Neuropsychological performance in 151 patients with schizophrenia was examined using cluster analysis to identify neurocognitive subtypes. Hierarchical and iterative partitioning methods identified four clusters using an extended neuropsychological battery. Consistent with previous findings two extreme clusters were characterized by near normative performance and profound global dysfunction, respectively. The two remaining neurocognitive clusters displayed moderate-severe dysfunction and were differentiated by unique patterns of abstraction and flexibility, attention, spatial memory, and sensory-perception. Analysis of variance revealed an interaction between global memory and executive function for clusters III and IV. Although limited cluster differences were found relative to clinical and historical data, the distribution of previously defined clinical subtypes was uneven among neurocognitive clusters. Paranoid patients were significantly more likely to be classified into cluster II and disproportionately absent from clusters I and IV. Patients with negative and disorganized clinical subtypes comprised a disproportionate component of clusters I and IV but were less likely to be classified in cluster II. This suggests greater correspondence than previously postulated between systems responsible for clinical symptomatology and those moderating neurocognitive dysfunction.
The neurocognitive processes involved during classic spatial working memory (SWM) assessment were investigated by examining naturally preferred eye movement strategies. Cognitively healthy adult volunteers were tested in a computerized version of the Corsi Block-Tapping Task — a spatial span task requiring the short term maintenance of a series of locations presented in a specific order — coupled with eye-tracking. Modeling analysis was developed to characterize eye-tracking patterns across all task phases, including encoding, retention, and recall. Results revealed a natural preference for local gaze maintenance during both encoding and retention, with fewer than 40% fixated targets. These findings contrasted with the stimulus retracing pattern expected during recall as a result of task demands, with 80% fixated targets. Along with participants’ self-reported strategies of mentally “making shapes”, these results suggest the involvement of covert attention shifts and higher-order cognitive Gestalt processes during spatial span tasks, challenging instrument validity as single measure of SWM storage capacity.
spatial working memory; spatial span; Corsi Block-Tapping Task; eye-tracking; descriptive modeling
Despite a strong historical association between frontal lobe lesions and executive dysfunction, questions remain regarding the neuropsychological characterization of specific regions within the prefrontal cortex, as well as the utility of some executive function measures. The Delis-Kaplan Executive Function System (D-KEFS; Delis, Kaplan, & Kramer, 2001) has gained popularity as a collection of executive function tests, but its sensitivity and specificity for detecting focal frontal lobe dysfunction remain uncertain. The current study investigated performances of patients with focal ventromedial prefrontal (vmPFC, n=13), dorsolateral prefrontal (dlPFC, n=14), and non-frontal (NF, n=18) lesions on the entire D-KEFS battery. We also obtained IQ data from conventional measures (the WAIS-III/IV). On six D-KEFS indices, patients with dlPFC lesions performed lower than patients with vmPFC and NF lesions. On three other indices, the performances of the dlPFC group were lower than the NF group, but did not differ from the vmPFC group. However, none of these between-group differences were statistically significant after Full Scale IQ and processing speed were controlled for, suggesting that the observed weaknesses in patients with dlPFC lesions were not specific to executive functions. Patients with vmPFC and NF lesions could not be differentiated based on their performances on any D-KEFS measures. While some D-KEFS measures show promise in differentiating patients with dlPFC lesions, the clinical advantage of using the D-KEFS over more traditional measures is not empirically compelling.
Prefrontal lesions; D-KEFS; Executive function; Frontal lobe; vmPFC
Apathy is a relatively common psychiatric syndrome in HIV infection, but little is known about its neural correlates. In the present study, we examined the associations between apathy and diffusion tensor imaging (DTI) indices in key frontal white matter regions in the thalamocorticostriatal circuit that has been implicated in the expression of apathy. Nineteen participants with HIV infection and 19 demographically comparable seronegative comparison subjects completed the Apathy subscale of the Frontal Systems Behavioral Scale as a part of a comprehensive neuropsychiatric research evaluation. When compared to the seronegative participants, the HIV+ group had significantly more frontal white matter abnormalities. Within HIV+ persons, and as predicted, higher ratings of apathy were associated with greater white matter alterations in the anterior corona radiata, genu, and orbital medial prefrontal cortex. The associations between white matter alterations and apathy were independent of depression and were stronger among participants with lower current CD4 counts. All told, these findings indicate that apathy is independently associated with white matter abnormalities in anterior, medial brain regions in persons infected with HIV, particularly in the setting of lower current immune functioning, which may have implications for antiretroviral therapy.
Diffusion tensor imaging; apathy; HIV/AIDS; Prefrontal cortex; depression
We examined the relationship of apathy with neurocognitive performance, age, disease markers, and functional disability in 61-HIV-infected individuals. Apathy was assessed with the Apathy Evaluation Scale and was significantly associated with highest HIV plasma level, functional disability, and neurocognitive performance. individuals with higher apathy levels demonstrated a stronger association between age and processing speed performance. Our findings suggest that apathy is related to poor neuropsychological functioning, HIV plasma levels, and increased functional disability in individuals with HIV Additionally, to our knowledge, this is the first study to demonstrate an interactive effect of age and apathy on neuropsychological performance in HIV.
HIV; Aging; Apathy; Cognitive performance; Functional disability
This study sought to deconstruct gambling task (GT) performance among HIV+ individuals (N=143) and intended to capture other cognitive features of task performance (i.e., problem-solving and strategy preference). Consistent with our hypotheses, cluster analysis identified three GT groups: a safe/advantageous (AS) strategy group, a risky/disadvantageous (RS) strategy group, as well as a novel third group who failed to develop a strategy (NS). The NS group performed worst on global neuropsychological performance, processing speed, and executive function. Our results support a novel measure of GT task performance, and suggest that failure to develop/implement a strategy reflects cognitive dysfunction.
Slowed information processing is a prominent deficit in late-life depression (LLD). To better differentiate processing speed components in LLD, we examined characteristics of visual search performance in 32 LLD and 32 control participants. Data showed specific slowing in the comparison stage of visual search in LLD, rather than in encoding/response stages, but also greater overall slowing in LLD during inefficient versus efficient search. We found no group differences on traditional neuropsychological measures of processing speed. Slowed processing speed in LLD may be specific rather than general, which underscores the need to link components of processing speed to underlying neural circuitry.
Depression; Aging; Cognition; Visual Search; Reaction Time
Letter-cued word fluency is conceptualized as a phonemically guided word retrieval process. Accordingly, word clusters typically are defined solely by their phonemic similarity. We investigated semantic clustering in two letter-cued (P and S) word fluency task performances by 315 healthy adults, each for 1 min. Singular value decomposition (SVD) and generalized topological overlap measure (GTOM) were applied to verbal outputs to conservatively extract clusters of high frequency words. The results generally confirmed phonemic clustering. However, we also found considerable semantic/associative clusters of words (e.g., pen, pencil, and paper), and some words showed both phonemic and semantic associations within a single cluster (e.g., pair, pear, peach). We conclude that letter-cued fluency is not necessarily a purely phonemic word retrieval process. Strong automatic semantic activation mechanisms play an important role in letter-cued lexical retrieval. Theoretical conceptualizations of the word retrieval process with phonemic cues may also need to be re-examined in light of these analyses.
verbal fluency; cued-word retrieval; semantic system; clustering; switching
Treatment with combination antiretroviral therapy (cART) regimens with a high capacity to penetrate the blood-brain barrier has been associated with lower levels of human immunodeficiency virus (HIV) in the central nervous system (CNS). This study examined neurocognitive performance among a sample of 118 HIV+ substance dependent individuals (SDIs) and 310 HIV− SDIs. HIV+ participants were prescribed cART regimens with varying capacity to penetrate the CNS as indexed by the revised CNS penetration effectiveness (CPE) scale. Participants completed the Rotary Pursuit Task (RPT) and the Weather Prediction Task (WPT)--two measures of procedural learning (PL) with known sensitivity to HIV infection--and a control task of sustained attention. HIV+ SDIs prescribed cART with relatively high CNS penetrance performed significantly more poorly on both tasks than HIV− controls. Task performance of HIV+ SDIs prescribed cART with relatively low CNS penetrance did not differ significantly from either HIV− controls or the HIV+/High CPE group, although a trend towards lower RPT performance relative to HIV− participants was observed. Between-group differences were not seen on a control task of motor impulsivity (Immediate Memory Task), indicating that the observed deficits among HIV+/High CPE SDIs may have some specificity.
HIV; neurocognition; substance abuse; antiretroviral therapy; addiction; procedural learning; CPE
The everyday, functional impairments associated with dementia remain poorly understood from a neuropsychological perspective. This study investigated relations between brain structure volumes and two measures of everyday action – caregiver questionnaire and direct assessment – in 57 participants with dementia. Results showed that caregiver ratings reflecting more functional impairment were strongly associated with smaller volumes of deep white matter. Direct assessment of everyday task performance in a subsample revealed relations between unique neurological substrates and discrete everyday action error types. Findings emphasize differences in functional assessment methods and highlight the role of white matter in functional deficits in dementia.
dementia; everyday action; executive control; episodic memory; white matter alterations
Study of repeated learning mechanisms has been limited in amnestic mild cognitive impairment, a preclinical stage of Alzheimer disease modifiable by cognitive rehabilitation. We assessed repeated contextual working memory decline as an indicator of amnestic mild cognitive impairment in a sample of 45 older adults recruited from the tertiary care setting. Results indicated that contextual working memory impairment distinguished adults with preclinical disease from those without impairment despite similar overall cognitive performance, and comparison of the indicator with standard-of-care neuropsychological measures indicated discriminant validity. Contextual working memory impairment may represent a novel predictor of Alzheimer disease conversion risk.
Alzheimer disease; mild cognitive impairment; working memory; repetition priming; neuropsychological tests; cognitive therapy; aging
The current study investigated the effect of education on retrospective metamemory accuracy in 143 healthy older adults and 143 early to moderate AD patients, using retrospective measures of confidence in the accuracy of retrieval responses in an episodic odor recognition memory task. Relative confidence accuracy was computed as the difference between confidence judgments for correct and incorrect responses. In both AD patients and controls, individuals reporting 17 years of education or more had significantly more accurate levels of confidence than individuals with 12 years or less. Thus, education was a significant predictor of retrospective metamemory accuracy in healthy aging and AD.
Metamemory; Confidence; Education; Aging; Alzheimer’s disease
It is unclear how standardized neuropsychological measures of motor function relate to brain volumes of motor regions in autism spectrum disorder (ASD). An all male sample composed of 59 ASD and 30 controls (ages 5–33 years) completed three measures of motor function: strength of grip (SOG), finger tapping test (FTT), and grooved peg-board test (GPT). Likewise, all participants underwent magnetic resonance imaging with region of interest (ROI) volumes obtained to include the following regions: motor cortex (pre-central gyrus), somatosensory cortex (post-central gyrus), thalamus, basal ganglia, cerebellum and caudal middle frontal gyrus. These traditional neuropsychological measures of motor function are assumed to differ in motor complexity with GPT requiring the most followed by FTT and SOG. Performance by ASD participants on the GPT and FTT differed significantly from controls, with the largest effect size differences observed on the more complex GPT task. Differences on the SOG task between the two groups were non-significant. Since more complex motor tasks tap more complex networks, poorer GPT performance by those with ASD may reflect less efficient motor networks. There was no gross pathology observed in classic motor areas of the brain in ASD, as region of interest (ROI) volumes did not differ, but FTT was negatively related to motor cortex volume in ASD. The results suggest a hierarchical motor disruption in ASD, with difficulties evident only in more complex tasks as well as a potential anomalous size-function relation in motor cortex in ASD.
autism; network disruption; motor impairment; brain volume differences; motor cortex volume
Although cognitive ability is a known predictor of real-world functioning in schizophrenia, there has been an expanded interest in understanding the mechanisms by which it explains real-world functioning in this population. We examined the extent to which functional capacity (i.e., skills necessary to live independently) mediated the relationship between cognitive ability and both observer and self-reported real-world functioning in 138 outpatients with schizophrenia. Functional capacity significantly mediated the relations between cognitive ability and observer rated real world functioning, but not self-reported real world functioning, with small to medium effect sizes observed for all outcomes. The role of cognitive ability in observer vs. self-reported real-world functioning may be explained by different mechanisms.
Functioning; Impairment; Cognition; Self-report; Observer report
The Boston Naming Test is a neuropsychological measure of confrontation naming, short forms of which can be advantageous with various populations. The purpose of this study was to establish a Spanish-English equivalent version of the BNT using item response theory. Data were analyzed from 380 Project FRONTIER participants; 27 items differed between groups and were removed from the measure. Additionally, 18 items did not differ between groups but were poor items. The current 15-item Spanish-English equivalent version of the BNT offers significant advantages. Future work is required to validate the diagnostic utility of the instrument in various settings and populations.
Confrontation naming; Item response theory; Language of administration; Boston Naming Test; Hispanic
Fatigue and cognitive impairment are common in HIV+ adults and may occur independently or be causally linked. This study examined whether alleviation of fatigue with armodafinil in a placebo-controlled double-blind 4-week trial had an effect on cognitive function among those with and without mild neuropsychological impairment at baseline. Sixty-one patients completed a standard battery of neuropsychological tests at study entry and Week 4: 33 were randomized to armodafinil and 28 to placebo. While there was a significant effect of active medication on fatigue, cognitive performance measured by a global change score did not differ between treatment groups, or those on active treatment with or without mild neuropsychological impairment.
Olfactory impairment is associated with cognitive impairment in older adults but less is known about the association of olfactory impairment and cognitive function in middle-aged adults. The association between olfactory impairment and cognitive function tests of attention, processing speed and executive and psychomotor function was explored in 2837 participants (21–84 years; mean age 49 years) in the Beaver Dam Offspring Study. Among middle-aged participants (aged 35–64 years), those with impairment on an odor identification test took significantly longer to complete the Trail Making Test (TMT-A and TMT-B) and the Grooved Peg Board (GPB) test, than those without olfactory impairment in regression models adjusted for multiple factors. Similar results were found for the TMT-A and TMT-B, but not the GPB, in the whole cohort. Olfactory impairment was associated with poorer performance on cognitive function tests in a primarily middle-aged cohort.
Olfaction; Odor Identification; Cognitive Function; Executive Function; Epidemiology
The primary purpose of the current study was to examine the relationship between performance on executive tasks and white matter integrity, assessed by diffusion tensor imaging (DTI) in Multiple Sclerosis (MS). A second aim was to examine how processing speed affects the relationship between executive functioning and FA. This relationship was examined in two executive tasks that rely heavily on processing speed: the Color-Word Interference Test and Trail-Making Test (Delis-Kaplan Executive Function System). It was hypothesized that reduced fractional anisotropy (FA) is related to poor performance on executive tasks in MS, but that this relationship would be affected by the statistical correction of processing speed from the executive tasks. 15 healthy controls and 25 persons with MS participated. Regression analyses were used to examine the relationship between executive functioning and FA, both before and after processing speed was removed from the executive scores. Before processing speed was removed from the executive scores, reduced FA was associated with poor performance on Color-Word Interference Test and Trail-Making Test in a diffuse network including corpus callosum and superior longitudinal fasciculus. However, once processing speed was removed, the relationship between executive functions and FA was no longer significant on the Trail Making test, and significantly reduced and more localized on the Color-Word Interference Test.
Multiple Sclerosis; Executive; Processing Speed; Diffusion Tensor Imaging; White Matter
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder associated with a premutation trinucleotide repeat expansion in the fragile X mental retardation 1 gene (FMR1). Symptoms include gait ataxia, action tremor, and cognitive impairment. The objectives of the study were to clarify the nature of the dysexecutive syndrome observed in FXTAS and to assess the contribution of executive impairment to deficits in nonexecutive cognitive functions. Compared to controls, men with FXTAS demonstrated significant executive impairment, which was found to mediate group differences in most other cognitive abilities. Asymptomatic premutation carriers performed similarly to controls on all but two measures of executive functioning. These findings suggest that the impairment of non-executive cognitive skills in FXTAS is in large part secondary to executive dysfunction.
fragile X; premutation; cognition disorders; trinucleotide repeats; executive cognitive function; spinocerebellar degeneration; fragile x-associated tremor/ataxia syndrome
HIV+ substance dependent individuals (SDIs) make significantly poorer decisions compared with HIV− SDIs, but the neurocognitive mechanisms underlying this impairment have not been identified. We administered the Iowa Gambling Task, a measure of decision making under uncertain risk, and the Cups Task, a measure of decision making under specified risk, to a group of 56 HIV+ and 23 HIV− men who have sex with men (MSMs) with a history of substance dependence enrolled in the Multicenter AIDS Cohort Study. The IGT provides no explicit information regarding the contingencies for each possible choice, and the probability of each outcome remains ambiguous at least for the early trials; in contrast, the Cups Task provides explicit information about the probability of each outcome. The HIV+ group made significantly poorer decisions on the IGT compared with the HIV− group. Cups Task performance did not differ significantly between HIV− and HIV+ groups. Exploratory analyses of the IGT data suggested that HIV+ subjects tended to perform more poorly during the early learning phase when uncertainty about specific outcomes was greatest. Additionally, performance on the final two trial blocks was significantly correlated with Stroop Interference scores, suggesting IGT performance is driven increasingly by executive control during the later portion of the task. Potential cognitive mechanisms to be explored in later studies are discussed, including impairment in implicit learning processing
HIV; drug abuse; decision making; executive function; AIDS; neurocognition
Although recent theories of brain and cognitive aging distinguish
among normal, exceptional, and impaired groups, further empirical evidence
is required. We adapted and applied standard procedures for classifying
groups of cognitively impaired (CI) and cognitively normal (CN) older adults
to a third classification, cognitively healthy, exceptional, or elite (CE)
aging. We then examined concurrent and two-wave longitudinal performance on
composite variables of episodic, semantic, and working memory.
We began with a two-wave source sample from the Victoria Longitudinal
Study (VLS) (source n=570; baseline age=53–90
years). The goals were to: (a) apply standard and objective classification
procedures to discriminate three cognitive status groups, (b) conduct
baseline comparisons of memory performance, (c) develop two-wave status
stability and change subgroups, and (d) compare of stability subgroup
differences in memory performance and change.
As expected, the CE group performed best on all three memory
composites. Similarly, expected status stability effects were observed: (a)
stable CE and CN groups performed memory tasks better than their unstable
counterparts and (b) stable (and chronic) CI group performed worse than its
unstable (variable) counterpart. These stability group differences were
maintained over two waves.
New data validate the expectations that (a) objective clinical
classification procedures for cognitive impairment can be adapted for
detecting cognitively advantaged older adults and (b) performance in three
memory systems is predictably related to the tripartite classification.
normal cognitive aging; cognitively elite aging; mild cognitive impairment; memory; Victoria Longitudinal Study
Mucopolysaccharidosis type IIIA (MPS IIIA) is a neurodegenerative disease with behavioral symptoms unique among the mucopolysaccharidoses. Children with MPS IIIA reportedly mouth things, explore novel environments almost continuously, disregard danger, and empathize/socialize and comply less with parents. These characteristics resemble Klüver–Bucy syndrome (K-Bs). To test the K-Bs hypothesis, 30 children with MPS IIIA were compared to 8 ‘post-transplant’ Mucopolysaccharidosis type IH patients in an experimental “Risk Room”. The room contained attractive and mildly frightening objects, exposure to a 92 dB startle noise triggered by contact with an attractive toy, mother’s return after a brief absence, and compliance with her clean-up directive. Children with MPS IIIA: 1) left mother sooner, 2) wandered more, 3) were more likely to approach frightening objects, 4) were less likely to respond to loud noise with whole body startle, 5) were less likely to avoid the toy associated with the startle noise, 6) interacted less with mother upon her return, and 7) complied less with her clean-up command. K-Bs is associated with loss of amygdala function. Brain MRIs of a subset of the children with MPS IIIA showed volume loss that was greater in the amygdala than the hippocampus; only amygdala loss correlated with reduced fearfulness. MPS IIIA may be the first identified pediatric disease presenting systematically as a K-Bs variant. If validated by further studies, the K-Bs hypothesis of MPS IIIA would provide important clinical and theoretical information for the guidance of families as well as markers for natural disease progression and treatment effects.
amygdala; fear conditioning; orality; Sanfilippo syndrome; startle
Performance on part B of the Trail Making Test (TMT) contributes to the prediction of ability to complete instrumental activities of daily living (IADLs) in Parkinson’s disease (PD). Although this suggests that cognitive flexibility is important in the everyday functioning of individuals with PD, this may not be that case as the TMT is multifactorial, involving motor speed, visual scanning, sequencing, and cognitive flexibility. The purpose of the current study was to determine which elements of the task contribute to the prediction of IADLs in a sample of 30 non-demented individuals with PD. Correlational analyses indicated strong relationships between a performance-based measure of IADLs and measures involving scanning, sequencing, and cognitive flexibility from the Delis-Kaplan Executive Function System (D-KEFS) TMT. Results from standard regressions indicated that measures of sequencing and level of depression but not scanning, cognitive flexibility, or demographic variables made a significant, independent contribution to the prediction of IADLs. These results suggest that the sequencing element of the TMT is paramount in the prediction of IADLs in PD.
Parkinson’s disease; cognitive flexibility; trail making; IADLs
Social isolation is common among individuals with isolated cleft lip and palate (ICLP), but the available data on why this may be are mixed. We present a novel theory relating to reduced social motivation in ICLP, called the social abulia hypothesis. Based on this hypothesis, we predicted that reduced social motivation would lead to reduced responsiveness to negative social feedback, both in terms of explicit responses and non-controlled, psychophysiological responses.
Twenty males with ICLP and 20 normal comparison males (NC group) between 13 and 25 years old participated in the study. Social motivation was examined by measuring participants’ response to negative social feedback (social exclusion). Additionally, psychophysiological reactivity to positive and negative social stimuli was measured. In order to rule out other potential contributors to social isolation, we tested basic social perception, emotion recognition, and social anxiety.
In line with the social abulia hypothesis, we show that negative social feedback had less of an effect on males with ICLP relative to healthy male peers, which was evident in explicit responses, and non-controlled, psychophysiological responses to negative social feedback. Our results could not be attributed to problems in social perception, a lack of understanding facial expressions, or increased social anxiety, as groups did not differ on these constructs.
This study suggests that current views on social isolation in ICLP may need to be reconsidered to include the possibility that isolation in this population may be the direct result of reduced social motivation.