Williams syndrome (WS) is a neurodevelopmental disorder that results from a heterozygous microdeletion on chromosome 7q11.23. Most of the time, the affected region contains ~1.5 Mb of sequence encoding approximately 24 genes. Some 5–8% of patients with WS have a deletion exceeding 1.8 Mb, thereby affecting two additional genes, including GTF2IRD2. Currently, there is no consensus regarding the implications of GTF2IRD2 loss for the neuropsychological phenotype of WS patients. Objectives: The present study aimed to identify the role of GTF2IRD2 in the cognitive, behavioral, and adaptive profile of WS patients. Methods: Twelve patients diagnosed with WS participated, four with GTF2IRD2 deletion (atypical WS group), and eight without this deletion (typical WS group). The age range of both groups was 7–18 years old. Each patient’s 7q11.23 deletion scope was determined by chromosomal microarray analysis. Cognitive, behavioral, and adaptive abilities were assessed with a battery of neuropsychological tests. Results: Compared with the typical WS group, the atypical WS patients with GTF2IRD2 deletion had more impaired visuospatial abilities and more significant behavioral problems, mainly related to the construct of social cognition. Conclusions: These findings provide new evidence regarding the influence of the GTF2IRD2 gene on the severity of behavioral symptoms of WS related to social cognition and certain visuospatial abilities. (JINS, 2018, 24, 896–904)

Objectives: Stroke could lead to deficits in organization of visual search. Cancellation tests are frequently used in standard neuropsychological assessment and appear suitable to measure search organization. The current aim was to evaluate which cognitive functions are associated with cancellation organization measures after stroke. Methods: Stroke patients admitted to inpatient rehabilitation were included in this retrospective study. We performed exploratory factor analyses to explore cognitive domains. A digital shape cancellation test (SC) was administered, and measures of search organization (intersections rate and best r) were computed. The following cognitive functions were measured by neuropsychological testing: neglect (SC, line bisection; LB, Catherine Bergego Scale; CBS, and Balloons Test), visuospatial perception and construction (Rey Complex Figure Test, RCFT), psychomotor speed (Trail Making Test; TMT-A), executive functioning/working memory (TMT-B), spatial planning (Tower Test), rule learning (Brixton Test), short-term auditory memory (Digit Span Forward; DSF), and verbal working memory (Digit Span Backward; DSB). Results: In total, 439 stroke patients were included in our analyses. Four clusters were separated: “Executive functioning” (TMT-A, TMT-B, Brixton Test, and Tower Test), “Verbal memory” (DSF and DSB), “Search organization” (intersections rate and best r), and “Neglect” (CBS, RCFT copy, Balloons Test, SC, and LB). Conclusions: Search organization during cancellation, as measured with intersections rate and best r, seems a distinct cognitive construct compared to existing cognitive domains that are tested during neuropsychological assessment. Administering cancellation tests and analyzing measures of search organization could provide useful additional insights into the visuospatial processes of stroke patients. (JINS, 2018, 24, 424–436)

Objectives: There is increasing evidence of non-motor, sensory symptoms, mainly involving the spatial domain, in cervical dystonia (CD). These manifestations are likely driven by dysfunctional overactivity of the parietal cortex during the execution of a sensory task. Few studies also suggest the possibility that visuospatial attention might be specifically affected in patients with CD. Therefore, we asked whether non-motor manifestations in CD might also comprise impairment of higher level visuospatial processing. Methods: To this end, we investigated visuospatial attention in 23 CD patients and 12 matched healthy controls (for age, gender, education, and ocular dominance). The patients were identified according to the dystonia pattern type (laterocollis vs. torticollis). Overall, participants were right-handers, and the majority of them was right-eye dominant. Visuospatial attention was assessed using a line bisection task. Participants were asked to bisect horizontal lines, using their right or left hand. Results: Participants bisected more to the left of true center when using their left hand to perform the task than when using their right hand. However, overall, torticollis patients produced a significantly greater leftward deviation than controls. Conclusions: These data are consistent with preliminary findings suggesting the presence of biased spatial attention in patients with idiopathic cervical dystonia. The presence of an attentional bias in patients with torticollis seem to indicate that alterations of attentional circuits might be implicated in the pathophysiology of this type of CD. (JINS, 2018, 24, 23–32)

Objectives: The goal of the present study was to elucidate the influence of demographic and neuropathological moderators on the longitudinal trajectory neuropsychological functions during the first year after moderate to severe traumatic brain injury (TBI). In addition to examining demographic moderators such as age and education, we included a measure of whole-brain diffuse axonal injury (DAI), and examined measures of processing speed (PS), executive function (EF), and verbal learning (VL) separately. Methods: Forty-six adults with moderate to severe TBI were examined at 3, 6, and 12 months post-injury. Participants underwent neuropsychological evaluation and neuroimaging including diffusion tensor imaging. Using linear mixed effects modeling, we examined longitudinal trajectories and moderating factors of cognitive outcomes separately for three domains: PS, VL, and EF. Results: VL and EF showed linear improvements, whereas PS exhibited a curvilinear trend characterized by initial improvements that plateaued or declined, depending on age. Age moderated the recovery trajectories of EF and PS. Education and DAI did not influence trajectory but were related to initial level of functioning for PS and EF in the case of DAI, and all three cognitive domains in the case of education. Conclusions: We found disparate recovery trajectories across cognitive domains. Younger age was associated with more favorable recovery of EF and PS. These findings have both clinical and theoretical implications. Future research with a larger sample followed over a longer time period is needed to further elucidate the factors that may influence cognitive change over the acute to chronic period after TBI. (JINS, 2018, 24, 237–246)

Objectives: To test the hypothesis that brain arterial diameters are associated with cognitive performance, particularly in arteries supplying domain-specific territories. Methods: Stroke-free participants in the Northern Manhattan Study were invited to have a brain MRI from 2003–2008. The luminal diameters of 13 intracranial arterial segments were obtained using time-of-flight magnetic resonance angiogram (MRA), and then averaged and normalized into a global score and region-specific arterial diameters. Z-Scores for executive function, semantic memory, episodic memory and processing speed were obtained at MRI and during follow-up. Adjusted generalized additive models were used to assess for associations. Results: Among the 1034 participants with neurocognitive testing and brain MRI, there were non-linear relationships between left anterior (ACA) and middle cerebral artery (MCA) diameter and semantic memory Z-scores (χ2=10.00; DF=3; p=.019), and left posterior cerebral artery (PCA) and posterior communicating artery (Pcomm) mean diameter and episodic memory Z-scores (χ2=9.88; DF=3; p=.020). Among the 745 participants who returned for 2nd neuropsychological testing, on average 5.0±0.4 years after their MRI, semantic memory change was associated non-linearly with the left PCA/Pcomm mean diameter (χ2=13.09; DF=3; p=.004) and with the right MCA/ACA mean diameter (χ2=8.43; DF=3; p=.03). In both cross-sectional and longitudinal analyses, participants with the larger brain arterial diameters had more consistently lower Z-scores and greater decline than the rest of the participants. Conclusions: Brain arterial diameters may have downstream effects in brain function presenting as poorer cognition. Identifying the mechanisms and the directionality of such interactions may increase the understanding of the vascular contribution to cognitive impairment and dementia. (JINS, 2018, 24, 335–346)

Objectives: Concussions affect the processing of emotional stimuli. This study aimed to investigate how sex interacts with concussion effects on early event-related brain potentials (ERP) measures (P1, N1) of emotional facial expressions (EFE) processing in asymptomatic, multi-concussion athletes during an EFE identification task. Methods: Forty control athletes (20 females and 20 males) and 43 multi-concussed athletes (22 females and 21 males), recruited more than 3 months after their last concussion, were tested. Participants completed the Beck Depression Inventory II, the Beck Anxiety Inventory, the Post-Concussion Symptom Scale, and an Emotional Facial Expression Identification Task. Pictures of male and female faces expressing neutral, angry, and happy emotions were randomly presented and the emotion depicted had to be identified as fast as possible during EEG acquisition. Results: Relative to controls, concussed athletes of both sex exhibited a significant suppression of P1 amplitude recorded from the dominant right hemisphere while performing the emotional face expression identification task. The present study also highlighted a sex-specific suppression of the N1 component amplitude after concussion which affected male athletes. Conclusions: These findings suggest that repeated concussions alter the typical pattern of right-hemisphere response dominance to EFE in early stages of EFE processing and that the neurophysiological mechanisms underlying the processing of emotional stimuli are distinctively affected across sex. (JINS, 2018, 24, 1–11)

Objectives: The aim of this study was to investigate alterations in functional connectivity, white matter integrity, and cognitive abilities due to sports-related concussion (SRC) in adolescents using a prospective longitudinal design. Methods: We assessed male high school football players (ages 14–18) with (n=16) and without (n=12) SRC using complementary resting state functional MRI (rs-fMRI) and diffusion tensor imaging (DTI) along with cognitive performance using the Immediate Post-Concussive Assessment and Cognitive Testing (ImPACT). We assessed both changes at the acute phase (<7 days post-SRC) and at 21 days later, as well as, differences between athletes with SRC and age- and team-matched control athletes. Results: The results revealed rs-fMRI hyperconnectivity within posterior brain regions (e.g., precuneus and cerebellum), and hypoconnectivity in more anterior areas (e.g., inferior and middle frontal gyri) when comparing SRC group to control group acutely. Performance on the ImPACT (visual/verbal memory composites) was correlated with resting state network connectivity at both time points. DTI results revealed altered diffusion in the SRC group along a segment of the corticospinal tract and the superior longitudinal fasciculus in the acute phase of SRC. No differences between the SRC group and control group were seen at follow-up imaging. Conclusions: Acute effects of SRC are associated with both hyperconnectivity and hypoconnectivity, with disruption of white matter integrity. In addition, acute memory performance was most sensitive to these changes. After 21 days, adolescents with SRC returned to baseline performance, although chronic hyperconnectivity of these regions could place these adolescents at greater risk for secondary neuropathological changes, necessitating future follow-up. (JINS, 2018, 24, 781–792)

Objectives: People living with HIV (PLWH) are more likely to report sleep difficulties and cognitive deficits. While cognitive impairment associated with sleep problems have been found in healthy and medical populations, less is known about the effects of poor sleep health (SH) on cognition among PLWH. This study examined differences in cognitive performance among participants classified based upon their HIV status and reported SH. Methods: One hundred sixteen (N=116) adults recruited from the Greater Los Angeles community were administered a comprehensive cognitive test battery and completed a questionnaire about SH. Participants were classified into the following HIV/SH groups: [HIV+/good sleep health (SH+; n=34); HIV−/SH+ (n=32); HIV−/poor sleep health (SH−; n=18) and HIV+/SH− (n=32)]. Results: For both HIV+ and HIV− individuals, poor SH was associated with lower cognitive performance, with the domains of learning and memory driving the overall relationship. The HIV+/SH− group had poorer scores in domains of learning and memory compared to the SH+ groups. Additionally, the HIV−/SH− group demonstrated poorer learning compared to the HIV−/SH+ group. Conclusions: Our findings suggest that sleep problems within medical populations are relevant to cognitive functioning, highlighting the clinical and scientific importance of monitoring sleep health and cognition to help identify individuals at greatest risk of poor health outcomes. Longitudinal investigations using both objective and subjective measures of sleep are needed to determine the robustness of the current findings and the enduring effects of poor SH in the context of chronic disease. (JINS, 2018, 24, 1038–1046)

Objectives: Alzheimer’s disease (AD) patients may show the Closing-in (CI), a tendency to reproduce figures close to or superimposed on the model. AD patients with CI might manifest reduced functional independence compared to AD patients without CI, but no study directly assessed if CI can hamper common daily living activities. To address this issue here we investigated whether AD patients with CI veer their walking trajectory toward irrelevant objects more often than AD patients without CI. Methods: Fifty AD individuals, and 20 age- and education-matched healthy adults, underwent a graphic copying task to detect CI and a newly developed walking task to assess the tendency to veer toward irrelevant objects and to bump into them. All participants also completed a comprehensive neuropsychological battery to assess dementia severity; impairments in frontal/executive, visuo-spatial, visuo-constructional, and memory domains; and functional independence in daily living activities. Results: Graphic CI occurred in 34/50 (68%) AD patients (AD-CI group) who achieved significantly lower scores on frontal/executive abilities, and daily living functioning than AD individuals not showing CI. Most AD-CI patients (20/34; 58.8%) also showed at least one veering error in the walking task. Participants with CI and veering errors showed significantly poorer performance on Stroop test, and lower level of functional independence than AD individuals with CI in isolation. Conclusions: CI on graphic tasks can identify difficulties in walking and in complying with everyday activities in AD patients. These observations demonstrate the value of assessing CI in copying tasks. (JINS, 2018, 24, 437–444)

Background: Age and time post-diagnosis can significantly impact cognitive and motor functions in multiple sclerosis (MS); however, studies often fail to account for these factors when assessing differences between disease courses. Objectives: Examine differences between relapsing-remitting and progressive MS in cognition, motor function, and everyday activities, controlling for age, education, and time post-diagnosis. Methods: Twenty-one persons with relapsing-remitting MS (RRMS group), 21 with progressive MS (PMS group), and 21 healthy participants (HCs), matched on age, education, and time post-diagnosis, completed tests of cognitive abilities, motor functions, and everyday functional activities. Results: The two groups with MS did not differ on cognitive performance. Poorer performance in processing speed was noted in both MS groups in comparison with the HC group. Motor function was worse for the PMS group compared with the HC and RRMS groups. The RRMS group showed poorer upper limb functioning compared to the HC group. The PMS group had more difficulty with everyday activities as compared with both the RRMS and HC group. Conclusions: When comparing differences in functioning between MS disease courses, attention should be paid to the demographic characteristics of the samples. (JINS, 2018, 24, 139–146)

Objective: While individuals with 22q11.2 deletion syndrome (22q11DS) are at increased risk for a variety of functional impairments and psychiatric disorders, including psychosis, not all individuals with 22q11DS experience negative outcomes. Efforts to further understand which childhood variables best predict adult functional outcomes are needed, especially those that investigate childhood executive functioning abilities. Methods: This longitudinal study followed 63 individuals with 22q11DS and 43 control participants over 9 years. Childhood executive functioning ability was assessed using both rater-based and performance-based measures and tested as predictors of young adult outcomes. Results: Childhood global executive functioning abilities and parent report of child executive functioning abilities were the most consistent predictors of young adult outcomes. The study group moderated the relationship between child executive functioning and young adult outcomes for several outcomes such that the relationships were stronger in the 22q11DS sample. Conclusion: Rater-based and performance-based measures of childhood executive functioning abilities predicted young adult outcomes in individuals with and without 22q11DS. Executive functioning could be a valuable target for treatment in children with 22q11DS for improving not only childhood functioning but also adult outcomes. (JINS, 2018, 24, 905–916)

Objectives: The aim of this study was to evaluate the impact of computer-assisted “drill-and-strategy” cognitive remediation (CR) for community-dwelling individuals with schizophrenia on cognition, everyday self-efficacy, and independent living skills. Methods: Fifty-six people with schizophrenia or schizoaffective disorder were randomized into CR or computer game (CG) playing (control), and offered twenty 1-hr individual sessions in a group setting over 10 weeks. Measures of cognition, psychopathology, self-efficacy, quality of life, and independent living skills were conducted at baseline, end-group and 3 months following intervention completion. Results: Forty-three participants completed at least 10 sessions and the end-group assessment. Linear mixed-effect analyses among completers demonstrated a significant interaction effect for global cognition favoring CR (p=.028). CR-related cognitive improvement was sustained at 3-months follow-up. At end-group, 17 (77%) CR completers showed a reliable improvement in at least one cognitive domain. A significant time effect was evident for self-efficacy (p=.028) with both groups improving over time, but no significant interaction effect was observed. No significant effects were found for other study outcomes, including the functional measure. Conclusions: Computer-assisted drill-and-strategy CR in schizophrenia improved cognitive test performance, while participation in both CR and CG playing promoted enhancements in everyday self-efficacy. Changes in independent living skills did not appear to result from CR, however. Adjunctive psychosocial rehabilitation is likely necessary for improvements in real-world community functioning to be achieved. (JINS, 2018, 24, 549–562)

Background: Substance dependence is associated with deficits in several areas of executive functioning, such as planning and multitasking. Traditional tests of executive functioning have been criticized for their low ecological validity. Shallice and Burgess (1991) developed the Multiple Errands Test (MET), where participants are required to perform multiple tasks in a real-world setting. In this study, we aimed to adapt the MET for use in populations with substance dependence. Objectives: This study aimed to: (1) examine the applicability of a contextualized version of the Multiple Errands Test, namely, the Multiple Errands Test – Contextualized Version (MET-CV); (2) study the testing context reliability and convergent validity of MET-CV scores; (3) compare the performance of people with substance dependence to a control group. Methods: Data were collected from 60 participants with substance dependence and 30 healthy controls. Both groups performed a neuropsychological assessment, which consisted of the MET-CV and traditional neuropsychological tests (Letter Number Sequencing, Zoo Map Test, Revised Strategy Application Test, Information Sampling Test, Stockings of Cambridge). Results: The MET-CV has adequate testing context reliability and moderate convergent validity relative to traditional planning measures. People with substance dependence (PWSD) showed significant deficits in executive function tests compared to healthy controls, most notably on the MET-CV rather than on traditional neuropsychological tests. Conclusions: The MET-CV can be feasibly applied in the context of therapeutic communities treatment in PWSD. The MET-CV showed adequate reliability and validity, and detected planning deficits in PWSD. (JINS, 2018, 24, 347–359)

Objectives: Agenesis of the corpus callosum (AgCC), characterized by developmental absence of the corpus callosum, is one of the most common congenital brain malformations. To date, there are limited data on the neuropsychological consequences of AgCC and factors that modulate different outcomes, especially in children. This study aimed to describe general intellectual, academic, executive, social and behavioral functioning in a cohort of school-aged children presenting for clinical services to a hospital and diagnosed with AgCC. The influences of age, social risk and neurological factors were examined. Methods: Twenty-eight school-aged children (8 to 17 years) diagnosed with AgCC completed tests of general intelligence (IQ) and academic functioning. Executive, social and behavioral functioning in daily life, and social risk, were estimated from parent and teacher rated questionnaires. MRI findings reviewed by a pediatric neurologist confirmed diagnosis and identified brain characteristics. Clinical details including the presence of epilepsy and diagnosed genetic condition were obtained from medical records. Results: In our cohort, ~50% of children experienced general intellectual, academic, executive, social and/or behavioral difficulties and ~20% were functioning at a level comparable to typically developing children. Social risk was important for understanding variability in neuropsychological outcomes. Brain anomalies and complete AgCC were associated with lower mathematics performance and poorer executive functioning. Conclusions: This is the first comprehensive report of general intellectual, academic, executive social and behavioral consequences of AgCC in school-aged children. The findings have important clinical implications, suggesting that support to families and targeted intervention could promote positive neuropsychological functioning in children with AgCC who come to clinical attention. (JINS, 2018, 24, 445–455)

Objectives: The present study examined the relative contribution of recent or long-term heading to neuropsychological function in amateur adult soccer players. Participants and Methods: Soccer players completed a baseline questionnaire (HeadCount-12m) to ascertain heading during the prior 12 months (long-term heading, LTH) and an online questionnaire (HeadCount-2w) every 3 months to ascertain heading during the prior 2 weeks (recent heading, RH). Cogstate, a battery of six neuropsychological tests, was administered to assess neuropsychological function. Generalized estimating equations were used to test if LTH or RH was associated with neuropsychological function while accounting for the role of recognized concussion. Results: A total of 311 soccer players completed 630 HeadCount-2w. Participants had an average age of 26 years. Participants headed the ball a median of 611 times/year (mean=1,384.03) and 9.50 times/2 weeks (mean=34.17). High levels of RH were significantly associated with reduced performance on a task of psychomotor speed (p=.02), while high levels of LTH were significantly associated with poorer performance on tasks of verbal learning (p=.03) and verbal memory (p=.04). Significantly better attention (p=.02) was detectable at moderately high levels of RH, but not at the highest level of RH. One hundred and seven (34.4%) participants reported a lifetime history of concussion, but this was not related to neuropsychological function and did not modify the association of RH or LTH with neuropsychological function. Conclusion: High levels of both RH and LTH were associated with poorer neuropsychological function, but on different domains. The clinical manifestations following repetitive exposure to heading could change with chronicity of exposure. (JINS, 2018, 24, 147–155)

Objectives: Concussions cause diverse symptoms that are often measured through a single symptom severity score. Researchers have postulated distinct dimensions of concussion symptoms, raising the possibility that total scores may not accurately represent their multidimensional nature. This study examined to what degree concussion symptoms, assessed by the Sport Concussion Assessment Tool 3 (SCAT3), reflect a unidimensional versus multidimensional construct to inform how the SCAT3 should be scored and advance efforts to identify distinct phenotypes of concussion. Methods: Data were aggregated across two prospective studies of sport-related concussion, yielding 219 high school and college athletes in the acute (<48 hr) post-injury period. Item-level ratings on the SCAT3 checklist were analyzed through exploratory and confirmatory factor analyses. We specified higher-order and bifactor models and compared their fit, interpretability, and external correlates. Results: The best-fitting model was a five-factor bifactor model that included a general factor on which all items loaded and four specific factors reflecting emotional symptoms, torpor, sensory sensitivities, and headache symptoms. The bifactor model demonstrated better discriminant validity than the counterpart higher-order model, in which the factors were highly correlated (r=.55–.91). Conclusions: The SCAT3 contains items that appear unidimensional, suggesting that it is appropriate to quantify concussion symptoms with total scores. However, evidence of multidimensionality was revealed using bifactor modeling. Additional work is needed to clarify the nature of factors identified by this model, explicate their clinical and research utility, and determine to what degree the model applies to other stages of injury recovery and patient subgroups. (JINS, 2018, 24, 793–804)

Background: People with relapsing remitting multiple sclerosis (PwRRMS) suffer disproportionate decrements in gait under dual-task conditions, when walking and a cognitive task are combined. There has been much less investigation of the impact of cognitive demands on balance. Objectives: This study investigated whether: (1) PwRRMS show disproportionate decrements in postural stability under dual-task conditions compared to healthy controls, and (2) dual-task decrements are associated with everyday dual-tasking difficulties. The impact of mood, fatigue, and disease severity on dual-tasking was also examined. Methods: A total of 34 PwRRMS and 34 matched controls completed cognitive (digit span) and balance (movement of center of pressure on Biosway on stable and unstable surfaces) tasks under single- and dual-task conditions. Everyday dual-tasking was measured using the Dual-Tasking Questionnaire. Mood was measured by the Hospital Anxiety & Depression Scale. Fatigue was measured via the Modified Fatigue Index Scale. Results: No differences in age, gender, years of education, estimated pre-morbid IQ, or baseline digit span between groups. Compared with controls, PwRRMS showed significantly greater decrement in postural stability under dual-task conditions on an unstable surface (p=.007), but not a stable surface (p=.679). Balance decrement scores were not correlated with everyday dual-tasking difficulties or fatigue. Stable surface balance decrement scores were significantly associated with levels of anxiety (rho=0.527; p=.001) and depression (rho=0.451; p=.007). Conclusions: RRMS causes dual-tasking difficulties, impacting balance under challenging conditions, which may contribute to increased risk of gait difficulties and falls. The relationship between anxiety/depression and dual-task decrement suggests that emotional factors may be contributing to dual-task difficulties. (JINS, 2018, 24, 247–258)

Objectives: Cognitive reserve (CR), defined as individual differences in the ability to cope with brain damage, seem to be associated to the several psychopathological features in psychiatric patients, such as the functional outcome. This study aims to identify different profiles of CR by combining intelligence quotient (IQ) and premorbid functioning, two measures independently associated to CR in previous works, as well as to explore CR effect on both Theory of Mind (ToM) baseline performance and improvement after socio-cognitive trainings. Methods: Sixty patients with chronic schizophrenia underwent a socio-cognitive rehabilitation. All patients were assessed for psychopathology, neurocognition, and ToM at baseline and post-treatment. CR profiles were explored with K-means cluster analysis, while differences between clusters in both baseline assessments and post-treatment ToM improvement, were analyzed by means of analysis of variance and repeated measures analysis of covariance. Results: The analysis revealed three CR profiles, respectively, characterized by low early premorbid functioning and mild intellectual impairment, average/high early premorbid functioning trend with moderate intellectual impairment and good early premorbid functioning associated to IQ within normal limits. Analyses showed a significant effect of CR on both baseline ToM performance and treatment outcome: patients with higher CR reached significantly better ToM scores. Conclusions: These results underline the clinical relevance of defining CR profiles of patients to customize trainings: subjects with a lower CR may benefit from more intensive programs. A deeper knowledge about CR may considerably increase our understanding of individual differences and thus potentiate treatment outcome. (JINS, 2018, 24, 563–571)

Objectives: Deficits in semantic verbal fluency (SVF) can stem from dysfunction of an executive control system and/or of semantic knowledge. Previous analyses of SVF responses were devised to characterize these two components including switching and mean cluster size (MCS) indices, but these rely on subjective experimenter-based assessment of the words’ relatedness. To address this limitation, computational data-driven SVF indices have been developed. Our aim is to assess the validity and usefulness of these automated indices in the context of cognitive decline in Parkinson’s disease (PD). Methods: This is a retrospective study including 50 advanced PD patients with (n=28) or without (n=22) mild cognitive impairment (PD-MCI). We analyzed animal SVF outputs using an automated computational approach yielding switching, MCS, and cumulative relatedness (CuRel) indices. We compared these indices to the classic experimenter-based switching and MCS indices to assess concurrent validity, and against neuropsychological measures of executive functioning and semantic knowledge to assess construct validity. We also examined whether these indices were impaired and predicted PD-MCI. Results: Automated switching indices, but not MCS or CuRel, showed evidence of concurrent and construct validity, and characterized individual difference in advanced PD. Automated switching indices also outperformed the experimenter-dependent index in predicting the presence of PD-MCI. Conclusion: Computational methods hold promise as fine-grained, unbiased indices reflecting the executive component of SVF, but none of the methods provided valid measures of semantic knowledge in PD. Our data also confirm that SVF are not adequate tests of semantic memory in patients with executive dysfunction such as PD. (JINS, 2018, 24, 1047–1056)

Background: Diagnosis of mild cognitive impairment in Parkinson’s disease (PD) is relevant because it is a marker for evolution to dementia. However, the selection of suitable tests to evaluate separate cognitive domains in mild cognitive impairment related to PD remains an open question. The current work aims to investigate the neuroanatomical correlates of several visuospatial/visuoperceptual tests using the same sample and a multimodal MRI approach. Methods: The study included 36 PD patients and 20 healthy subjects matched for age, sex, and education. The visuospatial/visuoperceptual tests selected were: Pentagon Copying Test (PCT), Judgment of Line Orientation Test (JLOT), Visual Form Discrimination Test (VFDT), Facial Recognition Test (FRT), Symbol Digit Modalities Test (SMDT), and clock copying task (CLOX2). FreeSurfer was used to assess cortical thickness, and tract-based spatial statistics was used for fractional anisotropy analysis. Results: Lower performance in the PCT, JLOT, and SDMT was associated with extensive cortical thickness reductions in lateral parietal and temporal regions. VFDT and CLOX2 did not show this common pattern and correlated with more limited medial occipito-temporal and occipito-parietal regions. Performance in all visuospatial/visuoperceptual tests correlated with fractional anisotropy in the corpus callosum. Conclusions: Our findings show that JLOT, SDMT, and PCT, in addition to differentiating patients from controls, are suitable visuospatial/visuoperceptual tests to reflect cortical thinning in lateral temporo-parietal regions in PD patients. We did not observe the dissociation between dorsal and ventral streams that was expected according to the neuropsychological classification of visuospatial and visuoperceptual tests. (JINS, 2018, 24, 33–44)