment Metrics (ANAM), Axon Sports, and Immediate Post-Concussion and Cognitive Testing (ImPACT). Study Design: Controlled laboratory study. Methods: High school and collegiate athletes (N = 2063) completed 2 of 3 CNTs each during preseason evaluations. All possible pairings were present across the sample, and the order of administration was randomized. Examiners provided 1-on-1, scripted pretest instructions, emphasizing the importance of good effort. Profile validity was determined by the manufacturers’ standard criteria. Results: The overall percentage of tests flagged as of questionable validity was lowest for ImPACT (2.7%) and higher for ANAM and Axon (10.7% and 11.3%, respectively). The majority of invalid baseline profiles were flagged as such because of failure on only 1 validity criterion. Several athlete and testing factors (eg, attention deficit hyperactivity disorder [ADHD], estimated general intellectual ability, administration order) predicted validity status for 1 or more CNTs. Considering only first CNT administrations and participants without ADHD and/or a learning disability (n = 1835) brought the rates of invalid baseline performances to 2.1%, 8.8%, and 7.0% for ImPACT, ANAM, and Axon, respectively. Invalid profiles on the Medical Symptom Validity Test (MSVT) were rare (1.8% of participants) and demonstrated poor correspondence to CNT validity outcomes. Conclusion: The validity criteria for these CNTs may not identify the same causes of invalidity or be equally sensitive to effort. The validity indicators may not be equally appropriate for some athletes (eg, those with neurodevelopmental disorders). Clinical Relevance: The data suggest that athletes do not put forth widespread low effort or that some validity criteria are more sensitive to invalid performance than others. It is important for examiners to be aware of the conditions that maximize the quality of baseline assessments and to understand what sources of invalid performance are captured by the validity criteria that they obtain.