Imaginative elaboration in agenesis of the corpus callosum: topic modeling and perplexity.

OBJECTIVE: Previous studies have found deficits in imaginative elaboration and social inference to be associated with agenesis of the corpus callosum (ACC; Renteria-Vasquez et al., 2022; Turk et al., 2009). In the current study, Thematic Apperception Test (TAT) responses from a neurotypical control group and a group of individuals with ACC were used to further study the capacity for imaginative elaboration and story coherence. METHOD: Topic modeling was employed utilizing Latent Diritchlet Allocation to characterize the narrative responses to the pictures used in the TAT. A measure of the difference between models (perplexity) was used to compare the topics of the responses of individual participants to the common core model derived from the responses of the control group. Story coherence was tested using sentence-to-sentence Latent Semantic Analysis. RESULTS: Group differences in perplexity were statistically significant overall, and for each card individually (p < .001). There were no differences between the groups in story coherence. CONCLUSIONS: TAT narratives from persons with ACC were normally coherent, but more conventional (i.e., more similar to the core text) compared to those of neurotypical controls. Individuals with ACC can make conventional social inferences about socially ambiguous stimuli, but are restricted in their imaginative elaborations, resulting in less topical variability (lower perplexity values) compared to neurotypical controls.

Resting heart rate (variability) and cognition relationships reveal cognitively healthy individuals with pathological amyloid/tau ratio.

Introduction: Resting heart rate (HR) and heart rate variability (HRV) have been linked with cognition in the general population and in older individuals. The knowledge of this aspect of heart-brain relationship is relatively absent in older individuals with early Alzheimer's disease (AD) pathology. This study explores relationships of the HR, HRV, and cognition in cognitively healthy individuals with pathological amyloid/tau ratio (CH-PATs) in cerebral spinal fluid (CSF) compared to those with normal ratio (CH-NATs). Methods: We examined therelationshipsbetween1) resting HR and Mini-Mental State Examination (MMSE); 2) resting HR and brain processing during Stroop interference; and 3) resting vagally mediated HRV (vmHRV) and task switching performance. Results: Our studies showed that compared to CH-NATs, those CH-PATs with higher resting HR presented with lower MMSE, and less brain activation during interference processing. In addition, resting vmHRV was significantly correlated with task switching accuracy in CH-NATs, but not in CH-PATs. Discussion: Thesethreedifferenttestsindicatedysfunctionalheart-brainconnections in CH-PATs, suggesting a potential cardio-cerebral dysfunctional integration.

Biomarkers - Part 1.

BACKGROUND: The CSF amyloid to tau ratio can isolate cognitively healthy participants into normal Aß42/tau (CH-NAT) or a pathological Aß42/tau (CH-PAT) with a low or high risk of cognitive decline, respectively. We aim to determine if plasma Aß42/tau ratios can differentiate CH-NAT from CH-PAT participants. METHOD: Study participants (> 65 years of age) were recruited, and demographic, neurological, and neuropsychological data were obtained in an ongoing HMRI Brain Aging study. Overnight fasting plasma and CSF were collected within a month of examination, and the levels of Aß38, Aß40, Aß42 (MSD 6E10 kit), and total tau were quantified using the MSD electrochemiluminescence platform. Differences in fluid biomarker levels and the plasma ratios (n = 55) and CSF ratios (Aß42/Aß40, n = 41, Aß42/tau, n = 55) were determined using nonparametric student t-test and correlations using a Spearman test. RESULT: Aß40 and Aß42 levels were higher (15-18-fold, and 10-14-fold, respectively), while tau levels are 8-13-fold higher in CSF than in plasma. Plasma and CSF Aß40 were not distinct in CH-NAT compared with CH-PAT. In contrast, Aß42 levels were 30.9% lower in CH-PAT (16.3 ± 18.3 pg/ml) compared with CH-NAT plasma (23.6 ± 26.4 pg/mL) (p < 0.05). CSF Aß42 levels in CH-PAT (171.6 ± 124.6 pg/mL) were lower by 47.6% compared with CH-NAT (327.6 ± 182.6 pg/ml) (p < 0.0001). The Aß42/Aß40 ratio was significantly lower in both plasma and CSF (Table 1A). Similarly, the Aß42/tau ratio was significantly lower in plasma and CSF (Table 1B). Individually, plasma levels of Aß42 and tau did not correlate with CSF levels. However, the ratio of Aß42 to total tau in plasma significantly correlated with the CSF ratios (Spearman r = 0.36, p = 0.0071). Finally, CSF Aß42/Aß40 ratio correlated with Aß42/tau ratio for all samples, CH (n = 100) and MCI (n = 35) (Fig. 1). CONCLUSION: While not as robust as CSF ratios, plasma Aß42/Aß40 and Aß42/tau ratios can isolate cognitively healthy participants with lower risk from participants with a higher risk of cognitive decline. Thus, plasma represents a less invasive medium for the biomarker classification of aging participants.

Everyday Executive Function and Self-Awareness in Agenesis of the Corpus Callosum.

OBJECTIVE: Agenesis of the corpus callosum (AgCC) is associated with a range of cognitive deficits, including mild to moderate problems in higher order executive functions evident in neuropsychological assessments. Previous research has also suggested a lack of self-awareness in persons with AgCC. METHOD: We investigated daily executive functioning and self-awareness in 36 individuals with AgCC by analyzing self-ratings on the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A), as well as ratings on the same instrument from close relatives. Discrepancies between self- and informant-ratings were compared to the normative sample and exploratory analyses examined possible moderating effects of participant and informant characteristics. RESULTS: Significant deficiencies were found in the Behavioral Regulation and Metacognitive indices for both the self and informant results, with elevated frequency of metacognition scores in the borderline to clinical range. Informants also endorsed elevated frequency of borderline to clinically significant behavioral regulation scores. The proportion of AgCC participants whose self-ratings indicated less metacognitive impairment than informant-ratings was greater than in the normative sample. Self-ratings of behavioral regulation impairment decreased with age and informant-ratings of metacognition were higher in males than females. CONCLUSIONS: These findings provide evidence that individuals with AgCC experience mild to moderate executive functioning problems in everyday behavior which are observed by others. Results also suggest a lack of self-understanding or insight into the severity of these problems in the individuals with AgCC, particularly with respect to their metacognitive functioning.

Threshold score for the self-report Pediatric Distress Thermometer Rating Scale in childhood cancer patients.

OBJECTIVE: Although there is enthusiasm for identifying and treating psychosocial problems in childhood cancer patients, there are few validated instruments to help providers identify at-risk children for further assessment. The study objective was to evaluate the sensitivity and specificity of the self-report pediatric Distress Thermometer Rating Scale (Peds DTRS) in childhood cancer survivors and identify a threshold score to help providers classify pediatric patients. METHODS: We evaluated 54 children 7-17 years old using 178 Peds DTRS longitudinal data points from the cohort that was used for the original pediatric adaptation of the DTRS. We compared Peds DTRS scores against two established standardized measures using a generalized linear mixed model to deal with the dependency in the longitudinal data to estimate ROC curves and related statistics. RESULTS: Results indicate that a score of 3 is a reasonable cutoff to identify distress with children 7-17 years old. This cutoff yielded high sensitivity (87.0%) and specificity (79.7%) using the PedsQL Emotional Domain score as the standard. Similar results were obtained using the CDI as the standard, but we are cautious as very few CDI scores reached the cutoff criterion. Exploratory analysis highlighted clinical factors that correlate with increased distress measured using the Peds DTRS. CONCLUSIONS: The Peds DTRS is a very brief, convenient, and rapid screening tool for global distress in children. Further investigation of the Peds DTRS and other tools can improve the ability of providers to prevent and treat the negative emotional consequences of cancer and improve the quality of survivorship.

Adaptation of an Intervention to Reduce Disparities in School HRQOL for Latino Childhood Cancer Survivors.

OBJECTIVE: Survivors of childhood leukemia, especially those from low socioeconomic status households, often experience persistent neurocognitive and academic impairment. This study adapted an existing parent training intervention to improve outcomes for low-acculturated, Spanish-speaking Latino parents of children with leukemia and pilot tested that intervention for feasibility. METHODS: Semistructured interviews were conducted with a focus group of 20 Latino parents of children treated for leukemia. Ten Latino families participated in a pilot study of the adapted parenting intervention, consisting of eight sessions over 6 months. RESULTS: Focus groups revealed that parents unanimously supported a parenting intervention but barriers to participation included time constraints, transportation issues, and anxiety in the hospital environment. The parents also highlighted cultural factors that could contribute to the health disparity, such as lack of knowledge and efficacy in facilitating their child's progress with learning and school. In the pilot study, adherence was 90%, establishing feasibility, and the adapted intervention was considered beneficial. The median parenting efficacy scores improved from preintervention to postintervention (median 3.40 vs. 3.94; p < .011), as did parent-reported school functioning of the child (median 50.00 vs. 60.00; p = .088). CONCLUSIONS: This study addressed a health disparity by culturally adapting a parenting intervention, which was designed to improve school functioning, to meet the needs and preferences of low-acculturated, Spanish-speaking families of children with leukemia in Southern California. The pilot study demonstrated that the adapted intervention is feasible and acceptable in the target population. A larger trial is underway to test the efficacy of this adapted parenting intervention.

Heart Rate Variability as an Index of Resilience.

INTRODUCTION: Resilience is the ability to maintain or quickly return to a stable physical and psychological equilibrium despite experiencing stressful events. Flexibility of the autonomic nervous system is particularly important for adaptive stress responses and may contribute to individual differences in resilience. Power spectrum analysis of heart rate variability (HRV) allows measurement of sympathovagal balance, which helps to evaluate autonomic flexibility. The present study investigated HRV as a broad index of resilience. MATERIALS AND METHODS: Twenty-four male participants from the Army National Guard Special Forces completed psychological measures known to relate to resilience and had HRV measured while undergoing stressful virtual environment scenarios. Pearson product-moment correlations were used to explore the relationships between HRV and resilience factors. All research was conducted with the oversight of the Human Subjects Review Committee of Fuller Theological Seminary. RESULTS: Trends toward significance were reported in order to provide results that would reasonably be expected in a study of higher power. Trends between resilience factors and HRV were found only during specific stress-inducing simulations (see Tables III). CONCLUSION: Greater resilience to stress was associated with HRV during nonstress periods. Higher levels of resilience to traumatic events were associated with HRV during circumstances that were more stressful and emotionally distressing. Post hoc analysis revealed that specific factors including flexibility, emotional control, and spirituality were driving the relationship between general resilience and HRV following emotionally laden stressors. Less stress vulnerability was associated with HRV following intermittent brief stressors. In sum, HRV appears to represent some aspects of an individual's overall resilience profile. Although resilience remains a complex, multidimensional construct, HRV shows promise as a global psychophysiological index of resilience. This study also offers important perspectives concerning ways to optimize both physical and psychological health.

Virtual Reality Assessment of Classroom - Related Attention: An Ecologically Relevant Approach to Evaluating the Effectiveness of Working Memory Training.

Computerized cognitive interventions to improve working memory also purport to improve ADHD-related inattention and off task behavior. Such interventions have been shown to improve working memory, executive functioning, and fluid reasoning on standardized neuropsychological measures. However, debate continues as to whether such programs lead to improvement on ecologically relevant outcomes, such as classroom behavior. This study sought to propose a novel, ecologically relevant approach to evaluate the effectiveness of working memory training on real-world attention performance. Participants included 15 children, aged 6-15, identified as having attention problems were assessed via the virtual classroom continuous performance task (VCCPT) before and after completing 5 weeks of Cogmed working memory training. The VCCPT is a validated measure of sustained and selective attention set within a virtual reality (VR) environment. Several key areas of attention performance were observed to improve, including omission errors, reaction time, reaction time variability, and hit variability. Results suggest that working memory training led to substantial improvements in sustained attention in a real-life scenario of classroom learning. Moreover, the use of psychometrically validated VR measurement provides incremental validity beyond that of teacher or parent report of behavior. Observing such improvements on ecologically relevant measures of attention adds to the discussion around how to evaluate the effectiveness of working memory training as it pertains to real-life improvements and serves to inform consumer awareness of such products and their claims.