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Experts have highlighted the importance of coaches knowing the level of mental fatigue (MF) induced by different tasks. This study aimed to compare the mentally fatiguing nature of cognitive, physical, and combined tasks and, additionally, assess the effect of different moderating variables on MF. Twenty-three physically active (16 males: Mage = 24 years; seven females: Mage = 22.57 years) participants performed three experimental sessions: (a) physically fatiguing: 30 min of cycloergometer work (at 65%–75% of maximum heart rate), (b) mentally fatiguing: 30 min of an incongruent Stroop task, and (c) mixed fatiguing: 30 min of combining the physically and mentally fatiguing protocols. Subjective MF (visual analog scale), reaction time (psychomotor vigilance task), and cognitive performance (Stroop) were measured throughout the different protocols. Results showed significant increments in subjective MF after all tasks, with the mental and mixed protocols showing significantly higher increases. Only the mentally fatiguing protocol caused significant impairments in reaction time. No significant effects of sex, years of experience, or degree of mental toughness were observed. These results suggest that the use of all these tasks, and especially the mentally fatiguing exercises, should be avoided immediately prior to competitions due to the negative consequences of MF on performance. Moreover, this effect seems to be independent of the sex, years of experience, or mental toughness of athletes.

Background The risk of dementia is higher in women than men. The metabolic consequences of estrogen decline during menopause accelerate neuropathology in women. The use of hormone replacement therapy (HRT) in the prevention of cognitive decline has shown conflicting results. Here we investigate the modulating role of APOE genotype and age at HRT initiation on the heterogeneity in cognitive response to HRT. Methods The analysis used baseline data from participants in the European Prevention of Alzheimer’s Dementia (EPAD) cohort (total n= 1906, women= 1178, 61.8%). Analysis of covariate (ANCOVA) models were employed to test the independent and interactive impact of APOE genotype and HRT on select cognitive tests, such as MMSE, RBANS, dot counting, Four Mountain Test (FMT), and the supermarket trolley test (SMT), together with volumes of the medial temporal lobe (MTL) regions by MRI. Multiple linear regression models were used to examine the impact of age of HRT initiation according to APOE4 carrier status on these cognitive and MRI outcomes. Results APOE4 HRT users had the highest RBANS delayed memory index score (P-APOE*HRT interaction = 0.009) compared to APOE4 non-users and to non-APOE4 carriers, with 6–10% larger entorhinal (left) and amygdala (right and left) volumes (P-interaction= 0.002, 0.003, and 0.005 respectively). Earlier introduction of HRT was associated with larger right (standardized β= −0.555, p=0.035) and left hippocampal volumes (standardized β= −0.577, p=0.028) only in APOE4 carriers. Conclusion HRT introduction is associated with improved delayed memory and larger entorhinal and amygdala volumes in APOE4 carriers only. This may represent an effective targeted strategy to mitigate the higher life-time risk of AD in this large at-risk population subgroup. Confirmation of findings in a fit for purpose RCT with prospective recruitment based on APOE genotype is needed to establish causality.

Recent research in rodents and humans revealed that Whole-Body Vibration (WBV) is beneficial for cognitive functions. However, the optimal WBV conditions are not established: contrary to vertical WBV, side-alternating WBV was not investigated before. The present study investigated the short-term effects of side-alternating WBV in standing and sitting posture on specific cognitive function of young adults. We used a balanced cross-over design. Sixty healthy young adults (mean age 21.7 ± 2.0 years, 72% female) participated. They were exposed to three bouts of two-minute side-alternating WBV (frequency 27 Hz) and three control conditions in two different sessions. In one session a sitting posture was used and in the other session a standing (semi-squat) posture. After each condition selective attention and inhibition was measured with the incongruent condition of the Stroop Color-Word Interference Test. WBV significantly (p = 0.026) improved selective attention and inhibition in the sitting posture, but not in the standing posture. The sitting posture was perceived as more comfortable, joyous and less exhaustive as compared to the standing posture. This study demonstrated that side-alternating WBV in sitting posture improves selective attention and inhibition in healthy young adults. This indicates that posture moderates the cognitive effect of WBV, although the effects are still small. Future studies should focus on the working mechanisms and further optimization of settings, especially in individuals who are unable to perform active exercise.

Sleep continuity and efficacy are essential for optimal cognitive functions. How sleep fragmentation (SF) impairs cognitive functioning, and especially cognitive fatigue (CF), remains elusive. We investigated the impact of induced SF on CF through the TloadDback task, measuring interindividual variability in working memory capacity. Sixteen participants underwent an adaptation polysomnography night and three consecutive nights, once in a SF condition induced by non-awakening auditory stimulations, once under restorative sleep (RS) condition, counterbalanced within-subject. In both conditions, participants were administered memory, vigilance, inhibition and verbal fluency testing, and for CF the TloadDback, as well as sleep questionnaires and fatigue and sleepiness visual analog scales were administered. Subjective fatigue increased and sleep architecture was altered after SF (reduced sleep efficiency, percentage of N3 and REM, number of NREM and REM phases) despite similar total sleep time. At the behavioral level, only inhibition deteriorated after SF, and CF similarly evolved in RS and SF conditions. In line with prior research, we show that SF disrupts sleep architecture and exerts a deleterious impact on subjective fatigue and inhibition. However, young healthy participants appear able to compensate for CF induced by three consecutive SF nights. Further studies should investigate SF effects in extended and/or pathological disruption settings.

Background: Cognitive training elicits mild-to-moderate improvements in cognitive functioning in people with multiple sclerosis (PwMS), although response heterogeneity limits overall effectiveness. Objective: To identify patient characteristics associated with response and non-response to cognitive training. Methods: Eighty-two PwMS were randomized into a 7-week attention training ( n = 58, age = 48.4 ± 10.2 years) or a waiting-list control group ( n = 24, age = 48.5 ± 9.4 years). Structural and functional magnetic resonance imaging (MRI) was obtained at baseline and post-intervention. Twenty-one healthy controls (HCs, age = 50.27 ± 10.15 years) were included at baseline. Responders were defined with a reliable change index of 1.64 on at least 2/6 cognitive domains. General linear models and logistic regression were applied. Results: Responders ( n = 36) and non-responders ( n = 22) did not differ on demographics, clinical variables and baseline cognition and structural MRI. However, non-responders exhibited a higher baseline functional connectivity (FC) between the default-mode network (DMN) and the ventral attention network (VAN), compared with responders ( p = 0.018) and HCs ( p = 0.001). Conversely, responders exhibited no significant baseline differences in FC compared with HCs. Response to cognitive training was predicted by lower DMN-VAN FC ( p = 0.004) and DMN-frontoparietal FC ( p = 0.029) (Nagelkerke R2 = 0.25). Conclusion: An intact pre-intervention FC is associated with cognitive training responsivity in pwMS, suggesting a window of opportunity for successful cognitive interventions.

Implicit motor sequence learning (IMSL) is a cognitive function that is known to be directly associated with impaired motor function in Parkinson's disease (PD). Research on healthy young participants shows the potential for transcranial direct current stimulation (tDCS), a noninvasive brain stimulation technique, over the primary motor cortex (M1) to enhance IMSL. tDCS has direct effects on the underlying cortex, but also induces distant (basal ganglia) network effects-hence its potential value in PD, a prime model of basal ganglia dysfunction. To date, only null effects have been reported in persons with PD. However, these studies did not determine the reacquisition effects, although previous studies in healthy young adults suggest that tDCS specifically exerts its beneficial effects on IMSL on reacquisition rather than acquisition. In the current study, we will therefore establish possible reacquisition effects, which are of a particular interest, as long-term effects are vital for the successful functional rehabilitation of persons with PD. Using a sham-controlled, counterbalanced design, we will investigate the potential of tDCS delivered over M1 to enhance IMSL, as measured by the serial reaction time task, in persons with PD and a neurologically healthy age- and sex-matched control (HC) group. Multilevel Mixed Models will be implemented to analyze the sequence-specific aspect of IMSL (primary outcome) and general learning (secondary outcome). We will determine not only the immediate effects that may occur concurrently with the application of tDCS but also the short-term (5 min post-tDCS) and long-term (1 week post-tDCS) reacquisition effects.

Through long-term training, music experts acquire complex and specialized sensorimotor skills, which are paralleled by continuous neuro-anatomical and -functional adaptations. The underlying neuroplasticity mechanisms have been extensively explored in decades of research in music, cognitive, and translational neuroscience. However, the absence of a comprehensive review and quantitative meta-analysis prevents the plethora of variegated findings to ultimately converge into a unified picture of the neuroanatomy of musical expertise. Here, we performed a comprehensive neuroimaging meta-analysis of publications investigating neuro-anatomical and -functional differences between musicians (M) and non-musicians (NM). Eighty-four studies were included in the qualitative synthesis. From these, 58 publications were included in coordinate-based meta-analyses using the anatomic/activation likelihood estimation (ALE) method. This comprehensive approach delivers a coherent cortico-subcortical network encompassing sensorimotor and limbic regions bilaterally. Particularly, M exhibited higher volume/activity in auditory, sensorimotor, interoceptive, and limbic brain areas and lower volume/activity in parietal areas as opposed to NM. Notably, we reveal topographical (dis-)similarities between the identified functional and anatomical networks and characterize their link to various cognitive functions by means of meta-analytic connectivity modelling. Overall, we effectively synthesized decades of research in the field and provide a consistent and controversies-free picture of the neuroanatomy of musical expertise.

Previous studies have shown that serial order in verbal working memory is spontaneously coded along the horizontal axis (i.e., the spatial positional association response codes (SPoARC) effect), with the initial items being associated with left and the last items being associated with right. These studies have led to the idea that when the cognitive system is confronted with a sequence of items processed verbally and semantically, it internally generates a spatial coordinate frame onto which memoranda can be bound to maintain their serial information. In this study, the interplay between internal and external spatial codes in the mind was investigated by testing the flexibility of the SPoARC effect. A verbal Sternberg probe detection task was used in which the displayed direction of the items during encoding (centrally, from left-to-right and from right-to-left) and the presentation rate (1- and 5-s/item) were manipulated. SPoARC effects were found in all conditions but were reversed in the right-to-left presentation condition. Follow-up analyses revealed no evidence of any spatial cost for the reversal; moreover, it was not influenced by the presentation rates. These findings suggest that space can be flexibly recruited for the spontaneous coding of serial order. The theoretical implications of these observations are discussed.

The perceived duration of an interval depends on numerous aspects of the passed event both endogenous, including physiological arousal, level of wakefulness, attention, and surprise, as well as exogenous such as valence, salience, or context in the environment. There is some evidence that "time-giving" cues from the environment (zeitgebers) are coupled with time perception. The movement of the sun on the horizon was demonstrated to affect interval perception in a study conducted by Schatzschneider et al. (2016) claiming that the sun’s motion is a zeitgeber that influences time perception. In the present study, we undertake the first to our knowledge replication of this effect, extending the analysis to confounding aspects of the used paradigm. We aimed to test the effect of immersion, cognitive load, and changes in the speed of the sun on the horizon of the virtual environment on the perceived interval duration. We did not replicate the original effect, as reported by Schatzschneider et al., however, we did find that the perceived duration of an interval was affected by cognitive load, fatigue, and unpleasant symptoms caused by VR. In our analysis, we used Bayesian statistics to support our conclusion and offer its results as having some important consequences for the field.

The coupling of gamma oscillation (~ 40+ Hz) amplitude to the phase of ongoing theta (~ 6 Hz) oscillations has been proposed to be directly relevant for memory performance. Current theories suggest that memory capacity scales with number of gamma cycles that can be fitted into the preferred phase of a theta cycle. Following this logic, transcranial alternating current stimulation (tACS) may be used to adjust theta cycles (increasing/decreasing theta frequency) to decrease or increase memory performance during stimulation. Here, we used individualized EEG-informed theta tACS to (1) experimentally “slow down” individual theta frequency (ITF), (2) evaluate cognitive after effects on a battery of memory and learning tasks, and (3) link the cognitive performance changes to tACS-induced effects on theta-band oscillations as measured by post EEG. We found frequency- and task-specific tACS after effects demonstrating a specific enhancement in memory capacity. This tACS-induced cognitive enhancement was specific to the visual memory task performed immediately after tACS offset, and specific to the ITF-1 Hz (slowing) stimulation condition and thus following a protocol specifically designed to slow down theta frequency to enhance memory capacity. Follow-up correlation analyses in this group linked the enhanced memory performance to increased left frontal-parietal theta-band connectivity. Interestingly, resting-state theta power immediately after tACS offset revealed a theta power increase not for the ITF-1 Hz group, but only for the ITF group where the tACS frequency was ‘optimal’ for entrainment. These results suggest that while individually calibrated tACS at peak frequency maximally modulates resting-state oscillatory power, tACS stimulation slightly below this optimal peak theta frequency is better suited to enhance memory capacity performance. Importantly, our results further suggest that such cognitive enhancement effects can last beyond the period of stimulation and are linked to increased network connectivity, opening the door towards more clinical and applied relevance of using tACS in cognitive rehabilitation and/or neurocognitive enhancement.

The endeavor to understand the human brain has seen more progress in the last few decades than in the previous two millennia. Still, our understanding of how the human brain relates to behavior in the real world and how this link is modulated by biological, social, and environmental factors is limited. To address this, we designed the Healthy Brain Study (HBS), an interdisciplinary, longitudinal, cohort study based on multidimensional, dynamic assessments in both the laboratory and the real world. Here, we describe the rationale and design of the currently ongoing HBS. The HBS is examining a population-based sample of 1,000 healthy participants (age 30–39) who are thoroughly studied across an entire year. Data are collected through cognitive, affective, behavioral, and physiological testing, neuroimaging, bio-sampling, questionnaires, ecological momentary assessment, and real-world assessments using wearable devices. These data will become an accessible resource for the scientific community enabling the next step in understanding the human brain and how it dynamically and individually operates in its bio-social context. An access procedure to the collected data and bio-samples is in place and published on https://www.healthybrainstudy.nl/en/data-and-methods/access. Trail registration: https://www.trialregister.nl/trial/7955.

Significance Statistical learning mechanisms enable extraction of patterns in the environment from infancy to adulthood. For example, they enable segmentation of continuous speech streams into novel words. Adults typically become aware of the hidden words even when passively listening to speech streams. It remains poorly understood how cognitive development and brain maturation affect implicit statistical learning (i.e., infant-like learning without awareness). Here, we show that the depletion of the cognitive control system by noninvasive brain stimulation or by demanding cognitive tasks boosts adults’ implicit but not explicit word-segmentation abilities. These findings suggest that the adult cognitive architecture constrains statistical learning mechanisms that are likely to contribute to early language acquisition and opens avenues to enhance language-learning abilities in adults., Human learning is supported by multiple neural mechanisms that maturate at different rates and interact in mostly cooperative but also sometimes competitive ways. We tested the hypothesis that mature cognitive mechanisms constrain implicit statistical learning mechanisms that contribute to early language acquisition. Specifically, we tested the prediction that depleting cognitive control mechanisms in adults enhances their implicit, auditory word-segmentation abilities. Young adults were exposed to continuous streams of syllables that repeated into hidden novel words while watching a silent film. Afterward, learning was measured in a forced-choice test that contrasted hidden words with nonwords. The participants also had to indicate whether they explicitly recalled the word or not in order to dissociate explicit versus implicit knowledge. We additionally measured electroencephalography during exposure to measure neural entrainment to the repeating words. Engagement of the cognitive mechanisms was manipulated by using two methods. In experiment 1 (n = 36), inhibitory theta-burst stimulation (TBS) was applied to the left dorsolateral prefrontal cortex or to a control region. In experiment 2 (n = 60), participants performed a dual working-memory task that induced high or low levels of cognitive fatigue. In both experiments, cognitive depletion enhanced word recognition, especially when participants reported low confidence in remembering the words (i.e., when their knowledge was implicit). TBS additionally modulated neural entrainment to the words and syllables. These findings suggest that cognitive depletion improves the acquisition of linguistic knowledge in adults by unlocking implicit statistical learning mechanisms and support the hypothesis that adult language learning is antagonized by higher cognitive mechanisms.

Predictive models in the brain rely on the continuous extraction of regularities from the environment. These models are thought to be updated by novel information, as reflected in prediction error responses such as the mismatch negativity (MMN). However, although in real life individuals often face situations in which uncertainty prevails, it remains unclear whether and how predictive models emerge in high-uncertainty contexts. Recent research suggests that uncertainty affects the magnitude of MMN responses in the context of music listening. However, musical predictions are typically studied with MMN stimulation paradigms based on Western tonal music, which are characterized by relatively high predictability. Hence, we developed an MMN paradigm to investigate how the high uncertainty of atonal music modulates predictive processes as indexed by the MMN and behavior. Using MEG in a group of 20 subjects without musical training, we demonstrate that the magnetic MMN in response to pitch, intensity, timbre, and location deviants is evoked in both tonal and atonal melodies, with no significant differences between conditions. In contrast, in a separate behavioral experiment involving 39 non-musicians, participants detected pitch deviants more accurately and rated confidence higher in the tonal than in the atonal musical context. These results indicate that contextual tonal uncertainty modulates processing stages in which conscious awareness is involved, although deviants robustly elicit low-level pre-attentive responses such as the MMN. The achievement of robust MMN responses, despite high tonal uncertainty, is relevant for future studies comparing groups of listeners’ MMN responses to increasingly ecological music stimuli.

Through long-term training, music experts acquire complex and specialized sensorimotor skills, which are paralleled by continuous neuro-anatomical and -functional adaptations. The underlying neuroplasticity mechanisms have been extensively explored in decades of research in music, cognitive, and translational neuroscience. However, the absence of a comprehensive review and quantitative meta-analysis prevents the plethora of variegated findings to ultimately converge into a unified picture of the neuroanatomy of musical expertise. Here, we performed a comprehensive neuroimaging meta-analysis of publications investigating neuro-anatomical and -functional differences between musicians (M) and non-musicians (NM). Eighty-four studies were included in the qualitative synthesis. From these, 58 publications were included in coordinate-based meta-analyses using the anatomic/activation likelihood estimation (ALE) method. This comprehensive approach delivers a coherent cortico-subcortical network encompassing sensorimotor and limbic regions bilaterally. Particularly, M exhibited higher volume/activity in auditory, sensorimotor, interoceptive, and limbic brain areas and lower volume/activity in parietal areas as opposed to NM. Notably, we reveal topographical (dis-)similarities between the identified functional and anatomical networks and characterize their link to various cognitive functions by means of meta-analytic connectivity modelling. Overall, we effectively synthesized decades of research in the field and provide a consistent and controversies-free picture of the neuroanatomy of musical expertise.

Cognitive assessment is a cornerstone of geriatric care. Cognitive impairment has the potential to significantly impact multiple phases of a person’s cancer care experience. Accurately identifying this vulnerability is a challenge for many cancer care clinicians, thus the use of validated cognitive assessment tools are recommended. As international cancer guidelines for older adults recommend Geriatric Assessment (GA) which includes an evaluation of cognition, clinicians need to be familiar with the overall interpretation of the commonly used cognitive assessment tools. This rapid review investigated the cognitive assessment tools that were most frequently recommended by Geriatric Oncology guidelines: Blessed Orientation-Memory-Concentration test (BOMC), Clock Drawing Test (CDT), Mini-Cog, Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Short Portable Mental Status Questionnaire (SPMSQ). A detailed appraisal of the strengths and limitations of each tool was conducted, with a focus on practical aspects of implementing cognitive assessment tools into real-world clinical settings. Finally, recommendations on choosing an assessment tool and the additional considerations beyond screening are discussed.

Objective Many tinnitus patients report cognitive deficits such as concentration and attention difficulties. The aim of this study was to comprehensively assess cognitive functioning in tinnitus patients using a standardized test battery, the repeatable battery for the assessment of neuropsychological status adjusted for hearing impaired individuals (RBANS-H). Study design Cross-sectional study. Setting Tertiary referral center. Participants Twenty-eight chronic tinnitus patients and 28 control participants, matched for sex, age, hearing loss, and education level. Intervention Diagnostic. Main outcome measures All participants completed the RBANS-H, which includes subtests probing immediate and delayed memory, visuospatial capabilities, language, and attention. The tinnitus patients completed the tinnitus functional index (TFI), a visual analogue scale (VAS) measuring subjective mean tinnitus loudness and the hyperacusis questionnaire (HQ). Results The total RBANS-H scores did not differ between tinnitus patients and controls. However, on the language subscale, mean scores of the tinnitus group (97.6 ± 11.0) were significantly lower than those of controls (104.4 ± 12.0), with correction for sex, age, hearing level, and education level (general linear model: p = 0.034). Post hoc t tests revealed a specific deficit concerning the semantic fluency subtest (tinnitus: 19.5 ± 6.2; control: 23.1 ± 5.9; p = 0.015). VAS scores for tinnitus loudness were negatively correlated to scores on the RBANS-H attention subscale (r = -0.48, p = 0.012). Conclusions The current study successfully employed the RBANS-H to provide a broader view on cognitive functioning in tinnitus patients. The results showed a specific negative influence of tinnitus on verbal fluency, which could be related to a deficit in executive cognitive control. Moreover, patients experiencing louder tinnitus performed worse on specific subtests concerning attention.

Purpose: To assess the contribution of rare variants in the genetic background toward variability of neurodevelopmental phenotypes in individuals with rare copy-number variants (CNVs) and gene-disruptive variants. Methods: We analyzed quantitative clinical information, exome sequencing, and microarray data from 757 probands and 233 parents and siblings who carry disease-associated variants. Results: The number of rare likely deleterious variants in functionally intolerant genes (“other hits”) correlated with expression of neurodevelopmental phenotypes in probands with 16p12.1 deletion (n=23, p=0.004) and in autism probands carrying gene-disruptive variants (n=184, p=0.03) compared with their carrier family members. Probands with 16p12.1 deletion and a strong family history presented more severe clinical features (p=0.04) and higher burden of other hits compared with those with mild/no family history (p=0.001). The number of other hits also correlated with severity of cognitive impairment in probands carrying pathogenic CNVs (n=53) or de novo pathogenic variants in disease genes (n=290), and negatively correlated with head size among 80 probands with 16p11.2 deletion. These co-occurring hits involved known disease-associated genes such as SETD5, AUTS2, and NRXN1, and were enriched for cellular and developmental processes. Conclusion: Accurate genetic diagnosis of complex disorders will require complete evaluation of the genetic background even after a candidate disease-associated variant is identified.

BACKGROUND: Trunk training after stroke is an effective method for improving trunk control, standing balance and mobility. The SWEAT2 study attempts to discover the underlying mechanisms leading to the observed mobility carry-over effects after trunk training. AIM: A secondary analysis investigating the effect of trunk training on muscle activation patterns, muscle synergies and motor unit recruitment of trunk and lower limbs muscles, aimed to provide new insights in gait recovery after stroke. DESIGN: Randomized controlled trial. SETTING: Monocentric study performed in the RevArte Rehabilitation Hospital (Antwerp, Belgium). POPULATION: Forty-five adults diagnosed with first stroke within five months, of which 39 completed treatment and were included in the analysis. METHODS: Participants received 16 hours of additional trunk training (N.=19) or cognitive training (N.=20) over the course of four weeks (1 hour, 4 times a week). They were assessed by an instrumented gait analysis with electromyography of trunk and lower limb muscles. Outcome measures were linear integrated normalized envelopes of the electromyography signal, the amount and composition of muscle synergies calculated by nonnegative matrix factorization and motor unit recruitment calculated, by mean center wavelet frequencies. Multivariate analysis with post-hoc analysis and statistical parametric mapping of the continuous curves were performed. RESULTS: No significant differences were found in muscle activation patterns and the amount of muscle synergies. In 42% of the subjects, trunk training resulted in an additional muscle synergy activating trunk muscles in isolation, as compared to 5% in the control group. Motor unit recruitment of the of trunk musculature showed decreased fast-twitch motor recruitment in the erector spinae muscle after trunk training: for the hemiplegic (t[37]=2.44, P=0.021) and non-hemiplegic erector spinae muscle (t[37]=2.36, P=0.024). CONCLUSIONS: Trunk training improves selective control and endurance of trunk musculature after sub-acute stroke. CLINICAL REHABILITATION IMPACT: What is new to the actual clinical rehabilitation knowledge is that: trunk training does not alter muscle activation patterns or the amount of muscle synergies over time; a decrease in fast-twitch motor recruitment in the erector spinae muscle was found during walking after trunk training; trunk training seems to increase the fatigue-resistance of the back muscles and enables more isolated activation.

The SNARC (Spatial-Numerical Association of Response Codes) effect (i.e., a tendency to associate small/large magnitude numbers with the left/right hand side) is prevalent across the whole lifespan. Because the ability to relate numbers to space has been viewed as a cornerstone in the development of mathematical skills, the relationship between the SNARC effect and math skills has been frequently examined. The results remain largely inconsistent. Studies testing groups of people with very low or very high skill levels in math sometimes found relationships between SNARC and math skills. So far, however, studies testing such extreme math skills level groups were mostly investigating the SNARC effect in individuals revealing math difficulties. Groups with above average math skills remain understudied, especially in regard to children. Here, we investigate the SNARC effect in gifted children, as compared to normally developing children (overall n = 165). Frequentist and Bayesian analysis suggested that the groups did not differ from each other in the SNARC effect. These results are the first to provide evidence for the SNARC effect in a relatively large sample of gifted (and mathematically highly skilled) children. In sum, our study provides another piece of evidence for no direct link between the SNARC effect and mathematical ability in childhood. The SNARC (Spatial-Numerical Association of Response Codes) effect (i.e., a tendency to associate small/large magnitude numbers with the left/right hand side) is prevalent across the whole lifespan. Because the ability to relate numbers to space has been viewed as a cornerstone in the development of mathematical skills, the relationship between the SNARC effect and math skills has been frequently examined. The results remain largely inconsistent. Studies testing groups of people with very low or very high skill levels in math sometimes found relationships between SNARC and math skills. So far, however, studies testing such extreme math skills level groups were mostly investigating the SNARC effect in individuals revealing math difficulties. Groups with above average math skills remain understudied, especially in regard to children. Here, we investigate the SNARC effect in gifted children, as compared to normally developing children (overall n = 165). Frequentist and Bayesian analysis suggested that the groups did not differ from each other in the SNARC effect. These results are the first to provide evidence for the SNARC effect in a relatively large sample of gifted (and mathematically highly skilled) children. In sum, our study provides another piece of evidence for no direct link between the SNARC effect and mathematical ability in childhood.

Variance in IQ is associated with a wide range of health outcomes, and 1% of the population are affected by intellectual disability. Despite a century of research, the fundamental neural underpinnings of intelligence remain unclear. We integrate results from genome-wide association studies (GWAS) of intelligence with brain tissue and single cell gene expression data to identify tissues and cell types associated with intelligence. GWAS data for IQ (N = 78,308) were meta-analyzed with a study comparing 1247 individuals with mean IQ ~170 to 8185 controls. Genes associated with intelligence implicate pyramidal neurons of the somatosensory cortex and CA1 region of the hippocampus, and midbrain embryonic GABAergic neurons. Tissue-specific analyses find the most significant enrichment for frontal cortex brain expressed genes. These results suggest specific neuronal cell types and genes may be involved in intelligence and provide new hypotheses for neuroscience experiments using model systems.

Spontaneous future cognitions refer to mental representations about the future that enter consciousness with no immediately preceding attempt of bringing them to mind. They are studied under different terms in several areas of psychology, but with little interdisciplinary exchange of findings and theoretical developments. Different conceptions of spontaneous future cognition derive from separate literatures and are rarely considered together, leaving their potential conceptual overlaps as well as their unique features unclarified. In this article, I review research on spontaneous future cognitions in relation to mind wandering, involuntary episodic future thoughts, and intrusive future imagery in cravings and clinical disorders. I conclude that more research is needed to clarify the potential functions served by spontaneous future cognitions in everyday life, under which conditions they may become dysfunctional, how they are triggered by situational cues, and how their content may be constrained by motivational factors and beliefs. The burgeoning field of spontaneous future cognitions forms a promising novel approach to the cognitive and motivational regulation of behavior in everyday life.

AIMS: Psychosocial factors are rarely collected in studies investigating the prognosis of patients with heart failure (HF), and only time to first event is commonly reported. We investigated the prognostic value of psychosocial factors for predicting first or recurrent events after discharge following hospitalization for HF. METHODS AND RESULTS: OPERA-HF is an observational study enrolling patients hospitalized for HF. In addition to clinical variables, psychosocial variables are recorded. Patients provide the information through questionnaires that include social information, depression and anxiety scores, and cognitive function. Kaplan-Meier, Cox regression and the Andersen-Gill model were used to identify predictors of first and recurrent events (readmissions or death). Of 671 patients (age 76 ± 15 years, 66% men) with 1-year follow-up, 291 had no subsequent event, 34 died without being readmitted, 346 had one or more unplanned readmissions, and 71 patients died after a first readmission. Increasing age, higher urea and creatinine, and the presence of co-morbidities (diabetes, history of myocardial infarction, chronic obstructive pulmonary disease) were all associated with increasing risk of first or recurrent events. Psychosocial variables independently associated with both the first and recurrent events were: presence of frailty, moderate-to-severe depression, and moderate-to-severe anxiety. Living alone and the presence of cognitive impairment were independently associated only with an increasing risk of recurrent events. CONCLUSION: Psychosocial factors are strongly associated with unplanned recurrent readmissions or mortality following an admission to hospital for HF. Further research is needed to show whether recognition of these factors and support tailored to individual patients' needs will improve outcomes.

Background and purpose Mechanisms underlying cognitive impairment in patients with small vessel disease (SVD) are still unknown. We hypothesized that cognition is affected by the cumulative effect of multiple SVD-related lesions on brain connectivity. We therefore assessed the relationship between the total SVD burden on MRI, global brain network efficiency, and cognition in memory clinic patients with vascular brain injury. Methods 173 patients from the memory clinic of the University Medical Center Utrecht underwent a 3 T brain MRI scan (including diffusion MRI sequences) and neuropsychological testing. MRI markers for SVD were rated and compiled in a previously developed total SVD score. Structural brain networks were reconstructed using fiber tractography followed by graph theoretical analysis. The relationship between total SVD burden score, global network efficiency and cognition was assessed using multiple linear regression analyses. Results Each point increase on the SVD burden score was associated with 0.260 [−0.404 - -0.117] SD units decrease of global brain network efficiency (p, Highlights • Increasing small vessel disease burden (SVD) related to decreasing network efficiency. • Network efficiency mediates association between SVD burden and processing speed. • Cumulative effect of SVD might partly affect cognition through disrupted connectivity.

This study aimed at examining cognitive predictors of reactive and proactive aggression in a forensic-psychiatric (n = 80) and a non-clinical sample (n = 98; Brugman et al., 2015). Three different cognitive predictors were incorporated: (1) attentional bias towards aggressive stimuli (measured with Emotional Stroop task) and towards angry faces (measured with a visual search task); (2) interpretation biases (measured with Aggressive Interpretative Bias Task (AIBT) and a vignette task), and (3) implicit self-aggression association (measured with a Single-Target Implicit Association Task). To measure aggression, the Reactive-Proactive Aggression Questionnaire (RPQ) and the Taylor Aggression Paradigm (TAP) were used. An automatic self-aggression association positively predicted proactive aggressive behavior on the TAP in both samples. Furthermore, this self-aggression association predicted, increased self-reported proactive aggression (RPQ) in the forensic sample only. Pain, injury, and danger interpretations reported on the vignettes, negatively predicted self-reported proactive aggression in both samples. A stronger aggressive interpretation bias on the AIBT predicted more reactive aggressive behavior (TAP) in the non-clinical sample only. Taken together, findings show both common and distinct mechanisms in reactively vs. proactively driven aggressive behavior.

Background Movement simulation helps increasing the chances to reach goals. A cognitive task used to study the neuro-behavioral aspects of movement simulation is mental rotation: people mentally re-orient rotated pictures of hands. However, the involvement of the primary motor cortex (M1) in mental rotation is largely controversial. Hypothesis Such inconsistency could arise from potential methodological flaws in experimental procedures and data analysis. In particular, until now, the timing of M1 activity has been computed in absolute terms: from the onset of mental rotation (onset-locked), neglecting intra- and inter-subject variability. Methods A novel phase-locked approach is introduced to synchronize the same phases of cognitive processing among different subjects and sessions. This approach was validated in the particular case of corticospinal excitability of the motor cortex during mental rotation. Results We identified the relative time-windows during which the excitability of M1 is effector-specifically modulated by different features of mental rotation. These time windows correspond to the 55%–85% of the subjective timing. Conclusions In sum, (i) we introduce a new method to study the neurophysiology of motor cognition, and (ii) validating this method, we shed new light on the involvement of M1 in movement simulation.

This large multi-center study investigates the relationships between genetic risk for schizophrenia and bipolar disorder, and multi-modal endophenotypes for psychosis. The sample included 4,242 individuals; 1,087 patients with psychosis, 822 unaffected first-degree relatives of patients, and 2,333 controls. Endophenotypes included the P300 event-related potential (N=515), lateral ventricular volume (N=798), and the cognitive measures block design (N=3,089), digit span (N=1,437), and the Ray Auditory Verbal Learning Task (N=2,406). Data were collected across 11 sites in Europe and Australia; all genotyping and genetic analyses were done at the same laboratory in the United Kingdom. We calculated polygenic risk scores for schizophrenia and bipolar disorder separately, and used linear regression to test whether polygenic scores influenced the endophenotypes. Results showed that higher polygenic scores for schizophrenia were associated with poorer performance on the block design task and explained 0.2% (p=0.009) of the variance. Associations in the same direction were found for bipolar disorder scores, but this was not statistically significant at the 1% level (p=0.02). The schizophrenia score explained 0.4% of variance in lateral ventricular volumes, the largest across all phenotypes examined, although this was not significant (p=0.063). None of the remaining associations reached significance after correction for multiple testing (with alpha at 1%). These results indicate that common genetic variants associated with schizophrenia predict performance in spatial visualization, providing additional evidence that this measure is an endophenotype for the disorder with shared genetic risk variants. The use of endophenotypes such as this will help to characterize the effects of common genetic variation in psychosis.

After a brief introduction to the background, significance and unique features of the centenarian population in China, we describe the Chinese Longitudinal Healthy Longevity Study (CLHLS), which is the world's largest study of centenarians, nonagenarians, octogenarians, and compatible young-old aged 65-79. Based on the CLHLS data and other relevant studies, we summarize demographic and socioeconomic characteristics as well as self-reported and objectively-tested health indicators of centenarians in China, with an emphasis on gender differences and rural/urban disparities. We then compare five-year-age-specific trajectories of physical and cognitive functions, self-reported health, and life satisfactions from ages 65-69 to 100+, concluding that good psychological resilience and optimism are keys to the exceptional longevity enjoyed by centenarians. We discuss recent findings of novel loci and pathways that are significantly associated with longevity based on the genome-wide association study (GWAS) of the CLHLS centenarian sample, which is 2.7 times as large as prior GWAS of longevity. We also highlight colleagues' and our own studies on longevity candidate genes and gene-environment interaction analyses. Finally, we discuss limitations inherent in our studies of centenarians in China and further research perspectives. After a brief introduction to the background, significance and unique features of the centenarian population in China, we describe the Chinese Longitudinal Healthy Longevity Study (CLHLS), which is the world's largest study of centenarians, nonagenarians, octogenarians, and compatible young-old aged 65-79. Based on the CLHLS data and other relevant studies, we summarize demographic and socioeconomic characteristics as well as self-reported and objectively-tested health indicators of centenarians in China, with an emphasis on gender differences and rural/urban disparities. We then compare five-year-age-specific trajectories of physical and cognitive functions, self-reported health, and life satisfactions from ages 65-69 to 100+, concluding that good psychological resilience and optimism are keys to the exceptional longevity enjoyed by centenarians. We discuss recent findings of novel loci and pathways that are significantly associated with longevity based on the genome-wide association study (GWAS) of the CLHLS centenarian sample, which is 2.7 times as large as prior GWAS of longevity. We also highlight colleagues' and our own studies on longevity candidate genes and gene-environment interaction analyses. Finally, we discuss limitations inherent in our studies of centenarians in China and further research perspectives.

Introduction: Reference values to define cognitive impairment in individuals aged 90 years and older are lacking. We systematically reviewed the literature to determine the level of cognitive functioning of individuals aged 90 years and older without dementia. Methods: The search identified 3972 articles of which 20 articles were included in the review. We calculated mean cognitive test scores and cut-off scores for cognitive tests published in two or more articles. Results: The mean cognitive test scores (SD)/cut-off scores for individuals aged 90 years and older without dementia of the five most commonly used cognitive tests were: MMSE: 26.6 (2.6)/23.3 points, Digit Span forward: 5.9 (1.8)/3.6 digits, Digit Span backward: 4.4 (1.6)/2.4 digits, TMT-A: 85.8 (42.5)/140.2 s and TMT-B: 220.3 (99.2)/347.3 s. Discussion: We provided mean cognitive test scores and cut-off scores that will improve the diagnostic process of cognitive impairment in individuals aged 90 years and older. (C) 2017 Elsevier B.V. All rights reserved.

Exposure to childhood trauma has been associated with psychotic symptoms, being at ultra-high risk for psychosis (UHR), and psychotic disorders such as schizophrenia. Negative self-beliefs have been shown to partially mediate the relationship between childhood trauma and paranoia and have been shown to be characteristic of patients with psychosis. However, whether the association between childhood trauma and being at high risk of developing psychosis (e.g., UHR) and paranoia symptoms is mediated by altered cognitive schema is unknown and warrants investigation to inform preventive interventions. Data was collected on 30 UHR patients from Outreach and Support in South London about exposure to childhood trauma, cognitive schema, paranoia and cannabis use. Relative to healthy controls (n = 38), UHR patients were significantly more likely to report exposure to various types of childhood trauma (emotional and sexual abuse, and emotional and physical neglect), had more negative schema and less positive schema about themselves and others, and were more likely to use cannabis more than once a month. Emotional neglect was found to be significantly associated with UHR status even after controlling for the effects of previous exposure to cannabis use (b = 0.262, 95% CI: 0.115–0.408), and this association was partially mediated by negative self-schema (b = 0.045, 95% CI: 0.004–0.159). Similarly, emotional neglect was significantly associated with paranoia (b = 1.354, 95% CI: 0.246-2.462), and this association was partially mediated by negative self-schema (b = 0.988, 95% CI: 0.323-1.895). These findings provide preliminary evidence about the cognitive mechanisms that may underlie the association between childhood trauma and later risk for psychosis.

Microvascular dysfunction may be associated with worse cognitive performance. Most previous studies did not adjust for important confounders, evaluated only individual measures of microvascular dysfunction, and showed inconsistent results. We evaluated the association between a comprehensive set of measures of microvascular dysfunction and cognitive performance in the population-based Maastricht Study. We used cross-sectional data including 3011 participants (age 59.5 +/- 8.2; 48.9% women; 26.5% type 2 diabetes mellitus [oversampled by design]). Measures of microvascular dysfunction included magnetic resonance imaging features of cerebral small vessel disease, plasma biomarkers of microvascular dysfunction, albuminuria, flicker light-induced retinal arteriolar and venular dilation response and heat-induced skin hyperemia. These measures were summarized into a microvascular dysfunction composite score. Cognitive domains assessed were memory, processing speed, and executive function. A cognitive function score was calculated as the sum of the scores on these 3 cognitive domains. The microvascular dysfunction score was associated with a worse cognitive function score (standardized beta, -0.087 [95% CI, -0.127 to -0.047]), independent of age, education level, sex, type 2 diabetes mellitus, smoking, alcohol use, hypertension, total/HDL (high-density lipoprotein) cholesterol ratio, triglycerides, lipid-modifying medication, prior cardiovascular disease, depression and plasma biomarkers of low-grade inflammation. The fully adjusted beta-coefficient of the association between the microvascular dysfunction score and the cognitive function score was equivalent to 2 (range, 1-3) years of aging for each SD higher microvascular dysfunction score. The microvascular dysfunction score was associated with worse memory and processing speed but not with worse executive function. The present study shows that microvascular dysfunction is associated with worse cognitive performance.

Purpose Premorbid conditions affect prognosis of acutely-ill aged patients. Several lines of evidence suggest geriatric syndromes need to be assessed but little is known on their relative effect on the 30-day survival after ICU admission. The primary aim of this study was to describe the prevalence of frailty, cognition decline and activity of daily life in addition to the presence of comorbidity and polypharmacy and to assess their influence on 30-day survival. Methods Prospective cohort study with 242 ICUs from 22 countries. Patients 80 years or above acutely admitted over a six months period to an ICU between May 2018 and May 2019 were included. In addition to common patients’ characteristics and disease severity, we collected information on specific geriatric syndromes as potential predictive factors for 30-day survival, frailty (Clinical Frailty scale) with a CFS > 4 defining frail patients, cognitive impairment (informant questionnaire on cognitive decline in the elderly (IQCODE) with IQCODE ≥ 3.5 defining cognitive decline, and disability (measured the activity of daily life with the Katz index) with ADL ≤ 4 defining disability. A Principal Component Analysis to identify co-linearity between geriatric syndromes was performed and from this a multivariable model was built with all geriatric information or only one: CFS, IQCODE or ADL. Akaike’s information criterion across imputations was used to evaluate the goodness of fit of our models. Results We included 3920 patients with a median age of 84 years (IQR: 81–87), 53.3% males). 80% received at least one organ support. The median ICU length of stay was 3.88 days (IQR: 1.83–8). The ICU and 30-day survival were 72.5% and 61.2% respectively. The geriatric conditions were median (IQR): CFS: 4 (3–6); IQCODE: 3.19 (3–3.69); ADL: 6 (4–6); Comorbidity and Polypharmacy score (CPS): 10 (7–14). CFS, ADL and IQCODE were closely correlated. The multivariable analysis identified predictors of 1-month mortality (HR; 95% CI): Age (per 1 year increase): 1.02 (1.–1.03, p = 0.01), ICU admission diagnosis, sequential organ failure assessment score (SOFA) (per point): 1.15 (1.14–1.17, p

Contains fulltext : 218973.pdf (Publisher’s version ) (Open Access) Aging is associated with cognitive decline, specifically in episodic memory. However, there are large individual differences in the extent of this decline and previous research suggests that these are associated with differences in executive functioning (EF). These EF differences, and associated differences in the encoding and retrieval of episodic information, have been linked to differences in the activation of particular brain regions. The "encoding/retrieval flip" (E/R flip) framework assumes deactivation and activation of specific brain regions during successful encoding and retrieval, respectively. The present study assessed whether this framework can be used to explain EF-based individual differences in memory performance of young and older participants. Young adults (N = 19) and older adults (N = 39) performed an incidental semantic encoding and memory recognition task in an fMRI setting, focusing on brain regions that show the E/R flip. The association between an index of EF and fMRI activity in brain regions showing the E/R flip was tested in each age group. EF predicted E/R flip activity in the older, but not young adults. These findings underscore the importance of individual differences in ageing research and provide empirical evidence for the association between EF and the E/R flip. 5 p.

In this study we aimed to determine whether decision-making ability, cognitive inflexibility and emotion-driven impulsiveness are associated with weight status as expressed by body mass index (BMI), percentage body fat, waist circumference and skinfold thickness in adults from eight different European countries taking part in the I.Family study. The Bechara Gambling Task was used to assess decision-making ability (n = 1717). The Berg Card Sorting Test was used to measure cognitive inflexibility (n = 1509). Lastly, the negative urgency subscale from the UPPS-P Impulsive Behavior Scale was used to measure emotion-driven impulsiveness (n = 4450). Hierarchical regression analyses showed that more emotion-driven impulsiveness was statistically significantly associated with a higher BMI, a higher percentage body fat, and a larger waist circumference in adults, controlling for age, sex, socioeconomic status, country and binge eating; but not with skinfold thickness. Cognitive inflexibility and decision-making ability were not statistically significantly associated with any of the weight status related variables. These results support that impulsivity in response to negative emotions, but not decision-making ability or cognitive inflexibility, is associated with the susceptibility to excessive weight (as indicated by a higher BMI, a higher percentage body fat, and a larger waist circumference). In people behaving impulsively when emotional, focusing on reducing negative affect or improving coping skills is of interest in interventions targeting obesity. CLINICAL TRIAL REGISTRATION: The I.Family study is registered in the ISRCTN registry (ISRCTN62310987) on February 23, 2018.

Neuroscience findings have recently received critique on the lack of replications. To examine the reproducibility of brain indices of speech sound discrimination and their role in dyslexia, a specific reading difficulty, brain event-related potentials using EEG were measured using the same cross-linguistic passive oddball paradigm in about 200 dyslexics and 200 typically reading 8–12-year-old children from four countries with different native languages. Brain responses indexing speech and non-speech sound discrimination were extremely reproducible, supporting the validity and reliability of cognitive neuroscience methods. Significant differences between typical and dyslexic readers were found when examined separately in different country and language samples. However, reading group differences occurred at different time windows and for different stimulus types between the four countries. This finding draws attention to the limited generalizability of atypical brain response findings in children with dyslexia across language environments and raises questions about a common neurobiological factor for dyslexia. Our results thus show the robustness of neuroscience methods in general while highlighting the need for multi-sample studies in the brain research of language disorders.

AIM: To investigate the effects of 8-weeks of CT on specific domains of cognitive function, metabolic and cardiovascular parameters of subjects with Type 2 Diabetes Mellitus (T2DM). METHODS: 31 sedentary T2DM adults and older divided into CT (3x/week, during 8-week, n = 16) or Control group (CONT, n = 15). Before and after the intervention, a cognitive task battery, blood samples, and functional tests were assessed. RESULTS: CT improved inhibitory control (d = 0.89), working memory (d = 0.88), cognitive flexibility (d = 0.67) and attention/concentration (d = 0.64) in T2DM subjects. However, memory, verbal fluency, and processing speed (d < 0.1, p > 0.05 for all) were not changed. The CT-induced improvements on global cognitive z-score (r = -0.51; p < 0.001) were inversely correlated to cognitive screening scores. Moreover, CT improved functional performance (p < 0.05) and reduced insulin levels (p = 0.04). Although there was no statistical significance, there were a clinically relevant reduction of peripheral insulin sensitivity (d = 0.51, p = 0.09), resistin levels (d = 0.53, p = 0.08), diastolic (d = 0.63, p = 0.09) and mean blood pressure (d = 0.50, p = 0.09). Conversely, no changes were observed for glucose, fructosamine and blood lipids (d < 0.2 for all). CONCLUSION: CT partially reversed the negative effects of T2DM on specific cognitive domains possibly by amelioration of metabolic regulation. Moreover, lower cognitive scores may modulate the responsivity of cognitive function to CT.

Major mood disorders, which primarily include bipolar disorder and major depressive disorder, are the leading cause of disability worldwide and pose a major challenge in identifying robust risk genes. Here, we present data from independent large-scale clinical data sets (including 29 557 cases and 32 056 controls) revealing brain expressed protocadherin 17 (PCDH17) as a susceptibility gene for major mood disorders. Single-nucleotide polymorphisms (SNPs) spanning the PCDH17 region are significantly associated with major mood disorders; subjects carrying the risk allele showed impaired cognitive abilities, increased vulnerable personality features, decreased amygdala volume and altered amygdala function as compared with non-carriers. The risk allele predicted higher transcriptional levels of PCDH17 mRNA in postmortem brain samples, which is consistent with increased gene expression in patients with bipolar disorder compared with healthy subjects. Further, overexpression of PCDH17 in primary cortical neurons revealed significantly decreased spine density and abnormal dendritic morphology compared with control groups, which again is consistent with the clinical observations of reduced numbers of dendritic spines in the brains of patients with major mood disorders. Given that synaptic spines are dynamic structures which regulate neuronal plasticity and have crucial roles in myriad brain functions, this study reveals a potential underlying biological mechanism of a novel risk gene for major mood disorders involved in synaptic function and related intermediate phenotypes.