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1.  Increased Sensitivity to Perceptual Interference in Adults with Attention Deficit Hyperactivity Disorder 
Difficulty with selective attention is a frequent complaint of adult patients with ADHD, but selective attention tasks have not provided robust evidence of attentional dysfunction in this group. Two experiments examine this puzzle by distinguishing between failures of spatial selection and problems due to sensitivity to perceptual interference. In Experiment 1, we measured the level of perceptual interference generated by targets in crowded displays with nearby distractors by comparing luminance thresholds in both distractor-present (noise) and distractor-absent (clean) displays. ADHD and control participants had comparable thresholds for clean displays, but ADHD individuals had elevated thresholds to crowded displays. These effects could be explained in two distinct ways. Deficits may have arisen from amplified visual interference in the noise condition, or from abnormalities in top-down attentional processes that reduce visual interference. Experiment 2 adjusted for individual perceptual differences with clean and noise displays, before measuring visual interference resolution at attended versus unattended locations. ADHD and control groups had comparable interference resolution at attended locations. These results suggest that perceptual interference rather than spatial attention deficits may account for some deficits in ADHD. This putative deficit in sensory function highlights a potential early-stage perceptual processing deficit in ADHD distinct from selective attention.
PMCID: PMC4321800  PMID: 22433515
Cognition; Contrast sensitivity; Visual crowding; Psychophysics; Visual cortex; Spatial selective attention
2.  Cognitive functioning in young children with type 1 diabetes 
To assess cognitive functioning in children with type 1 diabetes (T1D) and examine whether glycemic history influences cognitive function.
Research Design and Methods
Neuropsychological evaluation of 216 children (healthy controls, n = 72; T1D, n = 144) ages 4-10yrs across five DirecNet sites. Cognitive domains included IQ, Executive Functions, Learning and Memory, and Processing Speed. Behavioral, mood, parental IQ data and T1D glycemic history since diagnosis were collected.
The cohorts did not differ in age, gender or parent IQ. Median T1D duration was 2.5yrs and average onset age was 4yrs. After covarying age, gender, and parental IQ, the IQ and the Executive Functions domain scores trended lower (both p = .02, not statistically significant adjusting for multiple comparisons) with T1D relative to controls. Children with T1D were rated by parents as having more depressive and somatic symptoms (p < 0.001). Learning and memory (p = 0.46) and processing speed (p = 0.25) were similar. Trends in the data supported that the degree of hyperglycemia was associated with Executive Functions, and to a lesser extent, Child IQ and Learning and Memory.
Differences in cognition are subtle in young children with T1D within 2 years of onset. Longitudinal evaluations will help determine whether these findings change or become more pronounced with time.
PMCID: PMC4123061  PMID: 24512675
cognition; early onset; T1DM; hyperglycemia; hypoglycemia; children
3.  Merging Clinical Neuropsychology and Functional Neuroimaging to Evaluate the Construct Validity and Neural Network Engagement of the n-Back Task 
The n-back task is a widely used neuroimaging paradigm for studying the neural basis of working memory (WM); however, its neuropsychometric properties have received little empirical investigation. The present study merged clinical neuropsychology and functional magnetic resonance imaging (fMRI) to explore the construct validity of the letter variant of the n-back task (LNB) and to further identify the task-evoked networks involved in WM. Construct validity of the LNB task was investigated using a bootstrapping approach to correlate LNB task performance across clinically validated neuropsychological measures of WM to establish convergent validity, as well as measures of related but distinct cognitive constructs (i.e., attention and short-term memory) to establish discriminant validity. Independent component analysis (ICA) identified brain networks active during the LNB task in 34 healthy control participants, and general linear modeling determined task-relatedness of these networks. Bootstrap correlation analyses revealed moderate to high correlations among measures expected to converge with LNB (|ρ| ≥0.37) and weak correlations among measures expected to discriminate (|ρ| ≤0.29), controlling for age and education. ICA identified 35 independent networks, 17 of which demonstrated engagement significantly related to task condition, controlling for reaction time variability. Of these, the bilateral frontoparietal networks, bilateral dorsolateral prefrontal cortices, bilateral superior parietal lobules including precuneus, and frontoinsular network were preferentially recruited by the 2-back condition compared to 0-back control condition, indicating WM involvement. These results support the use of the LNB as a measure of WM and confirm its use in probing the network-level neural correlates of WM processing.
PMCID: PMC4290162  PMID: 24963641
Working memory; Convergent validity; Discriminant validity; Divergent validity; Reliability and validity; Bootstrap; fMRI; Independent component analysis; Frontoparietal; Lag task
4.  Digital clock drawing: Differentiating ‘thinking’ versus ‘doing’ in younger and older adults with depression 
Psychomotor slowing has been documented in depression. The digital Clock Drawing Test (dCDT) provides: i) a novel technique to assess both cognitive and motor aspects of psychomotor speed within the same task and ii) the potential to uncover subtleties of behavior not previously detected with non-digitized modes of data collection.
Using digitized pen technology in 106 participants grouped by Age (younger/older) and Affect (euthymic/unmedicated depressed), we recorded cognitive and motor output by capturing how the clock is drawn rather than focusing on the final product. We divided time to completion (TTC) for Command and Copy conditions of the dCDT into metrics of percent of drawing (%Ink) versus non-drawing (%Think) time. We also obtained composite z-scores of cognition, including attention/ information processing (AIP), to explore associations of %Ink and %Think times to cognitive and motor performance.
Despite equivalent TTC, %Ink and %Think Command times (Copy n.s.) were significant (AgeXAffect interaction:p=.03)—younger depressed spent a smaller proportion of time drawing relative to thinking compared to the older depressed group. Command %Think time negatively correlated with AIP in the older depressed group (r=−.46;p=.02). Copy %Think time negatively correlated with AIP in the younger depressed (r=−.47;p=.03) and older euthymic groups (r=−.51;p=.01).
The dCDT differentiated aspects of psychomotor slowing in depression regardless of age, while dCDT/cognitive associates for younger adults with depression mimicked patterns of older euthymics.
PMCID: PMC4310546  PMID: 25222513
psychomotor slowing; clock drawing; digital technologies; age; major depressive disorder
5.  Cognitive and Psychosocial Phenotype of Young Children with Neurofibromatosis-1 
Children with neurofibromatosis-1 (NF1), a neurodevelopmental disorder resulting from a mutation of the NF1 gene (17q11.2), often have difficulties with learning and attention, but there is little research in the early childhood years. In this study, the cognitive and psychosocial functioning of 40 young children with NF1 (ages 3 through 6) was examined and compared both to normative data and to a contrast group comprised of unaffected siblings and community members matched for age and socio-economic status (n = 37). Children with NF1 showed significantly weaker cognitive abilities across all domains and for the vast majority of subtests. Consistent with research in older children, a variety of patterns of intra-individual strength and weakness were present for young children with NF1. Few significant group differences in psychosocial functioning were observed, but the children with NF1 showed significantly greater functional communication problems than did the unaffected group. Overall, the results indicate that in participant groups matched for age and socioeconomic status, cognitive vulnerabilities are evident for close to half of young children with NF1, with some relations to psychosocial functioning, particularly functional communication, attention problems and social skills.
PMCID: PMC4249943  PMID: 24229851
Behavior; Attention; Cognition; Communication disorders; Child-preschool; Genetic diseases; Inborn
6.  Neuroanatomical correlates of executive functions: A neuropsychological approach using the EXAMINER battery 
Executive functions (EF) encompass a variety of higher-order capacities such as judgment, planning, decision-making, response monitoring, insight, and self-regulation. Measuring such abilities quantitatively and establishing their neural correlates has proven to be challenging. Here, using a lesion-deficit approach, we report the neural correlates of a variety of EF tests that were developed under the auspices of the NINDS-supported EXAMINER project (Kramer, 2011; We administered a diverse set of EF tasks that tap three general domains—cognitive, social/emotional, and insight—to 37 patients with focal lesions to the frontal lobes, and 25 patients with lesions outside the frontal lobes. Using voxel-based lesion-symptom mapping (VLSM), we found that damage to the ventromedial prefrontal cortex (vmPFC) was predominately associated with deficits in social/emotional aspects of EF, while damage to dorsolateral prefrontal cortex (dlPFC) and anterior cingulate was predominately associated with deficits in cognitive aspects of EF. Evidence for an important role of some non-frontal regions (e.g., the temporal poles) in some aspects of EF was also found. The results provide further evidence for the neural basis of EF, and extend previous findings of the dissociation between the roles of the ventromedial and dorsolateral prefrontal sectors in organizing, implementing, and monitoring goal-directed behavior.
PMCID: PMC4176938  PMID: 23759126
insight; self-monitoring; FrSBe; lesion; cognitive control; empathy
7.  Cognitive development after traumatic brain injury in young children 
The primary aims of this study were to examine post-injury cognitive development in young children with traumatic brain injury (TBI) and to investigate the role of the proximal family environment in predicting cognitive outcomes. Age at injury was 3–6 years, and TBI was classified as severe (n = 23), moderate (n = 21), and complicated mild (n = 43). A comparison group of children who sustained orthopedic injuries (OI, n = 117) was also recruited. Child cognitive assessments were administered at a post-acute baseline evaluation and repeated at 6, 12, and 18 months post-injury. Assessment of the family environment consisted of baseline measures of learning support and stimulation in the home and of parenting characteristics observed during videotaped parent–child interactions. Relative to the OI group, children with severe TBI group had generalized cognitive deficiencies and those with less severe TBI had weaknesses in visual memory and executive function. Although deficits persisted or emerged across follow-up, more optimal family environments were associated with higher scores for all injury groups. The findings confirm other reports of poor recovery of cognitive skills following early childhood TBI and suggest environmental influences on outcomes.
PMCID: PMC4280794  PMID: 19849883
Head injuries; outcomes; Child development; Child; Preschool; Brain injuries; Neurobehavioral manifestations; Recovery of function
8.  Long-term neural processing of attention following early childhood traumatic brain injury: fMRI and neurobehavioral outcomes 
Attentional deficits are common and significant sequelae of pediatric traumatic brain injury (TBI). However, little is known about how the underlying neural processes that support different components of attention are affected. The present study examined brain activation patterns using fMRI in a group of young children who sustained a TBI in early childhood (n = 5; mean age = 9.4), and a group of age-matched control children with orthopedic injuries (OI) (n = 8) during a continuous performance task (CPT). Four children in the TBI group had moderate injuries, and one had a severe injury. Performance on the CPT task did not differ between groups. Both TBI and OI children activated similar networks of brain regions relevant to sustained attention processing, but the TBI group demonstrated several areas of significantly greater activation relative to controls, including frontal and parietal regions. These findings of over-activation of the relevant attention network in the TBI group contrast with those obtained in imaging studies of Attention-Deficit/Hyperactivity Disorder where under-activation of the attention network has been documented. This study provides evidence that young children’s brains function differently following a traumatic brain injury, and that these differences persist for years after the injury.
PMCID: PMC4278372  PMID: 18419841
Childhood brain disorder; Continuous performance test; Brain imaging; Children; Head injury; Neuropsychology
9.  Disrupted Structural Connectome Is Associated with Both Psychometric and Real-World Neuropsychological Impairment in Diffuse Traumatic Brain Injury 
Traumatic brain injury (TBI) is likely to disrupt structural network properties due to diffuse white matter pathology. The present study aimed to detect alterations in structural network topology in TBI and relate them to cognitive and real-world behavioral impairment. Twenty-two people with moderate to severe TBI with mostly diffuse pathology and 18 demographically matched healthy controls were included in the final analysis. Graph theoretical network analysis was applied to diffusion tensor imaging (DTI) data to characterize structural connectivity in both groups. Neuropsychological functions were assessed by a battery of psychometric tests and the Frontal Systems Behavior Scale (FrSBe). Local connection-wise analysis demonstrated reduced structural connectivity in TBI arising from subcortical areas including thalamus, caudate, and hippocampus. Global network metrics revealed that shortest path length in participants with TBI was longer compared to controls, and that this reduced network efficiency was associated with worse performance in executive function and verbal learning. The shortest path length measure was also correlated with family-reported FrSBe scores. These findings support the notion that the diffuse form of neuropathology caused by TBI results in alterations in structural connectivity that contribute to cognitive and real-world behavioral impairment.
PMCID: PMC4275544  PMID: 25287217
Graph theory; Diffusion tensor imaging; Observational rating scales; Frontal Systems Behavior Scale; Executive function; Verbal learning
10.  The Clinical Utility and Specificity of Parent Report of Executive Function among Children with Prenatal Alcohol Exposure 
Prenatal alcohol exposure and attention-deficit/hyperactivity disorder (ADHD) result in behavioral issues related to poor executive function (EF). This overlap may hinder clinical identification of alcohol-exposed children. This study examined the relation between parent and neuropsychological measures of EF and whether parent ratings aid in differential diagnosis. Neuropsychological measures of EF, including the Delis-Kaplan Executive Function System (D-KEFS), were administered to four groups of children (8–16 years): alcohol-exposed with ADHD (AE+, n = 80), alcohol-exposed without ADHD (AE−, n = 36), non-exposed with ADHD (ADHD, n = 93), and controls (CON, n = 167). Primary caregivers completed the Behavior Rating Inventory of Executive Function (BRIEF). For parent ratings, multivariate analyses of variance revealed main effects of Exposure and ADHD and an interaction between these factors, with significant differences between all groups on nearly all BRIEF scales. For neuropsychological measures, results indicated main effects of Exposure and ADHD, but no interaction. Discriminant function analysis indicated the BRIEF accurately classifies groups. These findings confirm compounded behavioral, but not neuropsychological, effects in the AE+ group over the other clinical groups. Parent-report was not correlated with neuropsychological performance in the clinical groups and may provide unique information about neurobehavior. Parent-report measures are clinically useful in predicting alcohol exposure regardless of ADHD. Results contribute to a neurobehavioral profile of prenatal alcohol exposure.
PMCID: PMC4228981  PMID: 25033032
Fetal alcohol spectrum disorders (FASD); Fetal alcohol syndrome (FAS); Behavior Rating Inventory of Executive Function (BRIEF); Pediatric neuropsychology; Parent-report; Attention-deficit/hyperactivity disorder (ADHD)
11.  Hippocampal Volume and Memory and Learning Outcomes at 7 Years in Children Born Very Preterm 
Using magnetic resonance imaging, this study compared hippocampal volume between 145 very preterm children and 34 children born full term at 7 years of age. The relationship between hippocampal volume and memory and learning impairments at 7 years was also investigated. Manual hippocampal segmentation and subsequent 3D volumetric analysis revealed reduced hippocampal volumes in very preterm children compared with term peers. However, this relationship did not remain after correcting for whole brain volume and neonatal brain abnormality. Contrary to expectations, hippocampal volume in the very preterm cohort was not related to memory and learning outcomes. Further research investigating the effects of very preterm birth on more extensive networks in the brain that support memory and learning in middle childhood is needed.
PMCID: PMC3964592  PMID: 23947431
Neonatal; Hippocampal Formation Segmentation; Memory and Learning
12.  Early Adolescent Cortical Thinning Is Related to Better Neuropsychological Performance 
Adolescence is characterized by significant neuromaturation, including extensive cortical thinning, particularly in frontal regions. The goal of this study was to examine the behavioral correlates of neurostructural development in early adolescence. Participants were 185 healthy 12- to 14-year-olds (44% female) recruited from local schools. Participants completed a comprehensive neuropsychological test battery and magnetic resonance imaging session. Cortical surface reconstruction and thickness estimates were performed via FreeSurfer. Age and cortical thickness were negatively correlated in 10 brain regions, 7 of which were in frontal areas (β = −.15 to −.25, ps ≤.05). Hierarchical linear regressions examined the influence of cortical thickness on working memory, attention, verbal learning and memory, visuospatial functioning, spatial planning and problem solving, and inhibition, controlling for age and intracranial volume. Thinner parietal cortices predicted better performances on tests of verbal learning and memory, visuospatial functioning, and spatial planning and problem solving (β = −.14 to −.24, ps ≤.05). Age, spanning from 12 to 14 years, accounted for up to 6% of cortical thickness, suggesting substantial thinning during early adolescence, with males showing more accelerated thinning than females between ages 12 and 14. For both males and females, thinner parietal association cortices corresponded with better neurocognitive functioning above and beyond age alone.
PMCID: PMC3791607  PMID: 23947395
Adolescence; Cortical thickness; FreeSurfer; Neurocognitive testing; Neuropsychology; Normal development
13.  Can Risk-Taking Be an Endophenotype for Bipolar Disorder? A Study on Patients with Bipolar Disorder Type I and Their First-Degree Relatives 
Risk-taking behavior and impulsivity are core features of bipolar disorder. Whether they are part of the inherited aspect of the illness is not clear. We aimed to evaluate risk-taking behavior as a potential endophenotype for bipolar disorders, and its relationship with impulsivity and illness features. The Balloon Analogue Risk Task (BART) and Barratt Impulsiveness Scale-11 (BIS-11) were used to assess risk-taking behavior and impulsivity respectively in 30 euthymic bipolar I patients (BD), their 25 asymptomatic first-degree relatives (BD-R), and 30 healthy controls (HC). The primary BART outcome measure was the behavioral adjustment score (number of pumps after trials where the balloon did not pop minus the number of pumps after trials where the balloon popped). BD (p < .001) and BD-R (p = .001) had similar and significantly lower adjustment scores than HC. Only BD scored significantly higher on BIS-11 total (p = .01) and motor (p = .04) subscales than HC. Neither the BART, nor impulsivity scores associated with illness features. A limitation of this study is medicated patients and a heterogeneous BD-R were included. Riskiness may be a candidate endophenotype for bipolar disorder as it appears independently from illness features, presents similarly in BD and BD-R groups and differs from impulsivity.
PMCID: PMC4180758  PMID: 23410848
Bipolar disorder; Risk-taking; Impulsive behavior; Endophenotype; First-degree relative; The Balloon Analogue Risk Task
14.  Subjective Cognitive Complaints Contribute to Misdiagnosis of Mild Cognitive Impairment 
Subjective cognitive complaints are a criterion for the diagnosis of mild cognitive impairment (MCI), despite their uncertain relationship to objective memory performance in MCI. We aimed to examine self-reported cognitive complaints in subgroups of the Alzheimer’s Disease Neuroimaging Initiative (ADNI) MCI cohort to determine whether they are a valuable inclusion in the diagnosis of MCI or, alternatively, if they contribute to misdiagnosis. Subgroups of MCI were derived using cluster analysis of baseline neuropsychological test data from 448 ADNI MCI participants. Cognitive complaints were assessed via the Everyday Cognition (ECog) questionnaire, and discrepancy scores were calculated between self- and informant-report. Cluster analysis revealed Amnestic and Mixed cognitive phenotypes as well as a third Cluster-Derived Normal subgroup (41.3%), whose neuropsychological and cerebrospinal fluid (CSF) Alzheimer’s disease (AD) biomarker profiles did not differ from a “robust” normal control group. This cognitively intact phenotype of MCI participants overestimated their cognitive problems relative to their informant, whereas Amnestic MCI participants with objective memory impairment underestimated their cognitive problems. Underestimation of cognitive problems was associated with positive CSF AD biomarkers and progression to dementia. Overall, there was no relationship between self-reported cognitive complaints and objective cognitive functioning, but significant correlations were observed with depressive symptoms. The inclusion of self-reported complaints in MCI diagnostic criteria may cloud rather than clarify diagnosis and result in high rates of misclassification of MCI. Discrepancies between self- and informant-report demonstrate that overestimation of cognitive problems is characteristic of normal aging while underestimation may reflect greater risk for cognitive decline.
PMCID: PMC4172502  PMID: 25156329
Mild cognitive impairment; Awareness; Cluster analysis; Diagnostic errors; Neuropsychology; Dementia; Alzheimer disease
15.  Neural Correlates of Interference Control in Adolescents with Traumatic Brain Injury: Functional Magnetic Resonance Imaging Study of the Counting Stroop Task 
Difficulty in inhibition or cognitive control is a common and significant sequela of pediatric traumatic brain injury (TBI). The present study used functional MRI to examine one specific inhibitory function, interference control, in 11 adolescents, aged 12–16 years, (mean age, 15.7 years) with TBI who were at least 1 year postinjury and 11 age-matched typically developing control participants (TC) (mean age, 15.2 years). Participants completed a Counting Stroop task with 2 main conditions: (1) a neutral condition requiring the counting of animal words and (2) an interference condition in which mismatched number words were counted. Both TBI and TC adolescents activated similar networks of brain regions relevant to interference control, but the TBI group showed higher levels of activation relative to the TC group in multiple brain areas within this network, including predominantly right frontal and parietal regions. Findings of greater activation of the relevant neural network in the TBI group are consistent with recent fMRI findings using other interference control paradigms with individuals with a history of TBI.
PMCID: PMC4164964  PMID: 21092356
Childhood brain disorder; Inhibition; Executive functions; Brain imaging; Adolescent; Head injury
16.  Behavioral and Cognitive Predictors of Educational Outcomes in Pediatric Traumatic Brain Injury 
Research reveals mixed results regarding the utility of standardized cognitive and academic tests to predict educational outcomes in youth following a traumatic brain injury (TBI). Yet, deficits in everyday school-based outcomes are prevalent after pediatric TBI. The current study used path modeling to test the hypothesis that parent ratings of adolescents’ daily behaviors associated with executive functioning (EF) would predict long-term functional educational outcomes following pediatric TBI, even when injury severity and patient demographics were included in the model. Furthermore, we contrasted the predictive strength of the EF behavioral ratings with that of a common measure of verbal memory. A total of 132 adolescents who were hospitalized for moderate to severe TBI were recruited to participate in a randomized clinical intervention trial. EF ratings and verbal memory were measured within 6 months of the injury; functional educational outcomes were measured 12 months later. EF ratings and verbal memory added to injury severity in predicting educational competence post injury but did not predict post-injury initiation of special education. The results demonstrated that measurement of EF behaviors is an important research and clinical tool for prediction of functional outcomes in pediatric TBI.
PMCID: PMC4160234  PMID: 23790158
Executive function; Neuropsychology; Adolescent; Language; Special education; Brain concussion
17.  Quantifying Cognitive Reserve in Older Adults by Decomposing Episodic Memory Variance: Replication and Extension 
The theory of cognitive reserve attempts to explain why some individuals are more resilient to age-related brain pathology. Efforts to explore reserve have been hindered by measurement difficulties. Reed et al. (2010) proposed quantifying reserve as residual variance in episodic memory performance that remains after accounting for demographic factors and brain pathology (whole brain, hippocampal, and white matter hyperintensity volumes). This residual variance represents the discrepancy between an individual’s predicted and actual memory performance. The goals of the present study were to extend these methods to a larger, community-based sample and to investigate whether the residual reserve variable is explained by age, predicts longitudinal changes in language, and predicts dementia conversion independent of age. Results support this operational measure of reserve. The residual reserve variable was associated with higher reading ability, lower likelihood of meeting criteria for mild cognitive impairment, lower odds of dementia conversion independent of age, and less decline in language abilities over 3 years. Finally, the residual reserve variable moderated the negative impact of memory variance explained by brain pathology on language decline. This method has the potential to facilitate research on the mechanisms of cognitive reserve and the efficacy of interventions designed to impart reserve.
PMCID: PMC3777696  PMID: 23866160
Cognition; Aging; Mild cognitive impairment; Dementia; Statistical models; Magnetic resonance imaging
18.  Naturalistic Assessment of Everyday Activities and Prompting Technologies in Mild Cognitive Impairment 
Older adults with mild cognitive impairment (MCI) often have difficulty performing complex instrumental activities of daily living (IADLs), which are critical to independent living. In this study, amnestic multi-domain MCI (N = 29), amnestic single-domain MCI (N = 18), and healthy older participants (N = 47) completed eight scripted IADLs (e.g., cook oatmeal on the stove) in a smart apartment testbed. We developed and experimented with a graded hierarchy of technology-based prompts to investigate both the amount of prompting and type of prompts required to assist individuals with MCI in completing the activities. When task errors occurred, progressive levels of assistance were provided, starting with the lowest level needed to adjust performance. Results showed that the multi-domain MCI group made more errors and required more prompts than the single-domain MCI and healthy older adult groups. Similar to the other two groups, the multi-domain MCI group responded well to the indirect prompts and did not need a higher level of prompting to get back on track successfully with the tasks. Need for prompting assistance was best predicted by verbal memory abilities in multi-domain amnestic MCI. Participants across groups indicated that they perceived the prompting technology to be very helpful.
PMCID: PMC4144192  PMID: 23351284
Ecological assessment; Instrumental activities of daily living; Aging; Dementia; Smart environment technologies; Rehabilitation
19.  Friendship Quality and Psychosocial Outcomes among Children with Traumatic Brain Injury 
This study examined differences in friendship quality between children with traumatic brain injury (TBI) and orthopedic injury (OI) and behavioral outcomes for children from both groups. Participants were 41 children with TBI and 43 children with OI (M age = 10.4). Data were collected using peer- and teacher-reported measures of participants’ social adjustment and parent-reported measures of children’s post-injury behaviors. Participants and their mutually nominated best friends also completed a measure of the quality of their friendships. Children with TBI reported significantly more support and satisfaction in their friendships than children with OI. Children with TBI and their mutual best friend were more similar in their reports of friendship quality compared to children with OI and their mutual best friends. Additionally, for children with TBI who were rejected by peers, friendship support buffered against maladaptive psychosocial outcomes, and predicted skills related to social competence. Friendship satisfaction was related to higher teacher ratings of social skills for the TBI group only. Positive and supportive friendships play an important role for children with TBI, especially for those not accepted by peers. Such friendships may protect children with TBI who are rejected against maladaptive psychosocial outcomes, and promote skills related to social competence.
PMCID: PMC4141005  PMID: 24840021
Pediatric; Behavior; Rejection; Head; Trauma; Social competence
20.  Decreased Cognitive Function in Extended Family Members from the Single Late-Onset-Alzheimer’s-Disease Pedigree 
A family history of dementia is associated with an increased risk of developing Alzheimer’s disease (AD) late in life (LOAD). This study marked the first attempt to assess the familial contribution to differences in cognitive performance in a large family-based group in the Chinese community. We enrolled 168 participants without dementia from a single pedigree with 9 probable AD patients diagnosed after age 65. These participants were evaluated with a comprehensive neuropsychological battery, the Chinese version of the Mini Mental State Examination, and the Alzheimer Disease Assessment Scale–Cognitive Subscale. Analyses found that extended family members of the LOAD pedigree showed similar performance on measures of global cognitive function and semantic memory compared to controls, but lower scores on episodic memory, attention, and executive function measures. These results indicate that the genetic influences on certain sub-cognitive domains are more detectable despite normal global cognitive function, and that family members with the LOAD pedigree are at risk for developing LOAD by virtue of their family history with an additive risk due to increased age. The findings in this study support the importance of documenting if there is a positive family history of AD in clinical evaluations.
PMCID: PMC3734807  PMID: 23742872
Alzheimer’s disease; Dementia; Genetics; Memory; Geriatric; Pedigree
21.  Cognitive and Brain Reserve in Prodromal Huntington Disease 
Huntington disease (HD) is associated with decline in cognition and progressive morphological changes in brain structures. Cognitive reserve may represent a mechanism by which disease-related decline may be delayed or slowed. The current study examined the relationship between cognitive reserve and longitudinal change in cognitive functioning and brain volumes among prodromal (gene expansion-positive) HD individuals.
Participants were genetically-confirmed individuals with prodromal HD enrolled in the PREDICT-HD study. Cognitive reserve was computed as the composite of performance on a lexical task estimating premorbid intellectual level, occupational status, and years of education. Linear mixed effects regression (LMER) was used to examine longitudinal changes on 4 cognitive measures and 3 brain volumes over approximately 6 years.
Higher cognitive reserve was significantly associated with a slower rate of change on one cognitive measure (Trail Making Test, Part B) and slower rate of volume loss in two brain structures (caudate, putamen) for those estimated to be closest to motor disease onset. This relationship was not observed among those estimated to be further from motor disease onset.
Our findings demonstrate a relationship between cognitive reserve and both a measure of executive functioning and integrity of certain brain structures in prodromal HD individuals.
PMCID: PMC3720793  PMID: 23702309
Huntington disease; prodromal; cognitive reserve; cognition; caudate; putamen
22.  Prefrontal cortex activity during response selection predicts processing speed impairment in schizophrenia 
Processing speed is the most impaired neuropsychological domain in schizophrenia and a robust predictor of functional outcome. Determining the specific cognitive operations underlying processing speed dysfunction and indentifying their neural correlates may assist in developing pro-cognitive interventions. Response selection, the process of mapping stimuli onto motor responses, correlates with neuropsychological tests of processing speed and may contribute to processing speed impairment in schizophrenia. This study investigated the relationship between behavioral and neural measures of response selection, and a neuropsychological index of processing speed in schizophrenia. 26 patients with schizophrenia and 21 healthy subjects underwent fMRI scanning during performance of 2 and 4-choice-reaction time (RT) tasks and completed the Wechsler Adult Intelligence Scale-III (WAIS) Processing Speed Index (PSI). Response selection, defined as RT slowing between 2 and 4-choice RT, was impaired in schizophrenia and correlated with psychometric processing speed. Greater activation of the dorsolateral prefrontal cortex (PFC) was observed in schizophrenia and correlated with poorer WAIS PSI scores. Deficient response selection and abnormal recruitment of the dorsolateral PFC during response selection contribute to processing speed impairment in schizophrenia. Interventions that improve response selection and normalize dorsolateral PFC function may improve processing speed in schizophrenia.
PMCID: PMC3910268  PMID: 23816240
Schizophrenia; Experimental Psychology; Intelligence; Prefrontal Cortex; Functional MRI
23.  PTSD Modifies Performance on a Task of Affective Executive Control among Deployed OEF/OIF Veterans with Mild Traumatic Brain Injury 
Individuals with post-traumatic stress disorder (PTSD) show a cognitive bias for threatening information, reflecting dysregulated executive control for affective stimuli. This study examined whether comorbid mild Traumatic Brain Injury (mTBI) with PTSD exacerbates this bias. A computer-administered Affective Go/No-Go task measured reaction times (RTs) and errors of omission and commission to words with a non–combat-related positive or negative valence in 72 deployed United States service members from the wars in Iraq and Afghanistan. Incidents of military-related mTBI were measured with the Boston Assessment of Traumatic Brain Injury-Lifetime. PTSD symptoms were measured with the Clinician-Administered PTSD Scale. Participants were divided into those with (mTBI+, n =34) and without a history of military-related mTBI (mTBI−, n =38). Valence of the target stimuli differentially impacted errors of commission and decision bias (criterion) in the mTBI+ and mTBI− groups. Specifically, within the mTBI+ group, increasing severity of PTSD symptoms was associated with an increasingly liberal response pattern (defined as more commission errors to negative distractors and greater hit rate for positive stimuli) in the positive compared to the negative blocks. This association was not observed in the mTBI− group. This study underscores the importance of considering the impact of a military-related mTBI and PTSD severity upon affective executive control.
PMCID: PMC4003877  PMID: 23823533
Post-traumatic stress disorder; Attention; Brain injury; Military; Cognition; Deployment
24.  Adolescent Heavy Episodic Drinking: Neurocognitive Functioning during Early Abstinence 
The present study investigated the rate and pattern of neuropsychological recovery in heavy episodic drinking teens during the initial days to weeks of abstinence from alcohol.
Adolescents (ages 16–18) with histories of heavy episodic drinking (HED; N=39) and socio-demographically similar control teens (CON; N=26) were recruited from San Diego area schools. HED and CON were comparable on 5th grade standardized math and language arts test performance to ensure similar functioning prior to onset of substance use. Participants were administered three neuropsychological test batteries with 2-week intervals during a 4-week monitored abstinence period.
HED teens performed worse overall than CON on tests of prospective memory (p=.005), cognitive switching (p=.039), inhibition task accuracy (p=.001), verbal memory (p's<.045), visuospatial construction (p’s<.043), and language and achievement (p’s<.008). The statistically significant group × time interaction for block design demonstrated normalization within the four weeks of abstinence for the HED (p=.009).
This study identified cognitive performance deficits associated with heavy episodic drinking in adolescence during early abstinence and with sustained 4-week abstention. These findings suggest alcohol-related influences on several underlying brain systems that may predate the onset of alcohol abuse or dependence or take longer than four weeks to recover.
PMCID: PMC4117934  PMID: 24512674
Adolescence; Neuropsychological Tests; Alcohol Consumption; Memory Deficits; Achievement; Adolescent Development
25.  Development of Memory for Spatial Locations and Object/Place Associations in Infant Rhesus Macaques with and without Neonatal Hippocampal Lesions 
This study traces the development of spatial memory abilities in monkeys and reports the effects of selective neonatal hippocampal lesions on performance across development. Two different versions of the visual paired-comparison (VPC) task were used. The VPC-Spatial-Location task tested memory for object-locations that could be solved using an egocentric spatial frame of reference and the VPC-Object-In-Place task taxed memory for spatial relations using an allocentric reference frame. Eleven rhesus macaques (6 neonatal sham-operated controls and 5 with neonatal neurotoxic hippocampal lesions) were tested on both tasks as infants (8 months), juveniles (18 months), and adults (5–6 years). Memory for spatial locations was present by 18 months of age, whereas memory for object-place relations was present only in adulthood. Also, neonatal hippocampal lesions delayed the emergence of memory for spatial locations and abolished memory for object-place associations, particularly in animals that had sustained extensive and bilateral hippocampal lesions. The differential developmental time course of spatial memory functions and of the effects of neonatal hippocampal lesions on these functions are discussed in relation to morphological maturation of the medial temporal lobe structures in monkeys. Implications of the findings for the neural basis of spatial memory development in humans are also considered.
PMCID: PMC4112569  PMID: 23880255
Macaca mulatta; Egocentric space; Allocentric space; Parahippocampal cortex; Visual-paired comparison task; Developmental amnesia

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