Objectives: A limited body of research is available on the relationships between multiplicity of birth and neuropsychological functioning in preterm children who were conceived in the age of assisted reproductive technology and served by the modern neonatal intensive care unit. Our chief objective was to evaluate whether, after adjustment for sociodemographic factors and perinatal complications, twin birth accounted for a unique portion of developmental outcome variance in children born at-risk in the surfactant era. Methods: We compared the neuropsychological functioning of 77 twins and 144 singletons born preterm (<34 gestational weeks) and served by William Beaumont Hospital, Royal Oak, MI. Children were evaluated at preschool age, using standardized tests of memory, language, perceptual, and motor abilities. Results: Multiple regression analyses, adjusting for sociodemographic and perinatal variables, revealed no differences on memory or motor indices between preterm twins and their singleton counterparts. In contrast, performance of language and visual processing tasks was significantly lower in twins despite reduced perinatal risk in comparison to singletons. Effect sizes ranged from .33 to .38 standard deviations for global language and visual processing ability indices, respectively. No significant group by sex interactions were observed, and comparison of first-, or second-born twins with singletons yielded medium effect sizes (Cohen’s d=.56 and .40, respectively). Conclusions: The modest twin disadvantage on language and visual processing tasks at preschool-age could not be readily attributable to socioeconomic or perinatal variables. The possibility of biological or social twinning-related phenomena as mechanisms underlying the observed performance gaps are discussed. (JINS, 2016, 22, 865–877)

Objectives: Elevated body mass index (BMI) is associated with deficits in working memory, reduced gray matter volume in frontal and parietal lobes, as well as changes in white matter (WM) microstructure. The current study examined whether BMI was related to working memory performance and blood oxygen level dependent (BOLD) activity, as well as WM microstructure during adolescence. Methods: Linear regressions with BMI and (1) verbal working memory BOLD signal, (2) spatial working memory BOLD signal, and (3) fractional anisotropy (FA), a measure of WM microstructure, were conducted in a sample of 152 healthy adolescents ranging in BMI. Results: BMI was inversely related to IQ and verbal and spatial working memory accuracy; however, there was no significant relationship between BMI and BOLD response for either verbal or spatial working memory. Furthermore, BMI was negatively correlated with FA in the left superior longitudinal fasciculus (SLF) and left inferior longitudinal fasciculus (ILF). ILF FA and IQ significantly mediated the relationship between BMI and verbal working memory performance, whereas SLF FA, but not IQ, significantly mediated the relationship between BMI and accuracy of both verbal and spatial working memory. Conclusions: These findings indicate that higher BMI is associated with decreased FA in WM fibers connecting brain regions that support working memory, and that WM microstructural deficits may underlie inferior working memory performance in youth with higher BMI. Of interest, BMI did not show the same relationship with working memory BOLD activity, which may indicate that changes in brain structure precede changes in function. (JINS, 2015, 21, 281–292)

Objectives: Excessive adipose tissue, especially in the abdominal area, is associated with increased risk of dementia in older adults. However, the mechanisms underlying this relationship are poorly understood. As increased adiposity is also associated with lower circulating levels of brain-derived neurotrophic factor (BDNF), a key molecule modulating brain plasticity and neuronal regeneration, we hypothesized that the changes in cognition that occur as a result of excessive abdominal adiposity would be driven by lower levels of circulating BDNF. Methods: Fasting blood samples were obtained from 60 participants aged 40–60 years (mean±SD=52.3±5.6) and BDNF levels were assessed with an enzyme linked immunosorbent assay. Abdominal adiposity was measured using a ratio of waist circumference to hip circumference (WHR). Participants also completed a neuropsychological assessment battery to assess executive function. Statistical mediation was assessed using traditional causal steps and nonparametric bootstrapping. Results: Higher WHR was significantly associated with poorer performance on the Controlled Oral Word Association (COWA) letter fluency test (β=−0.489; p=.003) and lower levels of circulating BDNF (β=−0.345; p=.006). Linear regression and bootstrapping methods indicated that BDNF fully mediated the relationship between WHR and performance on the COWA (β=0.60; 95% confidence interval [−3.79, −0.26]). Conclusions: The relationship between higher WHR and verbal fluency was fully statistically mediated by circulating BDNF levels. The BDNF pathway is thus a useful probable mechanism through which executive function decline occurs in individuals with high abdominal adiposity. BDNF enhancing interventions (physical exercise and dietary restriction) could thus be used to improve executive function in these individuals. (JINS, 2016, 22, 1–8)

Cognitive abilities can be acutely disrupted in children and adolescents who sustain a mild traumatic brain injury (mTBI), with the potential that these disruptions may be predictive of recovery. The objective of this study was to determine if cognitive abilities in the emergency department (ED) can differentiate and predict poor symptom recovery following a pediatric mTBI. Participants included 77 male and female youth with a mTBI (mean age=13.6; SD=2.6). All participants completed computerized cognitive testing (four subtests from the CNS Vital Signs) when they presented to the ED. Symptom measurement occurred in the ED (for pre-injury), at 7–10 days, 1 month, 2 months, and 3 months post-mTBI using the post-concussion symptom inventory (PCSI). Recovery was determined using reliable change scores for symptom ratings from 28 orthopedic injury controls (mean age=13.9 years; SD=2.1). Significantly worse Reaction Time scores (i.e., rapid information processing) in the ED were found in those who remained symptomatic at 1 month. Performances on the Reaction Time and Cognitive Flexibility domain scores were predictive of symptom outcome at 1 month for youth (above and beyond sex and baseline symptom burden). Youth with low scores on Reaction Time and/or Cognitive Flexibility were nearly 15 times (95%CI=1.8–323.5) more likely to remain symptomatic at 1 month post-mTBI. No significant group differences were found at 7–10 days, 2 months, or 3 months post-injury. Rapid computerized cognitive testing in the ED following a mTBI may help clinicians predict which youth may or may not remain symptomatic at follow-up. (JINS, 2016, 22, 379–387)

The aim of this study was to examine working memory (WM) modalities (visual-spatial and auditory-verbal) and processes (maintenance and manipulation) in children with and without attention-deficit/hyperactivity disorder (ADHD). The sample consisted of 63 8-year-old children with ADHD and an age- and sex-matched non-ADHD comparison group (N=51). Auditory-verbal and visual-spatial WM were assessed using the Digit Span and Spatial Span subtests from the Wechsler Intelligence Scale for Children Integrated - Fourth Edition. WM maintenance and manipulation were assessed via forward and backward span indices, respectively. Data were analyzed using a 3-way Group (ADHD vs. non-ADHD)×Modality (Auditory-Verbal vs. Visual-Spatial)×Condition (Forward vs. Backward) Analysis of Variance (ANOVA). Secondary analyses examined differences between Combined and Predominantly Inattentive ADHD presentations. Significant Group×Condition (p=.02) and Group×Modality (p=.03) interactions indicated differentially poorer performance by those with ADHD on backward relative to forward and visual-spatial relative to auditory-verbal tasks, respectively. The 3-way interaction was not significant. Analyses targeting ADHD presentations yielded a significant Group×Condition interaction (p=.009) such that children with ADHD-Predominantly Inattentive Presentation performed differentially poorer on backward relative to forward tasks compared to the children with ADHD-Combined Presentation. Findings indicate a specific pattern of WM weaknesses (i.e., WM manipulation and visual-spatial tasks) for children with ADHD. Furthermore, differential patterns of WM performance were found for children with ADHD-Predominantly Inattentive versus Combined Presentations. (JINS, 2016, 22, 1–11)

Objectives: A notable minority of children will experience persistent post-concussive symptoms (PCS) following mild traumatic brain injury (mTBI), likely maintained by a combination of injury and non-injury related factors. Adopting a prospective longitudinal design, this study aimed to investigate the relative influence of child, family, and injury factors on both acute and persistent PCS in young children. Methods: Participants were 101 children aged 2–12 who presented to an Emergency Department, with either mTBI or minor bodily trauma (control). PCS were assessed at time of injury, 1 week, and 1, 2, and 3 months post-injury. Predictors included injury and demographic variables, premorbid child behavior, sleep hygiene, and parental stress. Random effects ordinal logistic regression models were used to analyze the relative influence of these predictors on PCS at early (acute – 1 week) and late (1–3 month) post-injury phases. Results: Presence of mTBI was a stronger predictor of PCS in the early [odds ratio (OR)=18.2] compared with late (OR=7.3) post-injury phase. Older age at injury and pre-existing learning difficulties were significant predictors of PCS beyond 1 month post-injury. Family factors, including higher levels of parental stress, higher socio-economic status, and being of Anglo-Saxon descent, consistently predicted greater PCS. Conclusions: Injury characteristics were significantly associated with PCS for 3 months following mTBI but the association weakened over time. On the other hand, pre-existing child and family factors displayed an increasingly strong association with PCS over time. Follow-up for these “at-risk” children which also addresses family stress may minimize longer-term complications. (JINS, 2016, 22, 793–803)

Objectives: Imbalances in spatial attention are most often associated with right hemisphere brain injury. This report assessed 25 chronic left hemisphere stroke patients for attentional bias. Methods: Participants were evaluated with a computerized visual search task and a standardized neuropsychological assessment known as the Behavioral Inattention Test (BITC). Twenty age-matched controls were also tested. Results: Although little to no attentional impairment was observed on the BITC, the computerized visual search task revealed statistically significant contralesional attentional impairment in the left hemisphere stroke group. Specifically, these participants required 208 ms more viewing time, on average, to reliably detect visual targets on the right side of the display compared to detection on the left side, while controls showed a difference of only 8 ms between the two sides. Conclusions: The observation of significant leftward visuospatial bias in this chronic stroke group provides further evidence that the left hemisphere also plays a role in the balance of visual attention across space. These results have implications for left hemisphere patients who are often not screened for visuospatial problems, as well as for theories of visual attention which have primarily emphasized the role of the right hemisphere. (JINS, 2016, 22, 695–704)

Background: Over the past several years, the concept of prodromal Parkinson disease (PD) has been increasingly recognized. This term refers to individuals who do not fulfill motor diagnostic criteria for PD, but who have clinical, genetic, or biomarker characteristics suggesting risk of developing PD in the future. Clinical diagnosis of prodromal PD has low specificity, prompting the need for objective biomarkers with higher specificity. In this qualitative review, we discuss objectively defined putative biomarkers for PD and prodromal PD. Methods: We searched Pubmed and Embase for articles pertaining to objective biomarkers for PD and their application in prodromal cohorts. Articles were selected based on relevance and methodology. Key Findings: Objective biomarkers of demonstrated utility in prodromal PD include ligand-based imaging and transcranial sonography. Development of serum, cerebrospinal fluid, and tissue-based biomarkers is underway, but their application in prodromal PD has yet to meaningfully occur. Combining objective biomarkers with clinical or genetic prodromal features increases the sensitivity and specificity for identifying prodromal PD. Conclusions: Several objective biomarkers for prodromal PD show promise but require further study, including their application to and validation in prodromal cohorts followed longitudinally. Accurate identification of prodromal PD will likely require a multimodal approach. (JINS, 2016, 22, 956–967)

Objectives: Although chronic sleep loss is highly common among teens, few objective sleep studies have examined its effects on cognitive performance, and specifically on information processing speed (IPS), a measure of cognitive proficiency. Methods: Forty-five adolescents underwent four consecutive nights of monitored sleep restriction (6–6.5 hr/night) and four nights of sleep extension (10–10.5 hr/night), in counterbalanced order, and separated by a washout period. Following each sleep period, cognitive performance was assessed, at a fixed morning time, using a computerized neuropsychological battery including an IPS task, a timed test providing both accuracy and reaction time outcome measures. Results: Overall IPS performance was poorer in the restricted when compared to the extended condition. Increasing task load and pace were associated with increased accuracy for both sleep conditions. However, a significant pace by load interaction effect was only found in the extended condition, with post hoc tests showing that for medium and hard loads, IPS accuracies were better with increasing pace of task. Differences in IPS reaction times were not found between the sleep conditions. In addition, sleep-related changes in IPS indices were correlated with changes in executive function, motor skill, and attention performance. Conclusions: Adolescents’ ability to process information may be especially vulnerable to sleep loss. Under ideal sleep conditions, however, they seem to be able to achieve optimal performance, particularly on more challenging problems. The functional implications of these findings may be particularly relevant to teens, who are often sleep deprived and are constantly required to process academic, social, and emotional input. (JINS, 2016, 22, 388–398)

Objectives: Parkinson’s disease (PD) results in a range of non-motor deficits that can affect mood, cognition, and language, and many of these issues are unresponsive to pharmacological intervention. Aerobic exercise can improve mood and cognition in healthy older adults, although only a few studies have examined exercise effects on these domains in PD. The current study assesses the effects of aerobic exercise on aspects of cognition, mood, and language production in people with PD. Methods: This study compares the effects of aerobic exercise to stretch-balance training and a no-contact control group in participants with idiopathic PD. The aerobic and stretch-balance groups trained three times a week for 16 weeks, while controls continued normal activities. Outcome measures included disease severity, mood, cognition (speed of processing, memory, and executive function), and language production (picture descriptions). Cognition and language were assessed in single and dual task conditions. Results: Depressive symptoms increased only in the control group (p<.02). Executive function improved in the aerobic exercise group only in the single task (p=.007) and declined in controls in the dual task. Completeness of picture descriptions improved significantly more in the aerobic group than in the stretch-balance group (p<.02). Conclusions: Aerobic exercise is a viable intervention for PD that can be protective against increased depressive symptoms, and can improve several non-motor domains, including executive dysfunction and related aspects of language production. (JINS, 2016, 22, 878–889)

Objectives: The cerebellum (CB) is known for its role in supporting processing speed (PS) and cognitive efficiencies. The CB often sustains damage from treatment and resection in pediatric patients with posterior fossa tumors. Limited research suggests that CB atrophy may be associated with the radiation treatment experienced during childhood. The purpose of the study was to measure cerebellar atrophy to determine its neurobehavioral correlates. Methods: Brain magnetic resonance images were collected from 25 adult survivors of CB tumors and age- and gender-matched controls (Mage=24 years (SD=5), 52% female). Average age at diagnosis was 9 years (SD=5) and average time since diagnosis was 15 years (SD=5). PS was measured by the Symbol Digit Modality Test. To quantify atrophy, an objective formula was developed based on prior literature, in which Atrophy=[(CB White+CB Gray Volume)/Intracranial Vault (ICV)]controls-[(CB White+CB Gray+Lesion Size Volume)/ICV]survivors. Results: Regression analyses found that the interaction term (age at diagnosis*radiation) predicts CB atrophy; regression equations included the Neurological Predictor Scale, lesion size, atrophy, and the interaction term and accounted for 33% of the variance in oral PS and 48% of the variance in written PS. Both interactions suggest that individuals with smaller CB lesion size but a greater degree of CB atrophy had slower PS, whereas individuals with a larger CB lesion size and less CB atrophy were less affected. Conclusion: The results of the current study suggest that young age at diagnosis and radiation is associated with CB atrophy, which interacts with lesion size to impact both written and oral PS. (JINS, 2016, 23, 1–11)

Objectives: Engagement in risky sexual behavior (RSB) is a significant public health concern. A growing body of literature is elucidating the role of brain systems and neuropsychological constructs implicated in RSB, which may pave the way for novel insights and prevention efforts. Methods: In this article, we review studies incorporating neuropsychology into the study of RSB across the lifespan. The review of the literature on the neuropsychology of RSB is separated into three different sections by age of participants. Background is presented on research associating RSB with neurocognitive processes and the brain systems involved. Given the overlap between RSBs and substance use, studies addressing these problems in tandem are also discussed. Results: Neurocognitive constructs are implicated in RSB, including impulsivity, decision-making, and working memory. Discussion: Thus far, evidence suggest that neuropsychological factors are associated with engagement in RSB. More research on the influence of neuropsychological factors on engagement in RSB is necessary and may help inform future prevention efforts. (JINS, 2016, 22, 586–594)

Objectives: Although it has been well documented that traumatic brain injury (TBI) can result in communication impairment, little work to date has examined the relationship between social communication skills and structural brain integrity in patients with TBI. The aim of the current study was to investigate the association between self- and other-perceived communication problems and white matter integrity in patients with mild to severe TBI. Methods: Forty-four individuals (TBI=24) and people with whom they frequently communicate, as well as demographically matched normal healthy comparisons (NC) and their frequent communication partners, were administered, respectively, the La-Trobe Communication Questionnaire Self form (LCQ-SELF) and Other form (LCQ-OTHER). In addition, diffusion tensor imaging data were collected, and fractional anisotropy (FA) measures were extracted for each lobe in both hemispheres. Results: Within the TBI group, but not within the NC group, participants who were perceived by their close others as having more communication problems had lower FA in the left frontal and temporal lobes (p<.01), but not in other brain regions. Conclusions: Frontotemporal white matter microstructural integrity is associated with social communication abilities in adults with TBI. This finding contributes to our understanding of the mechanisms leading to communication impairment following TBI and can inform the development of new neuromodulation therapies as well as diagnostic tools. (JINS, 2016, 22, 705–716)

Objectives: Decrements in cognitive function may already be evident in young children with type 1 diabetes (T1D). Here we report prospectively acquired cognitive results over 18 months in a large cohort of young children with and without T1D. Methods: A total of 144 children with T1D (mean HbA1c: 7.9%) and 70 age-matched healthy controls (mean age both groups 8.5 years; median diabetes duration 3.9 years; mean age of onset 4.1 years) underwent neuropsychological testing at baseline and after 18-months of follow-up. We hypothesized that group differences observed at baseline would be more pronounced after 18 months, particularly in those T1D patients with greatest exposure to glycemic extremes. Results: Cognitive domain scores did not differ between groups at the 18 month testing session and did not change differently between groups over the follow-up period. However, within the T1D group, a history of diabetic ketoacidosis (DKA) was correlated with lower Verbal IQ and greater hyperglycemia exposure (HbA1c area under the curve) was inversely correlated to executive functions test performance. In addition, those with a history of both types of exposure performed most poorly on measures of executive function. Conclusions: The subtle cognitive differences between T1D children and nondiabetic controls observed at baseline were not observed 18 months later. Within the T1D group, as at baseline, relationships between cognition (Verbal IQ and executive functions) and glycemic variables (chronic hyperglycemia and DKA history) were evident. Continued longitudinal study of this T1D cohort and their carefully matched healthy comparison group is planned. (JINS, 2016, 21, 293–302)