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1.  Clinical Utility of the N-back Task in Functional Neuroimaging Studies of Working Memory 
N-back tasks are commonly used in functional neuroimaging studies to identify the neural mechanisms supporting working memory (WM). Despite widespread use, the clinical utility of these tasks is not well specified. This study compared N-back performance during functional magnetic resonance imaging (fMRI) with task data acquired outside of the scanner as a measure of reliability across environment. N-back task validity was examined in relation to performance and rater-based measures used clinically to assess working memory.
Forty-three healthy adults completed Verbal and Object N-back tasks during fMRI scanning and outside the scanner. Task difficulty was varied parametrically (0, 1, and 2-back conditions). Order of N-back task completion was stratified by modality (Verbal/Object) and environment. Participants completed the Digit Span [DS] and provided self-ratings using the Behavior Rating Inventory of Executive Function [BRIEF-WM]).
Mean Verbal and Object N-back accuracy was above 95% across load conditions; task difficulty was effectively manipulated across load conditions. Performance accuracy did not significantly differ by environment. N-back reaction time was slower during fMRI (F =6.52, p=.01, ηp2=.13); participants were faster when initially completing tasks outside the scanner (ηp2=.10–.15). Verbal 2-back accuracy was significantly related to DS performance (r = .36, p = .02). N-back performance was not related to BRIEF-WM.
Our results provide evidence for reliability of N-back accuracy during fMRI scanning; however, reliability of reaction time data is affected by order of task presentation. Data regarding construct validity are inconsistent and emphasize the need to consider clinical utility of behavioral measures in the design and interpretation of functional neuroimaging studies.
PMCID: PMC4229404  PMID: 25252868
Digit Span; N-back; BRIEF; working memory; validity; reliability
2.  Executive Function Late Effects in Survivors of Pediatric Brain Tumors and Acute Lymphoblastic Leukemia 
Survivors of pediatric brain tumors (BT) and acute lymphoblastic leukemia (ALL) are at risk for neurocognitive late effects related to executive function.
Survivors of BT (48) and ALL (50) completed neurocognitive assessment. Executive function was compared to estimated IQ and population norms by diagnostic group.
Both BT and ALL demonstrated relative executive function weaknesses. As a group, BT survivors demonstrated weaker executive functioning than expected for age. Those BT survivors with deficits exhibited a profile suggestive of global executive dysfunction, while affected ALL survivors tended to demonstrate specific rapid naming deficits.
Findings suggest that pediatric BT and ALL survivors may exhibit different profiles of executive function late effects, which may necessitate distinct intervention plans.
PMCID: PMC4229447  PMID: 25126830
pediatric; leukemia; brain tumor; executive function; late effects
3.  Utility of the N-back task in survivors of childhood acute lymphoblastic leukemia 
The N-back task is often used in functional brain imaging studies to activate working memory networks; however, limited information is available on its association to clinical outcomes in children or cancer survivors. One hundred thirty-seven survivors of ALL (mean [SD] current age = 14.3 [4.8] years; time since diagnosis = 7.6 [1.6] years) completed the N-back task and comprehensive neurocognitive testing, including standardized measures of attention, processing speed, and working memory. Results indicated females demonstrated significantly slower reaction times (0-back p=0.02; 1-back p=0.03) compared to males. Survivors < 15 years old at the time of testing demonstrated a significant decrease in accuracy as working memory load increased compared to survivors ≥ 15 years old (p<0.001). Performance on the N-back task was associated with nonverbal working memory (rs=0.56, p<0.001) in survivors ≥ 15 years of age. For younger survivors, N-Back performance was more strongly associated with attention skills. Results suggest the N-back assesses different cognitive constructs at younger compared to older childhood ages. These age differences should be considered in interpreting functional brain imaging results.
PMCID: PMC4355950  PMID: 25252969
childhood acute lymphoblastic leukemia; working memory; N-back
4.  Allowing Brief Delays in Responding Improves Event-Based Prospective Memory for Young Adults Living with HIV Disease 
Event-based prospective memory (PM) tasks require individuals to remember to perform an action when they encounter a specific cue in the environment, and have clear relevance for daily functioning for individuals with HIV. In many everyday tasks, the individual must not only maintain the intent to perform the PM task, but the PM task response also competes with the alternative and more habitual task response. The current study examined whether event-based PM can be improved by slowing down the pace of the task environment. Fifty-seven young adults living with HIV performed an ongoing lexical decision task while simultaneously performing a PM task of monitoring for a specific word (which was focal to the ongoing task of making lexical decisions) or syllable contained in a word (which was nonfocal). Participants were instructed to refrain from making task responses until after a tone was presented, which occurred at varying onsets (0–1600ms) after each stimulus appeared. Improvements in focal and non-focal PM accuracy were observed with response delays of 600ms. Furthermore, the difference in PM accuracy between the low demand focal PM task and the resource demanding non-focal PM task was reduced by half across increasingly longer delays, falling from 31% at 0ms delay to only 14% at 1600ms delay. The degree of ongoing task response slowing for the PM conditions, relative to a control condition that did not have a PM task and made lexical decisions only, also decreased with increased delay. Overall, the evidence indicates that delaying the task responses of younger HIV-infected adults increased the probability that the PM relevant features of task stimuli were adequately assessed prior to the ongoing task response, and by implication that younger HIV infected adults can more adequately achieve PM goals when the pace of the task environment is slowed down.
PMCID: PMC4205178  PMID: 25116075
HIV/AIDS; Prospective memory; Executive functions; Response delay; Cue focality
5.  Effects of Information Processing Speed on Learning, Memory, and Executive Functioning in People Living With HIV/AIDS 
It is unclear whether or to what degree literacy, aging, and other neurologic abnormalities relate to cognitive deficits among people living with HIV/AIDS in the combined antiretroviral therapy (CART) era. The primary aim of this study was to simultaneously examine the association of age, HIV-associated motor abnormalities, major depressive disorder, and reading level with information processing speed, learning, memory, and executive functions, and to determine if processing speed mediated any of the relationships between cognitive and non-cognitive variables.
Participants were 186 racially and ethnically diverse men and women living with HIV/AIDS who underwent comprehensive neurological, neuropsychological, and medical evaluations. Structural equation modeling was utilized to assess the extent to which information processing speed mediated the relationship between age, motor abnormalities, major depressive disorder, and reading level with other cognitive abilities.
Age, motor dysfunction, reading level, and current major depressive disorder were all significantly associated with information processing speed. Information processing speed fully mediated the effects of age on learning, memory, and executive functioning, and partially mediated the effect of major depressive disorder on learning and memory. The effect of motor dysfunction on learning and memory was fully mediated by processing speed.
These findings provide support for information processing speed as a primary deficit which may account, at least in part, for many of the other cognitive abnormalities recognized in complex HIV/AIDS populations. The association of age and information processing speed may account for HIV/aging synergies in the generation of CART-era cognitive abnormalities.
PMCID: PMC4338860  PMID: 25111120
information processing speed; memory; executive function; structural equation model; human immunodeficiency virus
6.  Impact of fMRI Scanner Noise on Affective State and Attentional Performance 
Previous research has shown that performance on cognitive tasks administered in the scanner can be altered by the scanner environment. There are no previous studies that have investigated the impact of scanner noise using a well-validated measure of affective change. The goal of this study was to determine whether performance on an affective attentional task or emotional response to the task would change in the presence of distracting acoustic noise, such as that encountered in an MRI environment.
Thirty-four young adults with no self-reported history of neurologic disorder or mental illness completed three blocks of the affective Posner task outside of the scanner. The task was meant to induce frustration through monetary contingencies and rigged feedback.
Participants completed a self-assessment manikin at the end of each block to rate their mood, arousal level, and sense of dominance. During the task, half of the participants heard noise (recorded from a 4T MRI system), and half heard no noise.
The affective Posner task led to significant reductions in mood and increases in arousal in healthy participants. The presence of scanner noise did not impact task performance; however, individuals in the noise group did report significantly poorer mood throughout the task.
The results of the present study suggest that the acoustic qualities of MRI enhance frustration effects on an affective attentional task and that scanner noise may influence mood during similar fMRI tasks.
PMCID: PMC4501887  PMID: 26059389
Attention; affect; imaging; fMRI; noise
7.  An Examination of Executive Dysfunction Associated with Frontostriatal Circuitry in Parkinson’s Disease 
Parkinson’s disease (PD) is a neurodegenerative movement disorder presenting with subcortical pathology and characterized by motor deficits. However, as is frequently reported in the literature, patients with PD can also exhibit cognitive and behavioral (i.e., nonmotor) impairments, cognitive executive deficits and depression being the most prominent. Considerable attention has addressed the role that disruption to frontostriatal circuitry can play in mediating nonmotor dysfunction in PD. The three nonmotor frontostriatal circuits, which connect frontal cortical regions to the basal ganglia, originate from the dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), and orbitofrontal cortex (OFC). The objective of the current study was to use our understanding of frontostriatal circuit function (via literature review) to categorize neuropsychological measures of cognitive and behavioral executive functions by circuit. To our knowledge, such an approach has not been previously attempted in the study of executive dysfunction in PD. Neuropsychological measures of executive functions and self-report behavioral inventories, categorized by circuit function, were administered to 32 nondemented patients with Parkinson’s disease (NDPD) and to 29 demographically matched, healthy normal control participants (NC). Our findings revealed significant group differences for each circuit, with the PD group performing worse than the NC group. Among the patients with PD, indices of impairment were greater for tasks associated with DLPFC function than with OFC function. Further, only an index of DLPFC test performance was demonstrated to significantly discriminate individuals with and without PD. In conclusion, our findings suggest that nondemented patients with PD exhibit greater impairment on neuropsychological measures associated with DLPFC than with ACC or OFC circuit function.
PMCID: PMC4456005  PMID: 16840240
8.  Altered Resting Functional Connectivity of Expressive Language Regions after Speed Reading Training 
A goal of interventions designed to increase reading speed is to reduce the practice of articulating words in an individual’s thoughts, or subvocalization. This practice may require redundant cognitive resources, slow reading speed, and detract from efficient transfer of written words to semantic understanding. It is unclear, however, whether exercises designed to promote faster reading speed generalize to cognitive function beyond the reading task itself. To investigate this possibility, we measured resting state functional connectivity in classical language regions before and after a course of cognitive exercise designed to increase reading speed in 9 healthy adolescent female volunteers. We found significantly decreased correlation between left Broca Area and right Broca Homologue and between right Broca Homologue and right Wernicke Homologue in the resting state after the training period compared to before training. Differences in functional connectivity after training to left Broca Area showed a spatial distribution reflecting decreased correlation to memory-associated brain regions and increased correlation to auditory regions, that might be consistent with a hypothesis that such training may decrease subvocalization associated with semantic memory function during the resting state.
PMCID: PMC4039565  PMID: 24766286
9.  Hemispheric side of damage influences sex-related differences in smoking cessation in neurological patients 
Patterns of smoking behavior vary between the sexes. There is evidence that decision-making, which is one of the key “executive functions” necessary for making life-style modifications such as smoking cessation, is relatively lateralized to the right hemisphere in males and left hemisphere in females. In the current study, we examined whether the side of brain lesion has a differential effect on smoking behavior between the sexes. We hypothesized sex differences in smoking cessation based on lesion side. Participants were 49 males and 50 females who were smoking at the time of lesion onset. The outcome variable was abstinence from smoking (quit rate) at least one year post lesion. We found that in patients with left hemisphere damage, quit rates were significantly higher in males than in females; however, in patients with right hemisphere damage, quit rates were not statistically different. The findings support previous cognitive neuroscience literature showing that components of behavior responsible for maintaining addiction tend to be more strongly lateralized in males, whereas in females there is a more bilateral distribution. Our study provides further evidence for differences in lateralization of complex behavior between the sexes, which has significant implications for differences in treatment strategies between the sexes.
PMCID: PMC4052374  PMID: 24872115
behavior lateralization; smoking cessation; addiction; gender differences; drug abuse
10.  Neurocognition in College-Aged Daily Marijuana Users 
Marijuana is the most commonly used illicit substance in the United States. Use, particularly when it occurs early, has been associated with cognitive impairments in executive functioning, learning, and memory.
This study comprehensively measured cognitive ability as well as comorbid psychopathology and substance use history to determine the neurocognitive profile associated with young adult marijuana use. College-aged marijuana users who initiated use prior to age 17 (n=35) were compared to demographically-matched controls (n=35).
Marijuana users were high functioning, demonstrating comparable IQs to controls and relatively better processing speed. Marijuana users demonstrated relative cognitive impairments in verbal memory, spatial working memory, spatial planning, and motivated decision-making. Comorbid use of alcohol, which was heavier in marijuana users, was unexpectedly found to be associated with better performance in some of these areas.
This study provides additional evidence of neurocognitive impairment in the context of adolescent and young adult marijuana use. Findings are discussed in relation to marijuana’s effects on intrinsic motivation and discrete aspects of cognition.
PMCID: PMC4074777  PMID: 24620756
marijuana; neurocognition; decision-making; memory; planning
11.  Performance Variability During a Multitrial List-Learning Task as a Predictor of Future Cognitive Decline in Healthy Elders 
In clinical settings, neuropsychological test performance is traditionally evaluated with total summary scores (TSS). However, recent studies demonstrated that indices of intraindividual variability (IIV) yielded unique information complementing TSS. This 18-month longitudinal study sought to determine whether IIV indices derived from a multitrial list-learning test (the Rey Auditory Verbal Learning Test) provided incremental utility in predicting cognitive decline in older adults compared to TSS.
Ninety-nine cognitively intact older adults (aged 65 to 89 years) underwent neuropsychological testing (including the Rey Auditory Verbal Learning Test) at baseline and 18-month follow-up. Participants were classified as cognitively stable (n = 65) or declining (n = 34) based on changes in their neuropsychological test performance. Logistic regression modeling tested the ability of baseline TSS indices (Sum of Trials 1-5, Immediate Recall, and Delayed Recall) and IIV indices (Lost Access and Gained Access) to discriminate between stable and declining individuals.
Higher values of both Lost Access and Gained Access at baseline were associated with an increased risk for decline at 18-month follow-up. Further, the IIV indices provided predictive utility above and beyond the TSS indices.
These results highlight the value of analyzing IIV in addition to TSS during neuropsychological evaluation in older adults. High levels of IIV may reflect impairment in anterograde memory systems and/or executive dysfunction that may serve as a prognostic indicator of cognitive decline.
PMCID: PMC3979935  PMID: 24552205
Intraindividual variability; cognitive aging; prediction of decline; Rey Auditory Verbal Learning Test
12.  The Effect of Parkinson's Disease Subgroups on Verbal and Nonverbal Fluency 
Parkinson's disease (PD) leads to deficits in executive function, including verbal and nonverbal fluency, as a result of compromised fronto-striatal circuits. It is unknown whether deficits in verbal and nonverbal fluency in PD are driven by certain subgroups of patients, or how strategy use may facilitate performance.
Sixty-five non-demented individuals with PD, including 36 with right-body onset (RPD; 20 with tremor as their initial symptom, 16 non-tremor) and 29 with left-body onset (LPD; 14 with tremor as their initial symptom, 15 non-tremor), and 52 normal control participants (NC).
Verbal fluency was assessed using the FAS and Animals tests. Nonverbal fluency was assessed using the Ruff Figural Fluency Test.
Both RPD and LPD were impaired in generating words and in using clustering and switching strategies on phonemic verbal fluency, whereas different patterns of impairment were found on nonverbal fluency depending on the interaction of side of onset and initial motor symptom (tremor vs. non-tremor). Strategy use correlated with number of correct responses on verbal fluency in LPD, RPD, and NC. By contrast, on nonverbal fluency, strategy use correlated with correct responses for RPD and LPD, but not for NC.
Our findings demonstrate the importance of considering subgroups in PD and analyzing subcomponents of verbal and nonverbal fluency (correct responses, errors, and strategies), which may depend differently on the integrity of dorsolateral prefrontal cortex, inferior frontal cortex, and anterior cingulate cortex.
PMCID: PMC4003916  PMID: 24533593
Parkinson's disease; verbal fluency; nonverbal fluency; executive function; prefrontal cortex
13.  Memory for performed and observed activities following traumatic brain injury 
Traumatic brain injury (TBI) is associated with deficits in memory for the content of completed activities. However, TBI groups have shown variable memory for the temporal order of activities. We sought to clarify the conditions under which temporal order memory for activities is intact following TBI. Additionally, we evaluated activity source memory and the relationship between activity memory and functional outcome in TBI participants. Thus, we completed a study of activity memory with 18 severe TBI survivors and 18 healthy age- and education-matched comparison participants. Both groups performed eight activities and observed eight activities that were fashioned after routine daily tasks. Incidental encoding conditions for activities were utilized. The activities were drawn from two counterbalanced lists, and both performance and observation were randomly determined and interspersed. After all of the activities were completed, content memory (recall and recognition), source memory (conditional source identification), and temporal order memory (correlation between order reconstruction and actual order) for the activities were assessed. Functional ability was assessed via the Community Integration Questionnaire (CIQ). In terms of content memory, TBI participants recalled and recognized fewer activities than comparison participants. Recognition of performed and observed activities was strongly associated with social integration on the CIQ. There were no between- or within-group differences in temporal order or source memory, although source memory performances were near ceiling. The findings were interpreted as suggesting that temporal order memory following TBI is intact under conditions of both purposeful activity completion and incidental encoding, and that activity memory is related to functional outcomes following TBI.
PMCID: PMC4148421  PMID: 24524393
Traumatic brain injury; Memory; Source memory; Temporal order memory; Activity memory
14.  Verbal Memory Declines More Rapidly with Age in HIV Infected versus Uninfected Adults 
In the current era of effective antiretroviral treatment, the number of older adults living with HIV is rapidly increasing. This study investigated the combined influence of age and HIV infection on longitudinal changes in verbal and visuospatial learning and memory.
In this longitudinal, case-control design, 54 HIV seropositive and 30 seronegative individuals aged 40–74 received neurocognitive assessments at baseline visits and again one year later. Assessment included tests of verbal and visuospatial learning and memory. Linear regression was used to predict baseline performance and longitudinal change on each test using HIV serostatus, age, and their interaction as predictors. MANOVA was used to assess the effects of these predictors on overall baseline performance and overall longitudinal change.
The interaction of HIV and age significantly predicted longitudinal change in verbal memory performance, as did HIV status, indicating that although the seropositive group declined more than the seronegative group overall, the rate of decline depended on age such that greater age was associated with a greater decline in this group. The regression models for visuospatial learning and memory were significant at baseline, but did not predict change over time. HIV status significantly predicted overall baseline performance and overall longitudinal change.
This is the first longitudinal study focused on the effects of age and HIV on memory. Findings suggest that age and HIV interact to produce larger declines in verbal memory over time. Further research is needed to gain a greater understanding of the effects of HIV on the aging brain.
PMCID: PMC4317358  PMID: 24645772
HIV; Memory; Cognitive Aging; Autoimmune Diseases; HIV-Associated Neurocognitive Disorder
15.  Functional polymorphisms in dopamine-related genes: Effect on neurocognitive functioning in HIV+ adults 
Dopaminergic dysfunction is a putative mechanism underlying HIV-associated neurocognitive disorders. Dopamine transporter (DAT), brain-derived neurotrophic factor (BDNF), and catechol-O-methyltransferase (COMT) have been specifically implicated. We report analyses examining the main effects of functional polymorphisms within dopamine-modulating genes, as well as their interactive effects with disease severity, upon neurocognitive functioning in HIV+ adults.
A total of 184 HIV+ adults were included in the analysis. Three polymorphisms were examined within dopamine-modulating genes: COMT val158met, BDNF val66met, and the DAT 3 variable number tandem repeat. Separate hierarchical regression analyses for five neurocognitive domains (working memory, processing speed, learning, memory, motor) were conducted. Predictor variables were age, ethnicity, gender, education, CD4+ T-cell count, current depression, genotype, and an interaction term capturing genotype and disease severity (CD4).
None of the polymorphisms or HIV disease variables significantly improved the hierarchical regression models. Younger age, higher education, and Caucasian ethnicity were almost invariably associated with better functioning across all five cognitive domains. A trend was noted for current depression as a predictor of motor and learning ability.
This study did not find evidence to support direct or interactive effects of dopamine-related genes and HIV disease severity on neurocognitive functioning.
PMCID: PMC4361028  PMID: 22082040
Catechol-O-methyltransferase; Brain-derived neurotrophic factor; Dopamine transporter; HIV-associated neurocognitive disorders; NeuroAIDS; Pharmacogenetic
16.  Neuropsychological Profiles Delineate Distinct Profiles of Schizophrenia, an Interaction Between Memory and Executive Function, and Uneven Distribution of Clinical Subtypes 
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.
PMCID: PMC4332574  PMID: 12424651
17.  Disentangling Working Memory Processes during Spatial Span Assessment: A Modeling Analysis of Preferred Eye Movement Strategies 
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.
PMCID: PMC3970432  PMID: 24499103
spatial working memory; spatial span; Corsi Block-Tapping Task; eye-tracking; descriptive modeling
18.  [No title available] 
PMCID: PMC3901522  PMID: 24417611
19.  A Neuropsychological Investigation of the Delis-Kaplan Executive Function System 
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.
PMCID: PMC4304768  PMID: 24236952
Prefrontal lesions; D-KEFS; Executive function; Frontal lobe; vmPFC
20.  Apathy is associated with white matter abnormalities in anterior, medial brain regions in persons with HIV infection 
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.
PMCID: PMC4303236  PMID: 25275424
Diffusion tensor imaging; apathy; HIV/AIDS; Prefrontal cortex; depression
21.  Apathy correlates with cognitive performance, functional disability, and HIV RNA plasma levels in HIV-positive individuals 
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.
PMCID: PMC4266413  PMID: 24090038
HIV; Aging; Apathy; Cognitive performance; Functional disability
22.  A deconstruction of gambling task performance among HIV+ individuals: The differential contributions of problem solving and risk taking 
Journal of clinical and experimental neuropsychology  2013;35(10):10.1080/13803395.2013.848842.
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.
PMCID: PMC3864679  PMID: 24168142
23.  Reduced Comparison Speed during Visual Search in Late Life Depression 
Journal of clinical and experimental neuropsychology  2013;35(10):10.1080/13803395.2013.856381.
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.
PMCID: PMC3869571  PMID: 24219302
Depression; Aging; Cognition; Visual Search; Reaction Time
24.  Evidence of Semantic Clustering in Letter-Cued Word Retrieval 
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.
PMCID: PMC4227503  PMID: 24134125
verbal fluency; cued-word retrieval; semantic system; clustering; switching
25.  An investigation of the effects of antiretroviral CNS penetration effectiveness on procedural learning in HIV+ drug users 
Journal of clinical and experimental neuropsychology  2013;35(9):10.1080/13803395.2013.838939.
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.
PMCID: PMC3856247  PMID: 24079384
HIV; neurocognition; substance abuse; antiretroviral therapy; addiction; procedural learning; CPE

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