Developmental dyslexia susceptibility genes DNAAF4, DCDC2, and NRSN1 are associated with brain function in fluently reading adolescents and young adults.

Reading skills and developmental dyslexia, characterized by difficulties in developing reading skills, have been associated with brain anomalies within the language network. Genetic factors contribute to developmental dyslexia risk, but the mechanisms by which these genes influence reading skills remain unclear. In this preregistered study (https://osf.io/7sehx), we explored if developmental dyslexia susceptibility genes DNAAF4, DCDC2, NRSN1, and KIAA0319 are associated with brain function in fluently reading adolescents and young adults. Functional MRI and task performance data were collected during tasks involving written and spoken sentence processing, and DNA sequence variants of developmental dyslexia susceptibility genes previously associated with brain structure anomalies were genotyped. The results revealed that variation in DNAAF4, DCDC2, and NRSN1 is associated with brain activity in key language regions: the left inferior frontal gyrus, middle temporal gyrus, and intraparietal sulcus. Furthermore, NRSN1 was associated with task performance, but KIAA0319 did not yield any significant associations. Our findings suggest that individuals with a genetic predisposition to developmental dyslexia may partly employ compensatory neural and behavioral mechanisms to maintain typical task performance. Our study highlights the relevance of these developmental dyslexia susceptibility genes in language-related brain function, even in individuals without developmental dyslexia, providing valuable insights into the genetic factors influencing language processing.

Strategy use and its evolvement in word list learning: a replication study.

Spontaneous strategy employment is important for memory performance, but systematic research on strategy use and within-task evolvement is limited. This online study aimed to replicate three main findings by Waris and colleagues in Quarterly Journal of Experimental Psychology (2021): in word-list learning, spontaneous strategy use (1) predicts better task performance, (2) stabilizes along the task, and (3) increases during the first two task blocks. We administered a shortened version of their original real-word list-learning task to 209 neurotypical adults. Their first finding was partly replicated: manipulation strategies (grouping, visualization, association, narrative, other strategy) but not maintenance strategies (rehearsal/repetition, selective focus) were associated with superior word recall. The second finding on the decrease in strategy changers over task blocks was replicated. The third finding turned out to be misguided: neither our nor the original study showed task-initial increase in strategy use in the real-word learning condition. Our results confirm the important role of spontaneous strategies in understanding memory performance and the existence of task-initial dynamics in strategy employment. They support the general conclusions by Waris and colleagues: task demands can trigger strategy use even in a familiar task like learning a list of common words, and evolution of strategy use during a memory task reflects cognitive skill learning.

Virtual reality tasks with eye tracking for mild spatial neglect assessment: a pilot study with acute stroke patients.

Objective: Increasing evidence shows that traditional neuropsychological tests are insensitive for detecting mild unilateral spatial neglect (USN), lack ecological validity, and are unable to clarify USN in all different spatial domains. Here we present a new, fully immersive virtual reality (VR) task battery with integrated eye tracking for mild visual USN and extinction assessment in the acute state of stroke to overthrow these limitations. Methods: We included 11 right-sided stroke patients and 10 healthy controls aged 18-75 years. Three VR tasks named the Extinction, the Storage and the Shoot the target tasks were developed to assess USN. Furthermore, neuropsychological assessment examining various parts of cognitive functioning was conducted to measure general abilities. We compared VR and neuropsychological task performance in stroke patients - those with (USN+, n = 5) and without USN (USN-, n = 6) - to healthy controls (n = 10) and tentatively reported the usability of VR system in the acute state of stroke. Results: Patients had mostly mild neurological and USN symptoms. Nonetheless, we found several differences between the USN+ and healthy control groups in VR task performance. Compared to controls, USN+ patients showed visual extinction and asymmetry in gaze behavior and detection times in distinct spatial locations. Extinction was most evident in the extrapersonal space and delayed detection times on the extreme left and on the left upper parts. Also, USN+ patients needed more time to complete TMT A compared with USN- patients and TMT B compared with controls. VR system usability and acceptance were rated high; no relevant adverse effects occurred. Conclusion: New VR technology with eye tracking enables ecologically valid and objective assessment methods with various exact measures for mild USN and thus could potentially improve future clinical assessments.

Self-reported strategy use in working memory tasks.

Mnemonic strategies can facilitate working memory performance, but our knowledge on strategy use as a function of task characteristics remains limited. We examined self-reported strategy use in several working memory tasks with pretest data from two large-scale online training experiments. A three-level measure of strategy sophistication (no strategy, maintenance, manipulation) was coded based on participants' open-ended strategy reports. A considerable portion of participants reported some memory strategy, and strategy sophistication was associated with objective task performance. We found a consistent effect of stimulus type: verbal stimuli (letters or digits) elicited higher strategy sophistication than nonverbal ones (colours or spatial positions). In contrast, the association between task paradigm and strategy sophistication was less consistent in the two experiments. The present results highlight the importance of self-generated strategies in understanding individual differences in working memory performance and the role of stimulus characteristics as one of the task-related determinants of strategy use.

Spontaneous memory strategies in a videogame simulating everyday memory tasks.

People can use different internal strategies to manage their daily tasks, but systematic research on these strategies and their significance for actual performance is still quite sparse. Here we examined self-reported internal strategy use with a 10-block version of the videogame EPELI (Executive Performance in Everyday LIving) in a group of 202 neurotypical adults of 18-50 years of age. In the game, participants perform lists of everyday tasks from memory while navigating in a virtual apartment. Open-ended strategy reports were collected after each EPELI task block, and for comparison also after an EPELI Instruction Recall task and a Word List Learning task assessing episodic memory. On average, 45% of the participants reported using some strategy in EPELI, the most common types being grouping (e.g., performing the tasks room by room), utilising a familiar action schema, and condensing information (e.g., memorising only keywords). Our pre-registered hypothesis on the beneficial effect of self-initiated strategy use gained support, as strategy users showed better performance on EPELI as compared with no strategy users. One of the strategies, grouping, was identified as a clearly effective strategy type. Block-by-block transitions suggested gradual stabilisation of strategy use over the 10 EPELI blocks. The proneness to use strategies showed a weak but reliable association between EPELI and Word List Learning. Overall, the present results highlight the importance of internal strategy use for understanding individual differences in memory performance, as well as the potential benefit for internal strategy employment when faced with everyday memory tasks.

Abnormal wiring of the structural connectome in adults with ADHD.

Current knowledge of white matter changes in large-scale brain networks in adult attention-deficit/hyperactivity disorder (ADHD) is scarce. We collected diffusion-weighted magnetic resonance imaging data in 40 adults with ADHD and 36 neurotypical controls and used constrained spherical deconvolution-based tractography to reconstruct whole-brain structural connectivity networks. We used network-based statistic (NBS) and graph theoretical analysis to investigate differences in these networks between the ADHD and control groups, as well as associations between structural connectivity and ADHD symptoms assessed with the Adult ADHD Self-Report Scale or performance in the Conners Continuous Performance Test 2 (CPT-2). NBS revealed decreased connectivity in the ADHD group compared to the neurotypical controls in widespread unilateral networks, which included subcortical and corticocortical structures and encompassed dorsal and ventral attention networks and visual and somatomotor systems. Furthermore, hypoconnectivity in a predominantly left-frontal network was associated with higher amount of commission errors in CPT-2. Graph theoretical analysis did not reveal topological differences between the groups or associations between topological properties and ADHD symptoms or task performance. Our results suggest that abnormal structural wiring of the brain in adult ADHD is manifested as widespread intrahemispheric hypoconnectivity in networks previously associated with ADHD in functional neuroimaging studies.

Narrative simulation of social experiences in naturalistic context - A neurocinematic approach.

Narratives may be regarded as simulations of everyday social situations. They are key to studying the human mind in socio-culturally determined contexts as they allow anchoring to the common ground of embodied and environmentally-engaged cognition. Here we review recent findings from naturalistic neuroscience on neural functions in conditions that mimic lifelike situations. We will focus particularly on neurocinematics, a research field that applies mediated narratives as stimuli for neuroimaging experiments. During the last two decades, this paradigm has contributed to an accumulation of insights about the neural underpinnings of behavior and sense-making in various narratively contextualized situations particularly pertaining to socio-emotional encounters. One of the key questions in neurocinematics is, how do intersubjectively synchronized brain activations relate to subjective experiences? Another question we address is how to bring natural contexts into experimental studies. Seeking to respond to both questions, we suggest neurocinematic studies to examine three manifestations of the same phenomenon side-by-side: subjective experiences of narrative situations, unfolding of narrative stimulus structure, and neural processes that co-constitute the experience. This approach facilitates identifying experientially meaningful activity patterns in the brain and points out what they may mean in relation to shared and communicable contents. Via rich-featured and temporally contextualized narrative stimuli, neurocinematics attempts to contribute to emerging holistic theories of neural dynamics and connectomics explaining typical and atypical interindividual variability.

Assessment of goal-directed behavior and prospective memory in adult ADHD with an online 3D videogame simulating everyday tasks.

The diagnosis of ADHD is based on real-life attentional-executive deficits, but they are harder to detect in adults than in children and objective quantitative measures reflecting these everyday problems are lacking. We developed an online version of EPELI 3D videogame for naturalistic and scalable assessment of goal-directed action and prospective memory in adult ADHD. In EPELI, participants perform instructed everyday chores in a virtual apartment from memory. Our pre-registered hypothesis predicted weaker EPELI performances in adult ADHD compared to controls. The sample comprised 112 adults with ADHD and 255 neurotypical controls comparable in age (mean 31, SD = 8 years), gender distribution (71% females) and educational level. Using web-browser, the participants performed EPELI and other cognitive tasks, including Conner's Continuous Performance Test (CPT). They also filled out questionnaires probing everyday executive performance and kept a 5-day diary of everyday prospective memory errors. Self-reported strategy use in the EPELI game was also examined. The ADHD participants' self-ratings indicated clearly more everyday executive problems than in the controls. Differences in the EPELI game were mostly seen in the ADHD participants' higher rates of task-irrelevant actions. Gender differences and a group × gender interaction was found in the number of correctly performed tasks, indicating poorer performance particularly in ADHD males. Discriminant validity of EPELI was similar to CPT. Strategy use strongly predicted EPELI performance in both groups. The results demonstrate the feasibility of EPELI for online assessment and highlight the role of impulsivity as a distinctive everyday life problem in adult ADHD.

Assessment of goal-directed behavior with the 3D videogame EPELI: Psychometric features in a web-based adult sample.

EPELI (Executive Performance in Everyday LIving) is a recently developed gaming tool for objective assessment of goal-directed behavior and prospective memory (PM) in everyday contexts. This pre-registered study examined psychometric features of a new EPELI adult online version, modified from the original child version and further developed for self-administered web-based testing at home. A sample of 255 healthy adults completed EPELI where their task was to perform household chores instructed by a virtual character. The participants also filled out PM-related questionnaires and a diary and performed two conventional PM tasks and an intelligence test. We expected that the more "life-like" EPELI task would show stronger associations with conventional PM questionnaires and diary-based everyday PM reports than traditional PM tasks would do. This hypothesis did not receive support. Although EPELI was rated as more similar to everyday tasks, performance in it was not associated with the questionnaires and the diary. However, there were associations between time-monitoring behavior in EPELI and the traditional PM tasks. Taken together, online adult-EPELI was found to be a reliable method with high ecological face validity, but its convergent validity requires further research.

EPELI: a novel virtual reality task for the assessment of goal-directed behavior in real-life contexts.

A recently developed virtual reality task, EPELI (Executive Performance in Everyday LIving), quantifies goal-directed behavior in naturalistic conditions. Participants navigate a virtual apartment, performing household chores given by a virtual character. EPELI aims to tap attention, executive function, and prospective memory. To ensure its applicability to further research and clinical work and to study its relationship to relevant background factors, we examined several key properties of EPELI in 77 typically developing 9-13-year-old children. These included EPELI's internal consistency, age and gender differences, sensitivity to gaming experience, head-mounted display (HMD) type, and verbal recall ability, as well as its relationships with parent-rated everyday executive problems. Of the eight EPELI measures, the following six showed acceptable internal consistency: task and navigation efficacy, number of correctly performed tasks and overall actions, time monitoring, and controller movement. Some measures were associated with age, gender, or verbal encoding ability. Moreover, EPELI performance was associated with parent-rated everyday executive problems. There were no significant associations of gaming background, task familiarity, or HMD type with the EPELI measures. These results attest to the reliability and ecological validity of this new virtual reality tool for the assessment of attention, executive functions, and prospective memory in children.

Eye movement behavior in a real-world virtual reality task reveals ADHD in children.

Eye movements and other rich data obtained in virtual reality (VR) environments resembling situations where symptoms are manifested could help in the objective detection of various symptoms in clinical conditions. In the present study, 37 children with attention deficit hyperactivity disorder and 36 typically developing controls (9-13 y.o) played a lifelike prospective memory game using head-mounted display with inbuilt 90 Hz eye tracker. Eye movement patterns had prominent group differences, but they were dispersed across the full performance time rather than associated with specific events or stimulus features. A support vector machine classifier trained on eye movement data showed excellent discrimination ability with 0.92 area under curve, which was significantly higher than for task performance measures or for eye movements obtained in a visual search task. We demonstrated that a naturalistic VR task combined with eye tracking allows accurate prediction of attention deficits, paving the way for precision diagnostics.

Grandiosity, vulnerability, and narcissistic fluctuation: Examining reliability, measurement invariance, and construct validity of four brief narcissism measures.

Continued interest in the distinction between grandiose narcissism, vulnerable narcissism and the fluctuation between grandiose and vulnerable states has expanded the repertoire of self-report instruments. The present study examined the psychometric properties of four brief narcissism measures [the Narcissistic Personality Inventory-13 (NPI-13), Hypersensitive Narcissism Scale (HSNS), Super-Brief Pathological Narcissism Inventory (SB-PNI), and the g-FLUX] in a Finnish sample of university students. Confirmatory factor analyses supported the reliability of the NPI-13, g-FLUX, SB-PNI Vulnerability, and two HSNS subfactors (Oversensitivity and Egocentrism). Tests of measurement invariance indicated the NPI-13, SB-PNI Vulnerability, HSNS Oversensitivity, and the g-FLUX perform similarly between males and females and are generally similar between individuals in younger and older age groups. Construct and predictive validity were evaluated by examining relations between narcissism measures and relevant criteria including psychopathology symptoms, self-esteem, well-being, five factor traits, and empathy. Results supported the construct validity of all four measures, while correlational profiles highlighted the convergence between the g-FLUX and measures of both grandiosity and vulnerability. The NPI-13 was most predictive of NPD symptoms, whereas vulnerable narcissism measures were most predictive of psychopathology. Results further establish the psychometric properties of the NPI-13, SB-PNI Vulnerability, HSNS Oversensitivity, Egocentrism, and provide new validation of the g-FLUX.

Early life stress is associated with the default mode and fronto-limbic network connectivity among young adults.

Exposure to early life stress (ELS) is associated with a variety of detrimental psychological and neurodevelopmental effects. Importantly, ELS has been associated with regional alterations and aberrant connectivity in the structure and functioning of brain regions involved in emotion processing and self-regulation, creating vulnerability to mental health problems. However, longitudinal research regarding the impact of ELS on functional connectivity between brain regions in the default mode network (DMN) and fronto-limbic network (FLN), both implicated in emotion-related processes, is relatively scarce. Neuroimaging research on ELS has mostly focused on single nodes or bi-nodal connectivity instead of functional networks. We examined how ELS is associated with connectivity patterns within the DMN and FLN during rest in early adulthood. The participants (n = 86; 47 females) in the current functional magnetic resonance imaging (fMRI) study were young adults (18-21 years old) whose families had participated in a longitudinal study since pregnancy. ELS was assessed both prospectively (parental reports of family relationship problems and mental health problems during pregnancy and infancy) and retrospectively (self-reported adverse childhood experiences). Inter-subject representational similarity analysis (IS-RSA) and multivariate distance matrix regression (MDMR) were used to analyze the association between ELS and the chosen networks. The IS-RSA results suggested that prospective ELS was associated with complex alterations within the DMN, and that retrospective ELS was associated with alterations in the FLN. MDMR results, in turn, suggested that that retrospective ELS was associated with DMN connectivity. Mean connectivity of the DMN was also associated with retrospective ELS. Analyses further showed that ELS-related alterations in the FLN were associated with increased connectivity between the prefrontal and limbic regions, and between different prefrontal regions. These results suggest that exposure to ELS in infancy might have long-lasting influences on functional brain connectivity that persist until early adulthood. Our results also speak for the importance of differentiating prospective and retrospective assessment methods to understand the specific neurodevelopmental effects of ELS.

Brain structural alterations in autism and criminal psychopathy.

The goal of this study was to elucidate the anatomical brain basis of social cognition through two disorders with distinctively different phenotypes of social interaction. We compared structural MR images of 20 individuals with autism spectrum disorder (ASD), 19 violent offenders with high psychopathic traits, and 19 control participants using voxel-based morphometry (VBM). Our earlier study showed lower grey matter volume (GMV) values in the insula, frontal cortex, and sensorimotor cortex of the offender group compared to controls. In the present study, the images of the ASD group revealed lower GMV in the left precuneus, right cerebellum, and right precentral gyrus in comparison with controls. The comparison between the offender and ASD groups showed lower GMV values for the right temporal pole and left inferior frontal gyrus in the offender group. There was also an overlap of both disorders in the right pre-central cortex, showing lower GMV compared to controls. Our findings suggest structural differences between violent offenders with high psychopathy traits and ASD individuals in the frontotemporal social brain network areas, previously associated with empathy. We also provide evidence of similar abnormal structures in the motor cortex for both of these disorders, possibly related to uniting issues of social cognition.

Quantifying ADHD Symptoms in Open-Ended Everyday Life Contexts With a New Virtual Reality Task.

OBJECTIVE: To quantify goal-directed behavior and ADHD symptoms in naturalistic conditions, we developed a virtual reality task, EPELI (Executive Performance in Everyday LIving), and tested its predictive, discriminant and concurrent validity. METHOD: We collected EPELI data, conventional neuropsychological task data, and parent-ratings of executive problems and symptoms in 38 ADHD children and 38 typically developing controls. RESULTS: EPELI showed predictive validity as the ADHD group exhibited higher percentage of irrelevant actions reflecting lower attentional-executive efficacy and more controller movements and total game actions, both indicative of hyperactivity-impulsivity. Further, the five combined EPELI measures showed excellent discriminant validity (area under curve 88 %), while the correlations of the EPELI efficacy measure with parent-rated executive problems (r = .57) and ADHD symptoms (r = .55) pointed to its concurrent validity. CONCLUSION: We provide a proof-of-concept validation for a new virtual reality tool for ecologically valid assessment of ADHD symptoms.

Disentangling the Role of Working Memory in Parkinson's Disease.

Working memory (WM) represents a core cognitive function with a major striatal contribution, and thus WM deficits, commonly observed in Parkinson's disease (PD), could also relate to many other problems in PD patients. Our online study aimed to determine the subdomains of WM that are particularly affected in PD and to clarify the links between WM and everyday cognitive deficits, other executive functions, psychiatric and PD symptoms, as well as early cognitive impairment. Fifty-two mild-to-moderate PD patients and 54 healthy controls performed seven WM tasks tapping selective updating, continuous monitoring, or maintenance of currently active information. Self-ratings of everyday cognition, depression, and apathy symptoms, as well as screenings of global cognitive impairment, were also collected. The data were analyzed using structural equation modeling. Of the three WM domains, only selective updating was directly predictive of PD group membership. More widespread WM deficits were observed only in relation to global cognitive impairment in PD patients. Self-rated everyday cognition or psychiatric symptoms were not linked to WM performance but correlated with each other. Our findings suggest that WM has a rather limited role in the clinical manifestation of PD. Nevertheless, due to its elementary link to striatal function, the updating component of WM could be a candidate for a cognitive marker of PD also in patients who are otherwise cognitively well-preserved.

Working memory training restores aberrant brain activity in adult attention-deficit hyperactivity disorder.

The development of treatments for attention impairments is hampered by limited knowledge about the malleability of underlying neural functions. We conducted the first randomized controlled trial to determine the modulations of brain activity associated with working memory (WM) training in adults with attention-deficit hyperactivity disorder (ADHD). At baseline, we assessed the aberrant functional brain activity in the n-back WM task by comparing 44 adults with ADHD with 18 healthy controls using fMRI. Participants with ADHD were then randomized to train on an adaptive dual n-back task or an active control task. We tested whether WM training elicits redistribution of brain activity as observed in healthy controls, and whether it might further restore aberrant activity related to ADHD. As expected, activity in areas of the default-mode (DMN), salience (SN), sensory-motor (SMN), frontoparietal (FPN), and subcortical (SCN) networks was decreased in participants with ADHD at pretest as compared with healthy controls, especially when the cognitive load was high. WM training modulated widespread FPN and SN areas, restoring some of the aberrant activity. Training effects were mainly observed as decreased brain activity during the trained task and increased activity during the untrained task, suggesting different neural mechanisms for trained and transfer tasks.

ADHD desynchronizes brain activity during watching a distracted multi-talker conversation.

Individuals with attention-deficit/hyperactivity disorder (ADHD) have difficulties navigating dynamic everyday situations that contain multiple sensory inputs that need to either be attended to or ignored. As conventional experimental tasks lack this type of everyday complexity, we administered a film-based multi-talker condition with auditory distractors in the background. ADHD-related aberrant brain responses to this naturalistic stimulus were identified using intersubject correlations (ISCs) in functional magnetic resonance imaging (fMRI) data collected from 51 adults with ADHD and 29 healthy controls. A novel permutation-based approach introducing studentized statistics and subject-wise voxel-level null-distributions revealed that several areas in cerebral attention networks and sensory cortices were desynchronized in participants with ADHD (n = 20) relative to healthy controls (n = 20). Specifically, desynchronization of the posterior parietal cortex occurred when irrelevant speech or music was presented in the background, but not when irrelevant white noise was presented, or when there were no distractors. We also show regionally distinct ISC signatures for inattention and impulsivity. Finally, post-scan recall of the film contents was associated with stronger ISCs in the default-mode network for the ADHD and in the dorsal attention network for healthy controls. The present study shows that ISCs can further our understanding of how a complex environment influences brain states in ADHD.

Training working memory updating in Parkinson's disease: A randomised controlled trial.

Frontostriatal dysfunction in Parkinson's disease (PD) increases the risk for working memory (WM) impairment and depression, calling for counteractive measures. Computerised cognitive rehabilitation is a promising option, but targeted training protocols are lacking and lab-based training can be demanding due to the repeated visits. This study tested the feasibility and efficacy of home-based computerised training targeting mainly WM updating in PD. Fifty-two cognitively well-preserved PD patients were randomised to a WM training group and an active control group for five weeks of training (three 30-min sessions per week). WM training included three computerised adaptive WM tasks (two updating, one maintenance). The outcomes were examined pre- and post-training with trained and untrained WM tasks, tasks tapping other cognitive domains, and self-ratings of executive functioning and depression. Home-based training was feasible for the patients. The training group improved particularly on the updating training tasks, and showed posttest improvement on untrained WM tasks structurally similar to the trained ones. Moreover, their depression scores decreased compared to the controls. Our study indicates that patients with mild-to-moderate PD can self-administer home-based computerised WM training, and that they yield a similar transfer pattern to untrained WM tasks as has been observed in healthy older adults.

Working memory updating training modulates a cascade of event-related potentials depending on task load.

The brain mechanisms of working memory (WM) training in humans remain unclear. Here we examined how WM updating training modulates a cascade of event-related potentials (ERPs) elicited at different processing stages. We hypothesized that WM updating training results to decreases in the early responses reflecting stimulus selection and response preparation, and increases the late slow responses reflecting maintenance of to-be-remembered materials. Healthy adults were randomized to a WM updating group that trained an adaptive dual n-back task (n = 20), and an active control group that played a computer game (n = 20). Both groups performed three 25-min training sessions per week for five weeks. Pretest-posttest comparisons showed that the training group significantly improved their performance as compared to the active controls, but this was limited to the trained task. In line with our hypothesis, P2-N2-P3 complex showed changes from pre- to posttest. In the training group this was observed as decreased load-effect while in the control group there was an opposite pattern at some latencies. Slow waves elicited during the maintenance were decreased in the easy task and increased in the difficult task. Taken together, our findings suggest that the early and late ERPs are differentially affected by training. When task demands are high, training may lead to an improved ability to actively maintain several stimuli in memory, and when they are low, training results in more efficient processing and automatization.