A Double-Blind Placebo-Controlled, Randomized Trial of Divalproex Sodium for Posttraumatic Irritability Greater Than 1 Year After Mild to Moderate Traumatic Brain Injury.

OBJECTIVE: Posttraumatic irritability after traumatic brain injury (TBI) may become a chronic problem and contribute to impaired everyday function, either alone or in combination with alcohol use disorder. The authors hypothesized that divalproex sodium (VPA) would improve posttraumatic irritability and result in lessened alcohol use. METHODS: This randomized, placebo-controlled double-blind clinical trial recruited participants with an index TBI occurring 1 or more years prior to enrollment, a history of alcohol use disorder, and posttraumatic irritability corroborated by a knowledgeable informant. An 8-item subset of the Agitated Behavior Scale served as the primary outcome measure of VPA efficacy. Doses of VPA were titrated to standard serum concentrations of 50 µg/ml to 100 µg/ml. RESULTS: Forty-eight persons completed this clinical trial (VPA, N=22; placebo, N=26). At baseline, participants rated their posttraumatic irritability as less severe than did their informants (p<0.05). During the trial, informants reported significant and sustained reduction of posttraumatic irritability (p=0.03) in the study participants. Biweekly averages during drug exposure confirmed this (p<0.03, Cohen's d=0.44). Treatment efficacy was not related to measures of anxiety, posttraumatic stress disorder, sedation, or veteran versus nonveteran status. Alcohol use did not change as a result of treatment. There were no serious adverse events. CONCLUSIONS: This study demonstrated an effect of VPA on posttraumatic irritability, and VPA was well tolerated. Further definition of treatment efficacy and safety requires a large-scale multisite trial, using a randomized, double-blind placebo-controlled design.

Psychological Adaptive Mechanism Maturity, Age, and Depression Symptoms in Advanced-Stage Cancer Patients.

Background: Previously, we reported that the maturity of Psychological Adaptive Mechanism (PAM; alternatively, ego defense mechanism) endorsement, but not depression symptom severity, predicted 5-year survival rates in adult cancer patients and that study controlled for age as a significant variable. In this investigation, we hypothesized that greater PAM maturity would correlate significantly with age and with fewer depression symptoms in a larger sample. Methods: In this cross-section study, adult cancer outpatients (N=293) completed the Defense Style Questionnaire (DSQ), the Beck Depression Inventory (BDI), and provided additional clinical data. Spearman's correlation and multiple regression modeling provided statistical tests of the study hypotheses. Results: Contrary to our hypothesis, DSQ PAM maturity endorsement did not correlate significantly with increasing age. Greater PAM maturity ratio on the DSQ (p<0.0001) and current antidepressant use (p<0.05), however, both provided inverse associations with total BDI symptom frequency (p<0.01). Age was inversely associated with BDI mood (p<0.0001) and somatic scores (p<0.04). Items that worsened BDI symptom frequency included self-reported mood-altering anti-cancer medications and any psychiatric history. Cancer stage, time since diagnosis, and chemotherapy treatment did not correlate with DSQ or BDI scores. Multiple regression analysis found that the correlated items accounted for 17.2% of the variance in mood symptoms and 4.9% in somatic symptoms. Specifically, adaptive maturity and age associated with fewer depression symptoms, while cancer medications affecting mood, and a previous psychiatric history each predicted higher frequency of depression scores. Conclusion: The results suggest that PAM maturity likely predicts fewer depression symptoms while younger age associates with more depression symptoms in this clinical sample. Centrally, acting cancer medications, such as glucocorticoids, and any history of psychiatric disorder correlated with increased depression symptom frequencies. In this cross-section study, antidepressant medications indicated higher frequencies of depressive symptoms, likely reflecting their use in persons previously diagnosed with depression. Further research should target factors that improve PAM maturity as a potential treatment target, especially in younger age groups.

Psychological Adaptive Mechanism Maturity Predicts Good Outcomes in Treatment for Refractory PTSD.

Background: Post-traumatic Stress Disorder (PTSD) severity follows a bell-shaped curve ranging from mild to severe. Those in the severe range often receive the most intensive treatments, including targeted residential rehabilitation stays. These are expensive and welcome ways to improve their effectiveness. We hypothesized that positive change among subjects treated in a 45-day residential rehabilitation format would be associated with the maturity levels of measurable Psychological Adaptive Mechanisms (PAMs), alternately ego defense mechanisms. Methods: In this association study, adult male patients (N = 115) with a history of combat related PTSD treated in a residential rehabilitation setting completed the Defense Style Questionnaire (DSQ) on admission, as well as the Post-Traumatic Stress Disorder Checklist-Military Version (PCL-M) and the Mississippi Scale for Combat-Related Post-traumatic Stress Disorder (M-PTSD) on admission and again at discharge. This allowed prospectively calculated change scores on each of the PTSD measures for each patient. The change scores allowed association testing with averaged admission DSQ scores using Pearson's correlation probability with significance held at p < 0.05. Results: As hypothesized, averaged individual Mature scores on the DSQ were associated with improved change scores on both the PCL-M (p = 0.03) and the M-PTSD (p = 0.04). By contrast neither averaged DSQ Neurotic or Immature scores associated significantly with either PTSD scale change scores. Conclusion: These results, the first of their kind to our knowledge, suggest that patients presenting with predominantly Mature level PAMs are likely to benefit from residential rehabilitation treatment of PTSD. By contrast, those presenting with Neurotic or Immature PAMs predominantly are less likely to encounter positive change in this type of treatment. Although residential treatment is often reserved for the most refractory PTSD cases, it appears that those endorsing Mature level PAMs will make use of residential treatment whereas other forms of treatment may be better suited to those with Neurotic and Immature adjustment mechanisms.

A 5-Minute Cognitive Assessment for Safe Remote Use in Patients With COVID-19: Clinical Case Series.

BACKGROUND: Early clinical experience during the COVID-19 pandemic has begun to elucidate that the disease can cause brain function changes that may result in compromised cognition both acutely and during variable recovery periods. Reports on cognitive assessment of patients with COVID-19 are often limited to orientation alone. Further assessment may seem to create an inappropriate burden for patients with acute COVID-19, which is characterized by fatigue and confusion, and may also compromise examiner safety. OBJECTIVE: The aims of this study were to assess cognition in patients with COVID-19 as comprehensively as possible in a brief format, while observing safety precautions, and to establish a clear face value of the external validity of the assessment. METHODS: We adapted a brief cognitive assessment, previously applied to liver transplant candidates and medical/surgical inpatients, for remote use in patients hospitalized for COVID-19 treatment. Collecting quality assurance data from telephone-administered assessments, this report presents a series of 6 COVID-19 case vignettes to illustrate the use of this 5-minute assessment in the diagnosis and treatment of brain effects. Primary medical teams referred the cases for neuropsychiatric consultation. RESULTS: The age of the patients varied over four decades, and none of them were able to engage meaningfully with their surroundings on admission. On follow-up examination 6 to 10 days later, 4 of the 6 patients had recovered working memory, and only 1 had recovered calculation ability. Of the 6 patients, 2 were capable of complex judgment responses, while none of the cases completed frontal executive function testing in the normal range. CONCLUSIONS: Cognitive assessment in patients with COVID-19 using this remote examination reveals patterns of cognitive recovery that vary among cases and are far more complex than loss of orientation. In this series, testing of specific temporal, parietal, and frontal lobe functions suggests that calculation ability, judgment, and especially frontal executive functions may characterize the effects of COVID-19 on the brain. Used widely and serially, this examination method can potentially inform our understanding of the effects of COVID-19 on the brain and of healing from the virus.

Change deafness for real spatialized environmental scenes.

The everyday auditory environment is complex and dynamic; often, multiple sounds co-occur and compete for a listener's cognitive resources. 'Change deafness', framed as the auditory analog to the well-documented phenomenon of 'change blindness', describes the finding that changes presented within complex environments are often missed. The present study examines a number of stimulus factors that may influence change deafness under real-world listening conditions. Specifically, an AX (same-different) discrimination task was used to examine the effects of both spatial separation over a loudspeaker array and the type of change (sound source additions and removals) on discrimination of changes embedded in complex backgrounds. Results using signal detection theory and accuracy analyses indicated that, under most conditions, errors were significantly reduced for spatially distributed relative to non-spatial scenes. A second goal of the present study was to evaluate a possible link between memory for scene contents and change discrimination. Memory was evaluated by presenting a cued recall test following each trial of the discrimination task. Results using signal detection theory and accuracy analyses indicated that recall ability was similar in terms of accuracy, but there were reductions in sensitivity compared to previous reports. Finally, the present study used a large and representative sample of outdoor, urban, and environmental sounds, presented in unique combinations of nearly 1000 trials per participant. This enabled the exploration of the relationship between change perception and the perceptual similarity between change targets and background scene sounds. These (post hoc) analyses suggest both a categorical and a stimulus-level relationship between scene similarity and the magnitude of change errors.

The development of contour processing: evidence from physiology and psychophysics.

Object perception and pattern vision depend fundamentally upon the extraction of contours from the visual environment. In adulthood, contour or edge-level processing is supported by the Gestalt heuristics of proximity, collinearity, and closure. Less is known, however, about the developmental trajectory of contour detection and contour integration. Within the physiology of the visual system, long-range horizontal connections in V1 and V2 are the likely candidates for implementing these heuristics. While post-mortem anatomical studies of human infants suggest that horizontal interconnections reach maturity by the second year of life, psychophysical research with infants and children suggests a considerably more protracted development. In the present review, data from infancy to adulthood will be discussed in order to track the development of contour detection and integration. The goal of this review is thus to integrate the development of contour detection and integration with research regarding the development of underlying neural circuitry. We conclude that the ontogeny of this system is best characterized as a developmentally extended period of associative acquisition whereby horizontal connectivity becomes functional over longer and longer distances, thus becoming able to effectively integrate over greater spans of visual space.

The human visual system uses a global closure mechanism.

Research asserting that the visual system instantiates a global closure heuristic in contour integration has been challenged by an argument that behaviorally-detected closure enhancement could be accounted for by low-level local mechanisms driven by collinearity or "good continuation" interacting with proximity. The present study investigated this issue in three experiments. Exp. 1 compared the visibility of closed and open contours using circles and S-contours from low to moderately high angles of path curvature in a temporal alternative-forced choice task. Circles were more detectable than S-contours, an effect that increased with curvature. The closure enhancement observed can, however, be explained by the fact that circles contain more 'contiguity' than S-contours. Additional tests added discontinuities to otherwise closed paths to control for the effects of good continuation and closure independently. Exp. 2 compared the visibility of incomplete circles (C-contours) and S-contours derived from the full circles and S-contours in Exp. 1. Exp. 3a compared the visibility of arc pairs arranged in an enclosed position similar to "()" and a non-enclosed position similar to ")(". Results consistently showed enhanced visibility of contour configurations enclosing a region even after controlling for differences in contiguity and changes of curvature direction. A control test (Exp. 3b) demonstrated that the gap in the contours of Exp. 3a was too large to be bridged by local-level collinearity/proximity alone. The combination of good continuation and proximity alone does not explain the closure effects observed across these tests, as demonstrated through the application of a Bayesian model of collinearity and proximity (Geisler et al., 2001) to the stimuli in Exps. 3a and 3b. These results argue for the presence of a global closure-driven contour enhancing mechanism in human vision.

Early operant learning is unaffected by socio-economic status and other demographic factors: a meta-analysis.

The relation between SES (socioeconomic status) and academic achievement in school-aged children is well established; children from low SES families have more difficulty in school. However, few studies have been able to establish a link between SES and learning in infancy, and thus the developmental onset of SES effects remains unknown. The limited studies that have been conducted to explore the link between SES and learning in infancy have generated mixed results; some demonstrate a link between SES and learning in infants as young as 6-9 months (Smith, Fagan, & Ulvund, 2002) while others do not. Further, studies examining the genetic as well as environmental contributors to learning in infancy and early childhood suggest that the effect of SES is likely cumulative and that as children develop, the effect of a low SES environment will become more pronounced (Tucker-Drob, Rhemtulla, Harden, Turkheimer, & Fask, 2011). Using aggregated data from 790 infants collected across 18 studies, we examined the contribution of SES and other demographic factors to learning of an operant kicking task in 2-4-month-old infants in a meta-analysis. Results indicated that, at least with respect to operant conditioning, an infant is an infant; that is SES did not affect learning rate or ability to learn in infants under 4-months of age. SES effects may therefore be better characterized as cumulative, with tangible effects emerging sometime later in life.