Traumatic brain injury (TBI) is a prevalent cause of long-term morbidity in children and adolescents and can lead to persistent difficulties with social and behavioral function. TBI may impact brain structures that support social cognition, social perception, and day-to-day social interactions—termed the social brain network (SBN). We examined differences in links among the SBN and regions of interest from other neural networks thought to support social outcomes, i.e., the default mode network (DMN) and salience network (SN). Furthermore, we examined how differences in co-activation among the SBN and these other key networks were associated with ratings of social and day-to-day adaptive outcomes.

Participants included children and adolescents with moderate to severe TBI (msTBI; n=11, Mage=11.78, 6 male), complicated-mild TBI (cmTBI; n=12, Mage=12.59, 9 male), and orthopedic injury (OI; n=22, Mage=11.69, 15 male). Participants underwent resting-state functional MRI on a 3Tesla Siemens Prisma scanner. Parents rated their child’s social and adaptive function on the Child Behavior Checklist (CBCL) and Adaptive Behavior Assessment System-Third Edition (ABAS-3). Resting-state connectivity was assessed using the CONN Toolbox, including preprocessing, denoising, and alignment to the participants’ processed T1 MPRAGE sequence followed by seed-to-voxel analysis using a SBN mask and targeted regions of interest within the DMN and SN. Individual-level r-to-z correlations were extracted from resulting clusters of co-activation with the SBN mask and exported into SPSSv28.0 for integration with behavioral data.

One-way ANOVAs used to examine group differences in social and adaptive outcome revealed significant group differences in CBCL Social Competence (F=4.49, p=.019) and all composite scores on the ABAS-3 (Fs=3.78 to 5.17, ps=.031 to .010). In each domain, children with msTBI were rated as having elevated difficulties relative to cmTBI or OI, whereas cmTBI and OI groups did not differ. Connectivity also differed significantly between groups, with children with OI demonstrating greater connectivity between the SBN and the anterior cingulate cortex of the SN (t=5.19, p(FDR)<.0001) and posterior cingulate cortex of the DMN (f=4.30, p(FDR)<.001) than children with msTBI. Children with cmTBI also showed greater connectivity between the SBN and left temporal pole of the DMN (t=7.45, p(FDR)<.000001) than children with msTBI. Degree of connectivity between the SBN and posterior cingulate was significantly positively correlated across all domains of adaptive function (rs=.451 to .504, ps=.010 to .003), whereas degree of connectivity between the SBN and left temporal pole was strongly positively related to Social Competence (a=.633, p=.006) and conceptual adaptive skills on the ABAS (A=.437, p=.037).

Our findings provide insights into the neural substrates of social and adaptive morbidity after pediatric TBI, particularly msTBI, by linking alterations in connectivity among the SBN, DMN, and SN with measures of social and adaptive outcome. While the posterior cingulate was broadly associated with adaptive outcome, the temporal pole was particularly strongly associated with social competence. This may reflect the diverse functions and high degree of interconnectivity of the posterior cingulate, which contributes to various cognitive and attentional processes, relative to the strong amygdala/limbic connections of the temporal pole.

Imitation has pervasive associations with social and communicative development. However, few methods have been developed to measure this construct in typically developing infants, and even less is available for at-risk populations, such as infants born preterm. Autism spectrum disorder (ASD), a particular risk of premature birth, is associated with atypical imitation and social communication. Although imitation emerges in infancy, most current screening and diagnostic tools for ASD cannot be utilized prior to 12 months. The present study aimed to develop and validate a caregiver-report measure of infant imitation, characterize imitation profiles at 4, 6, and 9 months in term and preterm infants, and explore the relationship between imitation and scores on an ASD screening questionnaire at 18 months.

Participants (N = 571) were recruited from a larger multi-site study of PediaTrac™ v3.0, a web-based tool for monitoring and tracking infant development, and were surveyed longitudinally at birth, 2, 4, 6, 9, 12, 15, and 18 months. Participants completed the online PediaTrac™ survey and several reliable and validated questionnaires via pen-and-paper format. For the purposes of this study, only the Ages and Stages Questionnaire (3rd ed.; ASQ-3), Communication and Symbolic Behavior Scales-Developmental Profile (CSBS-DP), Brief Infant Sleep Questionnaire (BISQ), and the Modified Checklist for Autism in Toddlers - Revised with Follow-Up (M-CHAT-R/F) were examined. The following hypotheses were tested: (1) proposed imitation items will represent a unitary latent construct, for which convergent and discriminant validity will be demonstrated, (2) there will be measurement invariance between term status groups at each assessment period, (3) preterm infants will obtain lower caregiver-reported imitation scores compared to term infants, and (4) imitation abilities at the assessment period with the most robust imitation factor will predict M-CHAT-R/F scores at 18 months.

Distinct imitation factors at 4, 6, and 9 months were modeled with confirmatory and exploratory factor analyses. Relationships between the factors and established measures of infant communication (CSBS; ASQ) and sleep (BISQ) revealed convergent and discriminant validity, respectively. Strict measurement invariance was demonstrated for the 4- and 9-month factors, and metric invariance for the 6-month measure. Full term infants scored higher on imitation at 9 months, though variance in this outcome was related to term status differences in sensorimotor skills. Lastly, the 9-month imitation factor, coupled with 6-month sensorimotor skills, predicted 18-month ASD risk over and above gestational age.

This study provides support for the assessment of infant imitation, utilizing imitation to detect risk in preterm infants, and extending the age of identification for ASD risk into the first year. PediaTrac™ imitation, in combination with the PediaTrac™ sensorimotor domain, may be useful in detecting developmental risk, and specifically risk for ASD, within the first year, leading to earlier initiation of intervention. Further, with its minimal completion time and ease of dissemination through digital platforms, this measure can expand access to care and improve long-term outcomes for children and families.

Survivors of childhood ALL treated with CNS-directed chemotherapy are at risk for neurocognitive deficits that emerge during treatment and impact functional and quality of life outcomes throughout survivorship. Neurocognitive monitoring is the recommended standard of care for this population; however, information on assessment timing and recommendations for assessment measures are limited. We examined the role of serial neurocognitive monitoring completed during protocol-directed therapy in predicting parent-reported neurocognitive late effects during survivorship.

Parents of 61 survivors of childhood ALL completed a semi-structured survey focused on parent perspective of neurocognitive late effects as part of a quality improvement project. Survivors completed protocol-directed treatment for newly diagnosed ALL on two consecutive clinical trials (St. Jude Total Therapy Study 15, 47.5%; Total Therapy 16, 52.5%). The majority of survivors were White (86.9%), 52.5% were male, and 49% were treated for low risk disease. Mean age at diagnosis was 7.77 years (standard deviation [SD] = 5.31). Mean age at survey completion was 15.25 years (SD = 6.29). Survivors completed neurocognitive monitoring at two prospectively determined time points during and at the end of protocol-directed therapy for childhood ALL.

During survivorship, parents reported that 73.8% of survivors experienced neurocognitive late effects, with no difference in frequency of endorsement by protocol (p = .349), age at diagnosis (p = .939), patient sex (p = .417), or treatment risk arm (p = .095). In survivors with late effects, 44.3% sought intervention in the form of educational programming (i.e., 504 or Individualized Education Program). Among the group with late effects, compared to those without educational programming, those with educational programming had worse verbal learning (CVLT Trials 1-5 Total, Mean[SD]; T = 56.36 [11.19], 47.00 [10.12], p = .047) and verbal memory (CVLT Short Delay Free Recall, Z = 0.86 [0.67], -0.21 [1.01], p = .007); Long Delay Free Recall, Z = 0.91 [0.92], -0.25 [1.25], p = .020) during therapy. Compared to those without educational programming, survivors with educational programming had lower estimated IQ (SS = 109.25 [13.48], 98.07 [15.74], p = .045) and greater inattention [CPT Beta T = 56.80 [13.95], 75.70 [22.93], p = .017) at the end of therapy.

Parents report that nearly three quarters of children treated for ALL with chemotherapy only experience neurocognitive late effects during early survivorship, with no difference in frequency by established risk factors. Of those with late effects, nearly half required educational programming implemented after diagnosis, suggesting a significant impact on school performance. Results from neurocognitive monitoring beginning during therapy has utility for predicting educational need in survivors experiencing late effects. Our findings provide direction on the timing and content of neurocognitive monitoring, which is the recommended standard of care for childhood cancer patients treated with CNS-directed therapy.

A common assumption to maximise cognitive training outcomes is that training tasks should be adaptive, with difficulty adjusted to the individual’s performance. This has only been tested once in adults (von Bastian & Eschen, 2016). We aimed to examine children’s outcomes of working memory training using adaptive, self-select and stepwise approaches to setting the difficulty of training tasks compared to an active control condition.

In a randomised controlled trial (ACTRN 12621000990820), children in Grades 2-5 (7 to 11 years) were allocated to one of four conditions: adaptive working memory training, self-select working memory training, stepwise working memory training, or active control. An experimental intervention embedded in Minecraft was developed for teachers to deliver in the classroom over two weeks (10 x 20-minute sessions). The working memory training comprised two training tasks with processing demands similar to daily activities: backward span with digits and following instructions with objects. The control condition comprised creative building tasks. As part of a larger protocol, children completed at baseline and immediately post-intervention working memory measures similar to the training activities (primary outcome): backward span digits and letters versions, following instructions objects and letters versions. Primary analyses were intention-to-treat. Secondary analyses included only children who completed 10 sessions.

Of 204 children recruited into the study, 203 were randomised, with 95% retention at post-intervention. 76% of children completed all 10 training sessions. Comparisons between each working memory training condition and the active control on working memory measures were non-significant (f 2 = 0.00), with one exception. Children in the self-select condition on average performed 1-point better than the controls on the following instructions objects measure (p = .02, f2 = 0.03). A pattern emerged that the self-select condition performed better on most measures.

We found little evidence that an adaptive approach to setting the difficulty of training tasks maximises training outcomes for children. Findings suggest that working memory outcomes following training are limited and are not modulated by the approach to setting the difficulty of training tasks. This is consistent with findings from von Bastian & Eschen (2016), who also observed that the self-select condition (and not the adaptive condition) showed a slightly larger change in working memory performance following training than the control. It is helpful for clinicians to be aware that adaptive working memory training programs might not be superior in improving children’s working memory, and the benefits of programs are limited.

Hemispherectomy (HE) is a surgical intervention to treat intractable epilepsy. It involves disconnecting or removing the right or left cerebral hemisphere, depending on the location of the pathological substrate or epileptogenic activity. HE impacts neural functions related to social cognition (Fournier et al., 2008). This study investigates the effects of childhood HE on social deception and sarcasm using the Thames Awareness of Social Inferences Task (TASIT; McDonald, Flanagan, & Rollins, 2010) to explore emotion identification and social inference appraisal as adults.

Fifteen adults with hemispherectomy and 16 neurotypical controls completed the TASIT. All HE patients underwent hemispherectomy (right-HE = 10) during childhood (age of surgery = 3 months to 16 years) and had FSIQ > 70 at the time of study. HE and control groups were matched for age (HE M = 25.7, SD = 5.4; control M = 27.1, SD = 10.7) and education (HE M = 14.0, SD = 1.88; control M = 13.3, SD = 1.8). FSIQ was significantly lower in the HE group than control group (HE M= 90.8, SD = 9.4; control (M = 100.4, SD = 7.1). TASIT uses videotaped vignettes to assess aspects of social perception: emotion recognition (Part 1), social inference regarding sincerity, simple sarcasm, and paradoxical sarcasm (Part 2) and social inference regarding sincerity of speech (lie vs sarcasm) in the presence of additional text or visual cues (Part 3).

For Part 1, MANCOVA (covarying FSIQ) found no group difference in emotion identification. Analysis of data from Part 2 was conducted using repeated measures ANCOVA accounting for 2 groups x 3 conditions (sincere, simple sarcasm, and paradoxical sarcasm) and revealed only a significant overall group effect, F (1, 28) = 5.72, p = .024, np2 = .170. Likewise, analysis of Part 3 using repeated measures ANCOVA accounting for 2 groups x 2 cue types (visual, text) and 2 actor intentions (lie, sarcasm) revealed only a significant overall group effect, F (1,28) = 11.35, p = .002, np2 = .288, with no interaction of group by condition.

HE patients exhibited no difficulty identifying basic emotional expressions. Performance was significantly impaired when additional social information was added to the context (i.e., detecting sarcasm or deception). HE patients begin to struggle with the complexity of new social information or how it changes the meaning of a conversation. Even simple sarcastic exchanges are difficult to interpret. When a visual or textual cue was introduced to reveal the true state of affairs, HE patients could not could integrate the information into their interpretations of the scenario. There are unique contributions of the left and right hemispheres to cognitive processes for complex social behavior, and absence of an entire hemisphere results in deficits in social language comprehension. Future research should investigate performance differences in left vs. right HE patients.

Youth with sickle cell disease (SCD) are at increased risk of neurocognitive difficulties with and without neurological complications. Research has identified disease-related, socioeconomic, and sociodemographic risk factors as independently having significant associations with brain physiology for youth with SCD. Notably, sleep has a profound effect on youth’s neurocognitive abilities including learning, executive function, memory, attention, and processing speed. Furthermore, youth with SCD are at an increased risk for poor sleep measured by self-report questionnaires and by polysomnography (PSG). Within the SCD literature, only a few studies have examined the relationship between sleep and cognition. Of these, the majority examined individuals with SCD and comorbid sleep disorder diagnoses. The aim of this study is to identify associations between subjective sleep measures and neurocognitive outcomes in youth with SCD.

This study investigated a cohort of 24 youth with SCD (ages 9-16, 11 males, 13 females; HbSS [63%], HbSB+ [8%], HbSC [21%], HbSB0 [8%]) who received sleep questionnaires and a neuropsychological evaluation. Exclusion criteria included a history of neurological disorder (e.g., overt stroke, seizures, or moyamoya disease) or prescribed psychotropic medication. Sleep questionnaires measuring sleep disturbance (e.g., sleep onset, sleep continuity, and sleep quality) and sleep-related impairments (e.g., daytime sleepiness, sleepiness interference with concentration, and difficulty with activities of daily living skills) were collected. Executive function, working memory, processing speed, and verbal comprehension measures were assessed. Demographics and disease-related risk factors were analyzed individually from medical records.

All analyses were controlled for age, the time between neuropsychological testing and sleep questionnaires, SCD genotype, and sex. Partial correlations were conducted to explore associations with neurocognitive outcomes. Verbal comprehension was significantly correlated with sleep disturbance (r= -.673, p=.001). Multiple linear regressions revealed that sleep disturbance significantly predicts verbal comprehension (ß= -.572, p=.003). Specifically, verbal comprehension decreased by 4.4 standard points for every one-point increase in sleep disturbance. Additionally, total sleep problems significantly predicted working memory (ß=-.414, p=.044) and processing speed (ß= -.411, p= .046). Specifically, working memory decreased by 3.5 standard points while processing speed decreased by 3.3 standard points for every one-point increase in total sleep problems reported. Sleep parameters did not significantly predict executive function.

Results support the association between poor sleep and neurocognitive difficulty in youth with SCD. Three of the participants in this study received a PSG, which further demonstrates the importance of the current findings. This study serves to identify potential risk factors for neurocognitive deficits and provides potential methods for identifying youth with SCD who may need to be referred for a PSG assessment. Research should replicate these findings with increased sample sizes including utilizing PSG and investigating neurobiological effects. Findings may inform future screening tools, treatment approaches, and advanced cognitive initiatives and resources for this population.

Attention-Deficit/Hyperactivity Disorder (ADHD) is associated with impaired executive functioning and anxiety/depressive symptoms, which may contribute to reduced quality of life. We tested the hypotheses that (1) a childhood diagnosis of ADHD is related to reduced quality of life in emerging adulthood and that (2) this relationship is mediated by impaired executive functioning and anxiety/depressive symptoms.

We assessed 85 children and adolescents with ADHD and 50 typically developing peers at baseline (Mean age = 11.6 years, 58% males), two-year follow-up, and 10-year follow-up with neuropsychological tests of executive functioning, the Behavioral Rating Inventory of Executive Function (BRIEF), the Short Moods and Feelings Questionnaire (SMFQ), and the Revised Children’s Manifest Anxiety Scale, second edition (RCMAS-2), as well as the Perceived Quality of Life scale (PQoL) at the 10-year follow-up. Four neuropsychological tests of executive functioning, the Letter-Number Sequencing test (working memory), the Color-Word Interference test condition 3 (response inhibition), the Color-Word Interference test condition 4 (shifting), and the trail making test condition 4 (cognitive flexibility) were combined into a neuropsychological executive functioning composite score based on high factor loadings (> .73). the parent-reported BRIEF indexes, the behavioral regulation index, and the metacognition index were used as measures of everyday executive functioning. We conducted independent samples t-tests to compare the groups and simple and parallel mediation analyses with full information maximum likelihood estimation to examine whether the different executive functioning measures and anxiety/depressive symptoms at two-year follow-up mediated the relationship between baseline ADHD and self-reported quality of life at 10-year follow-up.

Baseline ADHD was associated with more difficulties with executive functioning on a composite measure of neuropsychological tests (p < .001, Hedges g = .79) and parent-reported everyday metacognitive (p < .001, Hedges g = 2.37) and behavioral regulation executive functioning (p < .001, Hedges g = 1.55), as well as self-reported anxiety (p < .001, Hedges g = 1.05) and depressive symptoms (p < .001, Hedges g = 1.00) at two-year follow-up. Baseline ADHD was associated with lower self-reported quality of life (p = .001, Hedges g = -.67) at 10-year follow-up. The mediation analysis showed that everyday metacognitive executive functioning (p = .011, ß = -.497) and an anxiety/depressive symptoms composite (p < .001, ß = -.404) parallelly mediated the relationship between ADHD and quality of life.

Impaired everyday executive functioning and anxiety/depressive symptoms may represent two distinct pathways to reduced quality of life in emerging adults with a childhood diagnosis of ADHD. These findings stress the importance of targeting both cognitive and emotional aspects in interventions for children and adolescents with ADHD to improve later quality of life.

Mild traumatic brain injury (mTBI), depression, and posttraumatic stress disorder (PTSD) are a notable triad in Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn (OEF/OIF/OND) Veterans. With the comorbidity of depression and PTSD in Veterans with mTBI histories, and their role in exacerbating cognitive and emotional dysfunction, interventions addressing cognitive and psychiatric functioning are critical. Compensatory Cognitive Training (CCT) is associated with improvements in areas such as prospective memory, attention, and executive functioning and has also yielded small-to-medium treatment effects on PTSD and depressive symptom severity. Identifying predictors of psychiatric symptom change following CCT would further inform the interventional approach. We sought to examine neuropsychological predictors of PTSD and depressive symptom improvement in Veterans with a history of mTBI who received CCT.

37 OEF/OIF/OND Veterans with mTBI history and cognitive complaints received 10-weekly 120-minute CCT group sessions as part of a clinical trial. Participants completed a baseline neuropsychological assessment including tests of premorbid functioning, attention/working memory, processing speed, verbal learning/memory, and executive functioning, and completed psychiatric symptom measures (PTSD Checklist-Military Version; Beck Depression Inventory-II) at baseline, post-treatment, and 5-week follow-up. Paired samples t-tests were used to examine statistically significant change in PTSD (total and symptom cluster scores) and depressive symptom scores over time. Pearson correlations were calculated between neuropsychological scores and PTSD and depressive symptom change scores at post-treatment and follow-up. Neuropsychological measures identified as significantly correlated with psychiatric symptom change scores (p^.05) were entered as independent variables in separate multiple linear regression analyses to predict symptom change at post-treatment and follow-up.

Over 50% of CCT participants had clinically meaningful improvement in depressive symptoms (>17.5% score reduction) and over 20% had clinically meaningful improvement in PTSD symptoms (>10-point improvement) at post-treatment and follow-up. Examination of PTSD symptom cluster scores (re-experiencing, avoidance/numbing, and arousal) revealed a statistically significant improvement in avoidance/numbing at follow-up. Bivariate correlations indicated that worse baseline performance on D-KEFS Category Fluency was moderately associated with PTSD symptom improvement at post-treatment. Worse performance on both D-KEFS Category Fluency and Category Switching Accuracy was associated with improvement in depressive symptoms at post-treatment and follow-up. Worse performance on D-KEFS Trail Making Test Switching was associated with improvement in depressive symptoms at follow-up. Subsequent regression analyses revealed worse processing speed and worse aspects of executive functioning at baseline significantly predicted depressive symptom improvement at post-treatment and follow-up.

Worse baseline performances on tests of processing speed and aspects of executive functioning were significantly associated with improvements in PTSD and depressive symptoms during the trial. Our results suggest that cognitive training may bolster skills that are helpful for PTSD and depressive symptom reduction and that those with worse baseline functioning may benefit more from treatment because they have more room to improve. Although CCT is not a primary treatment for PTSD or depressive symptoms, our results support consideration of including CCT in hybrid treatment approaches. Further research should examine these relationships in larger samples.

Neuropsychiatric symptoms due to Alzheimer’s disease (AD) and mild cognitive impairment (MCI) can decrease quality of life for patients and increase caregiver burden. Better characterization of neuropsychiatric symptoms is needed to identify effective treatment targets. The current investigation leveraged the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set (UDS) to examine the network structure of neuropsychiatric symptoms among symptomatic older adults with cognitive impairment.

The identified sample includes those from the NACC UDS (all versions) with complete data on the Neuropsychiatric Inventory Questionnaire (NPI-Q) at initial visit. The NPI-Q is an informant-based estimation of the presence and severity of neuropsychiatric symptoms (delusions, hallucinations, agitation or aggression, depression or dysphoria, anxiety, elation or euphoria, apathy or indifference, disinhibition, irritability or lability, motor disturbance, nighttime behaviors, appetite and eating problems). The following inclusionary criteria were applied for sample identification: age 50+; cognitive status of MCI or dementia; AD was the primary or contributing cause of observed impairment; and at least one symptom on the NPI-Q was endorsed. Participants were excluded if they endorsed “unknown” or “not available” on any NPI-Q items. The final sample (n = 12,507) consisted of older adults (Mage=73.94, SDage=9.41; 46.2% male, 53.8% female) who predominantly identified as non-Hispanic white (NHW) (74.5% NHW, 10.9% non-Hispanic Black, 8.5% other, 5.8% Hispanic white, .3% Hispanic Black). The majority of the sample met criteria for dementia (77.6% dementia, 22.4% MCI) and AD was the presumed primary etiology in 93.9%.

The eLasso method was used to estimate the binary network, wherein nodes represent NPI-Q variables and edges represent their pairwise dependency after controlling for all other symptom variables in the network. In other words, the network represents the conditional probability of an observed binary variable (e.g., presence/absence of delusions) given all other measured variables (e.g., presence/absence of all other NPI-Q symptoms) (Finnemann et al., 2021; van Borkulo et al., 2014). Strength centrality and expected influence were calculated to determine relative importance of each symptom variable in the network. Network accuracy was examined with methods recommended by Epskamp et al. (2018), including edge-weight accuracy, centrality stability, and difference tests.

Edge weights and node centrality (CS(cor=.7)=.75) were stable and interpretable. The network (M=.28) consisted of mostly positive edges and some negative edges. The strongest edges linked nodes within symptom domain (e.g., strong positive associations among externalizing symptoms). Disinhibition and agitation/aggression were the most central and influential symptoms in the network, respectively. Depression or dysphoria was the most frequently endorsed symptom, followed by anxiety, apathy or indifference, and irritability or lability.

Endorsed disinhibition and agitation yielded a higher probability of additional neuropsychiatric symptoms and influenced the activation, persistence, and remission of other neuropsychiatric symptoms within the network. Thus, interventions targeting these symptoms may lead to greater neuropsychiatric symptom improvement overall. Depression or dysphoria, while highly endorsed, was least influential in the network. This may suggest that depression and dysphoria are common, but not central neuropsychiatric features of AD pathology. Future work will compare neuropsychiatric symptom networks across racial and ethnic groups and between MCI and dementia.

Around 200,000 veterans (up to 32% of those deployed) of the 1991 Gulf War (GW) suffer from GW veterans’ illness (GWVI). GWVI is a poorly understood chronic medical condition, characterized by symptoms indicative of brain function deficits in multiple domains. Among the symptoms of brain impairment GWVI-related chronic headaches and body muscle and joint pain conditions (GWVI-HAP) are the most debilitating, affecting around 64% of the GWVI veterans. Further, depression carries a very high co-morbid rate (>50%) in patients with chronic pain, including GWVI-HAP. In this preliminary study, we examined the integrity of brain function networks in a group of GWI-HAP veterans, with resting state fMRI (rsfMRI).

Data from the first twenty-two GWVI-HAP veterans from two ongoing parallel clinical trials was examined. Of these 14 subjects (GWVI-HAP-DM) had mild depression (Hamilton Rating Scale for Depression (HSRD < 13); and 8 subjects (GWVI-HAP-DS) had moderate to severe depression (HSRD > 14). Written informed consent was obtained from all participants in the protocol approved by the local Institutional Review Board. RsfMRI data was acquired on a Siemens 3T Prisma-Fit MRI scanner using a 10-minute whole-brain high resolution simultaneous multi-slice (SMS) gradient echo echo-planar imaging (EPI) sequence: TR/TE/FA = 2.2 sec/ 27 msec/80°, and analyzed with well-established image processing pipelines. Functional connectivity (FC) to different regions implicated in depression and chronic pain was assessed with seed-based correlation analysis. Between group differences in FC were obtained with 2-sample t-tests.

GWVI-HAP-DS group exhibited significantly (p < 0.05) reduced FC compared to GWVI-HAP-DM between frontal lobe (medial (mPFC), and dorsolateral (dlPFC) prefrontal cortex) and the striatum. This indicates that malfunction of fronto-striatal circuits could be a source of the increased chronic pain and depression seen in veterans with GWVI- HAP-DS. Dysregulation of fronto-striatal networks has been implicated in major depressive disorder as well as many chronic pain conditions. In addition, FC between mPFC, and salience network (SN; anterior insula and dorsal anterior cingulate) and limbic (subgenual and ventral anterior cingulate) regions were also reduced in GWVI-HAP-DS. Similarly, mPFC and SN also exhibited reduced FC to pain processing regions (posterior insula, centromedian thalamus and cerebellum). These FC impairments could reflect greater deficits in regulation of and salience attribution to emotions and nociception in the GWVI-HAP-DS group. Finally, GWVI-HAP-DS also exhibited reduced FC between nodes of the default mode network. DMN impairments also have been observed in many depressive and chronic pain conditions.

The results of this preliminary analysis implicate impairments in cognitive control of emotion and nociception as a mechanism underlying the enhanced chronic pain and depression observed in GWVI-HAP veterans, especially those with moderate to severe depression. A fuller picture of deficits in FC in brain function networks is expected to emerge as more GWI-HAP subjects of both groups along with age matched healthy controls are examined in this ongoing project. Better understanding of impairments in these networks in GWI-HAP will benefit the rehabilitation of veterans with GWI-HAP.

Machine learning studies of PTSD show promise for identifying neurobiological signatures of this disorder, but studies to date have largely excluded Black American women, who experience disproportionately greater trauma and have relatively higher rates of PTSD. PTSD is characterized by four symptom clusters: trauma reexperiencing, trauma avoidance, hyperarousal, and anhedonia. A prior machine learning study reported successful PTSD symptom cluster severity prediction using functional MRI data but did not examine white matter predictors. White matter microstructural integrity has been related to PTSD presence and symptoms, and unexplored metrics such as estimates of tract shape may provide unique predictive utility. Therefore, this study examines the relationship between white matter tract shape and PTSD symptom cluster severity amongst trauma-exposed Black American women using multiple machine learning models.

Participants included 45 Black American women with PTSD (Mage=40.4(12.9)) and 89 trauma-exposed controls (Mage=39.8(11.6)). Shape and diffusion metrics for the cingulum, corpus callosum, fornix, inferior longitudinal fasciculus, superior longitudinal fasciculus, and uncinate fasciculus were calculated using deterministic tractography. Current symptom severity was calculated using the PTSD Symptom Scales. Input features included tract metrics, questionnaire responses, and age. The following regression models were generated: least absolute shrinkage and selection operator (LASSO), ridge, elastic net, and gaussian process (GPR). Additionally, two forms of latent-scale GPR, one without (lsGPR) and with (sp-lsGPR) node selection via spike and slab priors, were calculated. The performance of regression models was estimated using mean square error (MSE) and R2.

sp-lsGPR performed at or above other models across all symptom clusters. LASSO models were comparable to sp-lsGPR for avoidance and hyperarousal clusters. Ridge regression and GPR had the weakest performance across clusters. Scores for sp-lsGPR by cluster are as follows: reexperiencing Mmse =0.70(0.17), Mr2=0.56(0.13); avoidance Mmse =0.75(0.17), Mr2= 0.51(0.13); hyperarousal Mmse =0.57(0.18), Mr2=0.66(0.12); anhedonia Mmse =0.74(0.27), Mr2=0.57(0.13). The top three ranked posterior inclusion probabilities for white matter tracts across sp-lsGPR models include four sections of the cingulum, three sections of the corpus callosum, the right fornix, the left inferior longitudinal fasciculus, the first segment of the right superior longitudinal fasciculus, and the right uncincate fasciculus. The greatest posterior inclusion probability value for the sp-lsGPR models was the left frontal parahippocampal cingulum for the hyperarousal cluster.

Results support the combined predictive utility of white matter metrics for brain imaging regression models of PTSD. Results also support the use of sp-lsGPR models, which are designed to balance interpretable linear models and highly-flexible non-linear models. The sp-lsGPR model performance was similar across clusters but was relatively better for the hyperarousal cluster. This finding contrasts with prior machine learning work using functional data which was unable to predict hyperarousal scores above chance (MR2=0.06). These diverging findings highlight the importance of examining both functional and structural data in PTSD populations. Differing findings may also be related to sample characteristics as the prior study was conducted in China. Black American women and Chinese individuals have unique lived experiences that may differentially impact brain structure and function. Future work should continue to include diverse research samples to account for such experiences.

Most emotion perception assessments were developed in western societies using English terms and Caucasian faces, so the extent to which they are cross-culturally valid is in question. To sort this, understanding the mechanisms of cultural variations is the key. In the past half-century, cross-cultural differences in perceiving facial emotions have been consistently reported and discussed, advancing knowledge to feed theoretical and practical interests. However, as these studies are heterogeneous in the questions asked and methods used, without understanding their association, we cannot provide a clear answer to the simple question: why do people from different cultures perceive facial emotions differently? This limitation represents a bottleneck for adapting western clinical assessments cross-culturally to suit the increasing trend of globalisation in research and testing. To address this issue, we conducted a systematic review aiming to reveal the effect of culture on emotion perception from past cross-cultural studies on healthy people. We expected this review to bridge findings in basic research and clinical application.

The systematic review followed the framework outlined in Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We searched five databases using three groups of keywords. We included all peer-reviewed original studies that 1) conducted cross-cultural comparison in facial emotion perception with healthy adults and 2) used a design that allowed identifying specific mechanisms to explain cultural variations.

The qualitative data synthesis included three steps: 1) categorising eligible studies according to the type of cross-cultural differences they investigated, 2) summarising the findings of each cluster, and 3) summarising the mechanisms revealed by the findings.

We found the 122 eligible articles clustered into five groups that investigated 1) how race and in-group and out-group status affected facial emotion perception; 2) cultural differences in using context to identify facial expressions; 3) cultural differences in emotion conceptualisation and how they affected facial emotion perception; 4) cultural differences in interpreting facial muscle configurations; 5) how culture interacted with the inference making process.

Seven mechanisms underlying cultural variations in facial emotion perception were revealed. These are facial emotion templates, emotion conceptualisation, in/out-group differentiation, information surveying strategies, belief that expressers are independent agents, reliance on the face and other emotion expressing channels, and stereotypes. The relative importance of these factors may depend on the cultures chosen to compare and the situational settings that affect how they work together in real life.

This review, for the first time, systematically addresses the mechanisms underlying cross-cultural differences in facial emotion perception. Besides advancing knowledge about this rapidly growing area, it guides what needs to be considered when designing new tests, adapting existing tests, and assessing the risk of bias brought about by cross-cultural issues.

Both Apolipoprotein z4 (APOz4) and Brain-Derived Neurotropic Factor val66met (BDNF-met) have been implicated as cognitive risk polymorphisms and may signal a more rapid trajectory of cognitive decline (Boots et al., 2017; Lim et al., 2015). The presence of both risk alleles may additively result in greater cognitive difficulties (Cechova et al., 2020), specifically executive functioning (Sapkota et al., 2017). As executive functioning difficulties can be associated with Posttraumatic Stress Disorder (PTSD; Woon et al., 2017), individuals with PTSD who carry these polymorphisms may be at higher risk for decline in executive functioning. In this study, we examined the cross-sectional and longitudinal impact of these alleles on executive functioning performance in Veterans with PTSD.

Seventy community-dwelling male Veterans were enrolled as part of a larger study at VAPAHCS and consented to genetic analysis. A current or lifetime history of PTSD (score > 40 on the CAPS-IV; Blake et al., 1995) was required for study participation. Trail Making Test B (TMT-B; Army Individual Test Battery, 1994) was used to assess executive functioning. TMT-B was part of a comprehensive neuropsychological battery administered at baseline and yearly over the following three years. Mean age and education were 61 years old (SD = 4.5; range = 55-78) and 14 years (SD = 2.3; range = 8-20), respectively.

The majority of the sample was White (71%) and were from the Korean and Vietnam War eras.

APOz4 and BDNF-met were present in 29% and 27% of the sample, respectively; both were present in six participants. Regression models were fitted separately for TMT-B raw time-to-complete and number of errors, both cross-sectionally at screening and then longitudinally. The presence of BDNF-met was a significant predictor of TMT-B time and number of errors in both models (Time: ß = 0.09, p = 0.03 and ß = 0.11, p < 0.01; Errors: IRR = 2.4, p = 0.01 and IRR = 1.9, p = 0.01), while APOz4 only predicted errors longitudinally (IRR = 1.8, p = 0.03). There was no significant allelic interaction; however, the presence of both alleles additively multiplied TMT-B errors by approximately 3.7 times at screening (IRR = 3.7; p = 0.01) and 3.3 times longitudinally (IRR = 3.3; p < 0.01).

Altogether, these results are suggestive of an adverse, additive, effect of the APOz4 and BDNF-met polymorphisms on executive functioning, in particular error-proneness, with their combined presence tripling the errors made on TMT-B cross-sectionally and longitudinally. Consistent with previous research, the TMT-B error analysis increases detection of cognitive impairment, similar to other clinical samples (Varjacic et al., 2018). While TMT-B errors are typically interpreted qualitatively, the strong effect of these established risk alleles on error rates further support this metric as a clinically useful indicator of executive dysfunction in a PTSD population. In keeping with the Boston Process approach, these findings support the importance of error analysis in clinical interpretation of neuropsychological performance.

The influence of prior knowledge on new learning is well established. However, there has been less research dedicated to teasing apart the key components of prior knowledge’s structure that contribute to memory enhancement. In the current study, we focused on event structures, which include various relations, such as associative, causal, and temporal. Given that events possess attributes relevant to numerous cognitive memory processes, we were most interested in exploring how event structures that possess causal relations enhance new memory formation. Specifically, we examined whether events that exhibit causal associative relations provide an additional boost to new learning compared to event structures with non-causal associative relations.

Forty-six undergraduate students took part in the study. Participants’ learning of the content of image pairs that exhibit everyday, real-world events were measured using a cued recall paradigm. The stimuli consisted of 60 image pairs that illustrated two events that were related causally and associatively (i.e., causal pairs); related only associatively (i.e., non-causal pairs); or not related at all (i.e., unrelated pairs). During an encoding phase, image pairs were presented one at a time, and after the presentation of each image pair, participants answered an encoding question that focused on the relationship between the two images. After the encoding phase and a short filler task, participants were shown a cue image (always the first picture from the pair) and were asked to provide a brief written description of the content of the second presented image from each pair. Also, as a manipulation check, we asked subjects to rate each image pair on causal direction and association strength after completion of the cued recall memory task.

We found that, relative to unrelated pairs, events that possess associative relations (i.e., both causal and non-causal items) benefit learning of new information. In addition, causal relations provided an additional boost to new learning. Specifically, cued recall performance is best for causal pairs, followed by non-causal pairs and unrelated pairs. Moreover, causal direction ratings significantly predict overall itemlevel accuracy above and beyond general associative relations that exist in events. We also examined recall accuracy for specific content information within each event (i.e., agent, action, object) and found that causal relations uniquely contribute to recall performance of objects and actions.

Overall, the present study’s findings suggest that prior event knowledge structures possessing causal and non-causal associative relations support new learning, especially compared to image pairs with no relations. Of interest, causality provides an additional boost to new learning above and beyond general associative relations. By focusing on the role of causality in event structures, our findings informed our understanding of how prior knowledge supports new learning. Considering that the effect of prior knowledge on new episodic learning is especially evident in older adults, since they more readily rely on their schematic knowledge, a future direction would entail investigating how causal links influence new memory formation in older adults.

Context-Dependent Effect (CDE) is a process by which restoring the original learning context enhances recall ability of the material being studied. One type of context is body expressions. Memory is one of the most common areas affected by Traumatic Brain Injury (TBI). However, although the performance of people with TBI is lower than that of healthy people in most memory-related parameters, both groups show evidence for CDE. We examined the CDE via behavioral and eye movement measures.

Twenty-four healthy individuals and 27 patients with moderate-tosevere TBI participated in a memory task. Participants were exposed to pictures of people with neutral facial expression and neutral body expression and were asked to remember them for a subsequent memory test. In the testing session, they were asked to determine whether or not the person presented to them had appeared before, under two conditions: (1) where the context remains constant (facial expression and body expression remained neutral- the Repeat condition) (2) where the context changes (facial expression remained neutral and the body changed to angry or happy expression - the Re-pair condition).

While memory of the individuals with TBI was poorer than that of the control group, both groups exhibited CDE, as this effect was stronger in the Repeat condition compared to the Re-pair angry condition. We found that participants spent most of their time looking at the head. In addition, in both groups, we found a CDE and a group effect with regard to the difference in Dwell Time, so DT toward faces in the Repeat condition was higher than toward faces in the Re-pair condition. Also, DT toward correctly recognized people was higher among the control group than the TBI group. This effect appeared in the study and test phases.

This study supports previous research showing evidence for CDE using body expression in the TBI group, like the control group, and extends our comprehension of the relationship between eye movements, memory, and context of facial and body expression.

Executive functions have been shown to predict prospective memory (PM) performance (Martin, Kliegel, & McDaniel, 2003). PM performance has also been associated with retrospective memory and working memory (Smith, 2003; McDaniel & Einstein, 2000). We investigated the association between PM performance and cognitive domains (executive functions, episodic memory, working memory) in adults at 40 years.

The participants (n = 470, age 40) were part of a longitudinal study including a cohort with a history of a birth risk (eg. asphyxia, low birth weight, hyperbilirubinemia) prospectively followed since birth and controls without birth risks. PM performance was assessed using the new Finnish Proper Prospective Memory Test (PROPS) offering a score for laboratory tasks and naturalistic tasks separately, for event-based PM (EBPM) and time-based PM (TBPM) performance, and a total score. Composite scores of three cognitive domains - executive functions, episodic memory, working memory -were formed by converting raw scores of nine cognitive test (e.g. the Wechsler subtests, the Stroop test, the Trail Making Test) to z scores, summed up and averaged. We calculated Spearman’s correlation coefficient between the five PROPS scores and the composite scores of the cognitive domains.

The episodic memory domain score correlated significantly with the PROPS laboratory tasks (rs = .23, p = < .01), naturalistic tasks, (rs = .13, p = < .01), the total score (rs = .23, p = < .01), EBPM (rs = .25, p = < .01), and TBPM (rs = .15, p = < .01). The executive functions domain score correlated with the PROPS laboratory tasks (rs = .17, p = < .01), the total score (rs = .16, p = < .01) and EBPM (rs = .20, p = < .01). The associations between the working memory domain and the PROPS test varied, in the laboratory setting (rs = .14, p = < .01), in the total score (rs = .13, p = < .01) and in EBPM (rs = .21, p = < .01). Furthermore, the composite score of the combined episodic memory and executive functions domains correlated significantly with the PROPS test in the laboratory setting (rs = .25, p = < .01), in the total score (rs = .25, p = < .01) and in EBPM (rs = .28, p = < .01).

The combination of the episodic memory domain and the executive functions domain was most associated with PM performance measured with the new Finnish Prospective Memory test (PROPS). Only the episodic memory domain was linked with the PROPS tasks in the naturalistic setting. Although the episodic memory domain was more associated with PM performance, the results support the multidomain nature of PM functions.

Prospective memory (PM) tasks are common in everyday life and have been implicated in optimal daily functioning. However, less is known about the parameters of PM tasks that most influence functional decline, as well as the domains of everyday functioning most sensitive to PM impairment. The present study sought to examine these questions in individuals with traumatic brain injury (TBI).

Participants included 30 adults with chronic moderate-to-severe TBI who were at least one year removed from their injury (median [IQR] = 8.1 years [10.8]). Participants completed the Memory for Intentions Test (MIST), which is a 30-minute task that assesses time- and event-based PM with varying cue-intention delay length (2 versus 15 min) in the context of an ongoing task. Total scores were generated for each delay length and cue type. Additionally, participants completed a comprehensive neuropsychological battery, including assessments of processing speed, executive functions, attention, working memory, verbal fluency, and episodic learning and memory. Participants also completed questionnaires of self-reported cognitive and everyday functioning, including the Functional Behavior Profile (FBP), Prospective and Retrospective Memory Questionnaire (PRMQ) and a modified Lawton & Brody Instrumental Activities of Daily Living (IADL) Scale, which separately assessed 11 domains of everyday functioning.

Pearson’s r correlations revealed that total number of domains showing decline on the modified Lawton & Brody IADL scale was strongly correlated with MIST 15-min delay (MIST-15; r=-0.503, p=0.005), such that worse PM performance on long delay items was associated with more domains of IADL decline; this relationship was also reflected in the MIST Total Score (r=-0.389; p=0.033). No other MIST index was associated with IADL decline (ps>0.10). MIST-15 did not significantly correlate with any other measure of self-reported functioning (PRMQ, FBP; all ps>0.10), but was associated with specific declines in buying groceries (p=0.009), performing home repairs (p=0.021), shopping (p=0.033), and doing laundry (p=0.035). Relationships at a trend level included declines in housekeeping (p=0.05), managing finances (p=0.097), cooking (p=0.092), and taking medication (p=0.066). To determine specificity of the relationship between MIST-15 and everyday functioning, a linear regression was conducted using covariates that were significantly correlated with total number of domains of IADL decline (i.e., Selective Reminding Test total learning trials, CVLT-II Long Delay Free Recall, Symbol Digit Modalities Test total). This regression was statistically significant [F(4,24)=4.263; p=0.10; R2=0.415), and MIST-15 remained an independent predictor (p=0.047; R2 change=0.107).

Results suggest that the ability to remember to carry out intended actions after longer delay periods may be uniquely related to severity of declines in everyday functioning. Longer PM delays place higher demands on both memory and executive processes, as the encoded intention must survive a longer decay wherein monitoring for the appropriate cue is extended, and likely better mimic PM tasks in daily life (e.g., remembering to pick up milk after the workday). In light of these findings, clinicians may seek to include brief trials of long delay PM tasks as part of a comprehensive battery to screen for functional decline.

Evidence suggests that the most consistent cognitive impairment found in individuals experiencing posttraumatic stress disorder symptomology is verbal memory impairment (Johnsen & Asbjornsen, 2008). More specifically, research has shown that patients with PTSD perform poorer on verbal memory tasks relating to logical (story) memory than on word memory tasks, such as CVLT-III (Barrera-Valencia et al., 2017). While recent literature accounts for memory impairments related to PTSD, less is known about this relationship for individuals with mere trauma exposure compared to individuals without trauma exposure. The present research aims to determine if there is a significant impact on WMS-LM when compared to CVLT-III for individuals in a community sample that have been exposed to a traumatic event in their lifetime.

One hundred nineteen patients presented to a community-based practice for neuropsychological evaluation. Patients were screened for trauma exposure during a clinical interview. Immediate and long delay trials of Wechsler Memory Scale IV Logical Memory (WMS-LM) were used to examine structured learning and memory and the California Verbal Learning Test (CVLT-II) immediate and long delay recalls were used to examine unstructured learning and memory. Out of the 119 patients, 36 patients reported trauma exposure. Twenty-five were diagnosed as “normal,” 62 were diagnosed with mild cognitive impairment, and 32 were diagnosed with dementia. A one-way MANOVA was conducted to examine the relationship across the multiple dependent variables.

There was a statistically significant difference in immediate recall in memory based on exposure to trauma, F (2, 116) = 3.28, p < .05; Wilk’s A = 0.947, partial n2 = .53, such that individuals with trauma exposure performed better. For long delay recall performance, there was a similar trend though it did not reach statistical significance F (2, 114) = 3.03, p = .052; Wilk’s A = 0.949, partial n2 = .51.

Data showed that patients who reported trauma exposure scored significantly higher on immediate recall performance on CVLT and WMS-LM than those who did not report trauma exposure. Although research suggests that patients who were exposed to trauma often experience cognitive deficits on verbal memory tasks, evidence also shows that trauma exposure can lead to higher immediate recall performance in memory related to attentional allocation modeling (Hayes et al., 2012).

Given the results of the clinical trials for the disease-modifying therapy for Alzheimer's disease and its mechanism of action, it is necessary to start at the early stage as soon as possible. To this end, there is a need for a tool that allows easy periodic home assessment of memory change from the early stages of the disease. The purpose of this study is to establish a new method of memory evaluation showing well- correlated with Logical Memory (LM) II subtest score of the WMS-R and that, at the same time, can be done easily in a short time.

The subjects were 85 subjects (including 12 MCI, 8 AD, and 65 age people with normal cognitive function). In the new method, 8-picture recall and 16-word recognition were assessed, respectively, and the index was calculated by adding up the ratio ofcorrect responses to both tests (max point is two). The correlation with the LM II score was examined.

Our statistical analysis showed that 8-picture recall (R=0.872, p<0.001) and the index (R=0.857, p<0.001) showed a significantcorrelation with the LMII score. On the other hand, the 16-word regression and LM II score was R = 0.691(p<0.001), relatively lower than the other two scores, because this task may have been higher than the true ability due to the false recognition of words that were not there.

Our new method can easily predict the LM II score of WMS-R in about one third of the time required by conventional methods. We named this index as Self Assessment Memory Scale (SAMS), and are planning to develop a digital tool to enable easy andself-accessible evaluation of recall.