Objectives: It is well known that the carotenoids lutein (L) and zeaxanthin (Z) improve eye health and an accumulating evidence base suggests cognitive benefits as well. The present study investigated underlying neural mechanisms using functional magnetic resonance imaging (fMRI). It was hypothesized that lower L and Z concentrations would be associated with neurobiological inefficiency (i.e., increased activation) during cognitive performance. Methods: Forty-three community-dwelling older adults (mean age=72 years; 58% female; 100% Caucasian) were asked to learn and recall pairs of unrelated words in an fMRI-adapted paradigm. L and Z levels were measured in retina (macular pigment optical density) and serum using validated procedures. Results: Following first-level contrasts of encoding and retrieval trials minus control trials (p<.05, family-wise error corrected, minimum voxel cluster=8), L and Z were found to significantly and negatively relate to blood-oxygen-level-dependent signal in central and parietal operculum cortex, inferior frontal gyrus, supramarginal gyrus, planum polare, frontal and middle temporal gyrus, superior parietal lobule, postcentral gyrus, precentral gyrus, occipital cortex bilaterally, and cerebellar regions. Conclusions: To the authors’ knowledge, the present study represents the first attempt to investigate neural mechanisms underlying the relation of L and Z to cognition using fMRI. The observed results suggest that L and Z promote cognitive functioning in old age by enhancing neural efficiency. (JINS, 2017, 23, 11–22)

Objectives: Deficits in the recognition of negative emotions emerge before clinical diagnosis in Huntington’s disease (HD). To address emotion recognition deficits, which have been shown in schizophrenia to be improved by computerized training, we conducted a study of the feasibility and efficacy of computerized training of emotion recognition in HD. Methods: We randomly assigned 22 individuals with premanifest or early symptomatic HD to the training or control group. The training group used a self-guided online training program, MicroExpression Training Tool (METT), twice weekly for 4 weeks. All participants completed measures of emotion recognition at baseline and post-training time-points. Participants in the training group also completed training adherence measures. Results: Participants in the training group completed seven of the eight sessions on average. Results showed a significant group by time interaction, indicating that METT training was associated with improved accuracy in emotion recognition. Conclusions: Although sample size was small, our study demonstrates that emotion recognition remediation using the METT is feasible in terms of training adherence. The evidence also suggests METT may be effective in premanifest or early-symptomatic HD, opening up a potential new avenue for intervention. Further study with a larger sample size is needed to replicate these findings, and to characterize the durability and generalizability of these improvements, and their impact on functional outcomes in HD. (JINS, 2017, 23, 314–321)

Objectives: Body dysmorphic disorder (BDD) is characterized by repetitive behaviors and/or mental acts occurring in response to preoccupations with perceived defects or flaws in physical appearance. There are some similarities, but also important differences, between BDD and obsessive-compulsive disorder (OCD), not just in terms of core clinical symptoms, but possibly in the domain of perception. This study compared the nature and extent of perceptual anomalies in BDD versus OCD and health controls (HC), using a modified Mooney task. Methods: We included 21 BDD, 19 OCD, and 21 HC participants, who were age-, sex-, and IQ-matched. A set of 40 Mooney faces and 40 Mooney objects arranged in three configurations (i.e., upright, inverted, or scrambled) were presented under brief (i.e., 500 ms) free-viewing conditions. Participants were asked to decide whether each image represented a human face, an object, or neither in a forced-choice paradigm. Results: The BDD group showed significantly reduced face and object inversion effects relative to the other two groups. This was accounted for by BDD participants being significantly more accurate in identifying inverted Mooney faces and objects than the other participants. Conclusions: These data were interpreted as reflecting an overreliance on independent components at the expense of holistic (configural) processing in BDD. (JINS, 2017, 23, 471–480)

Thirty years ago, the neuropsychology of emotion started to emerge as a mainstream topic. Careful examination of individual patients showed that emotion, like memory, language, and so on, could be differentially affected by brain disorders, especially in the right hemisphere. Since then, there has been accelerating interest in uncovering the neural architecture of emotion, and the major steps in this process of discovery over the past 3 decades are detailed in this review. In the 1990s, magnetic resonance imaging (MRI) scans provided precise delineation of lesions in the amygdala, medial prefrontal cortex, insula and somatosensory cortex as underpinning emotion disorders. At the same time, functional MRI revealed activation that was bilateral and also lateralized according to task demands. In the 2000s, converging evidence suggested at least two routes to emotional responses: subcortical, automatic and autonomic responses and slower, cortical responses mediating cognitive processing. The discovery of mirror neurons in the 1990s reinvigorated older views that simulation was the means to recognize emotions and empathize with others. More recently, psychophysiological research, revisiting older Russian paradigms, has contributed new insights into how autonomic and other physiological indices contribute to decision making (the somatic marker theory), emotional simulation, and social cognition. Finally, this review considers the extent to which these seismic changes in understanding emotional processes in clinical disorders have been reflected in neuropsychological practice. (JINS, 2017, 23, 719–731)

Objectives: Previous studies have found that oxytocin (OXT) can improve the recognition of emotional facial expressions; it has been proposed that this effect is mediated by an increase in attention to the eye-region of faces. Nevertheless, evidence in support of this claim is inconsistent, and few studies have directly tested the effect of oxytocin on emotion recognition via altered eye-gaze Methods: In a double-blind, within-subjects, randomized control experiment, 40 healthy male participants received 24 IU intranasal OXT and placebo in two identical experimental sessions separated by a 2-week interval. Visual attention to the eye-region was assessed on both occasions while participants completed a static facial emotion recognition task using medium intensity facial expressions. Results: Although OXT had no effect on emotion recognition accuracy, recognition performance was improved because face processing was faster across emotions under the influence of OXT. This effect was marginally significant (p<.06). Consistent with a previous study using dynamic stimuli, OXT had no effect on eye-gaze patterns when viewing static emotional faces and this was not related to recognition accuracy or face processing time. Conclusions: These findings suggest that OXT-induced enhanced facial emotion recognition is not necessarily mediated by an increase in attention to the eye-region of faces, as previously assumed. We discuss several methodological issues which may explain discrepant findings and suggest the effect of OXT on visual attention may differ depending on task requirements. (JINS, 2017, 23, 23–33)

Objectives: Episodic memory deficits are both common and impactful among persons infected with HIV; however, we know little about how to improve such deficits in the laboratory or in real life. Retrieval practice, by which retrieval of newly learned material improves subsequent recall more than simple restudy, is a robust memory boosting strategy that is effective in both healthy and clinical populations. In this study, we investigated the benefits of retrieval practice in 52 people living with HIV and 21 seronegatives. Methods: In a within-subjects design, all participants studied 48 verbal paired associates in 3 learning conditions: Massed-Restudy, Spaced-Restudy, and Spaced-Testing. Retention of verbal paired associates was assessed after short- (30 min) and long- (30 days) delay intervals. Results: After a short delay, both HIV+ persons and seronegatives benefited from retrieval practice more so than massed and spaced restudy. The same pattern of results was observed specifically for HIV+ persons with clinical levels of memory impairment. The long-term retention interval data evidenced a floor effect that precluded further analysis. Conclusions: This study provides evidence that retrieval practice improves verbal episodic memory more than some other mnemonic strategies among HIV+ persons. (JINS, 2017, 23, 214–222)

Objectives: The negative effect of changes in social behavior following traumatic brain injury (TBI) are known, but much less is known about the neuropsychological impairments that may underlie and predict these changes. The current study investigated possible associations between post-injury behavior and neuropsychological competencies of emotion recognition, understanding intentions, and response selection, that have been proposed as important for social functioning. Methods: Forty participants with TBI and 32 matched healthy participants completed a battery of tests assessing the three functions of interest. In addition, self- and proxy reports of pre- and post-injury behavior, mood, and community integration were collected. Results: The TBI group performed significantly poorer than the comparison group on all tasks of emotion recognition, understanding intention, and on one task of response selection. Ratings of current behavior suggested significant changes in the TBI group relative to before the injury and showed significantly poorer community integration and interpersonal behavior than the comparison group. Of the three functions considered, emotion recognition was associated with both post-injury behavior and community integration and this association could not be fully explained by injury severity, time since injury, or education. Conclusions: The current study confirmed earlier findings of associations between emotion recognition and post-TBI behavior, providing partial evidence for models proposing emotion recognition as one of the pre-requisites for adequate social functioning. (JINS, 2017, 23, 400–411)

Objectives: Exploring the nature of defective pantomime in apraxia. Methods: Critical review of behavioral associations and dissociations between defective pantomime, imitation of gestures, and real tool use. Analysis of congruencies between crucial lesions for pantomime, imitation, and tool use. Results: There are behavioral double dissociations between pantomime and imitation, and their cerebral substrates show very little overlap. Whereas defective pantomime is bound to temporal and inferior frontal lesions, imitation is mainly affected by parietal lesions. Pantomime usually replicates the motor actions of real use but on scrutiny there are important differences between the movements of real use and of pantomime that cast doubt on the assumption that pantomime is produced by the same motor programs as actual use. A more plausible proposal posits that pantomime is a communicative gesture that uses manual actions for conveying information about objects and their use. The manual actions are constructed by selection and combination of distinctive features of tools and actions. They frequently include replications of characteristic motor actions of real use, but the main criterion for selection and modification of features is the comprehensibility of the gestures rather than the accurate replication of the motor actions of real use. Conclusions: Pantomime of tool use is a communicative gesture rather than a replication of the motor actions of real use. (JINS, 2017, 23, 121–127)

Objectives: The present study examined differences in neurocognitive outcomes among non-Hispanic Black and White stroke survivors using the NIH Toolbox-Cognition Battery (NIHTB-CB), and investigated the roles of healthcare variables in explaining racial differences in neurocognitive outcomes post-stroke. Methods: One-hundred seventy adults (91 Black; 79 White), who participated in a multisite study were included (age: M=56.4; SD=12.6; education: M=13.7; SD=2.5; 50% male; years post-stroke: 1–18; stroke type: 72% ischemic, 28% hemorrhagic). Neurocognitive function was assessed with the NIHTB-CB, using demographically corrected norms. Participants completed measures of socio-demographic characteristics, health literacy, and healthcare use and access. Stroke severity was assessed with the Modified Rankin Scale. Results: An independent samples t test indicated Blacks showed more neurocognitive impairment (NIHTB-CB Fluid Composite T-score: M=37.63; SD=11.67) than Whites (Fluid T-score: M=42.59, SD=11.54; p=.006). This difference remained significant after adjusting for reading level (NIHTB-CB Oral Reading), and when stratified by stroke severity. Blacks also scored lower on health literacy, reported differences in insurance type, and reported decreased confidence in the doctors treating them. Multivariable models adjusting for reading level and injury severity showed that health literacy and insurance type were statistically significant predictors of the Fluid cognitive composite (p<.001 and p=.02, respectively) and significantly mediated racial differences on neurocognitive impairment. Conclusions: We replicated prior work showing that Blacks are at increased risk for poorer neurocognitive outcomes post-stroke than Whites. Health literacy and insurance type might be important modifiable factors influencing these differences. (JINS, 2017, 23, 640–652)

Objectives: Cognitive impairment is an important aspect of Parkinson’s disease (PD), but there is considerable heterogeneity in its presentation. This investigation aims to identify and characterize latent cognitive phenotypes in early PD. Methods: Latent class analysis, a data-driven, person-centered, cluster analysis was performed on cognitive data from the Parkinson’s Progressive Markers Initiative baseline visit. This analytic method facilitates identification of naturally occurring endophenotypes. Resulting classes were compared across biomarker, symptom, and demographic data. Results: Six cognitive phenotypes were identified. Three demonstrated consistent performance across indicators, representing poor (“Weak-Overall”), average (“Typical-Overall”), and strong (“Strong-Overall”) cognition. The remaining classes demonstrated unique patterns of cognition, characterized by “Strong-Memory,” “Weak-Visuospatial,” and “Amnestic” profiles. The Amnestic class evidenced greater tremor severity and anosmia, but was unassociated with biomarkers linked with Alzheimer’s disease. The Weak-Overall class was older and reported more non-motor features associated with cognitive decline, including anxiety, depression, autonomic dysfunction, anosmia, and REM sleep behaviors. The Strong-Overall class was younger, more female, and reported less dysautonomia and anosmia. Classes were unrelated to disease duration, functional independence, or available biomarkers. Conclusions: Latent cognitive phenotypes with focal patterns of impairment were observed in recently diagnosed individuals with PD. Cognitive profiles were found to be independent of traditional biomarkers and motoric indices of disease progression. Only globally impaired class was associated with previously reported indicators of cognitive decline, suggesting this group may drive the effects reported in studies using variable-based analysis. Longitudinal and neuroanatomical characterization of classes will yield further insight into the evolution of cognitive change in the disease. (JINS, 2017, 23, 551–563)

Objectives: Previous studies have reported impairments in activities of daily living (ADL) performance in the presence of irrelevant but physically/functionally related objects in dementia patients. The aim of the present study was to increase our knowledge about the impact of the presence of contextually related non-target objects on ADL execution in patients with multi-domain mild cognitive impairment (MCI) and dementia. Methods: We compared ADL execution in patients with MCI, dementia, and healthy elderly participants under two experimental conditions: One in which the target objects were embedded with contextually related non-target items that constituted the object set necessary to complete two additional (but unrequired) ADL tasks related to the target task, and a second, control condition where target objects were surrounded by isolated objects (they never constituted a whole set needed to complete an alternative ADL task). Results: Separate analysis of ADL errors associated with the target task versus errors involving the non-target objects revealed that, although the presence of contextually related objects facilitated the accomplishment of the target task, such a condition also led to errors involving the use of irrelevant objects in dementia and MCI. Conclusions: The presence of contextually related non-target items produces both positive and negative effects on ADL performance. These types of non-target objects might help to cue the retrieval of the action schema related to the target task, particularly in patients with MCI. In contrast, the presence of these objects might also lead to distraction in dementia and MCI. (JINS, 2017, 23, 481–492)

Objectives: Research demonstrates heterogeneous neuropsychological profiles among individuals with mild cognitive impairment (MCI). However, few studies have included visuoconstructional ability or used latent mixture modeling to statistically identify MCI subtypes. Therefore, we examined whether unique neuropsychological MCI profiles could be ascertained using latent profile analysis (LPA), and subsequently investigated cerebrospinal fluid (CSF) biomarkers, genotype, and longitudinal clinical outcomes between the empirically derived classes. Methods: A total of 806 participants diagnosed by means of the Alzheimer’s Disease Neuroimaging Initiative (ADNI) MCI criteria received a comprehensive neuropsychological battery assessing visuoconstructional ability, language, attention/executive function, and episodic memory. Test scores were adjusted for demographic characteristics using standardized regression coefficients based on “robust” normal control performance (n=260). Calculated Z-scores were subsequently used in the LPA, and CSF-derived biomarkers, genotype, and longitudinal clinical outcome were evaluated between the LPA-derived MCI classes. Results: Statistical fit indices suggested a 3-class model was the optimal LPA solution. The three-class LPA consisted of a mixed impairment MCI class (n=106), an amnestic MCI class (n=455), and an LPA-derived normal class (n=245). Additionally, the amnestic and mixed classes were more likely to be apolipoprotein e4+ and have worse Alzheimer’s disease CSF biomarkers than LPA-derived normal subjects. Conclusions: Our study supports significant heterogeneity in MCI neuropsychological profiles using LPA and extends prior work (Edmonds et al., 2015) by demonstrating a lower rate of progression in the approximately one-third of ADNI MCI individuals who may represent “false-positive” diagnoses. Our results underscore the importance of using sensitive, actuarial methods for diagnosing MCI, as current diagnostic methods may be over-inclusive. (JINS, 2017, 23, 564–576)

Objectives: Multiple sclerosis (MS) can be associated with impaired social cognition. However, social cognition skills have never been explored in the different subtypes of MS. The first aim of this study was to examine whether MS subtypes differ on the course of social cognition. The second aim was to explore the relationship between social cognition performances and executive abilities and mood variables. Methods: Sixty-two patients with MS and 33 healthy matched controls performed experimental tasks assessing facial emotion recognition, theory of mind (ToM), and cognitive functioning, in particular executive functions. Results: Patients differed from controls on both measures of social cognition. On the ToM measures, patients with progressive MS scored significantly lower than healthy participants. Patients with primary progressive MS performed worse than both healthy participants and patients with relapsing-remitting MS on the recognition of fearful facial expressions, while patients with secondary progressive MS performed worse on the recognition of facial expressions of sadness. Patients’ social cognition difficulties were correlated with processing speed, working memory, and verbal fluency. Conclusions: These preliminary results suggested that there may be qualitative differences in social cognition difficulties among the phenotypes. Furthermore, these impairments were related to executive functions, but unrelated to patients’ disability or level of depression. These data highlight the need for research to determine the real impact of these deficits on interpersonal relationships among patients and to confirm these disorders in a larger population with progressive forms of MS. (JINS, 2017, 23, 653–664)

Objectives: Pantomiming the use of familiar tools is a central test in the assessment of apraxia. However, surprisingly, the nature of the underlying cognitive mechanisms remains an unresolved issue. The aim of this study is to shed a new light on this issue by exploring the role of functional, mechanical, and manipulation knowledge in patients with Alzheimer’s disease and semantic dementia and apraxia of tool use. Methods: We performed multiple regression analyses with the global performance and the nature of errors (i.e., production and conception) made during a pantomime of tool use task in patients and control participants as dependent variables and tasks investigating functional, mechanical, and manipulation knowledge as predictors. Results: We found that mechanical problem solving, assessing mechanical knowledge, was a good predictor of the global performance of pantomime of tool use. We also found that occurrence of conception errors was robustly predicted by the task assessing functional knowledge whereas that of production errors was not explained by only one predictor. Conclusions: Our results suggest that both functional and mechanical knowledge are important to pantomime the use of tools. To our knowledge, this is the first demonstration that mechanical knowledge plays a role in pantomime of tool use. Although impairment in pantomime of tool use tasks (i.e., apraxia) is widely explained by the disruption of manipulation knowledge, we propose that pantomime of tool use is a complex problem-solving task. (JINS, 2017, 23, 128–138)

Objectives: A wealth of studies provide evidence for action simulation during language comprehension. Recent research suggests such action simulations might be sensitive to fine-grained information, such as speed. Here, we present a crucial test for action simulation of speed in language by assessing speed comprehension in patients with Parkinson’s disease (PD). Based on the patients’ motor deficits, we hypothesized that the speed of motion described in language would modulate their performance in semantic tasks. Specifically, they would have more difficulty processing language about relatively fast speed than language about slow speed. Methods: We conducted a semantic similarity judgment task on fast and slow action verbs in patients with PD and age-matched healthy controls. Participants had to decide which of two verbs most closely matched a target word. Results: Compared to controls, PD patients were slower making judgments about fast action verbs, but not for judgments about slow action verbs, suggesting impairment in processing language about fast action. Moreover, this impairment was specific to verbs describing fast action performed with the hand. Conclusions: Problems moving quickly lead to difficulties comprehending language about moving quickly. This study provides evidence that speed is an important part of action representations. (JINS, 2017, 23, 412–420)

Objectives: This study examined whether individuals with Parkinson’s disease (PD) are at increased vulnerability for vascular-related cognitive impairment relative to controls. The underlying assumption behind this hypothesis relates to brain reserve and that both PD and vascular risk factors impair similar fronto-executive cognitive systems. Methods: The sample included 67 PD patients and 61 older controls (total N=128). Participants completed neuropsychological measures of executive functioning, processing speed, verbal delayed recall/memory, language, and auditory attention. Cardiovascular risk was assessed with the Framingham Cardiovascular Risk index. Participants underwent brain imaging (T1 and T2 FLAIR). Trained raters measured total and regional leukoaraiosis (periventricular, deep subcortical, and infracortical). Results: Hierarchical regressions revealed that more severe cardiovascular risk was related to worse executive functioning, processing speed, and delayed verbal recall in both Parkinson patients and controls. More severe cardiovascular risk was related to worse language functioning in the PD group, but not controls. In contrast, leukoaraiosis related to both cardiovascular risk and executive functioning for controls, but not the PD group. Conclusions: Overall, results revealed that PD and cardiovascular risk factors are independent risk factors for cognitive impairment. Generally, the influence of cardiovascular risk factors on cognition is similar in PD patients and controls. (JINS, 2017, 23, 322–331)

Objectives: The extent of vascular cognitive impairment (VCI) after stroke varies greatly across individuals, even when the same amount of brain damage is present. Education level is a potentially protective factor explaining these differences, but results on its effects on VCI are inconclusive. Methods: First, we performed a meta-analysis on formal education and VCI, identifying 21 studies (N=7770). Second, we examined the effect of formal education on VCI in young-stroke patients who were cognitively assessed on average 11.0 (SD=8.2) years post-stroke (the FUTURE study cohort). The total sample consisted of 277 young-stroke patients with a mean age at follow-up 50.9 (SD=10.3). Age and education-adjusted expected scores were computed using 146 matched stroke-free controls. Results: The meta-analysis showed an overall effect size (z') of 0.25 (95% confidence interval [0.18–0.31]), indicating that formal education level had a small to medium effect on VCI. Analyses of the FUTURE data showed that the effect of education on post-stroke executive dysfunction was mediated by age (β age −0.015; p<.05). Below-average performance in the attention domain was more frequent for low-education patients (χ2(2)=9.8; p<.05). Conclusions: While education level was found to be related to post-stroke VCI in previous research, the effects were small. Further analysis in a large stroke cohort showed that these education effects were fully mediated by age, even in relatively young stroke patients. Education level in and of itself does not appear to be a valid indicator of cognitive reserve. Multi-indicator methods may be more valid, but have not been studied in relation to VCI. (JINS, 2017, 23, 223–238)

The past 30 years of research on human amnesia has yielded important changes in our understanding of the role of the medial temporal lobes (MTL) in memory. On the one hand, this body of evidence has highlighted that not all types of memory are impaired in patients with MTL lesions. On the other hand, this research has made apparent that the role of the MTL extends beyond the domain of long-term memory, to include working memory, perception, and future thinking. In this article, we review the discoveries and controversies that have characterized this literature and that set the stage for a new conceptualization of the role of the MTL in cognition. This shift toward a more nuanced understanding of MTL function has direct relevance for a range of clinical disorders in which the MTL is implicated, potentially shaping not only theoretical understanding but also clinical practice. (JINS, 2017, 23, 732–740)

Objectives: With comparable baseline performance on executive functions (EF) and memory between Alzheimer’s disease (AD) and behavioral-variant frontotemporal dementia (bvFTD), it is currently unclear if both diseases can be distinguished longitudinally on these measures reliably. Methods: A total of 111 participants (33 AD, 31 bvFTD, and 47 controls) were followed-up annually over a 4-year period and tested on measures of EF, memory, and orientation. Linear mixed-effect models were constructed using disease severity as a nuisance variable to examine profiles of neuropsychological performance decline. Results: At baseline, overlap in terms of cognitive impairment between bvFTD and AD on multiple EF, memory, and orientation measures was present. Longitudinally, only disinhibition (Hayling total errors) appeared sensitive to discriminating AD from bvFTD; however, only after the first annual follow-up. Subgroup analyses on smaller samples revealed comparable profiles on EF tasks at baseline and over time between bvFTD and AD who presented with impaired EF at presentation, and on memory and orientation tasks between AD and bvFTD who presented with severe amnesia. Conclusions: Our results replicate previous findings showing only moderate discriminability between AD and bvFTD at clinical presentation on EF and memory measures. More importantly, we also show that longitudinal trajectories strongly overlap for both dementias on these measures. Disinhibition emerged as the sole measure that in the long run was significantly more impaired in bvFTD. Future studies should use tests designed to target cortical regions that are specifically impaired in bvFTD, such as the ventromedial prefrontal cortex, to improve the accurate discrimination of these diseases. (JINS, 2017, 23, 34–43)