The primary purpose of this study was to test the hypothesis that multiple sclerosis (MS) patients have impaired acquisition rather than a retrieval deficit. Verbal memory impairment in MS was examined in 53 relapsing-remitting MS patients and 31 healthy controls (HC), and in a meta-analysis of studies that examined memory functioning in MS with list-learning tasks. The MS group demonstrated significantly lower acquisition and delayed recall performance than the HC group, and the meta-analysis revealed that the largest effect sizes were obtained for acquisition measures relative to delayed recall and recognition. Our data argue against a retrieval deficit as the sole explanation for verbal memory impairment in MS, and make a consistent case for the position that deficient acquisition contributes to the memory dysfunction of MS patients. Deficient acquisition may result from demyelination in relevant white matter tracts that reduces encoding efficiency as a result of impaired speed of information processing. (JINS, 2013, 19, 995–1008)

In theory, semantic memory may trigger and support the execution of everyday activities. This study explored this question by comparing three patients with semantic dementia to 40 normal controls performing different everyday activities. Participants were tested in their home using the Instrumental Activities of Daily Living Profile, an ecological measure of everyday functioning. Participants were informed that they had unknowingly invited two guests for lunch and should prepare accordingly. With these instructions, they dress to go outdoors, go to the grocery store, shop for food, prepare a hot meal, have the meal with the guests, and clean up after the meal. Performance was analyzed on the basis of four operations related to problem solving: formulate a goal, plan, execute, and verify attainment of the goal. Results indicate that compared to normal controls, two patients had significant difficulties and needed assistance with all operations of problem-solving, particularly while preparing a meal and cleaning up after the meal. One patient showed no difficulties despite severe semantic deficits. These results suggest that semantic deficits alone cannot explain the difficulties observed, but may contribute to some aspects of everyday actions such as those involved in everyday problem-solving. (JINS, 2012, 18, 1–11)

Executive dysfunction causes significant real-life disability for patients with spina bifida (SB). However, no previous research has been directed toward the amelioration of executive functioning deficits amongst persons with SB. Goal Management Training (GMT) is a compensatory cognitive rehabilitation approach, addressing underlying deficits in sustained attention to improve executive function. GMT has received empirical support in studies of other patient groups. The purpose of the present study was to determine the efficacy of GMT in treating subjects with SB, using inpatient intervention periods. We hypothesized post-intervention changes in scores on neuropsychological measures to reflect improved attentional control, including sustained attention and inhibitory control. Thirty-eight adult subjects with SB were included in this randomized controlled trial. Inclusion was based upon the presence of executive functioning complaints. Experimental subjects (n = 24) received 21 hr of GMT, with efficacy of GMT being compared to results of subjects in a wait-list condition (n = 14). All subjects were assessed at baseline, post-intervention, and at 6-month follow-up. Findings indicated superior effects of GMT on domain-specific neuropsychological measures and on a functional “real-life” measure, all lasting at least 6 months post-treatment. These results show that deficits in executive functioning can be ameliorated in patients with congenital brain dysfunction. (JINS, 2013, 19, 1–14)

Deficits in prospective memory (PM; i.e., enacting previously learned actions at the right occasion) and risky decision-making (i.e., making choices with a high chance of undesirable/dangerous outcomes) are both common among individuals with substance use disorders (SUD). Previous research has raised the possibility of a specific relationship between PM and risk-taking, and the present study aimed to systematically study if PM provides unique variance in the prediction of risky decision-making. Two samples were included: (1) a group of 45 individuals with SUD currently in treatment, and (2) a nonclinical group of 59 university students with high-risk drinking and/or substance use. Regression analyses indicated that time-based, but not event-based, PM predicted increased risky behavior (e.g., risky sexual practices and criminal behaviors) in both groups after controlling for demographic, psychiatric, and substance use variables, as well as other neuropsychological functions. The current findings contribute to the growing literature supporting the role of PM as a predictor of everyday functioning, and suggest that cognitive rehabilitation may be an important avenue of research as an adjunct to traditional substance use treatment, particularly in addressing the potential adverse effects of PM deficits in the implementation of treatment-related homework activities and risk management strategies. (JINS, 2013, 19, 1–11)

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. (JINS, 2013, 19, 1–10)

Children with traumatic brain injury (TBI) are at risk for social impairment. This study aimed to examine social function at 6 months post-TBI and to explore the contribution of injury, cognitive, and environmental influences. The sample included 136 children, 93 survivors of TBI, and 43 healthy controls. TBI participants were recruited on admission and underwent magnetic resonance imaging scan within 8 weeks of injury and behavioral assessment at 6 months post-injury. Healthy controls underwent magnetic resonance imaging scans and behavioral assessment on recruitment. Assessment included parent and child questionnaires tapping social outcome and child-direct testing of cognitive abilities important for social competence (communication, attention/executive function, social cognition). Injury characteristics and environmental measures were collected. At 6-months post-injury, social problems were evident, but not global. Social participation appeared most vulnerable, with more severe injuries leading to greater problems. Greater injury severity and poorer communication skills were associated with poorer social adjustment and social participation, with the impact of family function also significant. Processing speed, younger age, and male gender also contributed to social outcomes. Further follow-up is required to track the recovery of social skills and the changing influences of cognition, brain, and environment over time. (JINS, 2013, 19, 1–12)

Impulsive behaviors and poor inhibition performances are frequently described in patients with traumatic brain injury (TBI). However, few studies have examined impulsivity and associated inhibition impairments in these patients. Twenty-eight patients with moderate to severe TBI and 27 matched controls performed a stop-signal task designed to assess prepotent response inhibition (the ability to inhibit a dominant or automatic motor response) in a neutral or emotional context and a recent negative task to assess resistance to proactive interference (the ability to resist the intrusion into memory of information that was previously relevant but has since become irrelevant). Informants of each patient completed a short questionnaire designed to assess impulsivity. Patients showed a significant increase in current urgency, lack of premeditation, and lack of perseverance when retrospectively compared with the preinjury condition. Group comparisons revealed poorer prepotent response inhibition and resistance to proactive interference performances in patients with TBI. Finally, correlation analyses revealed a significant positive correlation between urgency (the tendency to act rashly when distressed) and prepotent response inhibition in patients with TBI. This study sheds new light on the construct of impulsivity after a TBI, its related cognitive mechanisms, and its potential role in problematic behaviors described after a TBI. (JINS, 2013, 19, 1–9)

Williams syndrome (WS) is a neurodevelopmental disorder characterized by severe visuospatial deficits, particularly affecting spatial navigation and wayfinding. Creating egocentric (viewer-dependent) and allocentric (viewer-independent) representations of space is essential for the development of these abilities. However, it remains unclear whether egocentric and allocentric representations are impaired in WS. In this study, we investigate egocentric and allocentric frames of reference in this disorder. A WS group (n = 18), as well as a chronological age-matched control group (n = 20), a non-verbal mental age-matched control group (n = 20) and a control group with intellectual disability (n = 17), was tested with a computerized and a 3D spatial judgment task. The results showed that WS participants are impaired when performing both egocentric and allocentric spatial judgments even when compared with mental age-matched control participants. This indicates that a substantial deficit affecting both spatial representations is present in WS. The egocentric impairment is in line with the dorsal visual pathway deficit previously reported in WS. Interestingly, the difficulties found in performing allocentric spatial judgments give important cues to better understand the ventral visual functioning in WS. (JINS, 2013, 19, 1–9)

We examined cognitive predictors of speech and articulation rate in 50 individuals with multiple sclerosis (MS) and 23 healthy controls. We measured speech and articulation rate from audio-recordings of participants reading aloud and talking extemporaneously on a topic of their choice (i.e., self-generated speech). Articulation rate was calculated for each speech sample by removing lexically irrelevant vocalizations and pauses of >200 ms. Speech rate was similarly calculated including pauses. Concurrently, the Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) battery, as well as standardized tests of sentence intelligibility and syllable repetition were administered. Analysis of variance showed that MS patients were slower on three of the four rate measures. Greater variance in rate measures was accounted for by cognitive variables for the MS group than controls. An information processing speed composite, as measured by the Symbol Digit Modalities Test (SDMT) and the Paced Auditory Serial Addition Test (PASAT), was the strongest predictor among cognitive tests. A composite of memory tests related to self-generated speech, above and beyond information processing speed, but not to oral reading. Self-generated speech, in this study, was not found to relate more strongly to cognitive tests than simple reading. Implications for further research are discussed. (JINS, 2012, 18, 1–8)

Accumulating evidence suggests neuropsychological deficits from cannabis use, with a burgeoning area of preclinical research indicating possible sex-differences. However, few studies have examined how cannabis use may differentially impact neurocognition in male and female cannabis users. As such, we examined potential sex-differences in associations between amount of cannabis use (across several time frames) and neurocognitive performance among young adult regular cannabis users. Consistent with previous studies, more cannabis use was generally associated with poorer episodic memory and decision-making, but not other measures of inhibitory control. However, patterns of results suggested sex-specific dissociations. In particular, more cannabis use was more consistently associated with poorer episodic memory performance in females than males. Conversely, more cannabis use was associated with poorer decision-making performance for males, but not females. These results provide further evidence for residual cannabis-associated neurocognitive deficits and suggest the importance of examining the impact of cannabis on neurocognition separately for males and females. (JINS, 2013, 19, 1–7)

Impairments in attention and information processing speed are common in multiple sclerosis (MS) and may contribute to impairments of other cognitive abilities. This study examined attentional efficiency, information processing speed and intra-individual variability in response speed using the Attention Network Test-Interactions (ANT-I) in mildy-affected patients with MS. Thirty-one patients with relapsing-remitting MS and 30 age, sex, and education-matched controls completed the ANT-I, as well as the Paced Auditory Serial Attention Test (PASAT), as a standard clinical measure of information processing efficiency. As expected, patients with MS were slower in reaction time performance on the ANT-I and had poorer performance on the PASAT compared to controls. Patients with MS also demonstrated poorer efficiency in their executive control of attention on the ANT-I, suggesting difficulties with top-down allocation of attention. In addition, the MS group demonstrated greater intra-individual variability in the responses to the ANT-I even when their slower overall response time and other factors such as practice were accounted for. Intra-individual variability was found to best predict group membership compared to PASAT scores and other ANT-I scores. These results suggest that intra-individual variability may provide sensitive, unique and important information regarding cognitive functioning in early MS. (JINS, 2013, 19, 1–8)

Individuals with attention-deficit/hyperactivity disorder (ADHD) often exhibit deficits in processing information about time. Most studies, however, have required participants to perform active tasks and consequently it is unclear if performance deficits are due to impaired processing of temporal information, attentional deficits, or to impairments at a later stage of decision-making. This study used mismatch negativity (MMN) to examine automatic processing of temporal information in children with ADHD. The sample consisted of 11 children with typical development (8 boys; mean age/SD = 9.3/0.6 years) and 12 with ADHD (10 boys; mean age/SD = 8.9/0.8 years). Using the MMN paradigm, responses to standards and four deviants (hard/easy frequency, hard/easy duration) were elicited during the same sequence. The children's ability to actively discriminate each deviant was also assessed. Both groups exhibited MMNs to all deviants suggesting successful automatic discrimination. Furthermore, amplitude and latency measures were roughly comparable across groups. No group differences were seen on the active discrimination task, but performance was worse for duration than for frequency deviants. These results suggest that children with ADHD are able to automatically process temporal information, so deficits reported in active discrimination paradigms are likely due to deficits in subjective perception or usage of temporal information. (JINS, 2013, 19, 1–9)

Impairments of attention and executive functions are common sequelae of traumatic brain injury (TBI). The anterior cingulate is implicated in conflict-related task performance, such as the Stroop, and is susceptible to TBI-related injury due to its frontal location and proximity to the rough surface of the falx cerebri. We investigated the relationship between cingulate cortex volume and performance on tasks of selective attention and cognitive flexibility (single-trial Stroop and Auditory Consonant Trigrams [ACT]). Participants consisted of 12 adults with severe TBI and 18 controls. T1-weighted volumetric MRI data were analyzed using automated cortical reconstruction, segmentation, parcellation, and volume measurement. Cortical volume reductions were prominent bilaterally in frontal, temporal, and inferior parietal regions. Specific regional reduction of the cingulate cortex was observed only for cortical volume of right caudal anterior cingulate (cACC). The TBI group performed significantly worse than control participants on the Stroop and ACT tasks. Findings suggest that atrophy of the right cACC may contribute to reduced performance on executive function tasks, such as the Stroop and ACT, although this is likely but one node of an extensive brain network involved in these cognitive processes. (JINS, 2013, 19, 1–12)

The recently developed Everyday Cognition scales (ECog) measure multiple cognitively relevant functional domains (e.g., Everyday Memory, Everyday Language, Everyday Visuospatial abilities, and three everyday executive domains). The present study further evaluated the validity of the ECog by examining its relationship with objective measures of neuropsychological function, and neurobiological markers of disease as reflected by structural neuroimaging. Participants included 474 older adults (244 normals, 142 with MCI, 88 with dementia). The neuropsychological domains measured were episodic memory, semantic memory, spatial ability, and executive functioning. Brain MRI volumes included total brain (BV), hippocampus (HC) and dorsolateral prefrontal cortex (DLPFC). Neuropsychological measures of episodic memory and executive function were most consistently related to the ECog domains; spatial abilities had a specific relationship to the Everyday Visuospatial ECog domain. HC and BV volumes were related to most ECog domains, while DLPFC volume was independently related to two everyday executive domains (Everyday Planning and Everyday Organization). The pattern of associations varied somewhat as a function of diagnosis. Episodic memory and HC had more consistent associations with the ECog domains in older adults with MCI/dementia than in cognitively normal elderly. (JINS, 2013, 19, 1–12)

The present study analyzed the awareness of deficits in 117 mild Alzheimer's disease participants. Since few studies have examined the cognitive and behavioral domains of reduced awareness in detail, we performed a domain-specific assessment using the Awareness of deficit Questionnaire – Dementia scale with the novel aim of describing the relationship with everyday executive dysfunction. Through the use of the subtests of the Behavioral Assessment of the Dysexecutive Syndrome, we hypothesized that executive cognitive functions may play an important role in the reduced awareness of deficits. We also considered other variables of interest to provide a novel comprehensive explanation of this phenomenon. Our first approach to the study was a factor analysis considering the role of these variables in the awareness of deficits; subsequently, regression analysis models were used to define which variables were associated with a reduction of awareness in cognitive and behavioral domains. In particular, the factors retained from the factor analysis, in terms of inhibition, self-monitoring, set-shifting, and mood orientation changes, appear to be important skills for awareness of instrumental activities of daily living (R2 = .32). We also found hypo manic mood orientation and a tendency through apathy to be prominent indications of reduced behavioral awareness (R2 = .13). (JINS, 2013, 18, –)

Parkinson's disease (PD) patient and caregiver reports of patient functioning are often used interchangeably in clinical and research settings; however, the consistency of these reports is largely unknown. This study aimed to investigate the consistency and predictors of discrepancy between self- and caregiver reports of patient apathy, disinhibition, and executive dysfunction. Fifty-one pairs of nondemented PD patients and their caregivers completed the Frontal Systems Behavior Scale (FrSBe). Patients were administered a neuropsychological battery, and mood and burden were assessed in a subset of caregivers. Patients and caregivers significantly differed in their ratings of all retrospective prediagnosis behaviors and current levels of disinhibition. Current levodopa equivalent dosages predicted patient-caregiver rating differences in prediagnosis and current apathy and current executive dysfunction, while patient motor function, cognition, and mood failed to predict any disparities in ratings. Caregiver burden and depression were associated with apathy rating discrepancies, while burden was associated with discrepancies in ratings of disinhibition. These results suggest that consistency of patient and caregiver behavioral ratings may vary depending on the behavior assessed; and underscore the importance of considering the reporter when using subjective measures, as discrepancies in behavioral reports may be influenced by specific patient and/or caregiver symptoms or factors. (JINS, 2013, 19, 1–10)

Closing-in (CI) refers to copying drawings near to or superimposed on the original model, and is often observed in Alzheimer's disease (AD) patients. Contrasting hypotheses have been suggested to explain CI, but no prospective study has directly verified these interpretations. We evaluated the role of frontal/executive versus visuo-spatial impairments in a prospective sample of AD patients, and also explored whether different types of CI are related to specific neuropsychological tasks. We enrolled 64 AD patients who underwent copying tasks and an extensive neuropsychological assessment of visuo-spatial and visuo-constructional skills, frontal/executive abilities and anterograde memory. AD patients with CI showed more severe impairment on frontal/executive functions than AD patients without CI. Moreover, the tendency to produce copies superimposed on the model was selectively associated with poor inhibitory control for irrelevant responses. On this basis, we suggest that different CI phenomena could be ascribed to distinctive frontal/executive defects. (JINS, 2013, 19, 1–7)

Autobiographical memory involves the recall of personal facts (semantic memory) and re-experiencing of specific personal events (episodic memory). Although impairments in autobiographical memory have been found in adults with unilateral temporal lobe epilepsy (TLE) and attributed to compromised hippocampal integrity, it is not yet known whether this occurs in children with TLE. In the current study, 21 children with TLE and 24 healthy controls of comparable age, sex, and socioeconomic status were administered the Children's Autobiographical Interview. Compared to controls, children with TLE recalled fewer episodic details, but only when no retrieval prompts were provided. There was no difference between the groups for semantic autobiographic details. Interestingly, the number of episodic details recalled increased significantly from 6 to 16 years of age in healthy control children, but not in children with TLE. Exploratory analyses revealed that, within the group of children with TLE, epilepsy factors, including presence or absence of structural hippocampal abnormalities, did not relate to the richness of episodic recall. Our results provide first evidence of autobiographical episodic memory deficits in children with TLE. (JINS, 2013, 19, 1–12)

Outcome of moderate to severe traumatic brain injury (TBI) includes impaired emotion regulation. Emotion regulation has been associated with amygdala and rostral anterior cingulate (rACC). However, functional connectivity between the two structures after injury has not been reported. A preliminary examination of functional connectivity of rACC and right amygdala was conducted in adolescents 2 to 3 years after moderate to severe TBI and in typically developing (TD) control adolescents, with the hypothesis that the TBI adolescents would demonstrate altered functional connectivity in the two regions. Functional connectivity was determined by correlating fluctuations in the blood oxygen level dependent (BOLD) signal of the rACC and right amygdala with that of other brain regions. In the TBI adolescents, the rACC was found to be significantly less functionally connected to medial prefrontal cortices and to right temporal regions near the amygdala (height threshold T = 2.5, cluster level p < .05, FDR corrected), while the right amygdala showed a trend in reduced functional connectivity with the rACC (height threshold T = 2.5, cluster level p = .06, FDR corrected). Data suggest disrupted functional connectivity in emotion regulation regions. Limitations include small sample sizes. Studies with larger sample sizes are necessary to characterize the persistent neural damage resulting from moderate to severe TBI during development. (JINS, 2013, 19, 1–14)

Cognitive change is frequently observed in patients with Parkinson's disease (PD). However, the exact profile and extent of cognitive impairments remain unclear due to the clinical heterogeneity of PD and methodological issues in many previous studies. In this study, we aimed to examine the severity, frequency, and profile of cognitive changes in newly diagnosed PD patients over 5 years. At baseline and after 3 and 5 years, a hospital-based sample of PD patients (n = 59) and healthy controls (n = 40) were given neuropsychological tests covering six cognitive domains. Patients showed greater decline over time than healthy controls on all cognitive domains, except for attention. The profile of decline showed that psychomotor speed and memory were most affected. At the individual level 53% of the patients showed more cognitive decline than controls. Age at onset and memory impairment at baseline predicted cognitive decline. Cognitive functions in PD patients show greater decline in most domains than in healthy elderly over the course of 5 years. Due to selection bias as a result of attrition, the actual degree of decline may be greater than reported here. (JINS, 2013, 19, 1–14)