Search

BackgroundCognitive alterations are a central and heterogeneous trait in psychotic disorders, driven by environmental, familial and illness-related factors. In this study, we aimed to prospectively investigate the impact of high familial risk for cognitive alterations, unconfounded by illness-related factors, on symptomatic outcomes in patients.MethodsIn total, 629 probands with non-affective psychosis and their sibling not affected by psychosis were assessed at baseline, 3- and 6-year follow-up. Familial cognitive risk was modeled by three cognitive subtypes (‘normal’, ‘mixed’ and ‘impaired’) in the unaffected siblings. Generalized linear mixed models assessed multi-cross-sectional associations between the sibling cognitive subtype and repeated measures of proband symptoms across all assessments. Between-group differences over time were assessed by adding an interaction effect of time and sibling cognitive subtype.ResultsProbands affected by psychosis with a sibling of the impaired cognitive subtype were less likely to be in symptomatic remission and showed more disorganization across all time points. When assessing differences over time, probands of siblings with the impaired cognitive subtype showed less remission and less improvement of disorganization after 3 and 6 years relative to the other subtypes. They also showed less reduction of positive, negative and excitement symptoms at 6-year follow-up compared to probands with a sibling of the normal cognitive subtype.ConclusionsCross-sibling pathways from higher levels of familial cognitive vulnerability to worse long-term outcomes may be informative in identifying cognition-related environmental and genetic risks that impact psychotic illness heterogeneity over time.

Introduction Phenylketonuria (PKU) is a rare, treatable inborn error of metabolism with frequent neurological and neuropsychiatric complications, especially in undiagnosed or insufficiently treated individuals. Given the wide range of clinical presentations and the importance of treatment implications, we here delineate the neurological and neuropsychiatric symptom spectrum in a large cohort of previously unreported adults with late-treated PKU. Methods We consecutively evaluated late-treated PKU cases and pooled clinical and paraclinical data, including video-material, from three centers with expertise in complex movement disorders, inborn errors of metabolism and pediatrics. Results 26 individuals were included (10 females, median age 52 years). Developmental delay and intellectual disability were omnipresent with severe impairment of expressive communication noted in 50% of cases. Movement disorders were prevalent (77%), including tremor (38%, mostly postural), stereotypies (38%), and tics (19%). One case had neurodegenerative levodopa-responsive parkinsonism. Mild ataxia was noted in 54% of cases and 31% had a history of seizures. Neuropsychiatric characteristics included obsessive-compulsive (35%) and self-injurious behaviors (31%), anxiety (27%), depression (19%) and features compatible with those observed in individuals with autism spectrum disorder (19%). Neuroimaging revealed mild white matter changes. Adherence to dietary treatment was inconsistent in the majority of cases, particularly throughout adolescence. Conclusion A history of movement disorders, particularly tremor, stereotypies and tics, in the presence of developmental delay, intellectual disability and neuropsychiatric features, such as obsessive-compulsive and self-injurious behaviors in adults should prompt the diagnostic consideration of PKU. Initiation and adherence to (dietary) treatment can ameliorate the severity of these symptoms.

This study aimed to examine the relationship between gender, anxiety, mindfulness, and theory of mind (ToM). It was also aimed to investigate the mediating role of mindfulness in the relationship between anxiety and ToM. Additionally, the moderating role of gender in the relevant relationships was examined. The sample consisted of 323 people, including 260 (80.5%) females and 63 (19.5%) males, aged between 18-62 years. Data were collected by the Reading the Mind in the Eyes Test, the State-Trait Anxiety Inventory II, and the Mindful Attention Awareness Scale. It was found that ToM and anxiety levels were statistically significantly higher in women than men. In the regression analysis, it was detected that mindfulness predicts the 7% variance in ToM. The second predictor of ToM was found as anxiety, and both predictors explained the 9% variance in ToM. In the mediating analysis, it was found that mindfulness has a mediating role in the relationship between anxiety and ToM. In the moderated mediation analysis, it was determined that the pathway between anxiety and ToM was moderated by gender; the moderating role of gender also was found between mindfulness and ToM. In light of these findings, experimental future studies can be suggested with clinical samples for a better understanding of the relationships between gender, anxiety, mindfulness, and ToM.

Developmental dyslexia (DD) is the most prevalent neurodevelopmental disorder with a substantial negative influence on the individual's academic achievement and career. Research on its neuroanatomical origins has continued for half a century, yielding, however, inconsistent results, lowered total brain volume being the most consistent finding. We set out to evaluate the grey matter (GM) volume and cortical abnormalities in adult dyslexic individuals, employing a combination of whole-brain voxel- and surface-based morphometry following current recommendations on analysis approaches, coupled with rigorous neuropsychological testing. Whilst controlling for age, sex, total intracranial volume, and performance IQ, we found both decreased GM volume and cortical thickness in the left insula in participants with DD. Moreover, they had decreased GM volume in left superior temporal gyrus, putamen, globus pallidus, and parahippocampal gyrus. Higher GM volumes and cortical thickness in these areas correlated with better reading and phonological skills, deficits of which are pivotal to DD. Crucially, total brain volume did not influence our results, since it did not differ between the groups. Our findings demonstrating abnormalities in brain areas in individuals with DD, which previously were associated with phonological processing, are compatible with the leading hypotheses on the neurocognitive origins of DD. Developmental dyslexia (DD) is the most prevalent neurodevelopmental disorder with a substantial negative influence on the individual's academic achievement and career. Research on its neuroanatomical origins has continued for half a century, yielding, however, inconsistent results, lowered total brain volume being the most consistent finding. We set out to evaluate the grey matter (GM) volume and cortical abnormalities in adult dyslexic individuals, employing a combination of whole-brain voxel- and surface-based morphometry following current recommendations on analysis approaches, coupled with rigorous neuropsychological testing. Whilst controlling for age, sex, total intracranial volume, and performance IQ, we found both decreased GM volume and cortical thickness in the left insula in participants with DD. Moreover, they had decreased GM volume in left superior temporal gyrus, putamen, globus pallidus, and parahippocampal gyrus. Higher GM volumes and cortical thickness in these areas correlated with better reading and phonological skills, deficits of which are pivotal to DD. Crucially, total brain volume did not influence our results, since it did not differ between the groups. Our findings demonstrating abnormalities in brain areas in individuals with DD, which previously were associated with phonological processing, are compatible with the leading hypotheses on the neurocognitive origins of DD.

The kappa opioid receptor (KOP) system modulates social play responding, however a paucity of studies have examined effects on social motivation and cognition in the absence of play. Prenatal exposure to the anti epileptic and mood stabiliser valproic acid (VPA) is associated with impaired social responding and altered gene expression of KOP (oprk1) and dynorphin (pdyn) in several brain regions. The present study examined if pharmacological modulation of KOP altered social motivation and cognition, immediate early gene (IEG) and oprk1-pdyn expression in adolescent male rats and rats prenatally exposed to VPA. In control rats, the KOP antagonist DIPPA enhanced sociability, while both DIPPA and the KOP agonist U50488 decreased social novelty preference. In rats exposed prenatally to VPA, neither U50488 nor DIPPA altered sociability or social novelty preference. Analysis of IEG expression revealed that DIPPA reduced expression of egr-1 expression in the prefrontal cortex of control rats and U50488 increased junb expression in the PFC of both control and VPA-exposed rats. VPA-exposed rats exhibited increased expression of oprk1 and pdyn in the prefrontal cortex and amygdala compared with control rats. DIPPA and U50488 increased oprk1 expression in the amygdala of control rats and decreased oprk1 expression in the prefrontal cortex of VPA-exposed rats. Taken together, these data demonstrate that pharmacological modulation of the KOP system alters social motivation and cognition in control rats, an effect not observed in rats prenatally exposed to VPA. These data provide support that prenatal exposure to VPA is associated with alterations in the expression and functionality of KOP system. (C) 2020 The Author(s). Published by Elsevier Ltd on behalf of IBRO. The authors would like to thank Sonali Aggarwa1, Morgane Clarke and Patricia Calcagno for their technical assistance with experimental procedures. This study was supported by funding from Alkermes Inc (US) and Science Foundation Ireland (14/SPP/B3051) peer-reviewed

ObjectiveTo investigate the association between facial affect recognition (FAR) and type of adverse childhood experiences (ACEs) in a sample of clinical high risk (CHR) individuals and a matched sample of healthy controls (HCs).MethodsIn total, 309 CHR individuals and 51 HC were recruited as part of an European Union-funded multicenter study (EU-GEI) and included in this work. During a 2-year follow-up period, 65 CHR participants made a transition to psychosis (CHR-T) and 279 did not (CHR-NT). FAR ability was measured using a computerized version of the Degraded Facial Affect Recognition (DFAR) task. ACEs were measured using the Childhood Experience of Care and Abuse Questionnaire, the Childhood Trauma Questionnaire, and the Bullying Questionnaire. Generalized regression models were used to investigate the relationship between ACE and FAR. Logistic regressions were used to investigate the relationship between FAR and psychotic transition.ResultsIn CHR individuals, having experienced emotional abuse was associated with decreased total and neutral DFAR scores. CHR individuals who had experienced bullying performed better in the total DFAR and in the frightened condition. In HC and CHR, having experienced the death of a parent during childhood was associated with lower DFAR total score and lower neutral DFAR score, respectively. Analyses revealed a modest increase of transition risk with increasing mistakes from happy to angry faces.ConclusionsAdverse experiences in childhood seem to have a significant impact on emotional processing in adult life. This information could be helpful in a therapeutic setting where both difficulties in social interactions and adverse experiences are often addressed.

Contains fulltext : 222308.pdf (Publisher’s version ) (Open Access) Neurocognitive symptoms are common in individuals with somatic symptom and related disorders (SSRD), but little is known about the specific impairments in neurocognitive domains in patients with conversion disorder (CD)/functional neurological disorder (FND). This study examines neurocognitive functioning in patients with CD/FND compared to patients with other SSRD. The sample consisted of 318 patients. Twenty-nine patients were diagnosed with CD/FND, mean age 42.4, standard deviation (SD) = 13.8 years, 79.3% women, and 289 patients had other SSRD (mean age 42.1, SD = 13.3, 60.2% women). Patients completed a neuropsychological test battery that addressed a broad range of neurocognitive domains, including information processing speed, attention and executive functioning. Patients with CD/FND had clinically significant neurocognitive deficits in all neurocognitive domains based on normative data comparison. Patients with CD/FND also performed significantly worse than patients with other SSRD on information processing speed (Digit Symbol Substitution Test (V = .115, p = .035), Stroop Color-Word Test (SCWT) card 1 (V = .190, p = .006), and SCWT card 2 (V = .244, p

In healthy participants, the strength of task-evoked network reconfigurations is associated with cognitive performance across several cognitive domains. It is, however, unclear whether the capacity for network reconfiguration also plays a role in cognitive deficits in brain tumor patients. In the current study, we examined whether the level of reconfiguration of the fronto-parietal (‘FPN’) and default mode network (‘DMN’) during task execution is correlated with cognitive performance in patients with different types of brain tumors. For this purpose, we combined data from a resting state and task-fMRI paradigm in patients with a glioma or meningioma. Cognitive performance was measured using the in-scanner working memory task, as well as an out-of-scanner cognitive flexibility task. Task-evoked changes in functional connectivity strength (defined as the mean of the absolute values of all connections) and in functional connectivity patterns within and between the FPN and DMN did not differ significantly across meningioma and fast (HGG) and slowly growing glioma (LGG) patients. Across these brain tumor patients, a significant and positive correlation was found between the level of task-evoked reconfiguration of the FPN and cognitive performance. This suggests that the capacity for FPN reconfiguration also plays a role in cognitive deficits in brain tumor patients, as was previously found for normal cognitive performance in healthy controls.

Background: Social amotivation is a core element of the negative symptoms of schizophrenia. However, it is still largely unknown which neural substrates underpin social amotivation in people with schizophrenia, though deficiencies in the mesocorticolimbic dopamine system have been proposed.Methods: We examined the association between social amotivation and substantia nigra/ventral tegmental area-seeded intrinsic connectivity in 84 people with schizophrenia using resting state functional magnetic resonance imaging.Results: Spontaneous fluctuations of midbrain dopaminergic regions were positively associated with striatal and prefrontal fluctuations in people with schizophrenia. Most importantly, social amotivation was negatively associated with functional connectivity between the midbrain's substantia nigra/ventral tegmental area and medial-and lateral prefrontal cortex, the temporoparietal junction, and dorsal and ventral striatum. These associations were observed independently of depressive and positive symptoms.Conclusions: Our findings suggest that social amotivation in people with schizophrenia is associated with altered intrinsic connectivity of mesocorticolimbic pathways linked to cognitive control and reward processing. Dysconnectivity of dopaminergic neuronal ensembles that are fundamental to approach behavior and motivation may help explain the lack of initiative social behavior in people with social amotivation. (C) 2019 Elsevier B.V. All rights reserved.

BackgroundMotivational deficits in people with schizophrenia (PSZ) are associated with an inability to integrate the magnitude and probability of previous outcomes. The mechanisms that underlie probability-magnitude integration deficits, however, are poorly understood. We hypothesized that increased reliance on “value-less” stimulus-response associations, in lieu of expected value (EV)-based learning, could drive probability-magnitude integration deficits in PSZ with motivational deficits.MethodsHealthy volunteers (n= 38) and PSZ (n=49) completed a reinforcement learning paradigm consisting of four stimulus pairs. Reward magnitude (3/2/1/0 points) and probability (90%/80%/20%/10%) together determined each stimulus’ EV. Following a learning phase, new and familiar stimulus pairings were presented. Participants were asked to select stimuli with the highest reward value.ResultsPSZ with high motivational deficits made increasingly less optimal choices as the difference in reward value (probability*magnitude) between two competing stimuli increased. Using a previously-validated computational hybrid model, PSZ relied less on EV (“Q-learning”) and more on stimulus-response learning (“actor-critic”), which correlated with SANS motivational deficit severity. PSZ specifically failed to represent reward magnitude, consistent with model demonstrations showing that response tendencies in the actor-critic were preferentially driven by reward probability. ConclusionsProbability-magnitude deficits in PSZ with motivational deficits arise from underutilization of EV in favor of reliance on value-less stimulus-response associations. Consistent with previous work and confirmed by our computational hybrid framework, probability-magnitude integration deficits were driven specifically by a failure to represent reward magnitude. This work reconfirms the importance of decreased Q-learning/increased actor-critic-type learning as an explanatory framework for a range of EV deficits in PSZ.

Childhood and adolescence represent sensitive developmental periods for brain networks implicated in a range of complex skills, including executive functions (EF; inhibitory control, working memory, and cognitive flexibility). As a consequence, these skills may be particularly vulnerable to injuries sustained during these sensitive developmental periods. The present study investigated 1) whether age at injury differentially affects EF 6 months and 2 years after TBI in children aged 5-15 years, and 2) whether the association between brain lesions and EF depend on age at injury. Children with TBI (n = 105) were categorized into four age-at-injury groups based on previous studies and proposed timing of cerebral maturational spurts: early childhood (5-6 years, n = 14), middle childhood (7-9 years, n = 24), late childhood (10-12 years, n = 52), and adolescence (13-15 years, n = 15). EF were assessed with performance-based tasks and a parent-report of everyday EF. TBI patients' EF scores 6 months and 2 years post-injury were compared to those of typically developing (TD) controls (n = 42). Brain lesions were identified using susceptibility weighted imaging (SWI). Results indicated that inhibitory control performance 2 years post-injury was differentially affected by the impact of TBI depending on age at injury. Follow-up analyses did not reveal significant differences within the age groups, preventing drawing strong conclusions regarding the contribution of age at injury to EF outcome after TBI. Tentatively, large effect sizes suggest that vulnerability is most apparent in early childhood and adolescence. Everyday inhibitory control behaviour was worse for children with TBI than TD children across childhood and adolescence at the 2-year assessment. There was no evidence for impairment in working memory or cognitive flexibility after TBI at the group level. Given small group sizes, findings from analyses into correlations between EF and SWI lesions should be interpreted with caution. Extent, number and volume of brain lesions correlated with adolescent everyday EF behaviour 6 months post-injury. Taken together, the results emphasize the need for long-term follow-up after paediatric TBI during sensitive developmental periods given negative outcomes 2-year post injury. Inhibitory control seems to be particular vulnerable to the impact of TBI. Findings of associations between EF and SWI lesions need to be replicated with larger samples.

Background: The extent of radiation therapy (RT)-induced changes in cognitive function is unknown. RT with protons instead of photons spares the healthy brain tissue more and is believed to reduce the risk of cognitive dysfunction. There is modest knowledge on which parts of the brain we need to spare, to prevent cognitive dysfunction. To uncover which cognitive domains is most affected, we compared cognitive functioning in brain tumor patients treated with neurosurgery and RT with brain tumor patients treated with neurosurgery alone. Methods: A cross-sectional study assessing cognitive function in 110 patients with a primary brain tumor grades I-III or medulloblastoma (grade IV) treated at Aarhus University Hospital (AUH), Denmark between 2006 and 2016. Two cohorts were established: a cohort of 81 brain tumor patients who had received neurosurgery followed by RT (RT+), and a cohort of 29 brain tumor patients who had only received neurosurgery (RT-). The patients underwent questionnaires and neuropsychological assessment with standardized tests. Results: Mean age was 53.5 years with an average time since diagnosis of 7.3 years. Compared with normative data, lower average scores were observed for the entire group on domains concerning of verbal learning and memory ( p

OBJECTIVE: The Self-Awareness in Daily Life-3 Scale (SADL-3) was designed to assess self-awareness in the chronic phase after acquired brain injury (ABI). The main objective was to evaluate its feasibility and usability for clinical practice, reliability and validity.METHODS: Participants were 89 patients with ABI. SADL-3 core distributions, floor and ceiling effects and percentage of missing items were used. Ratings made by two staff members and ratings at two time points were compared. SADL-3 ratings were compared with Awareness Questionnaire (AQ) ratings, Patient Competency Rating Scale (PCRS) ratings, and ratings made on the Clinician's Rating Scale for evaluating Impaired Self-Awareness and Denial of Disability (CRS-ISA-DD). Staff members completed a questionnaire concerning the usability of the SADL-3.RESULTS: No floor or ceiling effects were present. Results show sufficient inter-rater reliability (ICC > .40), acceptable test-retest reliability (ρs > .75) and sufficient convergent validity (ρs > .30). The median administration time was 15 minutes (SD = 21.2). Most staff members rated the SADL-3 as fairly easy to very easy to complete.CONCLUSIONS: The SADL-3 is a brief scale with sufficient psychometric properties. Teams can use it in clinical practice to identify patients' self-awareness in the chronic phase after ABI.

BACKGROUND: A relationship between motor performance and cognitive functioning is increasingly being recognized. Yet, little is known about the precise nature of the relationship between both domains, especially in early childhood.AIMS: To identify distinct constellations of motor performance, executive functioning (EF), and verbal ability in preschool aged children; and to explore how individual and contextual variables are related to profile membership.METHODS AND PROCEDURES: The sample consisted of 119 3- to 4-year old children (62 boys; 52%). The home based assessments consisted of a standardized motor test (Movement Assessment Battery for Children - 2), five performance-based EF tasks measuring inhibition and working memory, and the Receptive Vocabulary subtest from the Wechsler Preschool and Primary Scale of Intelligence Third Edition. Parents filled out the Behavior Rating Inventory of Executive Function - Preschool version. Latent profile analysis (LPA) was used to delineate profiles of motor performance, EF, and verbal ability. Chi-square statistics and multinomial logistic regression analysis were used to examine whether profile membership was predicted by age, gender, risk of motor coordination difficulties, ADHD symptomatology, language problems, and socioeconomic status (SES).OUTCOMES AND RESULTS: LPA yielded three profiles with qualitatively distinct response patterns of motor performance, EF, and verbal ability. Quantitatively, the profiles showed most pronounced differences with regard to parent ratings and performance-based tests of EF, as well as verbal ability. Risk of motor coordination difficulties and ADHD symptomatology were associated with profile membership, whereas age, gender, language problems, and SES were not.CONCLUSIONS AND IMPLICATIONS: Our results indicate that there are distinct subpopulations of children who show differential relations with regard to motor performance, EF, and verbal ability. The fact that we found both quantitative as well as qualitative differences between the three patterns of profiles underscores the need for a person-centered approach with a focus on patterns of individual characteristics.

Background Fetal alcohol spectrum disorders (FASD) is a group of conditions resulting from prenatal alcohol exposure (PAE). Patients with FASD experience a variety of neuropsychological symptoms resulting from central nervous system impairment. Little is known about sleep disorders associated with PAE. The objective of this study was to investigate sleep problems related to FASD. Methods Forty patients (median age 8 years (6; 11)) diagnosed with FASD and forty typically developing children (median age 10 years (8; 13)) were recruited for the 1st phase of the study. In the 1st phase, the screening of sleep problems was performed with Child Sleep Habit Questionnaire (CSHQ) filled in by a caregiver. Those of the FASD group who scored above 41 points were qualified to the 2nd phase of the study and had an in-lab attended polysomnography (PSG) performed. The measurements consisted of electroencephalogram, electrooculograms, chin and tibial electromyogram, electrocardiogram, ventilatory monitoring, breathing effort, pulse oximetry, snoring and body position. Their results were compared to PSG laboratory reference data. Results The number of participants with sleep disturbances was markedly higher in the FASD group as compared to typically developing children (55% vs. 20%). The age-adjusted odds ratio for a positive result in CSHQ was 4.31 (95% CI: 1.54–12.11; p = 0.005) for FASD patients as compared to the control group. Significant differences between the FASD as compared to the typically developing children were observed in the following subscales: sleep onset delay, night wakings, parasomnias, sleep disordered breathing, and daytime sleepiness. Children from the FASD group who underwent PSG experienced more arousals during the sleep as compared with the PSG laboratory reference data. The respiratory indices in FASD group appear higher than previously published data from typically developing children. Conclusion The results support the clinical observation that sleep disorders appear to be an important health problem in individuals with FASD. In particular distorted sleep architecture and apneic/hypopneic events need further attention.

Funding Information: We thank Suvi Lehto for helping with the MEG recordings. This study was supported by the Sigrid Juselius foundation and the Academy of Finland to S.P. (SA 266402, SA 273807) and J.M.P. (SA 253130), and Oskar Öflund Foundation to H.J. Publisher Copyright: © 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved. Amblyopia is a developmental disorder associated with abnormal visual experience during early childhood commonly arising from strabismus and/or anisometropia and leading to dysfunctions in visual cortex and to various visual deficits. The different forms of neuronal activity that are attenuated in amblyopia have been only partially characterized. In electrophysiological recordings of healthy human brain, the presentation of visual stimuli is associated with event-related activity and oscillatory responses. It has remained poorly understood whether these forms of activity are reduced in amblyopia and whether possible dysfunctions would arise from lower- or higher-order visual areas. We recorded neuronal activity with magnetoencephalography (MEG) from anisometropic amblyopic patients and control participants during two visual tasks presented separately for each eye and estimated neuronal activity from source-reconstructed MEG data. We investigated whether event-related and oscillatory responses would be reducedfor amblyopia and localized their cortical sources. Oscillation amplitudes and evoked responses were reduced for stimuli presented to the amblyopic eye in higher-order visual areas and in parietal and prefrontal cortices. Importantly, the reduction of oscillation amplitudes but not that of evoked responses was correlated with decreased visual acuity in amblyopia. These results show that attenuated oscillatory responses are correlated with visual deficits in anisometric amblyopia.

Although mentalization is important in somatic symptom disorder (SSD) and major depressive disorder (MDD), it is not fully understood. In this study, we aimed to investigate the relation between somatic and depressive symptoms with mentalization. A total of 48 patients diagnosed with SSD, 50 patients diagnosed with MDD, and 50 healthy individuals, participated the study. The Montgomery-Asperg Depression Scale, Symptom Checklist-90 Revised, and Reading the Mind in the Eyes Test (RMET) were applied to the participants. The patients with SSD showed significantly the lowest performance of theory of mind. There was no significant difference between MDD and healthy controls. High somatization score was found to be a predictor for low RMET scores (95% confidence interval, -0.339; p = 0.014). Mentalization deficit seems to be associated with somatization rather than depression.

Objective In spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD), the expanded cytosine adenine guanine (CAG) repeat in ATXN3 is the causal mutation, and its length is the main factor in determining the age at onset (AO) of clinical symptoms. However, the contribution of the expanded CAG repeat length to the rate of disease progression after onset has remained a matter of debate, even though an understanding of this factor is crucial for experimental data on disease modifiers and their translation to clinical trials and their design. Methods Eighty-two Dutch patients with SCA3/MJD were evaluated annually for 15 years using the International Cooperative Ataxia Rating Scale (ICARS). Using linear growth curve models, ICARS progression rates were calculated and tested for their relation to the length of the CAG repeat expansion and to the residual age at onset (RAO): The difference between the observed AO and the AO predicted on the basis of the CAG repeat length. Results On average, ICARS scores increased 2.57 points/year of disease. The length of the CAG repeat was positively correlated with a more rapid ICARS progression, explaining 30% of the differences between patients. Combining both the length of the CAG repeat and RAO as comodifiers explained up to 47% of the interpatient variation in ICARS progression. Interpretation Our data imply that the length of the expanded CAG repeat in ATXN3 is a major determinant of clinical decline, which suggests that CAG-dependent molecular mechanisms similar to those responsible for disease onset also contribute to the rate of disease progression in SCA3/MJD. ANN NEUROL 2021;89:66-73.

Objective This study was undertaken to analyze longitudinal changes of retinal thickness and their predictive value as biomarkers of disease progression in idiopathic Parkinson's disease (iPD). Methods Patients with Lewy body diseases were enrolled and prospectively evaluated at 3 years, including patients with iPD (n = 42), dementia with Lewy bodies (n = 4), E46K-SNCA mutation carriers (n = 4), and controls (n = 17). All participants underwent Spectralis retinal optical coherence tomography and Montreal Cognitive Assessment, and Unified Parkinson's Disease Rating Scale score was obtained in patients. Macular ganglion cell-inner plexiform layer complex (GCIPL) and peripapillary retinal nerve fiber layer (pRNFL) thickness reduction rates were estimated with linear mixed models. Risk ratios were calculated to evaluate the association between baseline GCIPL and pRNFL thicknesses and the risk of subsequent cognitive and motor worsening, using clinically meaningful cutoffs. Results GCIPL thickness in the parafoveal region (1- to 3-mm ring) presented the largest reduction rate. The annualized atrophy rate was 0.63 mu m in iPD patients and 0.23 mu m in controls (p < 0.0001). iPD patients with lower parafoveal GCIPL and pRNFL thickness at baseline presented an increased risk of cognitive decline at 3 years (relative risk [RR] = 3.49, 95% confidence interval [CI] = 1.10-11.1, p = 0.03 and RR = 3.28, 95% CI = 1.03-10.45, p = 0.045, respectively). We did not identify significant associations between retinal thickness and motor deterioration. Interpretation Our results provide evidence of the potential use of optical coherence tomography-measured parafoveal GCIPL thickness to monitor neurodegeneration and to predict the risk of cognitive worsening over time in iPD This study was cofunded by the Michael J. Fox Foundation (RRIA [Rapid Response Innovation Awards] 2014 Program, grant ID: 10189), the Carlos III Health Institute, and the European Union (ERDF/ESF, "A Way to Make Europe"/"Investing in Your Future") through the projects PI14/00679 and PI16/00005; the Juan Rodes grant JR15/00008 (I.G.); and the Department of Health of the Basque Government through the projects 2016111009 and 2020333033. We thank all the patients and participants involved in the study.

The relative lack of sensitive and clinically valid tests of rodent behavior might be one of the reasons for the limited success of the clinical translation of preclinical Alzheimer's disease (AD) research findings. There is a general interest in innovative behavioral methodology, and protocols have been proposed for touchscreen operant chambers that might be superior to existing cognitive assessment methods. We assessed and analyzed touchscreen performance in several novel ways to examine the possible occurrence of early signs of prefrontal (PFC) functional decline in the APP/PS1 mouse model of AD. Touchscreen learning performance was compared between APP/PS1-21 mice and wildtype littermates on a C57BL/6J background at 3, 6 and 12 months of age in parallel to the assessment of spatial learning, memory and cognitive flexibility in the Morris water maze (MWM). We found that older mice generally needed more training sessions to complete the touchscreen protocol than younger ones. Older mice also displayed defects in MWM working memory performance, but touchscreen protocols detected functional changes beginning at 3 months of age. Histological changes in PFC of APP/PS1 mice indeed occurred as early as 3 months. Our results suggest that touchscreen operant protocols are more sensitive to PFC dysfunction, which is of relevance to the use of these tasks and devices in preclinical AD research and experimental pharmacology. ispartof: GENES BRAIN AND BEHAVIOR vol:20 issue:1 ispartof: location:England status: published

Alzheimer's disease (AD) is the most common form of dementia, impacting global cognitive performance, including episodic memory. Semantic clustering is a learning strategy involving grouping words of similar meaning and can improve episodic memory performance, e.g., list learning. As the APOE ε4 allele is the most validated genetic risk factor for AD, we predicted that its presence would be associated with poorer list learning performance, and we hypothesized that semantic clustering moderates or mediates this association. The sample comprised 699 healthy older adults participating in the CHARIOT PRO Main Study, 169 of whom were APOE ε4 carriers. Participants' ability to form groups of related stimuli (assessed via a categorization task, CAT), and their use of semantic clustering during list learning, were investigated using the Neuropsychological Assessment Battery (NAB). CAT scores predicted the use of semantic clustering in, and performance on, the list learning task. CAT scores were not significantly lower in APOE ε4 carriers, suggesting that the ability to categorize was preserved. However, APOE ε4 carriers made less use of semantic clustering in list learning. Semantic clustering use partially mediated the relationship between CAT scores and list learning performance, and, in women only, moderated the impact of APOE ε4 on list learning performance. The results suggest that better categorization ability is associated with greater use of mnemonic strategies and better performance on memory tasks regardless of genetic risk, but that APOE ε4 carriers make less use of such strategies. Furthermore, female APOE ε4 carriers may benefit more than their non-carriers from using semantic clustering to aid list learning. Thus, semantic clustering may be a contributing factor of their "cognitive reserve", compensating for potential deficits in episodic memory.

OBJECTIVE: To evaluate the relationship between age at seizure onset and neurodevelopmental outcome at age 24 months in infants with TSC, as well as the effect on neurodevelopmental outcome of early versus conventional treatment of epileptic seizures with vigabatrin (80-150 mg/kg/day). METHODS: Infants with TSC, aged ≤4 months and without previous seizures were enrolled in a prospective study and closely followed with monthly video EEG and serial standardized neurodevelopmental testing (Bayley Scales of Infant Development and Autism Diagnostic Observation Schedule). RESULTS: Eighty infants were enrolled. At the age of 24 months testing identified risk of Autism Spectrum Disorder (ASD) in 24/80 children (30.0%), and developmental delay (DD) in 26/80 (32.5%). Children with epilepsy (51/80; 63.8%) had a higher risk of ASD (P = 0.02) and DD (P = 0.001). Overall, no child presented with moderate or severe DD at 24 months (developmental quotient

Background and aims Pain-related fear and its subsequent generalization is key to the development and maintenance of chronic pain disability. Research has shown that pain-related fear acquired through classical conditioning generalizes following a gradient, that is, novel movements that are proprioceptively similar to the original pain-associated movement elicit more fear. Studies suggest that classical conditioning can also modulate pain and conditioned fear seems to mediate this effect. However, it remains uninvestigated whether this is also the case for generalized fear. Methods In a voluntary joystick movement paradigm, one movement (conditioned stimulus; CS+) was followed by pain (pain-US), and another was not (CS−). Generalization to five novel movements (generalization stimuli; GSs) with varying levels of similarity to the CSs was tested when paired with an at-pain-threshold intensity stimulus (threshold-USs). We collected self-reported fear and pain, as well as eyeblink startle responses as an additional index of conditioned fear. Results Results showed a fear generalization gradient in the ratings, but not in the startle measures. The data did not support the idea that fear generalization mediates spreading of pain. Conclusions Despite the lack of effects in the current study, this is a promising novel approach to investigate pain modulation in the context of chronic pain. Implications This study replicates the finding that pain-related fear spreads selectively towards movements that are proprioceptively more similar to the original pain-eliciting movement. Although results did not support the idea that such generalized fear mediates spreading of pain, the study provides a promising approach to investigate pain modulation by pain-associated movements.

Theory of Mind (ToM) refers to the ability to make inferences on other’s mental or emotional states. Although there is evidence suggesting that impaired executive functions due to aging could have a negative impact on cognitive ToM, there is still controversy about the effect of age and age-related executive dysfunctions on affective ToM. To investigate affective ToM in healthy aging and its relationship with executive functions, we examined Reading Mind in the Eyes Test (RMET) performance and executive functions among young and older adults. There was no significant difference between age groups regarding their RMET scores. While affective ToM was correlated to executive functioning within the younger group, short term memory was found to be associated with RMET performance among older participants. Furthermore, within the older group, women performed better than men. Our findings suggest a preserved ability of affective ToM in healthy aging, which appears to be independent of executive functioning. © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group.

Background: Psychotic disorders are characterized by prominent deficits in associative learning and memory for which there are currently no effective treatments. Functional magnetic resonance imaging (fMRI) studies in psychotic disorders have identified deficits in fronto-temporal activation during associative learning and memory. The underlying pathology of these findings remains unclear. Postmortem data have suggested these deficits may be related to loss of muscarinic M-1 receptor mediated signaling. This is supported by an in-vivo study showing improvements in these symptoms after treatment with the experimental M-1/4 receptor agonist xanomeline. The current study tests whether reported deficits in fronto-temporal activation could be mediated by loss of M-1 receptor signaling in psychotic disorders.Methods: Twenty-six medication-free subjects diagnosed with a psychotic disorder and 29 age-, gender-, and IQ-matched healthy controls underwent two functional magnetic resonance imaging (fMRI) sessions, one under placebo and one under selective M-1 antagonist biperiden, while performing the paired associated learning task. M-1 binding potentials (BPND) were measured in the dorsolateral prefrontal cortex (DLPFC) and hippocampus using I-123-IDEX single photon emission computed tomography.Results: In the subjects with psychotic disorders DLPFC hypoactivation was only found in the memory phase of the task. In both learning and memory phases of the task, M-1 antagonism by biperiden elicited significantly greater hyperactivation of the parahippocampal gyrus and superior temporal gyrus in subjects with a psychotic disorders compared to controls. Greater hyperactivation of these areas after biperiden was associated with greater hippocampal M-1 receptor binding during learning, with no association found with M-1 receptor binding in the DLPFC. M-1 receptor binding in the DLPFC was related to greater functional sensitivity to biperiden of the cingulate gyrus during the memory phase.Conclusion: The current study is the first to show differences in M-1 receptor mediated functional sensitivity between subjects with a psychotic disorder and controls during a paired associate learning and memory task. Results point to subjects with psychotic disorders having a loss of M-1 receptor reserve in temporal-limbic areas.

Actually, there is scarce literature looking for the relationship between inter-limb asymmetries and performance in youth elite team sports. The main purpose of this cross-sectional study was to examine the relationships between inter-limb asymmetries and physical performance in youth elite team-sports players. A secondary objective was to evaluate the presence of between-sexes differences in inter-limb asymmetries in elite youth team sports players. Eighty-one young elite team-sports athletes (age: u-14 to u-18) performed the star excursion balance test in the anterior direction (SEBT ANT), a single leg vertical countermovement jump test (SLCMJ), the one leg hop test for distance (OLHT), a 30 m sprint test, and the V-cut test. Inter-limb asymmetries were calculated for SEBT ANT, SLCMJ and OLHT. Pearson r was used to analyse the relationships between inter-limb asymmetries and physical performance. Results showed significant (p < 0.05) but small (r = 0.26) relationships between SLCMJ asymmetries and 30 m sprint time for the total group. Significant negative correlations with small to moderate magnitude of correlation were also found between SLCMJ asymmetries and SLCMJ performance on the lowest performing limb for the total group (p < 0.05; r = -0.26), males (p < 0.01; r = -0.48) and females (p < 0.05; r = -0.30). Moreover, significant negative correlations with moderate and large magnitude were also present between OLHT asymmetries and OLHT performance on the lowest performing limb for the total group (p < 0.01; r = -0.44), males (p < 0.01; r = -0.56) and females (p < 0.01; r = -0.64). No correlations were observed between asymmetries and either the V-cut test or SEBT ANT performance. No correlation were observed between SEBT ANT asymmetries and physical performance. In addition, when comparing asymmetry values between sexes there were no significant differences in vertical (p = 0.06) and horizontal (p = 0.61) jumping tests. However, there were significant differences in asymmetry between sexes in the ANT SEBT (p = 0.04). In conclusion, the current study indicated that jumping asymmetries were associated with decrements in sprint speed and jumping performance. Therefore, assessing inter-limb asymmetries would be recommended to improve training interventions for youth elite team-sports athletes.

Contains fulltext : 229419.pdf (Publisher’s version ) (Open Access) Objectives: Executive functioning and emotion recognition may be impaired in disruptive youth, yet findings in oppositional defiant disorder (ODD) and conduct disorder (CD) are inconsistent. We examined these functions related to ODD and CD, accounting for comorbid attention-deficit/hyperactivity disorder (ADHD) and internalising symptoms.Methods: We compared executive functioning (visual working memory, visual attention, inhibitory control) and emotion recognition between youth (8-18 years old, 123 boys, 55 girls) with ODD (n = 44) or CD (with/without ODD, n = 48), and healthy controls (n = 86). We also related ODD, CD, and ADHD symptom counts and internalising symptomatology to all outcome measures, as well as executive functioning to emotion recognition.Results: Visual working memory and inhibitory control were impaired in the ODD and CD groups versus healthy controls. Anger, disgust, fear, happiness, and sadness recognition were impaired in the CD group; only anger recognition was impaired in the ODD group. Deficits were not explained by comorbid ADHD or internalising symptoms. Visual working memory was associated with recognition of all basic emotions.Conclusions: Our findings challenge the view that neuropsychological impairments in youth with ODD/CD are driven by comorbid ADHD and suggest possible distinct neurocognitive mechanisms in CD versus ODD.

Introduction: Patients with obsessive-compulsive disorder (OCD) showed impaired spatial working memory (SWM). We evaluated whether patients and healthy controls (HCs) differed in spatial store capacity, and whether they differed in the relative weight of spatial store capacity and/or executive strategy in SWM. Methods: Thirty inpatients with OCD and 31 age- and education-matched HCs underwent the CANTAB SWM, SRM (a measure of spatial store). The severity of OC symptoms was assessed using the Y-BOCS. Statistical significance: alpha = 0.05. Results: Patients showed poorer performance than HCs in all neuropsychological outcomes. Both poorer SRM and SWM strategy were significantly associated with poorer SWM in the entire sample. No significant interaction between SRM and Group was found, while a significant interaction between SWM strategy and Group emerged; in patients the magnitude of this association was approximately twofold larger than in HCs. OC symptom severity did not correlate with neuropsychological performance. Conclusions: Patients with OCD had poorer spatial store capacity than HCs. However, the weight of poorer executive strategy in SWM was greater in patients than HCs, whereas the weight of spatial store was similar. We provided a direct evidence that an impairment in the executive component might be the crucial factor influencing the poorer SWM of these patients.

Background and Purpose— Delayed cerebral ischemia (DCI) is an important cause of poor outcome after aneurysmal subarachnoid hemorrhage. If clinical signs of DCI occur, induced hypertension is a plausible but unproven therapeutic intervention. There is clinical equipoise if the use of hypertension induction is useful or not with the consequence that this strategy is irregularly used. We explored the effect of blood pressure augmentation in preventing cerebral infarction in patients with clinical signs of DCI. Methods— We performed a retrospective observational study, totaling 1647 patients with aneurysmal subarachnoid hemorrhage admitted at 3 academic hospitals in the Netherlands between 2006 and 2015. To study the primary outcome DCI related cerebral infarcts, we only included patients with no cerebral infarct at the time of onset of clinical signs of DCI. Cox regression was used to test the association between induced hypertension after onset of clinical signs of DCI and the occurrence of DCI related cerebral infarcts. Logistic regression was used to relate hypertension induction with poor outcome after 3 months, defined as a modified Rankin score >3. Results were adjusted for treatment center and baseline characteristics. Results— Clinical signs of DCI occurred in 479 (29%) patients of whom 300 without cerebral infarction on computed tomography scan at that time. Of these 300 patients, 201 (67%) were treated with hypertension induction and 99 were not. Of the patients treated with hypertension induction, 41 (20%) developed a DCI related cerebral infarct compared with 33 (33%) with no induced hypertension: adjusted hazard ratio, 0.59; 95% CI, 0.35 to 0.99. Hypertension induction also prevented poor outcome: adjusted odds ratio, 0.27; 95% CI, 0.14 to 0.55. Conclusions— Hypertension induction seems an effective strategy for preventing DCI related cerebral infarcts if not already present at the time of onset of clinical signs of DCI. This may lead to a reduction in poor clinical outcome.

Contains fulltext : 199745.pdf (Publisher’s version ) (Open Access) Objective: This study evaluates the contribution of measures for social cognition (SC), executive functioning (EF) and dysexecutive behavior to the statistical prediction of social and vocational participation in patients with traumatic brain injury (TBI), taking into account age and injury severity. Method: A total 63 patients with moderate to severe TBI participated. They were administered a semi-structured Role Resumption List for social (RRL-SR) and vocational participation (RRL-RTW). EF was measured with planning- and switching tasks. Assessment of SC included tests for facial affect recognition and Theory of Mind (ToM). Dysexecutive behavior was proxy-rated with a questionnaire. Additionally, healthy controls were assessed with the same protocol. Results: Patients with TBI performed significantly worse on tests and had significantly more behavioral problems compared to healthy controls. Hierarchical multiple regression analyses for the TBI group revealed that SC accounted for 22% extra variance in RRL-RTW and 10% extra variance in RRL-SR, which was significant over and above the amounts of variance explained by EF, dysexecutive behavior, age and injury severity. Conclusions: Our findings underline the added value of measures of SC and dysexecutive behavior in the prediction of social and vocational participation post-TBI. In particular, impairments in ToM, and dysexecutive behavior were related to a lower participation making them important targets for rehabilitation. 9 p.

Objective: Pattern separation (PS) is the ability to represent similar experiences as separate, non-overlapping representations. It is usually assessed via the Mnemonic Similarity Task - Object Version (MST-O) which, however, assesses PS performance without taking behavioral context discrimination into account, since it is based on pictures of everyday simple objects on a white background. We here present a validation study for a new task, the Mnemonic Similarity Task - Context Version (MST-C), which is designed to measure PS while taking behavioral context discrimination into account by using real-life context photographs. Methods: Fifty healthy subjects underwent the two MST tasks to assess convergent evidence. Instruments assessing memory and attention were also administered to study discriminant evidence. The test-retest reliability of MST-C was analyzed. Results: Weak evidence supports convergent validity between the MST-C task and the MST-O as measures of PS (r(s) = 0.464; p < 0.01); PS performance assessed via the MST-C did not correlate with memory or attention; a moderate test-retest reliability was found (r(s) = 0.595; p < 0.01). Conclusion: The MST-C seems useful for assessing PS performance conceptualized as the ability to discriminate complex and realistic spatial contexts. Future studies are welcome to evaluate the validity of the MST-C task as a measure of PS in clinical populations.

OBJECTIVE: This study aimed to assess the heterogeneity and stability of cognition in patients with a non-affective psychotic disorder and their unaffected siblings. In addition, we aimed to predict the cognitive subtypes of siblings by their probands. METHOD: Assessments were conducted at baseline, 3 and 6 years in 1119 patients, 1059 siblings and 586 controls from the Genetic Risk and Outcome of Psychosis (GROUP) study. Group-based trajectory modeling was applied to identify trajectories and clustered multinomial logistic regression analysis was used for prediction modeling. A composite score of eight neurocognitive tests was used to measure cognitive performance. RESULTS: Five stable cognitive trajectories ranging from severely altered to high cognitive performance were identified in patients. Likewise, four stable trajectories ranging from moderately altered to high performance were found in siblings. Siblings had a higher risk of cognitive alteration when patients' alteration was mild (OR = 2.21), moderate (OR = 5.70), and severe (OR = 10.07) compared with patients with intact cognitive function. The familial correlation coefficient between pairs of index patients and their siblings was 0.27 (P = 0.003). CONCLUSIONS: The cognitive profiles identified in the current study might be suitable as endophenotypes and could be used in future genetic studies and predicting functional and clinical outcomes. ispartof: Acta Psychiatrica Scandinavica vol:138 issue:6 pages:591-604 ispartof: location:United States status: published

Impaired selective fear learning has been advanced as a core mechanism involved in excessive spreading of protective responses such as pain-related fear and avoidance leading to disability in chronic pain conditions. Using the litmus test for selective learning effects, the blocking procedure, we tested the hypothesis that patients with fibromyalgia (FM) show less selective threat learning than healthy controls (HCs). We introduce a novel selective learning task based around a clinical diary scenario. On a trial-by-trial basis, participants rated whether they expected certain situations (A, B, Z, and X) in the diary of a fictive FM patient would trigger pain in that patient. The procedure did not involve any experimental pain induction because the verbal outcomes "pain" or "no pain" were used. During the elemental acquisition phase, one situation was followed by "pain" (A+, eg, "Kim slept badly, and reports pain"), whereas another situation was followed by "no pain" (Z-, eg, "Kim was stressed, and reports no pain"). During the compound acquisition phase, another situation (X), referred to as the blocked stimulus, was presented in compound with a previously pain-eliciting situation and also paired with "pain" (AX+, eg, Kim slept badly" and "Kim has vacuumed," and reports pain). Simultaneously, a novel situation was introduced and also followed by "pain" (B+). Within-group comparisons showed blocking (ie, significant difference between B and X) in the HCs, but not in the patients with FM. This study is the first in directly assessing differences in selective learning between patients with FM and HCs using a blocking procedure. ispartof: Pain vol:159 issue:7 pages:1268-1276 ispartof: location:United States status: published

Background: Many patients with primary brain tumors suffer from cognitive deficits, which negatively impact their quality of life. However, cognitive rehabilitation programs for these patients are scarce. We developed an iPad-based cognitive rehabilitation program for brain tumor patients, which was based on our effective face-to-face cognitive rehabilitation program. After successful completion of a feasibility study, a randomized controlled trial has been started.Objective: To evaluate the immediate and long-term effects of the iPad-based program on cognitive performance and patient-reported outcome measures (PROMs) in patients with primary brain tumors in an early stage of the disease.Methods: Prior to surgery, patients with presumed low-grade glioma and meningioma are included. Before surgery and 3 mo after surgery, neuropsychological assessments are conducted. After the second neuropsychological assessment, patients are assigned to the intervention group or waiting-list control group. The intervention consists of psychoeducation,compensation training, and retraining. Patients are advised to spend 3 h perweek on the program for 10 wk. Immediately after completion of the program and a halfyear thereafter, postintervention assessments take place. Patients in the control group are offered the opportunity to follow the program after all study assessments.Expected outcomes: We expect that early cognitive rehabilitation has beneficial effects on cognitive performance and PROMs in brain tumor patients.Discussion: The iPad-based program allows brain tumor patients to follow a cognitive rehabilitation program from their homes. Forthcoming results may contribute to further improvement of supportive care for brain tumor patients.

Background: The longitudinal course of the negative symptoms subdomains social amotivation (SA) and expressive deficits (ED) remains largely unknown. We investigated i) the longitudinal course of SA and ED subdomain scores, ii) whether subgroups based on the course of SA and ED subdomain scores could be identified, iii) whether baseline SA and ED subdomain scores were related to functioning and quality of life six years later and iv) the longitudinal relationship between subgroups and outcomes. Methods: Measurements at baseline, three and six years from 1067 patients participating in the Genetic Risk and Outcome of Psychosis (GROUP) project were used. We applied mixed models analysis, regression analysis and trajectory analyses. Results: SA and ED subdomain scores decreased over time. Within both subdomains, four subgroups were identified: for both SA and ED a steady low course (+/- 60%), increased (+/- 15%) and decreased course (+/- 15%). Within SA only, a higher level decreased course (+/- 6%) and within ED only, a course with relatively stable high ED scores (+/- 6%) was found. Lower symptom levels at baseline were related to better functioning (SA & ED) and quality of life (SA) at six years. Overall, low SA and low ED subgroups showed better outcomes than the other subgroups. Conclusion: In many patients the course of negative symptoms is unstable and related to the course of outcome. Patients who do show steady low negative symptom levels (60%) may complicate the interpretation of treatment evaluation studies, as they may average out possible effects in subgroups with fluctuating symptom levels. (c) 2017 Elsevier B.V. All rights reserved.

Many patients with primary brain tumors experience cognitive deficits. Cognitive rehabilitation programs focus on alleviating these deficits, but availability of such programs is limited. Our large randomized controlled trial (RCT) demonstrated positive effects of the cognitive rehabilitation program developed by our group. We converted the program into the iPad-based cognitive rehabilitation program ReMind, to increase its accessibility. The app incorporates psychoeducation, strategy training and retraining. This pilot study in patients with primary brain tumors evaluates the feasibility of the use of the ReMind-app in a clinical (research) setting in terms of accrual, attrition, adherence and patient satisfaction. The intervention commenced 3 months after resective surgery and patients were advised to spend 3 h per week on the program for 10 weeks. Of 28 eligible patients, 15 patients with presumed low-grade glioma or meningioma provided informed consent. Most important reason for decline was that patients (7) experienced no cognitive complaints. Participants completed on average 71% of the strategy training and 76% of the retraining. Some patients evaluated the retraining as too easy. Overall, 85% of the patients evaluated the intervention as “good” or “excellent”. All patients indicated that they would recommend the program to other patients with brain tumors. The ReMind-app is the first evidence-based cognitive telerehabilitation program for adult patients with brain tumors and this pilot study suggests that postoperative cognitive rehabilitation via this app is feasible. Based on patients’ feedback, we have expanded the retraining with more difficult exercises. We will evaluate the efficacy of ReMind in an RCT.

Cognitive impairments are common in MS and affect personal, social, and occupational functioning. There is a developing body of evidence highlighting the role of cognitive rehabilitation, but there is still no evidence for a validated holistic approach. The aim of this study was to assess the effectiveness of Cognitive Occupation-Based Programme for People with Multiple Sclerosis (COB-MS) for improving daily life and cognitive impairment. This study used an experimental pretest/posttest design with eight-week follow-up. Participants were recruited from MS networks using convenience sampling. The primary outcome measure was the GAS. Secondary outcomes included the OSA-DLS, CVLT-II, BVMT-R, SDMT, TMT, BRIEF-A, and EMQ-R. Twelve participants were recruited, aged 39–73 years (mean: 55.08; SD: 9.61). There were statistically significant improvements in the GAS (p<.002), CVLT-II: total free recall (p<.000), short delay free recall (p<.018), long delay free recall (p<.008), BVMT-R total recall (p<.000), TMT part B (p<.044), and EMQ-R (p<.006). Except for the BRIEF-A, clinically significant improvements were observed in secondary outcome measures at posttest and follow-up. Limitations include selection bias and subtle practice effects in cognitive measures. Results suggest that a larger scale study is justified considering improvements seen in daily life and cognitive measures.

Contains fulltext : 195873.pdf (Publisher’s version ) (Open Access) Of the triad of symptoms found in autism spectrum disorder (ASD), that is, social impairments, communication difficulties and repetitive interests and behaviour, the social impairments are the most stable and common throughout the lifespan. They typically manifest themselves in abnormalities as reciprocal interactions and difficulties in the expression and recognition of emotions. Although peer interactions become especially important during adolescence, little is known about the mentalizing abilities of high-functioning adolescents with ASD. Here, we compared the mentalizing skills and emotion recognition abilities of 21 high-functioning adolescents with ASD and 21 matched controls. All adolescents had estimated above-average verbal intelligence levels. Spontaneous social abilities and task-related social abilities were measured using questionnaires, tasks and the Autism Diagnostic Observation Schedule. Results confirm social impairment in daily life situations in adolescents with ASD, but were not found on experimental tasks of social cognition. The use of more explicit cognitive or verbally mediating reasoning techniques and a lesser tendency of high-functioning adolescents with ASD to search for and use social information in natural environments are further discussed. 11 p.

Contains fulltext : 219907.pdf (Publisher’s version ) (Open Access) Objective: Mindfulness-Based Cognitive Therapy (MBCT) is a promising psychosocial intervention for adult ADHD. The feasibility and effectiveness of an adapted MBCT program is explored, together with the possible process of change. Method: Mixed-method study with 31 ADHD patients participating in an adapted MBCT program. Self-report questionnaires on ADHD symptoms, executive functioning, mindfulness skills, self-compassion, patient functioning, and health status were administered before and after MBCT. Semi-structured interviews were conducted with 24 patients. Results: A modest drop-out of n = 5 (16%) was found. MBCT resulted in a significant reduction of ADHD symptoms and improvements of executive functioning, self-compassion, and mental health. Qualitative analysis provided insight in facilitators and barriers participants experienced, and their process of change. Conclusion: The adapted MBCT program seemed to be feasible for adults with ADHD and preliminary evidence for the effectiveness is shown. An adequately powered Randomized Controlled Trial (RCT) is needed to further examine the effectiveness of MBCT for ADHD.

Background and Objectives Needle-induced nerve trauma and intraneural injection can lead to neurologic injury during peripheral nerve blocks. In this study, we assessed the utility of opening injection pressure (OIP), time to OIP, and rate of rise to OIP in detecting needle-nerve contact and intraneural injection. Methods Five common ultrasound-guided blocks of the femoral, saphenous, subgluteal sciatic, tibial, and common peroneal nerves were simulated in 10 fresh cadavers. Opening injection pressure was defined as peak psi in the 60-second interval during which the injection is initiated. Pressure-time curves were constructed separately for intraneural and perineural injections for each of the 5 nerves studied. Results Opening injection pressure was higher for intraneural than for perineural injections (P < 0.001), ranging from 21.5 psi (1111.9 mm Hg) to 25.8 psi (1334.2 mm Hg) for intraneural injections and from 3.8 psi (196.5 mm Hg) to 6.1 psi (315.5 mm Hg) for perineural injections. Time to OIP tended to be shorter for intraneural than for perineural injections, particularly for the subgluteal sciatic, tibial, and common peroneal nerves. Curves of intraneural injections had steep slopes with high peaks; curves of perineural injections had low slopes followed by plateaus. Rise to OIP was greater for intraneural than for perineural injections. Conclusions In our fresh human cadaver model, OIP detected intraneural needle placement. Monitoring of OIP could be useful in detecting and/or preventing intraneural injection during nerve blocks in the clinical setting. ispartof: Regional Anesthesia and Pain Medicine vol:42 issue:3 pages:362-367 ispartof: location:England status: published

OBJECTIVES: To investigate the direct, mediated and moderated relationships between executive functioning, coping and depressive symptoms in patients with multiple sclerosis (MS).METHODS: Cross-sectional cohort study of routine follow-up visits, including a standardized (neuro)psychological evaluation of 68 MS patients. Coping was measured with the Coping Inventory for Stressful Situations; Depressive symptoms with the subscale depression of the Hospital Anxiety and Depression Scale. Cognitive tests were reduced to a single 'executive function' factor by means of confirmatory factor analysis. Path analyses tested mediating and moderating effects of coping on the relation between executive functioning and depressive symptoms.RESULTS: Consistently, the executive functioning factor was not related to task-oriented and emotion-oriented coping. Better executive functioning, however, and less reliance on avoidance coping, was related to more depressive symptoms. Testing of the mediating path showed that executive dysfunctioning was indeed significantly related to more depressive symptoms by less reliance on avoidance coping. There was no additional direct effect of executive functioning on depressive symptoms and also no moderating effect of any coping style on the association between cognition and depressive symptoms.CONCLUSION: Our findings suggest that task-oriented and emotion-oriented coping do not influence the relationship between executive functioning and depression in MS patients, but their mental health might benefit from more reliance on avoidance coping.

Modified constraint-induced movement therapy (mCIMT) improves upper limb (UL) motor execution in unilateral cerebral palsy (uCP). As these children also show motor planning deficits, action-observation training (AOT) might be of additional value. Here, we investigated the combined value of AOT to mCIMT on UL kinematics in children with uCP in a randomized controlled trial. Thirty-six children with uCP completed an UL kinematic and clinical evaluation after participating in a 9-day mCIMT camp wearing a splint for 6 h/day. The experimental group (mCIMT + AOT, n = 20) received 15 h of AOT, i.e. video-observation and execution of unimanual tasks. The control group (mCIMT + placebo, n = 16) watched biological-motion free videos and executed the same tasks. We examined changes in motor control (movement duration, peak velocity, time-to-peak velocity, and trajectory straightness) and kinematic movement patterns (using Statistical Parametric Mapping) during the execution of three unimanual, relevant tasks before the intervention, after and at 6 months follow-up. Adding AOT to mCIMT mainly affected movement duration during reaching, whereas little benefit is seen on UL movement patterns. mCIMT, with or without AOT, improved peak velocity and trajectory straightness, and proximal movement patterns. Clinical and kinematic improvements are poorly related. Although there seem to be limited benefits of AOT to CIMT on UL kinematics, our results support the inclusion of kinematics to capture changes in motor control and movement patterns of the proximal joints., Scientific Reports, 10 (1), ISSN:2045-2322

The aims of this study were to 1) assess the predictive value of psychological assessment at five years of age on the need for educational support in very preterm children, and 2) report the neuropsychological profile of very preterm children at eleven years of age and risk factors for poorer neuropsychological functions. A cohort of 167 very preterm children was included (birth weight???1500?g and/or gestational age

Introduction: Mental Time Travel (MTT) is the people's ability to remember themselves in the past and to imagine themselves in the future, and influence important life domains such as making decisions and planning future actions. It is widely recognized that patients with aMCI have deficits in episodic memory, but they also show impairments in semantic memory. It has been controversial whether MTT tasks are disturbed in aMCI mainly in relation to internal details related to episodic information, or external details, representing semantic and other extraneous information. The present study assessed whether patients with aMCI are affected in MTT regarding generation of internal details and external details, in past and future dimensions. Furthermore, it analyzed production in individual detail categories (internal: event details, thought/emotion, place, time, perceptual external: extraneous events, semantic, other, repetitions). Method: Twenty-nine patients with aMCI and 29 healthy controls underwent a MTT task based on an Autobiographical Interview, where they had to generate past and future events in response to cue words. Transcriptions were segmented and classified into internal detail categories and external detail categories, and composite scores were obtained. Results: Patients with aMCI could globally produce significantly less details than controls. Similar to controls, patients with aMCI produced more internal details than external details, had more difficulty in generating details regarding the future as compared to the past, and scored higher in the detail categories event details and thought/emotion which represent internal detail types. Conclusions: Patients with aMCI showed widespread deficits in MTT, presumably reflecting deficiencies in the complex and multiple cognitive abilities required for MTT tasks. Fundacao para a Ciencia e a TecnologiaPortuguese Foundation for Science and Technology [JPND-HC/0003/2012]

Next to the typical motor signs, Parkinson's disease (PD) goes along with neuropsychiatric symptoms, amongst others affecting social cognition. Particularly, Theory of Mind (ToM) impairments have mostly been associated with right hemispherical brain dysfunction, so that it might prevail in patients with left dominant PD. Fourty-four PD patients, twenty-four with left and twenty with right dominant motor symptoms, engaged in the Reading the Mind in the Eyes (RME) and the Faux Pas Detection Test (FPD) to assess affective and cognitive ToM. The results were correlated with performance in further cognitive tests, and analyzed with respect to associations with the side of motor symptom dominance and severity of motor symptoms. No association of ToM performance with right hemispheric dysfunction was found. RME results were inversely correlated with motor symptom severity, while FPD performance was found to correlate with the performance in verbal fluency tasks and the overall cognitive evaluation. Affective ToM was found associated with motor symptom severity and cognitive ToM predominantly with executive function, but no effect of PD lateralization on this was identified. The results suggest that deficits in social cognition occur as a sequel of the general corticobasal pathology in PD, rather than as a result of hemisphere-specific dysfunction.

ObjectiveTo examine the presence of social cognition deficits and the relationship between social and general cognition (eg, attention, mental speed, verbal, visual, or memory abilities) in a large sample of chronic stroke patients and to identify stroke-related factors associated with social cognitive performance.DesignInception cohort study in which social cognition was assessed at 3-4 years post stroke.SettingStroke units in 6 general hospitals.ParticipantsThe data of 148 patients were available. Fifty controls without stroke (consisting of partners of patients and acquaintances of researchers) were recruited (N=198).InterventionsNot applicable.Main Outcome MeasuresPatients underwent neuropsychological assessment by means of tests for social cognition (emotion recognition, theory of mind [ToM], empathy, and behavior regulation) and general cognition. Subgroup analysis was performed to compare right hemisphere stroke patients with left hemisphere stroke patients. Correlations between general and social cognition tests were assessed. Multiple regression analyses were performed to identify demographic and stroke-related predictors of social cognitive performance.ResultsPatients performed significantly worse on emotion recognition (assessed with the Ekman 60-Faces test on total score as well as on the emotion anger), ToM (assessed with the Cartoon test), and behavior regulation (assessed with the Hayling test). Subgroup analysis revealed no differences between right and left hemisphere patients. Social cognition tests showed significant correlations with each other and with tests for visual perception, language, mental speed, cognitive flexibility, and memory. Older age, low level of education (and for ToM, also female sex) were predictors of worse performance on social cognition tests.ConclusionSocial cognition impairments are present in the long term post stroke, even in a group of mildly affected stroke patients, which may contribute to their long-term problems. Severity of impairments is determined mainly by demographic factors.

Aim As suggested by the Shared Vulnerability Model, impairment in executive functions could lead to worse creative performance among individuals with schizophrenia. Another impaired function in schizophrenia, previously related to creativity in healthy people, is theory of mind. However, little is known about the effect of theory of mind in creativity in schizophrenia. Therefore, the aim of this study was to analyze differences in creativity among patients with schizophrenia compared to healthy controls (HC) and to explore the potential role of executive functions and theory of mind as mediators of this relation. Methods Forty-five patients with schizophrenia and 45 HC underwent a neuropsychological assessment, including executive functions (cognitive flexibility and working memory), theory of mind, and verbal and figural creativity. Results As expected, patients with schizophrenia obtained lower scores in creativity, cognitive flexibility, working memory, and theory of mind compared to HC. Path analysis showed that theory of mind mediated the relation between group (schizophrenia or HC) and both figural (Z = 2.075, P = 0.037) and verbal creativity (Z = 2.570, P = 0.010). Working memory mediated the relation between group and figural creativity (Z = 2.034, P = 0.041) and was marginally significant for verbal creativity (Z = 1.930, P = 0.053). Finally, cognitive flexibility mediated between group and figural creativity (Z = 2.454, P = 0.014). Conclusion Results suggest that the lower performance in creativity among patients with schizophrenia was partly due to an impairment in executive functions and theory of mind. The involvement of theory of mind opens up a new field of research as a possible risk factor in the Shared Vulnerability Model. This study has been supported by the Ministry of Economy and Competitiveness (PI16/01022) from Spain. A.S. was supported by a Fellowship from the Fundacion Tatiana Perez de Guzman el Bueno. The funding agencies had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors thank all the participants and clinical clusters who were involved in the study.

Introduction: Empathy is an interpersonal process impaired in schizophrenia. Past studies have mainly used questionnaires or performance-based tasks with static cues to measure cognitive and affective empathy. We used the Empathic Accuracy Task (EAT) designed to capture dynamic aspects of empathy by using videoclips in which perceivers continuously judge emotionally charged stories. We compared individuals with schizophrenia with a healthy comparison group and assessed correlations among EAT and three other commonly used empathy measures.Method: Patients (n = 92) and a healthy comparison group (n = 42) matched for age, gender and education completed the EAT, the Interpersonal Reactivity Index, Questionnaire of Cognitive and Affective Empathy and Faux Pas. Differences between groups were analyzed and correlations were calculated between empathy measurement instruments.Results: The groups differed in EAT performance, with the comparison group outperforming patients. A moderating effect was found for emotional expressivity of the target: while both patients and the comparison group scored low when judging targets with low expressivity, the comparison group performed better than patients with more expressive targets. Though there were also group differences on the empathy questionnaires, EAT performance did not correlate with questionnaire scores.Conclusions: Individuals with schizophrenia benefit less from the emotional expressivity of other people than the comparison group, which contributes to their impaired empathic accuracy. The lack of correlation between the EAT and the questionnaires suggests a distinction between self-report empathy and actual empathy performance. To explore empathic difficulties in real life, it is important to use instruments that take the interpersonal perspective into account. (C) 2019 Published by Elsevier B.V.

Objective Brain tumor patients may suffer from a range of health-impairing problems reducing their quality of life. To identify potential targets for interventions, we examined the influence of different emotion regulation strategies on affective and cognitive functioning as indices of quality of life in patients and their caregivers in the early phase of treatment. Methods To this end, we conducted an exploratory longitudinal study on a small cohort, measuring emotion regulation, emotional well-being, and cognitive functioning on the day before each patient's tumor resection (28 patients and 11 caregivers) and several months after neurosurgery (22 patients and 10 caregivers). Results Results showed that emotion regulation strategies are relatively stable from preoperative to postoperative assessment. Nevertheless, several associations between emotion regulation strategies and quality of life indices were evident after tumor resection. In particular, our results were largely in line with previous research findings in healthy and other patient populations, corroborating the adaptive character of cognitive reappraisal, whereas suppression and expression of emotions were related to reduced cognitive and affective functioning, respectively. Conclusions Based on these results, we suggest that further intervention or qualitative studies explore whether therapeutic interventions directed toward mastery of cognitive reappraisal techniques and appropriate expression of emotions could lead to improved long-term adjustment among brain tumor patients and their caregivers.