Deficits in executive function (EF) are reported to occur in individuals with Klinefelter syndrome (XXY). The degree of impairment, if any, is variable and the nature of these deficits has not been clearly elucidated in young males. In this report, we (a) examine EF skills using multiple tasks in a non-clinic referred group of youth with XXY, (b) describe the extent of EF weaknesses in XXY when this group is compared with typical males of a similar SES or typical males with similar verbal abilities, and (c) evaluate the contribution of comorbid attention-deficit/hyperactivity disorder (ADHD) to EF skills. The sample included 27 males with XXY (ages 9–25), 27 typically developing age- and vocabulary-matched males, and 22 age- and socioeconomic status-matched males. EF tasks included Verbal Fluency, the Trail Making Test, and the CANTAB Spatial Working Memory and Stockings of Cambridge tasks. Mixed model analysis of variance was used to compare the groups on EF tasks and revealed a main effect of group but no group by task interaction. Overall, the XXY group performed less well than both control groups, but performance did not differ significantly as a function of task. ADHD comorbidity in males with XXY was related to poorer EF skills. (JINS, 2011, 17, 522–530)

Despite the potential impact on development, few studies have examined the influence of prefrontal lesions occurring prior to maturation of the central nervous system. This study investigates the effect of prefrontal lesions in general, as well as the impact of lesion laterality, with respect to attentional abilities. The sample comprised 36 children with prefrontal lesions and 40 healthy controls. Attentional function was assessed across four domains: selective, shifting and divided attention, and processing speed. Group mean performances for children with prefrontal lesions indicated global attentional deficits, with greatest difficulties for “higher-order” skills including shifting and divided attention. Children with left prefrontal lesions performed similarly to controls, with a specific deficit characterized by difficulties with on-line processing of auditory-verbal information. Right prefrontal lesions were primarily associated with impairments in day-to-day executive functions, including reduced monitoring, poor shifting attention and disinhibition. Children with bilateral prefrontal lesions performed worse than controls on tasks requiring greater cognitive resources. These results provide evidence of the important role played by prefrontal cortex in the development of attentional skills, and the particular role of the right prefrontal cortex. The pattern of attention deficits observed following early prefrontal lesions suggests some lateralization of function within the frontal lobes, even during childhood. (JINS, 2005, 11, 817–831.)Source of funding: Australian National Health and Medical Research Council, Australian Research Council, Murdoch Children's Research Institute.

Individuals with fetal alcohol spectrum disorders (FASD) have difficulties with cognitive-based executive function (EF) tasks. The goal of the present study was to determine if children with FASD have impairments on the Iowa Gambling Task (IGT), which measures affective EF (i.e., decision-making and risk-taking). Individuals with FASD (n = 31) and healthy controls (n = 31), aged 8–17 completed the IGT. Children with FASD were significantly impaired on the IGT compared to controls. Over the course of the task, control scores improved, whereas children with FASD exhibited an overall decrease in scores. Scores increased significantly with age in the control group but did not differ significantly with age for FASD participants. Children with FASD exhibited decision-making and risk-taking impairments on a hot EF task. Children with FASD did not appear to learn from negative experiences and shift to making more positive decisions over time and their performance did not improve with age. The implications of poor task performance and a lack of age-related findings in children with FASD are discussed. (JINS, 2012, 18, 1–8)

Short- and long-term cognitive declines after cardiac surgery with cardiopulmonary bypass have been reported, but the frequency, severity, nature, and etiology of postoperative cognitive changes have been difficult to quantify. Current studies have corrected the principal methodological shortcoming of earlier studies by including control groups, and have shown that while early postoperative cognitive decline does occur in some patients, it is generally mild and reversible by 3 months after surgery. Late cognitive changes do occur, but comparison with patients undergoing off-pump surgery or those being treated medically suggests that these changes are not specific to CABG or more specifically to the use of cardiopulmonary bypass. (JINS, 2010, 16, 221–226.)

The aim of the study was to determine whether the ε4 allele of the apolipoprotein E (ApoE) gene was associated primarily with context-specific memory among individuals at genetic risk for developing Alzheimer's disease. The effect of ApoE status on comprehensive neuropsychological results was examined in 176 healthy adults during baseline cognitive testing in the NIMH Prospective Study of Biomarkers for Older Controls at Risk for Alzheimer's Disease (NIMH Prospective BIOCARD Study). The presence of the ε4 allele was associated with significantly lower total scores on the Logical Memory II subtest of the Wechsler Memory Scale–Revised and percent of information retained after delay. Further analysis indicated the prose recall and retention effect was partially explained by a small subgroup of ε4 homozygotes, suggesting a gradually progressive process that may be presaged with specific cognitive measures. The current results may represent an ε4-associated breakdown between gist-related information and context-bound veridical recall. This relative disconnection may be understood in light of putative ε4-related preclinical accumulation of Alzheimer pathology (tangles and plaques) in the entorhinal cortex (EC) and among frontal networks, as well as the possibility of less-efficient compensatory strategies. (JINS, 2004, 10, 362–370.)

Objectives: The aim of this study was to investigate alterations in functional connectivity, white matter integrity, and cognitive abilities due to sports-related concussion (SRC) in adolescents using a prospective longitudinal design. Methods: We assessed male high school football players (ages 14–18) with (n=16) and without (n=12) SRC using complementary resting state functional MRI (rs-fMRI) and diffusion tensor imaging (DTI) along with cognitive performance using the Immediate Post-Concussive Assessment and Cognitive Testing (ImPACT). We assessed both changes at the acute phase (<7 days post-SRC) and at 21 days later, as well as, differences between athletes with SRC and age- and team-matched control athletes. Results: The results revealed rs-fMRI hyperconnectivity within posterior brain regions (e.g., precuneus and cerebellum), and hypoconnectivity in more anterior areas (e.g., inferior and middle frontal gyri) when comparing SRC group to control group acutely. Performance on the ImPACT (visual/verbal memory composites) was correlated with resting state network connectivity at both time points. DTI results revealed altered diffusion in the SRC group along a segment of the corticospinal tract and the superior longitudinal fasciculus in the acute phase of SRC. No differences between the SRC group and control group were seen at follow-up imaging. Conclusions: Acute effects of SRC are associated with both hyperconnectivity and hypoconnectivity, with disruption of white matter integrity. In addition, acute memory performance was most sensitive to these changes. After 21 days, adolescents with SRC returned to baseline performance, although chronic hyperconnectivity of these regions could place these adolescents at greater risk for secondary neuropathological changes, necessitating future follow-up. (JINS, 2018, 24, 781–792)

Both errorless learning (EL) and Goal Management Training (GMT) have been shown effective cognitive rehabilitation methods aimed at optimizing the performance on everyday skills after brain injury. We examine whether a combination of EL and GMT is superior to traditional GMT for training complex daily tasks in brain-injured patients with executive dysfunction. This was an assessor-blinded randomized controlled trial conducted in 67 patients with executive impairments due to brain injury of non-progressive nature (minimal post-onset time: 3 months), referred for outpatient rehabilitation. Individually selected everyday tasks were trained using 8 sessions of an experimental combination of EL and GMT or via conventional GMT, which follows a trial-and-error approach. Primary outcome measure was everyday task performance assessed after treatment compared to baseline. Goal attainment scaling, rated by both trainers and patients, was used as secondary outcome measure. EL-GMT improved everyday task performance significantly more than conventional GMT (adjusted difference 15.43, 95% confidence interval [CI] [4.52, 26.35]; Cohen’s d=0.74). Goal attainment, as scored by the trainers, was significantly higher after EL-GMT compared to conventional GMT (mean difference 7.34, 95% CI [2.99, 11.68]; Cohen’s d=0.87). The patients’ goal attainment scores did not differ between the two treatment arms (mean difference 3.51, 95% CI [−1.41, 8.44]). Our study is the first to show that preventing the occurrence of errors during executive strategy training enhances the acquisition of everyday activities. A combined EL-GMT intervention is a valuable contribution to cognitive rehabilitation in clinical practice. (JINS, 2015, 21, 639–649)

Since constructional apraxia is often concomitant with brain lesions, the study of constructional tasks in the non-brain-damaged population might be useful in helping to disentangle other causal factors. This paper explores the performance of illiterate individuals (N = 29) as compared to that of semiliterates (N = 21) and literates (N = 23) in order to see the effect of reading and writing abilities on constructional tasks. Each participant was asked to construct 4 figures based upon models having varying degrees of complexity. A global criterion of lack of fidelity and several analytic criteria (related to distortion, rotation, and disarticulation errors) were used to evaluate performance. Although illiterates generally made more errors than semiliterates and semiliterates more than literates, only some of these differences were statistically significant. Significant differences were found for lack of global fidelity and disarticulation errors when all 4 figures were considered together. Subtler data emerged with respect to single figures. (JINS, 2000, 6, 668–672.)

Measures of brain and hippocampal volume in 40 healthy young (aged 18–30 years) and 36 healthy elderly (aged 60–83 years) subjects were compared with composite cognitive function scores in three conceptual domains: memory ability, processing speed, and general fluid intelligence. Through a series of general linear models testing the relationship between these brain measures and cognitive performance scores, a significant positive relationship between hippocampal volume and fluid intelligence ability was found in elderly subjects but not in young. No relationship between the other cognitive domains and brain or hippocampal volume was found. The findings suggest a role of hippocampal atrophy in the decline in fluid intelligence in the elderly. (JINS, 2011, 17, 000–000)

Both HIV infection and high levels of early life stress (ELS) have been related to abnormalities in frontal-subcortical structures, yet the combined effects of HIV and ELS on brain structure and function have not been previously investigated. In this study we assessed 49 non-demented HIV-seropositive (HIV+) and 47 age-matched HIV-seronegative healthy control (HC) adults. Levels of ELS exposure were quantified and used to define four HIV-ELS groups: HC Low-ELS (N = 20); HC High-ELS (N = 27); HIV+ Low-ELS (N = 24); HIV+ High-ELS (N = 25). An automated segmentation tool measured volumes of brain structures known to show HIV-related or ELS-related effects; a brief neurocognitive battery was administered. A significant HIV-ELS interaction was observed for amygdala volumes, which was driven by enlargements in HIV+ High-ELS participants. The HIV+ High-ELS group also demonstrated significant reductions in psychomotor/processing speed compared with HC Low-ELS. Regression analyses in the HIV+ group revealed that amygdala enlargements were associated with higher ELS, lower nadir CD4 counts, and reduced psychomotor/processing speed. Our results suggest that HIV infection and high ELS interact to increase amygdala volume, which is associated with neurocognitive dysfunction in HIV+ patients. These findings highlight the lasting neuropathological influence of ELS and suggest that high ELS may be a significant risk factor for neurocognitive impairment in HIV-infected individuals. (JINS, 2012, 19, 1–12)

The relationship between MRI findings (i.e., subcortical hyperintensities; SH, whole brain volume) and the cognitive dysfunction of vascular dementia (VaD) was examined. Participants included 24 persons that met NINDS-AIREN criteria for VaD (MMSE = 19.9 ± 4.2) and underwent comprehensive neuropsychological assessment and MRI brain imaging. The volume of subcortical hyperintensities (SH) was strongly associated with executive–psychomotor performance, but not with performance across other cognitive domains or global cognitive functional level. Conversely, WBV was strongly associated with global cognitive functioning and performance across most cognitive domains (memory, language, visual integration), but not with executive–psychomotor functioning. The failure of SH to account for either the global dementia evident in these VaD patients or impairments across most cognitive domains suggests that deep subcortical white matter disease may only indirectly contribute to the global cognitive dysfunction of VaD. That WBV emerged as a stronger correlate of dementia raises further questions regarding the cerebral mechanisms that contribute to the development of VaD. (JINS, 2002, 8, 743–752.)

Treatment with interferon-alpha (IFN-α) has been shown to adversely affect cognitive functioning in patients with a variety of medical disorders, but information about the effects of IFN-α on cognitive functioning in patients with chronic hepatitis C (CHC) is limited. The purpose of this study was to examine the effects of IFN-α on neuropsychological test performance in CHC patients. Participants were 30 patients with CHC, 11 who underwent IFN-α therapy and 19 who did not. All participants were tested at baseline (i.e., pretreatment) and approximately 6 months later with the Symbol Digit Modalities Test and Trail Making Test. Results revealed that the treatment group performed significantly worse than untreated CHC patients on Part B of the Trail Making Test after approximately 6 months of treatment. No significant group differences were found on Part A of the Trail Making Test or Symbol Digit Modalities Test. Findings suggest that CHC patients undergoing treatment with IFN-α may experience reduced abilities to benefit from practice but suffer no decrements in performance after 6 months of treatment. Additional research is needed to replicate these findings and to explore risk factors for susceptibility to IFN-α-induced effects. (JINS, 2005, 11, 16–22.)

Response bias reflects the decision rule an individual uses when faced with uncertainty on recognition memory tasks. Recent studies indicate frontal regions may mediate response bias performance. One theory of aging also implicates frontal lobe contributions in age-related cognitive changes. This suggests that frontal lobe changes may mediate response bias in older adults. Consistent with this frontal aging hypothesis, we predicted that response bias would become more liberal with age. Methods: Participants were 181 younger (30–49) and 112 older normal adults (75+) that were part of the California Verbal Learning Test-second edition (CVLT-2) normative sample (total n = 1078). We used parametric measures of discriminability and response bias provided by the CVLT-2 scoring program. Groups were similar in IQ and education. Multi-level regression models were created to examine the effects of moderating variables. The interaction between age and age group significantly predicted response bias. Post hoc analysis indicated that increasing age was associated with more liberal bias in the older but not in the younger group. In the light of reported relationships between frontal regions and both aging and response bias, we hypothesize that frontal changes may be the underlying mechanism explaining the increase in liberal response bias with age. (JINS, 2006, 12, 1–7.)

The purpose of this study is to perform a meta-analysis assessing the effects of sport-related concussion as measured by computerized neurocognitive tests (NCT) 1-week post injury. Thirty-seven studies involving 3960 participants between 2000 and 2011 were included. Hedge's g provides an adjusted effect size for smaller sample sizes and was calculated for overall and cognitive task effects, and subgroup analyses were conducted for age, type of NCT, and sport. Concussions had a low negative effect (g = −0.16; p < .001) across all groups, outcomes, and time points. Code substitution (g = −0.27; p < .05), visual memory (g = −0.25; p < .05), processing speed (g = −0.18; p < .05), and memory (g = −0.21; p < .05) tasks demonstrated negative effects for concussion. Younger adolescents had lower (g = −0.29; p < .05) NCT performance than older adolescents (g = −0.01) and college aged athletes (g = −0.11). ImPACT studies (g = −0.19; p < .05) demonstrated a negative effect for concussion as did those involving contact sports (g = −0.20; p < .05). A low to moderate overall effect size of concussion on neurocognitive performance was supported. Subgroup analyses revealed different effect sizes for specific cognitive tasks, types of NCTs, age, and type of sport. (JINS, 2014, 20, 1–9)

Objectives: Agenesis of the corpus callosum (AgCC), characterized by developmental absence of the corpus callosum, is one of the most common congenital brain malformations. To date, there are limited data on the neuropsychological consequences of AgCC and factors that modulate different outcomes, especially in children. This study aimed to describe general intellectual, academic, executive, social and behavioral functioning in a cohort of school-aged children presenting for clinical services to a hospital and diagnosed with AgCC. The influences of age, social risk and neurological factors were examined. Methods: Twenty-eight school-aged children (8 to 17 years) diagnosed with AgCC completed tests of general intelligence (IQ) and academic functioning. Executive, social and behavioral functioning in daily life, and social risk, were estimated from parent and teacher rated questionnaires. MRI findings reviewed by a pediatric neurologist confirmed diagnosis and identified brain characteristics. Clinical details including the presence of epilepsy and diagnosed genetic condition were obtained from medical records. Results: In our cohort, ~50% of children experienced general intellectual, academic, executive, social and/or behavioral difficulties and ~20% were functioning at a level comparable to typically developing children. Social risk was important for understanding variability in neuropsychological outcomes. Brain anomalies and complete AgCC were associated with lower mathematics performance and poorer executive functioning. Conclusions: This is the first comprehensive report of general intellectual, academic, executive social and behavioral consequences of AgCC in school-aged children. The findings have important clinical implications, suggesting that support to families and targeted intervention could promote positive neuropsychological functioning in children with AgCC who come to clinical attention. (JINS, 2018, 24, 445–455)

Cognition and emotion, traditionally thought of as largely distinct, have recently begun to be conceptualized as dynamically linked processes that interact to influence functioning. This study investigated the moderating effects of cognitive functioning on the relationship between negative emotionality and attention deficit/hyperactivity disorder (ADHD) symptom severity. A total of 216 (140 hyperactive/inattentive; 76 typically developing) preschoolers aged 3–4 years were administered a neuropsychological test battery (i.e., NEPSY). To avoid method bias, child negative emotionality was rated by teachers (Temperament Assessment Battery for Children-Revised), and parents rated symptom severity on the ADHD Rating Scale (ADHD-RS-IV). Hierarchical Linear Regression analyses revealed that both negative emotionality and Perceptual-Motor & Executive Functions accounted for significant unique variance in ADHD symptom severity. Significant interactions indicated that when negative emotionality is low, but not high, neuropsychological functioning accounts for significant variability in ADHD symptoms, with lower functioning predicting more symptoms. Emotional and neuropsychological functioning, both individually and in combination, play a significant role in the expression of ADHD symptom severity. (JINS, 2011, 17, 502–510)

The remediative effect of galvanic vestibular stimulation (GVS) was investigated in a patient who, following right hemisphere damage, is profoundly unable to recognize faces. We administered a two-alternative forced choice match-to-sample task in which the patient had to choose which of two faces matched a sample face presented directly above, while bipolar, transcutaneous current was applied to the left and right vestibular nerves at a level below the patient's sensory threshold. Performance improved beyond the chance-level observed prestimulation, and relied on reversing the electrode polarity across two separate blocks of trials, such that each mastoid received positive current for one block and then negative charge for the next. Although our study involved only a single case, the data provide preliminary evidence that a deficit in perceptual face matching can be reduced by GVS. This raises the intriguing possibility that other unilateral visual disorders may also respond in such a manner. (JINS, 2005, 11, 925–929.)

Patients with bipolar disorder (BD) have difficulty in recognizing and discriminating facial emotions. However, beyond this broad finding, existing literature is equivocal about the specific nature of impairments, and progress toward adequately profiling facial emotion processing in BD is hampered by methodological inconsistencies. The current study aimed to advance the literature by comparing 50 BD patients and 52 controls on a series of facial emotion processing tasks. Results indicated that patients with BD had a small, yet consistent impairment in emotion processing overall. This impairment did not vary as a function of specific emotions, tasks, or intensities between groups, and was not influenced by current mood state. These results suggest that past inconsistencies in the literature are unlikely to be attributable to task related artifacts influencing the estimation of an effect. These findings add to our understanding of social cognition in BD, and have important implications for clinicians treating patients with the disorder. (JINS, 2014, 20, 1–9)