Studies involving brain-lesioned subjects have used the paced finger tapping (PFT) task to investigate the neural systems that govern motor timing. Patients with Parkinson's disease (PD), for example, demonstrate abnormal performance on the PFT, characterized by decreased accuracy and variability changes, suggesting that the basal ganglia may play a critical role in motor timing. Consistent with this hypothesis, an fMRI study of healthy participants demonstrated that the medial frontostriatal circuit (dorsal putamen, ventrolateral thalamus, SMA) correlated with explicit time-dependent components of the PFT task. In the current fMRI study, PD patients and healthy age-matched controls were imaged while performing the PFT. PD patients underwent 2 imaging sessions, 1 on and the other off dopamine supplementation. Relative to controls, PD patients were less accurate and showed greater variability on the PFT task relative to controls. No PFT performance differences were observed between the on and off medication states despite significantly greater motor symptoms on the Unified Parkinson's Disease Rating Scale (UPDRS) in the off medication state. Functional imaging results demonstrated decreased activation within the sensorimotor cortex (SMC), cerebellum, and medial premotor system in the PD patients compared to controls. With dopamine replacement, an increase in the spatial extent of activation was observed within the SMC, SMA, and putamen in the PD patients. These results indicate that impaired timing reproduction in PD patients is associated with reduced brain activation within motor and medial premotor circuits. Despite a lack of improvement in PFT performance, PD patient's brain activation patterns were partially “normalized” with dopamine supplementation. These findings could not be attributed to greater head movement artifacts or basal ganglia atrophy within the PD group. (JINS, 2003, 9, 1088–1098.)

Higher rates of alcohol use have been reported in HIV+ individuals compared to the general population. Both heavy alcohol use and HIV infection are associated with increased risk of neuropsychological (NP) impairment. We examined effects of heavy active alcohol use and HIV on NP functioning in a large sample of community-residing HIV+ individuals and HIV− controls. The four main study groups included 72 HIV− light/non-drinkers, 70 HIV− heavy drinkers (>100 drinks per month), 70 HIV+ light/non-drinkers, and 56 HIV+ heavy drinkers. The heavy drinking group was further subdivided to assess effects of the heaviest levels of active alcohol use (>6 drinks per day) on NP functioning. A comprehensive NP battery was administered. Multivariate analysis of covariance was employed to examine the effect of HIV and alcohol on NP functioning after adjusting for group differences in age and estimated premorbid verbal intellectual functioning. The analyses identified main effects of heavy drinking and HIV on NP function, with greatest effects involving the contrast of HIV+ heavy drinkers and the HIV− light drinkers. Synergistic effects of heaviest current drinking and HIV infection were identified in analyses of motor and visuomotor speed. Supplementary analyses also revealed better NP function in the HIV+ group with antiretroviral treatment (ART) and lower level of viral burden, a finding that was consistent across levels of alcohol consumption. Finally, heavy alcohol use and executive functioning difficulties were associated with lower levels of self-reported medication adherence in the HIV+ group. The findings suggest that active heavy alcohol use and HIV infection have additive adverse effects on NP function, that they may show synergistic effects in circumstances of very heavy active alcohol use, and that heavy drinking and executive functioning may mediate health-related behaviors in HIV disease. (JINS, 2005, 11, 70–83.)

The neuropsychological aspects of multiple sclerosis (MS) have evolved over the past three decades. What was once thought to be a rare occurrence, cognitive dysfunction is now viewed as one of the most disabling symptoms of the disease, with devastating effects on patients’ quality of life. This selective review will highlight major innovations and scientific discoveries in the areas of neuropathology, neuroimaging, diagnosis, and treatment that pertain to our understanding of the neuropsychological aspects of MS. Specifically, we focus on the recent discovery that MS produces pathogical lesions of gray matter (GM) that have consequences for cognitive functions. Methods for imaging these GM lesions in MS are discussed along with multimodal imaging studies that integrate structural and functional imaging methods to provide a better understanding of the relationship between cognitive test performance and functional reserve. Innovations in the screening and comprehensive assessment of cognitive disorders are presented along with recent research that examines cognitive dysfunction in pediatric MS. Results of innovative outcome studies in cognitive rehabilitation are discussed. Finally, we highlight trends for potential future innovations over the next decade. (JINS, 2017, 23, 832–842)

The aim of this study was to assess cognitive functioning in children with type 1 diabetes (T1D) and examine whether glycemic history influences cognitive function. Neuropsychological evaluation of 216 children (healthy controls, n = 72; T1D, n = 144) ages 4–10 years across five DirecNet sites. Cognitive domains included IQ, Executive Functions, Learning and Memory, and Processing Speed. Behavioral, mood, parental IQ data, and T1D glycemic history since diagnosis were collected. The cohorts did not differ in age, gender or parent IQ. Median T1D duration was 2.5 years and average onset age was 4 years. After covarying age, gender, and parental IQ, the IQ and the Executive Functions domain scores trended lower (both p = .02, not statistically significant adjusting for multiple comparisons) with T1D relative to controls. Children with T1D were rated by parents as having more depressive and somatic symptoms (p < .001). Learning and memory (p = .46) and processing speed (p = .25) were similar. Trends in the data supported that the degree of hyperglycemia was associated with Executive Functions, and to a lesser extent, Child IQ and Learning and Memory. Differences in cognition are subtle in young children with T1D within 2 years of onset. Longitudinal evaluations will help determine whether these findings change or become more pronounced with time. (JINS, 2014, 20, 238–247)

Past research has been inconsistent with regard to the effects of normal aging and sex on strategy use during verbal fluency performance. In the present study, both Troyer et al.’s (1997) and Abwender et al.’s (2001) scoring methods were used to measure switching and clustering strategies in 60 young and 72 older adults, equated on verbal ability. Young adults produced more words overall and switched more often during both phonemic and semantic fluency tasks, but performed similarly to older adults on measures of clustering. Although there were no sex differences in total words produced on either fluency task, males produced larger clusters on both tasks, and females switched more frequently than males on the semantic but not on the phonemic fluency task. Although clustering strategies appear to be relatively age-insensitive, age-related changes in switching strategies resulted in fewer overall words produced by older adults. This study provides evidence of age and sex differences in strategy use during verbal fluency tests, and illustrates the utility of combining Troyer’s and Abwender’s scoring procedures with in-depth categorization of clustering to understand interactions between age and sex during semantic fluency tasks. (JINS, 2009, 15, 196–204.)

To assess recovery of cognitive effects, we investigated neuropsychological performance after 1 month of monitored abstinence in teens with histories of heavy episodic drinking, protracted marijuana use, or concomitant use of alcohol and marijuana. Adolescents (ages 16–18 years) with histories of heavy episodic drinking (HED; n=24), marijuana use (MJ; n=20), both heavy alcohol and marijuana use (HED+MJ; n=29), and socio-demographically similar control teens (CON; n=55) completed a neuropsychological battery following 4 weeks of monitored abstinence. Groups were similar on 5th grade standardized test scores, suggesting comparable academic functioning before onset of substance use. Relative to CON, HED showed poorer cognitive flexibility (p=.006), verbal recall (p=.024), semantic clustering (p=.011), and reading skills (p=.018). MJ performed worse than CON on inhibition task accuracy (p=.015), cued verbal memory (p=.031), and psychomotor speed (p=.027). Similar to HED youth, HED+MJ showed differences relative to CON on cognitive flexibility (p=.024) and verbal recall (p=.049). As with MJ teens, HED+MJ showed poorer task accuracy (p=.020). Unique to the HED+MJ group was poorer working memory (p=.012) relative to CON. For all substance using participants, worse performance across domains correlated with more lifetime use of alcohol and of marijuana, more withdrawal symptoms from alcohol, and earlier age of onset of marijuana use (ps<.05). Heavy alcohol use, marijuana use, and concomitant use of both substances during adolescence appear to be associated with decrements in cognitive functioning, and each substance (or combination of substances) may be linked to poorer performance in specific cognitive domains (JINS, 2014, 20, 784–795).

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)

Objectives: Individuals with chronic traumatic brain injury (TBI) often show detrimental deficits in higher order cognitive functions requiring coordination of multiple brain networks. Although assessing TBI-related deficits in higher order cognition in the context of network dysfunction is promising, few studies have systematically investigated altered interactions among multiple networks in chronic TBI. Method: We characterized disrupted resting-state functional connectivity of the default mode network (DMN), dorsal attention network (DAN), and frontoparietal control network (FPCN) whose interactions are required for internally and externally focused goal-directed cognition in chronic TBI. Specifically, we compared the network interactions of 40 chronic TBI individuals (8 years post-injury on average) with those of 17 healthy individuals matched for gender, age, and years of education. Results: The network-based statistic (NBS) on DMN-DAN-FPCN connectivity of these groups revealed statistically significant (pNBS<.05; |Z|>2.58) reductions in within-DMN, within-FPCN, DMN-DAN, and DMN-FPCN connectivity of the TBI group over healthy controls. Importantly, such disruptions occurred prominently in between-network connectivity. Subsequent analyses further exhibited the disrupted connectivity patterns of the chronic TBI group occurring preferentially in long-range and inter-hemispheric connectivity of DMN-DAN-FPCN. Most importantly, graph-theoretic analysis demonstrated relative reductions in global, local and cost efficiency (p<.05) as a consequence of the network disruption patterns in the TBI group. Conclusion: Our findings suggest that assessing multiple networks-of-interest simultaneously will allow us to better understand deficits in goal-directed cognition and other higher order cognitive phenomena in chronic TBI. Future research will be needed to better understand the behavioral consequences related to these network disruptions. (JINS, 2016, 22, 263–279)

The interpretation of neurobehavioral change over time requires knowledge of the test–retest characteristics of the measures. Without this information it is not possible to distinguish a true change (i.e., one reflecting the occurrence or resolution of an intervening process) from that occurring on the basis of chance or systematic bias. We tested a group of 72 healthy young to middle aged adults twice over a 12-to-16-week interval in order to observe the change in scores over time when there was no known intervention. The test battery consisted of seven commonly used cognitive measures and the Profile of Mood States (POMS). Test–retest regression equations were calculated for each measure using initial performance, age, education, and a measure of general intellectual function (Wonderlic Personnel Test) as regressors. Test–retest correlations ranged from .39 (POMS Fatigue) to .89 (Digit Symbol). Cognitive measures generally yielded higher correlations than did the POMS. Univariate regressions based only on initial performance adequately predicted retest performance for the majority of measures. Age and education had a relatively minor influence. Practice effects and regression to the mean were common. These test–retest regression equations can be used to predict retest scores when there has been no known intervention. They can also be used to generate statistical statements regarding the significance of change in an individual's performance over a 12-to-16-week interval. (JINS, 2001, 7, 597–605.)

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)

Amnestic mild cognitive impairment (aMCI) is associated with neuropathological changes in medial-temporal and frontal-system structures. By definition, retrospective memory is mildly impaired in aMCI. We examined whether prospective memory (PM) is also impaired, in particular time-based PM, which requires considerable self-initiation and inhibition. We administered time- and event-based PM tasks to 42 healthy older adults, 45 individuals with aMCI, and 24 individuals with Alzheimer's disease (AD). The healthy group performed better than the aMCI group, and the aMCI group performed better than the AD group on both PM tasks. Importantly, the aMCI group performed more poorly on the time- than event-based task, whereas the other groups performed comparably on both tasks. Findings suggest that PM, particularly time-based PM, is sensitive to the earliest cognitive changes associated with aMCI, possibly reflecting decreased self-initiation, attention switching, and/or inhibition on memory tasks because of early involvement of the frontal system. (JINS, 2007, 13, 365–369.)

This study assessed two relevant aspects of executive dysfunction in children with either Tourette syndrome (TS) or ADHD. Process variables derived from existing neuropsychological measures were used to clarify the executive function construct. Clustering of responses on measures of verbal fluency, figural fluency, and verbal learning was examined to assess strategic response organization. Rule breaks, intrusions, and repetition errors were recorded to assess inhibition errors. No significant differences were found among the three groups (TS, ADHD, and controls) on tasks of response organization (clustering). In our sample, both the ADHD and the TS groups were largely free from executive function impairment, and their performance on the fluency and list learning tasks was in the average range. There was a significant group difference on one of the disinhibition variables, with both TS and ADHD groups showing significantly more intrusions on verbal list learning trials than controls. When more traditional total score variables were analyzed among the three groups, there were no significant differences; however, analysis of effect size revealed medium-to-large effect sizes for Letter Word Fluency total score differences (ADHD vs. controls), and for Semantic Word Fluency total score differences (ADHD vs. TS), with the ADHD group having weaker performance in both comparisons. Results provide some support for the use and analysis of process variables—particularly those related to inhibition and intrusion errors, in addition to the total score variables when assessing executive function deficits in children with ADHD and TS. While group differences may be found, children with uncomplicated TS should not routinely be considered to have significant executive function impairments, and when deficits are found, they may be attributable to other comorbid disorders. (JINS, 2001, 7, 102–111.)

The frontoparietal control network, anatomically and functionally interposed between the dorsal attention network and default mode network, underpins executive control functions. Individuals with attention-deficit/hyperactivity disorder (ADHD) commonly exhibit deficits in executive functions, which are mainly mediated by the frontoparietal control network. Involvement of the frontoparietal control network based on the anterior prefrontal cortex in neurobiological mechanisms of ADHD has yet to be tested. We used resting-state functional MRI and seed-based correlation analyses to investigate functional connectivity of the frontoparietal control network in a sample of 25 children with ADHD (7–14 years; mean 9.94±1.77 years; 20 males), and 25 age-, sex-, and performance IQ-matched typically developing (TD) children. All participants had limited in-scanner head motion. Spearman’s rank correlations were used to test the associations between altered patterns of functional connectivity with clinical symptoms and executive functions, measured by the Conners’ Continuous Performance Test and Spatial Span in the Cambridge Neuropsychological Test Automated Battery. Compared with TD children, children with ADHD demonstrated weaker connectivity between the right anterior prefrontal cortex (PFC) and the right ventrolateral PFC, and between the left anterior PFC and the right inferior parietal lobule. Furthermore, this aberrant connectivity of the frontoparietal control network in ADHD was associated with symptoms of impulsivity and opposition-defiance, as well as impaired response inhibition and attentional control. The findings support potential integration of the disconnection model and the executive dysfunction model for ADHD. Atypical frontoparietal control network may play a pivotal role in the pathophysiology of ADHD. (JINS, 2015, 21, 271–284)

Measuring recovery of function may mean testing the same individual many times, a procedure that is inevitably open to improvement due to learning on the specific tests rather than recovery per se. This is particularly likely to be an issue with measures of memory performance. We therefore studied the performance of normal and brain-injured people across 20 successive test sessions on measures of orientation, simple reaction time, forward and backward digit span, visual and verbal recognition, word list learning and forgetting, and on three semantic memory measures, namely, letter and category fluency and speed of semantic processing. Differences in overall performances between the two groups occurred for all tests other than orientation, digit span forward, and simple reaction time, although the tests differed in their degree of sensitivity. The tests varied in the presence or absence of practice effects and in the extent to which these differed between the two groups. Data are presented that should allow investigators to select measures that are likely to optimize sensitivity while minimizing possible confounding due to practice effects. (JINS, 2000, 6, 469–479.)

The objective of this study was to describe the neuropsychological profiles of the three variants of primary progressive aphasia (PPA). Based on a comprehensive speech and language evaluation, 91 subjects were classified as logopenic (lvPPA=51), semantic (svPPA=13), or agrammatic (agPPA=27). All subjects completed a separate neuropsychological evaluation assessing verbal and visual memory, processing speed, executive function, and visuospatial function. The groups did not differ on demographic variables or on measures of disease duration or aphasia severity. There were group differences on aspects of learning and memory, as well as aspects of executive and visuospatial functions, primarily with the lvPPA group performing lower than the agPPA and svPPA groups. The agPPA group showed subtle deficits consistent with frontal lobe impairment, whereas neurocognitive weaknesses in the svPPA group were restricted to temporal lobe functions. The pattern of neurocognitive dysfunction in lvPPA suggests disease involvement of frontal lobe functions in addition to temporoparietal functions. These neurocognitive findings emphasize the value of a comprehensive neuropsychological evaluation of individuals who present with primary language disturbance, given the pattern of cognitive deficits may provide additive information for differentiating these clinical syndromes. (JINS, 2015, 21, 429–435)

Emotional facial expressions evoke rapid, involuntary, and covert facial reactions in the perceiver that are consistent with the emotional valence of the observed expression. These responses are believed to be an important low-level mechanism contributing to the experience of empathy, which some have argued rely on a simulation mechanism subserved by the human mirror neuron system (MNS). Because schizophrenia is associated with pervasive social cognitive difficulties which have been linked to structural abnormalities in the MNS network, the aim of the present study was to provide the first assessment of how rapid facial mimicry reactions (within 1000 ms poststimulus onset) are affected in schizophrenia. Activity in the corrugator supercilii and zygomaticus major muscle regions was quantified using electromyography while individuals with schizophrenia (n = 25) and controls (n = 25) viewed images of happy and angry facial expressions. In contrast to controls, individuals with schizophrenia demonstrated atypical facial mimicry reactions which were not associated with any clinical features of the disorder. These data provide evidence for a low-level disruption that may be contributing to empathizing deficits in schizophrenia and are discussed in relation to neuropsychological models of empathy and schizophrenia. (JINS, 2010, 16, 621–629.)

The current project examined the impact of differential motivation on baseline versus post-mild traumatic brain injury (MTBI) neuropsychological measures in athletes. Collegiate athletes were administered a neuropsychological battery prior to and post-MTBI. High Motivation at Baseline (HMB) and Suspect Motivation at Baseline (SMB) groups were established for each measure based on whether baseline performance fell +/− one or more standard deviations from the mean of the given measure. Greater improvement was expected in the SMB group than the HMB group given hypothesized differences in baseline motivation. In repeated measures analysis of covariance (ANCOVA) that removed achievement performance, the SMB groups demonstrated greater improvement than the HMB groups for the Trail Making Test A & B (TMT-A & B), Digit Span, and Stroop-Color Word (Stroop-CW) tests. Also, the percentage of participants who improved according to reliable change indices was greater for the SMB groups on the TMT-A & B, Stroop-CW, and the Vigil. These findings are likely due to lower motivation in the SMB group for each test. However, results also suggest that some tests may be relatively unaffected by motivation. These data may have clinical implications and point to the need for better methods of identifying athletes with suspect motivation at baseline. (JINS, 2006, 12, 475–484.)

Prenatal exposure to sodium valproate (VPA) and polytherapy has been linked with increased risk of birth defects and cognitive impairment in young children. We evaluated the cognitive impact of prenatal exposure to VPA and polytherapy in school-aged children. Fifty-seven children exposed to VPA (n = 23), polytherapy with VPA (n = 15), or polytherapy without VPA (n = 19) were assessed using the Wechsler Intelligence Scale for Children—Fourth Edition. Information on maternal epilepsy, pregnancy, and medical history was obtained prospectively through the Australian Pregnancy Register for Women with Epilepsy and Allied Disorders. All groups had elevated frequencies of Extremely Low (<70) or Borderline (70–79) Full-Scale IQ (15.8–40.0%). Verbal Comprehension and Working Memory scores in all groups fell significantly below the standardized test mean, while Perceptual Reasoning and Processing Speed scores were relatively intact. Multivariate analysis of covariance analysis revealed significant main effects of VPA on Verbal Comprehension and Working Memory, and of polytherapy on Verbal Comprehension and Processing Speed. Our results suggest that VPA has a dose-dependent negative impact on verbal intellectual abilities, and may also affect working memory. The possibility that inclusion of VPA in many polytherapy regimens may underlie reduced mean scores of polytherapy-exposed children is discussed. (JINS, 2011, 17, 000–000)

Both HIV and aging impact performance on neuropsychological testing; however, evidence for differences between HIV effects in younger compared to older subjects (interaction effects) is limited and the findings have been inconsistent. Coexisting morbidities that contribute to cognitive impairment in HIV include those not directly referable to infection, per se, and are more prevalent with advancing age, increasing the likelihood that HIV and age effects may be largely independent. As individuals survive with HIV into geriatric age groups, greater clarity on these relationships is essential. We present cross-sectional data from a large (n = 450) cohort designed to analyze HIV, age, and interaction effects using a well-matched cohort of HIV-negative individuals. Results reveal limited evidence for interaction effects between HIV and age on neuropsychological performance. We conclude that older age does not significantly influence neuropsychological performance among HIV patients when seronegative controls are largely composed of individuals from a similar socioeconomic background. (JINS, 2011, 17, 1–6)

The aim of this study was to evaluate clinical, neuropsychological, and functional differences between severe traumatic brain injury (TBI) outpatients with good and/or heightened metacognitive self-awareness (SA) and those with impaired metacognitive SA, assessed by the Patient Competency Rating Scale (PCRS). Fifty-two outpatients were recruited from a neurorehabilitation hospital based on the following inclusion criteria: 1) age ≥ 15 years; 2) diagnosis of severe TBI; 3) availability of neuroimaging data; 4) post-traumatic amnesia resolution; 5) provision of informed consent. Measures: A neuropsychological battery was used to evaluate attention, memory and executive functions. SA was assessed by the PCRS, which was administered to patients and close family members. Patients were divided into two groups representing those with and without SA. Patients with poor SA had more problems than those with good SA in some components of the executive system, as indicated by the high percentage of perseverative errors and responses they made on the Wisconsin Card Sorting Test. Moreover, a decrease in metacognitive SA correlated significantly with time to follow commands (TFC). This study suggests the importance of integrating an overall assessment of cognitive functions with a specific evaluation of SA to treat self-awareness and executive functions together during the rehabilitation process. (JINS, 2010, 16, 360–368.)