Objective: Post-stroke cognitive impairment is common, but mechanisms and risk factors are poorly understood. Frailty may be an important risk factor for cognitive impairment after stroke. We investigated the association between pre-stroke frailty and acute post-stoke cognition. Methods: We studied consecutively admitted acute stroke patients in a single urban teaching hospital during three recruitment waves between May 2016 and December 2017. Cognition was assessed using the Mini-Montreal Cognitive Assessment (min=0; max=12). A Frailty Index was used to generate frailty scores for each patient (min=0; max=100). Clinical and demographic information were collected, including pre-stroke cognition, delirium, and stroke-severity. We conducted univariate and multiple-linear regression analyses with covariates forced in (covariates included were: age, sex, stroke severity, stroke-type, pre-stroke cognitive impairment, delirium, previous stroke/transient ischemic attack) to investigate the association between pre-stroke frailty and post-stroke cognition. Results: Complete data were available for 154 stroke patients. Mean age was 68 years (SD=11; range=32–97); 93 (60%) were male. Median mini-Montreal Cognitive Assessment score was 8 (IQR=4–12). Mean Frailty Index score was 18 (SD=11). Pre-stroke cognitive impairment was apparent in 13/154 (8%) patients. Pre-stroke frailty was significantly associated with lower post-stroke cognition (Standardized-Beta=−0.40; p<0.001) and this association was independent of covariates (Unstandardized-Beta=−0.05; p=0.005). Additional significant variables in the multiple regression model were age (Unstandardized-Beta=−0.05; p=0.002), delirium (Unstandardized-Beta=−2.81; p<0.001), pre-stroke cognitive impairment (Unstandardized-Beta=−2.28; p=0.001), and stroke-severity (Unstandardized-Beta=−0.20; p<0.001). Conclusions: Pre-stroke frailty may be a moderator of post-stroke cognition, independent of other well-established post-stroke cognitive impairment risk factors. (JINS, 2019, 25, 501–506)

Objectives: Individuals with moderate–severe traumatic brain injury (TBI) experience a transitory state of impaired consciousness and confusion often called posttraumatic confusional state (PTCS). This study examined the neuropsychological profile of PTCS. Methods: Neuropsychometric profiles of 349 individuals in the TBI Model Systems National Database were examined 4 weeks post-TBI (±2 weeks). The PTCS group was subdivided into Low (n=46) and High Performing PTCS (n=45) via median split on an orientation/amnesia measure, and compared to participants who had emerged from PTCS (n=258). Neuropsychological patterns were examined using multivariate analyses of variance and mixed model analyses of covariance. Results: All groups were globally impaired, but severity differed across groups (F(40,506)=3.44; p<.001; ŋp2 =.206). Rate of forgetting (memory consolidation) was impaired in all groups, but failed to differentiate them (F(4,684)=0.46; p=.762). In contrast, executive memory control was significantly more impaired in PTCS groups than the emerged group: Intrusion errors: F(2,343)=8.78; p<.001; ŋp2=.049; False positive recognition errors: F(2,343)=3.70; p<.05; ŋp2=.021. However, non-memory executive control and other executive memory processes did not differentiate those in versus emerged from PTCS. Conclusions: Executive memory control deficits in the context of globally impaired cognition characterize PTCS. This pattern differentiates individuals in and emerged from PTCS during the acute recovery period following TBI. (JINS, 2019, 25, 302–313)

Objective: The objective of this study was to evaluate the impact of directed and sustained attention on the allocation of visuospatial attention. Healthy people often have left lateral and upward vertical spatial attentional biases. However, it is not known whether there will be an increase in bias toward the attended portion of the stimulus when volitional spatial attention is allocated to a portion of a stimulus, whether there are asymmetrical spatial alterations of these biases, and how sustained attention influences these biases. Methods: We assessed spatial bias in 36 healthy, right-handed participants using a variant of horizontal and vertical line bisections. Participants were asked to focus on one or the other end of vertical or horizontal lines or entire vertical or horizontal lines, and then to bisect the line either immediately or after a 20 second delay. Results: We found a significant main effect of attentional focus and an interaction between attentional focus and prolonged viewing with delayed bisection. Focusing on a certain portion of the line resulting in a significant deviation toward the attended portion and prolonged viewing of the line prior to bisection significantly enhanced the degree of deviation toward the attended portion. Conclusions: The enhanced bias with directed and sustained attention may be useful modifications of the line bisection test, particularly in clinical populations. Thus, future studies should determine whether prolonged viewing with delayed bisection and spatially focused attention reveals attentional biases in patients with hemispheric lesions who perform normally on the traditional line bisection test. (JINS, 2019, 25, 65–71)

Objective: To increase understanding of the community neuropsychological rehabilitation goals of young people with acquired brain injuries (ABIs). Method: Three hundred twenty-six neuropsychological rehabilitation goals were extracted from the clinical records of 98 young people with ABIs. The participants were 59% male, 2–19 years old, and 64% had a traumatic brain injury. Goals were coded using the International Classification of Functioning, Disability and Health: Children and Youth Version (ICF-CY). Descriptive statistical analysis was performed to assess the distribution of goals across the ICF-CY. Chi-squared and Cramer’s V were used to identify demographic and injury-related associations of goal type. Results: The distribution of goals was 52% activities and participation (AP), 28% body functions (BF), 20% environmental factors (EF), and <1% body structures (BS). The number of EF goals increased with age at assessment (V = .14). Non-traumatic causes of ABIs were associated with more EF goals (V = .12). There was no association between sex or time post-injury and the distribution of goals across the ICF-CY. Conclusions: Young people with ABIs have a wide range of community neuropsychological rehabilitation goals that require an individualized, context-sensitive, and interdisciplinary approach. Community neuropsychological rehabilitation services may wish to ensure they are resourced to focus intervention on AP, with increasing consideration for EF as a young person progresses through adolescence. The findings of this research support models of community neuropsychological rehabilitation that enable wellness by combining direct rehabilitative interventions with attention to social context and systemic working across agencies. (JINS, 2019, 25, 403–412)

Objectives: Expressive suppression (i.e., effortful regulation of overt affect) has a deleterious impact on executive functioning (EF). This relationship has potential ramifications for daily functioning, especially among older adults, because a close relationship exists between EF and functional independence. However, past research has not directly examined whether expressive suppression impacts instrumental activities of daily living (IADL). The present study examined this association among older adults. Methods: One hundred ten community-dwelling older adults completed a self-report measure of acute (past 24 hr) and chronic (past 2 weeks) expressive suppression, a timed test of IADL, and the Behavioral Dyscontrol Scale as a measure of EF. Results: High chronic expressive suppression was related to slow IADL performance beyond covariates (age, IQ, depression), but only for individuals with low EF. High acute expressive suppression was associated with lower accuracy on IADL tasks beyond covariates (IQ, depression), but this association was fully explained by EF. Conclusions: The current results suggest that expressive suppression is associated with less efficient and more error-prone IADL performance. EF fully accounted for the relationship between acute expressive suppression and IADL performance, showing that suppression is a risk factor for both poorer EF performance and functional lapses in daily life. Furthermore, individuals with weaker EF may be particularly vulnerable to the effect of chronic expressive suppression. (JINS, 2019, 25, 718–728)

Objective: To provide a comprehensive systematic review of the literature by examining studies published on all cognitive aspects of children with early and continuously treated phenylketonuria (ECT-PKU) included in the databases Medline, PsycINFO, and PsycARTICLE. Method: In addition to a classical approach, we summarized methodology and results of each study in order to discuss current theoretical and methodological issues. We also examined recent advances in biochemical markers and treatments of PKU, with implications for future research on metabolic control and its role as a determinant of neuropsychological outcome. Results: Consistent with previous reviews, the hypothesis of a specific and central executive impairment in children with ECT-PKU was suggested. However, findings are inconclusive regarding the nature of executive impairments as well as their specificity, impact on everyday life, persistence over time, and etiology. Conclusion: Given the current state of the science, we suggest future directions for research that utilizes a developmental and integrative approach to examine the effects of recent advances in biochemical markers and treatment of PKU. (JINS, 2019, 25, 624–643)

Objectives: The cognitive indicators of preclinical behavioral variant Frontotemporal Dementia (bvFTD) have not been identified. To investigate these indicators, we compared cross-sectional performance on a range of cognitive measures in 12 carriers of pathogenic MAPT mutations not meeting diagnostic criteria for bvFTD (i.e., preclinical) versus 32 demographically-matched familial non-carriers (n = 44). Studying preclinical carriers offers a rare glimpse into emergent disease, environmentally and genetically contextualized through comparison to familial controls. Methods: Evaluating personnel blinded to carrier status administered a standardized neuropsychological battery assessing attention, speed, executive function, language, memory, spatial ability, and social cognition. Results from mixed effect modeling were corrected for multiplicity of comparison by the false discovery rate method, and results were considered significant at p < .05. To control for potential interfamilial variation arising from enrollment of six families, family was treated as a random effect, while carrier status, age, gender, and education were treated as fixed effects. Results: Group differences were detected in 17 of 31 cognitive scores and spanned all domains except spatial ability. As hypothesized, carriers performed worse on specific measures of executive function, and social cognition, but also on measures of attention, speed, semantic processing, and memory storage and retrieval. Conclusions: Most notably, group differences arose on measures of memory storage, challenging long-standing ideas about the absence of amnestic features on neuropsychological testing in early bvFTD. Current findings provide important and clinically relevant information about specific measures that may be sensitive to early bvFTD, and advance understanding of neurocognitive changes that occur early in the disease. (JINS, 2019, 25, 184–194)

Objectives: Studies of neurocognitively elite older adults, termed SuperAgers, have identified clinical predictors and neurobiological indicators of resilience against age-related neurocognitive decline. Despite rising rates of older persons living with HIV (PLWH), SuperAging (SA) in PLWH remains undefined. We aimed to establish neuropsychological criteria for SA in PLWH and examined clinically relevant correlates of SA. Methods: 734 PLWH and 123 HIV-uninfected participants between 50 and 64 years of age underwent neuropsychological and neuromedical evaluations. SA was defined as demographically corrected (i.e., sex, race/ethnicity, education) global neurocognitive performance within normal range for 25-year-olds. Remaining participants were labeled cognitively normal (CN) or impaired (CI) based on actual age. Chi-square and analysis of variance tests examined HIV group differences on neurocognitive status and demographics. Within PLWH, neurocognitive status differences were tested on HIV disease characteristics, medical comorbidities, and everyday functioning. Multinomial logistic regression explored independent predictors of neurocognitive status. Results: Neurocognitive status rates and demographic characteristics differed between PLWH (SA=17%; CN=38%; CI=45%) and HIV-uninfected participants (SA=35%; CN=55%; CI=11%). In PLWH, neurocognitive groups were comparable on demographic and HIV disease characteristics. Younger age, higher verbal IQ, absence of diabetes, fewer depressive symptoms, and lifetime cannabis use disorder increased likelihood of SA. SA reported increased independence in everyday functioning, employment, and health-related quality of life than non-SA. Conclusions: Despite combined neurological risk of aging and HIV, youthful neurocognitive performance is possible for older PLWH. SA relates to improved real-world functioning and may be better explained by cognitive reserve and maintenance of cardiometabolic and mental health than HIV disease severity. Future research investigating biomarker and lifestyle (e.g., physical activity) correlates of SA may help identify modifiable neuroprotective factors against HIV-related neurobiological aging. (JINS, 2019, 25, 507–519)

Objectives: To describe multivariate base rates (MBRs) of low scores and reliable change (decline) scores on Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) in college athletes at baseline, as well as to assess MBR differences among demographic and medical history subpopulations. Methods: Data were reported on 15,909 participants (46.5% female) from the NCAA/DoD CARE Consortium. MBRs of ImPACT composite scores were derived using published CARE normative data and reliability metrics. MBRs of sex-corrected low scores were reported at <25th percentile (Low Average), <10th percentile (Borderline), and ≤2nd percentile (Impaired). MBRs of reliable decline scores were reported at the 75%, 90%, 95%, and 99% confidence intervals. We analyzed subgroups by sex, race, attention-deficit/hyperactivity disorder and/or learning disability (ADHD/LD), anxiety/depression, and concussion history using chi-square analyses. Results: Base rates of low scores and reliable decline scores on individual composites approximated the normative distribution. Athletes obtained ≥1 low score with frequencies of 63.4% (Low Average), 32.0% (Borderline), and 9.1% (Impaired). Athletes obtained ≥1 reliable decline score with frequencies of 66.8%, 32.2%, 18%, and 3.8%, respectively. Comparatively few athletes had low scores or reliable decline on ≥2 composite scores. Black/African American athletes and athletes with ADHD/LD had higher rates of low scores, while greater concussion history was associated with lower MBRs (p < .01). MBRs of reliable decline were not associated with demographic or medical factors. Conclusions: Clinical interpretation of low scores and reliable decline on ImPACT depends on the strictness of the low score cutoff, the reliable change criterion, and the number of scores exceeding these cutoffs. Race and ADHD influence the frequency of low scores at all cutoffs cross-sectionally.

Objectives: Noninvasive brain stimulation methods, including high-definition transcranial direct current stimulation (HD-tDCS) and theta burst stimulation (TBS) have emerged as novel tools to modulate and explore brain function. However, the relative efficacy of these newer stimulation approaches for modulating cognitive functioning remains unclear. This study investigated the cognitive effects of HD-tDCS, intermittent TBS (iTBS) and prolonged continuous TBS (ProcTBS) and explored the potential of these approaches for modulating hypothesized functions of the left posterior parietal cortex (PPC). Methods: Twenty-two healthy volunteers attended four experimental sessions in a cross-over experimental design. In each session, participants either received HD-tDCS, iTBS, ProcTBS or sham, and completed cognitive tasks, including a divided attention task, a working memory maintenance task and an attention task (emotional Stroop test). Results: The results showed that compared to sham, HD-tDCS, iTBS and ProcTBS caused significantly faster response times on the emotional Stroop task. The effect size (Cohen’s d) was d = .32 for iTBS (p < .001), .21 for ProcTBS (p = .01) and .15 for HD-tDCS (p = .044). However, for the performance on the divided attention and working memory maintenance tasks, no significant effect of stimulation was found. Conclusions: The results suggest that repetitive transcranial magnetic stimulation techniques, including TBS, may have greater efficacy for modulating cognition compared with HD-tDCS, and extend existing knowledge about specific functions of the left PPC.

Despite the critical role of working memory (WM) in neuropsychiatric conditions, there remains a dearth of available WM-targeted interventions. Gamma and theta oscillations as measured with electroencephalography (EEG) or magnetoencephalography (MEG) reflect the neural underpinnings of WM. The WM processes that fluctuate in conjunction with WM demands are closely correlated with WM test performance, and their EEG signatures are abnormal in several clinical populations. Novel interventions such as transcranial magnetic stimulation (TMS) have been shown to modulate these oscillations and subsequently improve WM performance and clinical symptoms. Systematically identifying pathological WM-related gamma/theta oscillatory patterns with EEG/MEG and developing ways to target them with interventions such as TMS is an active area of clinical research. Results hold promise for enhancing the outcomes of our patients with WM deficits and for moving the field of clinical neuropsychology towards a mechanism-based approach.

Objective: Radiation therapy (RT) improves rates of survival of patients with childhood brain tumors but increases deficits in cognition and independent living skills. Previous literature has studied difficulties in basic cognitive processes, but few explore impairment in higher-order skills such as adaptive functioning. Some studies identify females as at risk for cognitive deficits due to RT, but few investigate sex differences in adaptive functioning. It was hypothesized that females would exhibit poorer long-term independent living skills and core cognitive skills relative to males following RT. Methods: Forty-five adult survivors of posterior fossa childhood brain tumors (24 females) completed the Wechsler Abbreviated Scale of Intelligence (WASI-II), Wechsler Memory Scale, Third Edition (WMS-III) Digit Span Forward (DSF) and Backward (DSB), and Oral Symbol Digit Modalities Test (OSDMT). Informants completed the Scales of Independent Behavior-Revised (SIB-R). Results: DSF and OSDMT were positively correlated with all five SIB-R domains, full-scale IQ (FSIQ) was positively correlated with four SIB-R domains, and DSB was positively correlated with three SIB-R domains. There was an interaction between sex and RT for OSDMT and community living skills with trend level interactions for personal living skills and broad independent living skills, where females without RT had higher scores than females with RT. Conclusions: Female survivors were more affected by RT than males across the community living skills domain of adaptive functioning as well as processing speed. Processing speed deficits may have a cascading impact on daily living skills. Future studies should investigate how clinical and biological factors may contribute to personalized treatment plans between sexes. (JINS, 2019, 25, 729–739)

Objectives: Craniopharyngioma survivors experience cognitive deficits that negatively impact quality of life. Aerobic fitness is associated with cognitive benefits in typically developing children and physical exercise promotes recovery following brain injury. Accordingly, we investigated cognitive and neural correlates of aerobic fitness in a sample of craniopharyngioma patients. Methods: Patients treated for craniopharyngioma [N=104, 10.0±4.6 years, 48% male] participated in fitness, cognitive and fMRI (n=51) assessments following surgery but before proton radiation therapy. Results: Patients demonstrated impaired aerobic fitness [peak oxygen uptake (PKVO2)=23.9±7.1, 41% impaired (i.e., 1.5 SD<normative mean)], motor proficiency [Bruininks-Oseretsky (BOT2)=38.6±9.0, 28% impaired], and executive functions (e.g., WISC-IV Working Memory Index (WMI)=96.0±15.3, 11% impaired). PKVO2 correlated with better executive functions (e.g., WISC-IV WMI r=.27, p=.02) and academic performance (WJ-III Calculation r=.24, p=.04). BOT2 correlated with better attention (e.g., CPT-II omissions r=.26, p=.04) and executive functions (e.g., WISC-IV WMI r=.32, p=.01). Areas of robust neural activation during an n-back task included superior parietal lobule, dorsolateral prefrontal cortex, and middle and superior frontal gyri (p<.05, corrected). Higher network activation was associated with better working memory task performance and better BOT2 (p<.001). Conclusions: Before adjuvant therapy, children with craniopharyngioma demonstrate significantly reduced aerobic fitness, motor proficiency, and working memory. Better aerobic fitness and motor proficiency are associated with better attention and executive functions, as well as greater activation of a well-established working memory network. These findings may help explain differential risk/resiliency with respect to acute cognitive changes that may portend cognitive late effects. (JINS, 2019, 25, 413–425)

Objective: Neuropsychological studies suggest that the ability to compensate for the presence of spatial neglect highly depends on the attentional resources a patient can rely on. The present research aimed to study neglect in situations where attentional resources are limited due to multitasking. Method: We examined two patients more than 3 years after a right-hemispheric stroke. Both had received neuropsychological rehabilitation for left neglect and did not show any impairment in standard tests. We used a dual-task paradigm combining a peripheral target detection task with a central shape recognition task. Peripheral targets could appear in left/right positions but also in lower/upper positions. Results: In patient #1, dual-task condition exacerbated left neglect and extinction. Patient #2 did not show any sign of neglect along the horizontal axis, but omitted half of the lower targets when they were presented simultaneously with upper targets under dual-task condition. This behavior reflects altitudinal extinction as the detection of single targets appearing either in upper or lower position was preserved. Conclusion: The present findings show that dual-tasking is a sensitive tool for the quantitative and qualitative assessment of spatial attention deficits, which are often overlooked by standard methods, especially in chronic stage. (JINS, 2019, 25, 644–653)

Objectives: This report examined theta-band neurodynamics for potential biomarkers of brain health in athletes with concussion. Methods: Participants included college-age contact/collision athletes with (N=24) and without a history of concussion (N=16) in Study 1. Study 2 (N=10) examined changes over time in contact/collision athletes. There were two primary dependent variables: (1) theta-band phase-synchronization (e.g., functional connectivity) between medial and right-lateral electrodes; and (2) the within-subject correlation between synchronization strength on error trials and post-error reaction time (i.e., operationalization of cognitive control). Results: Head injury history was inversely related with medial-lateral connectivity. Head injury was also related to declines in a neurobehavioral measure of cognitive control (i.e., the single-trial relationship between connectivity and post-error slowing). Conclusions: Results align with a theory of connectivity-mediated cognitive control. Mild injuries undetectable by behavioral measures may still be apparent on direct measures of neural functioning. This report demonstrates that connectivity and cognitive control measures may be useful for tracking recovery from concussion. Theoretically relevant neuroscientific findings in healthy adults may have applications in patient populations, especially with regard to monitoring brain health. (JINS 2019, 25, 314–323)

Objectives: Several studies on human risk taking and risk aversion have reported the involvement of the dorsolateral prefrontal cortex (DLPFC). Yet, current knowledge of the neural mechanisms of risk-related decision making is not conclusive, mainly relying on studies using non-motor tasks. Here we examine how modulation of DLPFC activity by repetitive transcranial magnetic stimulation (rTMS) affects risk-taking behavior during a motor response task. Methods: One-Hertz rTMS to the right DLPFC was applied to monitor risk-taking and risk-aversion performance during a goal-directed risky task with motor response. Healthy participants were instructed to aim for a high score by throwing a ball as close to the ceiling as possible, while avoiding touching the ceiling with the ball. Results: One-Hertz rTMS stimulation to the right DLPFC significantly increased the frequency of ceiling hits, compared to Sham-stimulation. Conclusions: Our results suggest that the right DLPFC is a valid target for manipulating risky behavior in tasks with a motor-response. Following rTMS stimulation participants' preference shifts toward immediate awards, while becoming significantly less sensitive to potential negative consequences. The results confirm that the right DLPFC is involved in impulse control in goal-directed executive tasks. (JINS, 2019, 25, 72–78)