Objectives: The current study examined neuropsychological performance among children with spina bifida (SB) to determine biological and functional correlates of distinct “profiles” of cognitive functioning. Methods: A total of 95 children with SB myelomeningocele (ages, 8–15 years) completed a neuropsychological assessment battery. Hierarchical and non-hierarchical cluster analyses were used to identify and confirm a cluster solution. Hypothesized predictors of cluster membership included lesion level, number of shunt surgeries, history of seizures, age, ethnicity, socio-economic status, and family stress. Outcomes included independence, academic success, expectations for the future, and quality of life. Results: Ward’s cluster method indicated a three-cluster solution, and was replicated with two other cluster analytic methods. The following labels were applied to the clusters: “average to low average” (n=39), “extremely low to borderline” (n=27), and “broadly average with verbal strength” (n=29). Socio-econimc status, lesion level, and seizure history significantly predicted group membership. Cluster membership significantly predicted independence, academic success, parent expectations for the future, and child reported physical quality of life. Conclusions: Findings from this study suggest qualitatively different cognitive profiles exist among children with SB, and the relevance of neuropsychological functioning for day-to-day adaptive functioning and quality of life. Clinical implications and future research are discussed. (JINS, 2016, 22, 804–815)

The aim of this study was to examine delay discounting in girls and boys with ADHD-Combined type (ADHD-C) relative to typically developing (TD) children on two tasks that differ in the extent to which the rewards and delays were experienced by participants. Children ages 8–12 years with ADHD-C (n=65; 19 girls) and TD controls (n=55; 15 girls) completed two delay discounting tasks involving a series of choices between smaller, immediate and larger, delayed rewards. The classic delay discounting task involved choices about money at delays of 1–90 days and only some of the outcomes were actually experienced by the participants. The novel real-time discounting task involved choices about an immediately consumable reward (playing a preferred game) at delays of 25–100 s, all of which were actually experienced by participants. Participants also provided subjective ratings of how much they liked playing the game and waiting to play. Girls with ADHD-C displayed greater delay discounting compared to boys with ADHD-C and TD girls and boys on the real-time discounting task. Diagnostic group differences were not evident on the classic discounting task. In addition, children with ADHD-C reported wanting to play the game more and liking waiting to play the game less than TD children. This novel demonstration of greater delay discounting among girls with ADHD-C on a discounting task in which the rewards are immediately consumable and the delays are experienced in real-time informs our understanding of sex differences and motivational processes in children with ADHD. (JINS, 2016, 22, 12–23)

Objectives: Connectionist theories of brain function took hold with the seminal contributions of Norman Geschwind a half century ago. Modern neuroimaging techniques have expanded the scientific interest in the study of brain connectivity to include the intact as well as disordered brain. Methods: In this review, we describe the most common techniques used to measure functional and structural connectivity, including resting state functional MRI, diffusion MRI, and electroencephalography and magnetoencephalography coherence. We also review the most common analytical approaches used for examining brain interconnectivity associated with these various imaging methods. Results: This review presents a critical analysis of the assumptions, as well as methodological limitations, of each imaging and analysis approach. Conclusions: The overall goal of this review is to provide the reader with an introduction to evaluating the scientific methods underlying investigations that probe the human connectome. (JINS, 2016, 22, 105–119)

Objectives: Visuospatial processing deficits have been reported in Huntington’s disease (HD). To date, no study has examined associations between visuospatial cognition and posterior brain findings in HD. Methods: We compared 119 premanifest (55> and 64<10.8 years to expected disease onset) and 104 early symptomatic (59 stage-1 and 45 stage-2) gene carriers, with 110 controls on visual search and mental rotation performance at baseline and 12 months. In the disease groups, we also examined associations between task performance and disease severity, functional capacity and structural brain measures. Results: Cross-sectionally, there were strong differences between all disease groups and controls on visual search, and between diagnosed groups and controls on mental rotation accuracy. Only the premanifest participants close to onset took longer than controls to respond correctly to mental rotation. Visual search negatively correlated with disease burden and motor symptoms in diagnosed individuals, and positively correlated with functional capacity. Mental rotation (“same”) was negatively correlated with motor symptoms in stage-2 individuals, and positively correlated with functional capacity. Visual search and mental rotation were associated with parieto-occipital (pre-/cuneus, calcarine, lingual) and temporal (posterior fusiform) volume and cortical thickness. Longitudinally, visual search deteriorated over 12 months in stage-2 individuals, with no evidence of declines in mental rotation. Conclusions: Our findings provide evidence linking early visuospatial deficits to functioning and posterior cortical dysfunction in HD. The findings are important since large research efforts have focused on fronto-striatal mediated cognitive changes, with little attention given to aspects of cognition outside of these areas. (JINS, 2016, 22, 595–608)

Objectives: To examine the effect of pre-injury alcohol use, acute alcohol intoxication, and post-injury alcohol use on outcome from mild to moderate traumatic brain injury (TBI). Methods: Prospective inception cohort of patients who presented to the Emergency Department with mild to moderate TBI and had a blood alcohol level (BAL) taken for clinical purposes. Those who completed the 1-year outcome assessment were eligible for this study (N=91). Outcomes of interest were the count of post-concussion symptoms (British Columbia Post-Concussion Symptom Inventory), low neuropsychological test scores (Neuropsychological Assessment Battery), and abnormal regions of interest on diffusion tensor imaging (low fractional anisotropy). The main predictors were pre-injury alcohol consumption (Cognitive Lifetime Drinking History interview), BAL, and post-injury alcohol use. Results: The alcohol use variables were moderately to strongly inter-correlated. None of the alcohol use variables (whether continuous or categorical) were related to 1-year TBI outcomes in generalized linear modeling. Participants in this cohort generally had a good clinical outcome, regardless of their pre-, peri-, and post-injury alcohol use. Conclusions: Alcohol may not significantly alter long-term outcome from mild to moderate TBI. (JINS, 2016, 22, 816–827)

Objectives: Recent advances in neuroimaging methodologies sensitive to axonal injury have made it possible to assess in vivo the extent of traumatic brain injury (TBI) -related disruption in neural structures and their connections. The objective of this paper is to review studies examining connectivity in TBI with an emphasis on structural and functional MRI methods that have proven to be valuable in uncovering neural abnormalities associated with this condition. Methods: We review studies that have examined white matter integrity in TBI of varying etiology and levels of severity, and consider how findings at different times post-injury may inform underlying mechanisms of post-injury progression and recovery. Moreover, in light of recent advances in neuroimaging methods to study the functional connectivity among brain regions that form integrated networks, we review TBI studies that use resting-state functional connectivity MRI methodology to examine neural networks disrupted by putative axonal injury. Results: The findings suggest that TBI is associated with altered structural and functional connectivity, characterized by decreased integrity of white matter pathways and imbalance and inefficiency of functional networks. These structural and functional alterations are often associated with neurocognitive dysfunction and poor functional outcomes. Conclusions: TBI has a negative impact on distributed brain networks that lead to behavioral disturbance. (JINS, 2016, 22, 120–137)

Objectives: The current study aimed to determine whether reversal learning impairments and feedback-related negativity (FRN), reflecting reward prediction error signals generated by negative feedback during the reversal learning tasks, were associated with social disinhibition in a group of participants with traumatic brain injury (TBI). Methods: Number of reversal errors on a social and a non-social reversal learning task and FRN were examined for 21 participants with TBI and 21 control participants matched for age. Participants with TBI were also divided into low and high disinhibition groups based on rated videotaped interviews. Results: Participants with TBI made more reversal errors and produced smaller amplitude FRNs than controls. Furthermore, participants with TBI high on social disinhibition made more reversal errors on the social reversal learning task than did those low on social disinhibition. FRN amplitude was not related to disinhibition. Conclusions: These results suggest that impairment in the ability to update behavior when social reinforcement contingencies change plays a role in social disinhibition after TBI. Furthermore, the social reversal learning task used in this study may be a useful neuropsychological tool for detecting susceptibility to acquired social disinhibition following TBI. Finally, that the FRN amplitude was not associated with social disinhibition suggests that reward prediction error signals are not critical for behavioral adaptation in the social domain. (JINS, 2016, 21, 303–313)

Previous studies have demonstrated that emotional facial expressions alter temporal judgments. Moreover, while some studies conducted with Parkinson's disease (PD) patients suggest dysfunction in the recognition of emotional facial expression, others have shown a dysfunction in time perception. In the present study, we investigate the magnitude of temporal distortions caused by the presentation of emotional facial expressions (anger, shame, and neutral) in PD patients and controls. Twenty-five older adults with PD and 17 healthy older adults took part in the present study. PD patients were divided into two sub-groups, with and without mild cognitive impairment (MCI), based on their neuropsychological performance. Participants were tested with a time bisection task with standard intervals lasting 400 ms and 1600 ms. The effect of facial emotional stimuli on time perception was evident in all participants, yet the effect was greater for PD-MCI patients. Furthermore, PD-MCI patients were more likely to underestimate long and overestimate short temporal intervals than PD-non-MCI patients and controls. Temporal impairment in PD-MCI patients seem to be mainly caused by a memory dysfunction. (JINS, 2016, 22, 890–899)

Limited data exist comparing the performance of computerized neurocognitive tests (CNTs) for assessing sport-related concussion. We evaluated the reliability and validity of three CNTs—ANAM, Axon Sports/Cogstate Sport, and ImPACT—in a common sample. High school and collegiate athletes completed two CNTs each at baseline. Concussed (n=165) and matched non-injured control (n=166) subjects repeated testing within 24 hr and at 8, 15, and 45 days post-injury. Roughly a quarter of each CNT’s indices had stability coefficients (M=198 day interval) over .70. Group differences in performance were mostly moderate to large at 24 hr and small by day 8. The sensitivity of reliable change indices (RCIs) was best at 24 hr (67.8%, 60.3%, and 47.6% with one or more significant RCIs for ImPACT, Axon, and ANAM, respectively) but diminished to near the false positive rates thereafter. Across time, the CNTs’ sensitivities were highest in those athletes who became asymptomatic within 1 day before neurocognitive testing but was similar to the tests’ false positive rates when including athletes who became asymptomatic several days earlier. Test–retest reliability was similar among these three CNTs and below optimal standards for clinical use on many subtests. Analyses of group effect sizes, discrimination, and sensitivity and specificity suggested that the CNTs may add incrementally (beyond symptom scores) to the identification of clinical impairment within 24 hr of injury or within a short time period after symptom resolution but do not add significant value over symptom assessment later. The rapid clinical recovery course from concussion and modest stability probably jointly contribute to limited signal detection capabilities of neurocognitive tests outside a brief post-injury window. (JINS, 2016, 22, 24–37)

Objectives: Evidence suggests that Alzheimer’s disease (AD) biomarkers become abnormal many years before the emergence of clinical symptoms of AD, raising the possibility that biomarker levels measured in cognitively normal individuals would be associated with cognitive performance many years later. This study examined whether performance on computerized cognitive tests is associated with levels of cerebrospinal fluid (CSF) biomarkers of amyloid, tau, and phosphorylated tau (p-tau) obtained approximately 10 years earlier, when individuals were cognitively normal and primarily middle-aged. Methods: Individuals from the BIOCARD cohort (mean age at testing=69 years) were tested on two computerized tasks hypothesized to rely on brain regions affected by the early accumulation of AD pathology: (1) a Paired Associates Learning (PAL) task (n=67) and (2) a visual search task (n=86). Results: In regression analyses, poorer performance on the PAL task was associated with higher levels of CSF p-tau obtained years earlier, whereas worse performance in the visual search task was associated with lower levels of CSF Aβ1-42. Conclusions: These findings suggest that AD biomarker levels may be differentially predictive of specific cognitive functions many years later. In line with the pattern of early accumulation of AD pathology, the PAL task, hypothesized to rely on medial temporal lobe function, was associated with CSF p-tau, whereas the visual search task, hypothesized to rely on frontoparietal function, was associated with CSF amyloid. Studies using amyloid and tau PET imaging will be useful in examining these hypothesized relationships further. (JINS, 2016, 22, 968–977)

Objectives: Following pediatric moderate-to-severe traumatic brain injury (msTBI), few predictors have been identified that can reliably identify which individuals are at risk for long-term cognitive difficulties. This study sought to determine the relative contribution of detailed descriptors of injury severity as well as demographic and psychosocial factors to long-term cognitive outcomes after pediatric msTBI. Methods: Participants included 8- to 19-year-olds, 46 with msTBI and 53 uninjured healthy controls (HC). Assessments were conducted in the post-acute and chronic stages of recovery. Medical record review provided details regarding acute injury severity. Parents also completed a measure of premorbid functioning and behavioral problems. The outcome of interest was four neurocognitive measures sensitive to msTBI combined to create an index of cognitive performance. Results: Results indicated that none of the detailed descriptors of acute injury severity predicted cognitive performance. Only the occurrence of injury, parental education, and premorbid academic competence predicted post-acute cognitive functioning. Long-term cognitive outcomes were best predicted by post-acute cognitive functioning. Discussion: The findings suggest that premorbid factors influence cognitive outcomes nearly as much as the occurrence of a msTBI. Furthermore, of youth with msTBI who initially recover to a level of moderate disability or better, a brief cognitive battery administered within several months after injury can best predict which individuals will experience poor long-term cognitive outcomes and require additional services. (JINS, 2016, 22, 1–8)

Objectives: Numerous studies have shown that individuals with posttraumatic stress disorder (PTSD) display reduced performances on neuropsychological tests, although most prior research has not adequately accounted for comorbidities or performance validity concerns that are common in this population and could partially account for the observed neurocognitive findings. Moreover, few studies have examined the functional implications of neuropsychological results in PTSD. Methods: We examined neuropsychological functioning in 44 veterans with PTSD and 40 veteran trauma comparison (TC) participants with combat exposure and no PTSD. Results: After excluding four veterans with PTSD for performance validity concerns, multivariate analyses of variance by neurocognitive domain revealed significantly worse performance by the PTSD group in the domains of speed of information processing (p=.035) and executive functions (p=.017), but no group differences in attention/working memory, verbal/language functioning, visuoconstruction, or episodic memory. Group differences by PTSD status were still present after covarying for depression, a history of head injuries, and substance use disorders. Executive functioning performance was associated with poorer self-reported occupational functioning and physical health-related quality of life, while speed of information processing performance was associated with poorer physical health-related quality of life. Discussion: These results are generally consistent with a fronto-limbic conceptualization of PTSD-associated neuropsychological dysfunction and show that cognitive functioning may be associated with critical functional outcomes. Taken together, results suggest that consideration of neurocognitive functioning may enhance the clinical management of individuals with PTSD. (JINS, 2016, 22, 399–411)

Objectives: Neuropsychological studies of posttraumatic stress disorder (PTSD) have revealed deficits in attention/working memory, processing speed, executive functioning, and retrospective memory. However, little is known about prospective memory (PM) in PTSD, a clinically relevant aspect of episodic memory that supports the encoding and retrieval of intentions for future actions. Methods: Here we examined PM performance in 40 veterans with PTSD compared to 38 trauma comparison (TC) veterans who were exposed to combat but did not develop PTSD. All participants were administered the Memory for Intentions Test (MIST; Raskin, Buckheit, & Sherrod, 2010), a standardized and validated measure of PM, alongside a comprehensive neurocognitive battery, structured diagnostic interviews for psychiatric conditions, and behavioral questionnaires. Results: Veterans with PTSD performed moderately lower than TC on time-based PM, with errors primarily characterized as PM failure errors (i.e., omissions). However, groups did not differ in event-based PM, ongoing task performance, or post-test recognition of PM intentions for each trial. Lower time-based PM performance was specifically related to hyperarousal symptoms of PTSD. Time-based-performance was also associated with neuropsychological measures of retrospective memory and executive functions in the PTSD group. Nevertheless, PTSD was significantly associated with poorer PM above and beyond age and performance in retrospective memory and executive functions. Discussion: Results provide initial evidence of PM dysfunction in PTSD, especially in strategic monitoring during time-based PM tasks. Findings have potential implications for everyday functioning and health behaviors in persons with PTSD, and deserve replication and future study. (JINS, 2016, 22, 724–734)

Background: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a recently described life-threatening autoimmune disorder associated with a characteristic multi-stage neuropsychiatric syndrome. Although it is known that the majority of patients experience neuropsychological disturbance post-treatment, some aspects of the cognitive profile remain unclear. Methods: This study sought to investigate patterns of cognitive functioning in a sample of anti-NMDAR encephalitis patients. Seven (6F:1M; mean age, 26.4 years; range, 16–37 years) treated patients completed a comprehensive set of neurocognitive and social functioning measures. Performance was analyzed using normative data (where available), and comparison with matched controls (10F:4M; mean age, 25.8 years; range, 16–38 years). Results: Individual cognitive profiles ranged from within normal limits to extensive dysfunction. Relative to controls, the patient group’s performance was affected in the domains of verbal/ visual memory, working memory, attention, processing speed, executive functioning, and social cognition. The patient group also reported significantly higher levels of anxiety compared to controls. Conclusions: These results add to the accumulating evidence that neurocognitive deficits, consistent with the distribution and functions of the NMDAR system can persist during recovery from anti-NMDAR encephalitis. This is the first study to provide evidence of performance decrements on measures of social cognition, including some involving theory of mind. (JINS, 2016, 22, 828–838)

Objectives: Previous evidence indicates that patients with schizophrenia exhibit reduced repetition priming in production tasks (in which each response cue engenders a competition between alternative responses), but not in identification tasks (in which each response cue allows a unique response). However, cross-task comparisons may lead to inappropriate conclusions, because implicit tests vary on several dimensions in addition to the critical dimension of response competition. The present study sought to isolate the role of response competition, by varying the number of solutions in the context of the same implicit tasks. Methods: Two experiments investigated the performance of patients with schizophrenia and healthy controls in the high-competition and low-competition versions of word-stem completion (Exp.1) and verb generation (Exp.2). Results: Response competition affected both the proportions of stems completed (higher to few-solution than to many-solution stems) and the reaction times of verb generation (slower to nouns having no dominant verb associates than to nouns having one dominant verb associate). Patients with schizophrenia showed significant (non-zero) priming in both experiments: crucially, the magnitude of this facilitation was equivalent to that observed in healthy controls and was not reduced in the high-competition versions of the two tasks. Conclusions: These findings suggest that implicit memory is spared in schizophrenia, irrespective of the degree of response competition during the retrieval phase; in addition, they add to the ongoing debate regarding the validity of the identification/production hypothesis of repetition priming. (JINS, 2015, 21, 314–321)

Objectives: Individuals with major depressive disorder (MDD) demonstrate poorer learning and memory skills relative to never-depressed comparisons (NDC). Previous studies report decreased volume and disrupted function of frontal lobes and hippocampi in MDD during memory challenge. However, it has been difficult to dissociate contributions of short-term memory and executive functioning to memory difficulties from those that might be attributable to long-term memory deficits. Methods: Adult males (MDD, n=19; NDC, n=22) and females (MDD, n=23; NDC, n=19) performed the Semantic List Learning Task (SLLT) during functional magnetic resonance imaging. The SLLT Encoding condition consists of 15 lists, each containing 14 words. After each list, a Distractor condition occurs, followed by cued Silent Rehearsal instructions. Post-scan recall and recognition were collected. Groups were compared using block (Encoding-Silent Rehearsal) and event-related (Words Recalled) models. Results: MDD displayed lower recall relative to NDC. NDC displayed greater activation in several temporal, frontal, and parietal regions, for both Encoding-Silent Rehearsal and the Words Recalled analyses. Groups also differed in activation patterns in regions of the Papez circuit in planned analyses. The majority of activation differences were not related to performance, presence of medications, presence of comorbid anxiety disorder, or decreased gray matter volume in MDD. Conclusions: Adults with MDD exhibit memory difficulties during a task designed to reduce the contribution of individual variability from short-term memory and executive functioning processes, parallel with decreased activation in memory and executive functioning circuits. Ecologically valid long-term memory tasks are imperative for uncovering neural correlates of memory performance deficits in adults with MDD. (JINS, 2016, 22, 412–425)

Objectives: The objective was to review the literature on diffusion tensor imaging as well as resting-state functional magnetic resonance imaging and electroencephalography (EEG) to unveil neuroanatomical and neurophysiological substrates of Alzheimer’s disease (AD) as a brain neural network pathology affecting structural and functional cortical connectivity underlying human cognition. Methods: We reviewed papers registered in PubMed and other scientific repositories on the use of these techniques in amnesic mild cognitive impairment (MCI) and clinically mild AD dementia patients compared to cognitively intact elderly individuals (Controls). Results: Hundreds of peer-reviewed (cross-sectional and longitudinal) papers have shown in patients with MCI and mild AD compared to Controls (1) impairment of callosal (splenium), thalamic, and anterior–posterior white matter bundles; (2) reduced correlation of resting state blood oxygen level-dependent activity across several intrinsic brain circuits including default mode and attention-related networks; and (3) abnormal power and functional coupling of resting state cortical EEG rhythms. Clinical applications of these measures are still limited. Conclusions: Structural and functional (in vivo) cortical connectivity measures represent a reliable marker of cerebral reserve capacity and should be used to predict and monitor the evolution of AD and its relative impact on cognitive domains in pre-clinical, prodromal, and dementia stages of AD. (JINS, 2016, 22, 138–163)

Objectives: Prominent impairment of visuospatial processing is a feature of dementia with Lewy bodies (DLB), and diagnosis of this impairment may help clinically distinguish DLB from Alzheimer’s disease (AD). The current study compared autopsy-confirmed DLB and AD patients on the Hooper Visual Organization Test (VOT), a test that requires perceptual and mental reorganization of parts of an object into an identifiable whole. The VOT may be particularly sensitive to DLB since it involves integration of visual information processed in separate dorsal and ventral visual “streams”. Methods: Demographically similar DLB (n=28), AD (n=115), and normal control (NC; n=85) participants were compared on the VOT and additional neuropsychological tests. Patient groups did not differ in dementia severity at time of VOT testing. High and Low AD-Braak stage DLB subgroups were compared to examine the influence of concomitant AD pathology on VOT performance. Results: Both patient groups were impaired compared to NC participants. VOT scores of DLB patients were significantly lower than those of AD patients. The diagnostic sensitivity and specificity of the VOT for patients versus controls was good, but marginal for DLB versus AD. High-Braak and low-Braak DLB patients did not differ on the VOT, but High-Braak DLB performed worse than Low-Braak DLB on tests of episodic memory and language. Conclusions: Visual perceptual organization ability is more impaired in DLB than AD but not strongly diagnostic. The disproportionate severity of this visual perceptual deficit in DLB is not related to degree of concomitant AD pathology, which suggests that it might primarily reflect Lewy body pathology. (JINS, 2016, 22, 609–619)

Objectives: This study aims to compare verbal and motor implicit sequence learning abilities in children with and without specific language impairment (SLI). Methods: Forty-eight children (24 control and 24 SLI) were administered the Serial Search Task (SST), which enables the simultaneous assessment of implicit spoken words and visuomotor sequences learning. Results: Results showed that control children implicitly learned both the spoken words as well as the motor sequences. In contrast, children with SLI showed deficits in both types of learning. Moreover, correlational analyses revealed that SST performance was linked with grammatical abilities in control children but with lexical abilities in children with SLI. Conclusions: Overall, this pattern of results supports the procedural deficit hypothesis and suggests that domain general implicit sequence learning is impaired in SLI. (JINS, 2016, 22, 1–10)