Donders Centre for Cognition

Our perception is facilitated if we know where and when a sensory stimulus will occur. This phenomenon is accounted for by spatial and temporal orienting of attention. Whereas spatial orienting of attention has repeatedly been shown to involve spatially specific modulations of ongoing oscillations within sensory cortex, it is not clear to what extent anticipatory modulations of ongoing oscillations are involved in temporal orienting of attention. To address this, we recorded magnetoencephalography while human participants performed a tactile discrimination task. We cued participants to the left or the right hand, after which a tactile stimulus was presented at one of several fixed temporal delays. We thus assessed whether and how ongoing sensorimotor oscillations are modulated during tactile anticipation. We provide evidence for three phenomena. First, orienting to an upcoming tactile event involves a spatially specific contralateral suppression of alpha- and beta-band oscillations within sensorimotor cortex. Second, this modulation is deployed with temporal specificity, and this is more pronounced for beta-band compared with alpha-band oscillations. Third, the contralateral suppression of beta-band oscillations is associated with faster responses to subsequently presented tactile stimuli. Control measures showed that these results cannot be explained by motor planning or execution. We conclude that the modulation of ongoing oscillations within sensory cortex reflects a unifying mechanism underlying both spatial and temporal orienting of attention.

Language is classically thought to be supported by perisylvian cortical regions. Here we provide intracranial evidence linking the hippocampal complex to linguistic processing. We used direct recordings from the hippocampal structures to investigate whether theta oscillations, pivotal in memory function, track the amount of contextual linguistic information provided in sentences. Twelve participants heard sentences that were either constrained ("She locked the door with the") or unconstrained ("She walked in here with the") before presentation of the final word ("key"), shown as a picture that participants had to name. Hippocampal theta power increased for constrained relative to unconstrained contexts during sentence processing, preceding picture presentation. Our study implicates hippocampal theta oscillations in a language task using natural language associations that do not require memorization. These findings reveal that the hippocampal complex contributes to language in an active fashion, relating incoming words to stored semantic knowledge, a necessary process in the generation of sentence meaning.

BACKGROUND AND PURPOSE: Fatigue is a common, persistent consequence of stroke, and no evidence-based treatments are currently available to alleviate fatigue. A new treatment combining cognitive therapy (CO) with graded activity training (GRAT), called COGRAT, was developed to alleviate fatigue and fatigue-related symptoms. This study compared the effectiveness of the COGRAT intervention with a CO-only intervention after a 3-month qualification period without intervention. METHODS: This randomized, controlled, assessor-blind clinical trial was conducted in 8 rehabilitation centers. Eighty-three stroke patients (>4 months after stroke) were randomly assigned to 12 weeks of CO or COGRAT after qualification. Seventy-three patients completed treatment and 68 were available at follow-up. Primary outcomes (Checklist Individual Strength-subscale Fatigue (CIS-f); self-observation list-fatigue (SOL-f)) and secondary outcomes (Hospital Anxiety and Depression Scale, Stroke-Adapted Sickness Impact Profile, SOL-pain, SOL-sleep-D, 6-minute walk test) were collected at baseline (before and after qualification period) and after treatment (immediate and 6-month follow-up). RESULTS: The qualification period showed stable outcome measures. Both treatments showed significant beneficial effects on fatigue (CIS-f: η(p)(2)=0.48, P<0.001) and other outcomes (except pain and anxiety) with intention-to-treat analyses. Gains for the COGRAT group exceeded those in the CO group on number of individuals showing clinical improvement on the CIS-f (≥8 points: 58% versus 24%) and on physical endurance (η(p)(2)=0.20, P<0.001). CONCLUSIONS: A 12-week cognitive therapy program can alleviate persistent fatigue after stroke. The best results are obtained when cognitive therapy is augmented with graded activity training. Clinical Trial Registration- URL: http://www.trialregister.nl. Unique identifier: NTR2704.

Researchers on bilingual processing can benefit from computational tools developed in artificial intelligence. We show that a normalized Levenshtein distance function can efficiently and reliably simulate bilingual orthographic similarity ratings. Orthographic similarity distributions of cognates and non-cognates were identified across pairs of six European languages: English, German, French, Spanish, Italian, and Dutch. Semantic equivalence was determined using the conceptual structure of a translation database. By using a similarity threshold, large numbers of cognates could be selected that nearly completely included the stimulus materials of experimental studies. The identified numbers of form-similar and identical cognates correlated highly with branch lengths of phylogenetic language family trees, supporting the usefulness of the new measure for cross-language comparison. The normalized Levenshtein distance function can be considered as a new formal model of cross-language orthographic similarity.

Transcranial alternating current stimulation (tACS) has been shown to modulate neural oscillations and excitability levels in the primary motor cortex (M1). These effects can last for more than an hour and an involvement of N-methyl-d-aspartate receptor (NMDAR) mediated synaptic plasticity has been suggested. However, to date the cortical mechanisms underlying tACS after-effects have not been explored. Here, we applied 20 Hz beta tACS to M1 while participants received either the NMDAR antagonist dextromethorphan or a placebo and the effects on cortical beta oscillations and excitability were explored. When a placebo medication was administered, beta tACS was found to increase cortical excitability and beta oscillations for at least 60 min, whereas when dextromethorphan was administered, these effects were completely abolished. These results provide the first direct evidence that tACS can induce NMDAR-mediated plasticity in the motor cortex, which contributes to our understanding of tACS-induced influences on human motor cortex physiology.

PURPOSE: A nonlinear association and a source localization technique were used to describe the onset and propagation of spike-and-slow-wave discharges (SWDs) in children with absence seizures. Previous studies have emphasized a leading cortical role in the generation of absence seizures in genetic epileptic rats. METHODS: Synchronization between all magnetoencephalography (MEG) sensor-couples before and during SWDs in five patients was investigated over time. A source localization [beamformer, SAM(g(2))] technique was used to find brain regions associated with the origin of the spikes of the SWDs. RESULTS: The onset of SWDs was characterized by high associations at left and right frontal regions. An alternating pattern of high synchronization was found during trains of SWDs: generalized during the wave and localized during the spike; the origin of the spike was different from the onset of SWDs, more frontal lateral and medial parietal. The localization of this latter region was confirmed with SAM(g(2)). DISCUSSION: The outcome of the nonlinear association techniques demonstrated that SWDs have a local cortical onset, whereas the association and beamformer technique support a local or even a focal cortical involvement in the occurrence of the spike in a train of SWDs. In all, the cortex contains local frontal and parietal sites relevant before the onset of the generalized pattern of SWDs and other ones that might contain the driving force behind the spike in trains of 3-4 Hz SWDs.

An arrow version of the Eriksen flanker task was employed to investigate the influence of conflict on the error-related negativity (ERN). The degree of conflict was modulated by varying the distance between flankers and the target arrow (CLOSE and FAR conditions). Error rates and reaction time data from a behavioral experiment were used to adapt a connectionist model of this task. This model was based on the conflict monitoring theory and simulated behavioral and event-related potential data. The computational model predicted an increased ERN amplitude in FAR incompatible (the low-conflict condition) compared to CLOSE incompatible errors (the high-conflict condition). A subsequent ERP experiment confirmed the model predictions. The computational model explains this finding with larger post-response conflict in far trials. In addition, data and model predictions of the N2 and the LRP support the conflict interpretation of the ERN.

OBJECTIVE: Companion robots, such as Paro, may reduce agitation and depression for older people with dementia. However, contradictory research outcomes suggest robot design is not always optimal. While many researchers suggest user-centred design is important, there is little evidence on the difference this might make. Here, we aimed to assess its importance by comparing companion robot design perceptions between older people (end users) and roboticists (developers). DESIGN: Older people and roboticists interacted with eight companion robots or alternatives at two separate events in groups of two to four people. Interactions were recorded, participants' comments and observations were transcribed, and content was analysed. Subsequently, each group participated in focus groups on perceptions of companion robot design. Discussions were recorded and transcribed, and content was analysed. PARTICIPANTS AND SETTINGS: Seventeen older people (5 male, 12 female, ages 60-99) at a supported living retirement complex, and 18 roboticists (10 male, 8 female, ages 24-37) at a research centre away-day. RESULTS: We found significant differences in design preferences between older people and roboticists. Older people desired soft, furry, interactive animals that were familiar and realistic, while unfamiliar forms were perceived as infantilising. By contrast, most roboticists eschewed familiar and realistic designs, thinking unfamiliar forms better suited older people. Older people also expressed desire for features not seen as important by developers. A large difference was seen in attitude towards ability to talk: 12/17 (71%) older people but only 2/18 (11%) roboticists requested speech. Older people responded positively towards life-simulation features, eye contact, robot personalisation and obeying commands, features undervalued by roboticists. These differences were reflected in preferred device, with 'Joy for All' cat chosen most often by older people, while roboticists most often chose Paro. CONCLUSION: The observed misalignment of opinion between end users and developers on desirable design features of companion robots demonstrates the need for user-centred design during development.

Sleep is essential for recovery and performance in elite athletes. While actigraphy-based studies revealed suboptimal sleep in athletes, information on their subjective experience of sleep is scarce. Relatively unexplored is also the extent to which athletes' sleep is adversely affected by environmental conditions and daytime behaviours, that is sleep hygiene. This study aimed to provide insight in sleep quantity, quality and its putative association with sleep hygiene. Participants were 98 elite (youth) athletes competing at the highest (inter-)national level. Sleep quantity, quality and sleep hygiene were assessed once covering a 1-month period by using established (sub)clinical questionnaires, and repeatedly during 7 consecutive days. Sleep quality was generally healthy, although 41% of all athletes could be classified as 'poor sleeper', and 12% were identified as having a sleep disorder. Daily self-monitoring revealed sleep durations of 8:11 ± 0:45 h, but elevated wake after sleep onset of 13 ± 19 min. Sleep quality, feeling refreshed, and morning vigor were moderate at best. Regarding sleep hygiene, general measures revealed irregular sleep-wake patterns, psychological strain and activating pre-sleep behaviours. At the daily level, blue-light exposure and late-evening consumption of heavy meals were frequently reported. General sleep hygiene revealed significant associations with sleep quality (0.45 < r > 0.50; P < 0.001). Results indicate that there is ample room for optimization, specifically in onset latency and in wake after sleep onset. Subtle improvements in sleep seem possible, and optimizing sleep hygiene, such as regular sleep-wake patterns and reducing psychological strain, may facilitate this sleep upgrading process.

The ultimate goal of epileptology is the complete abolishment of epileptic seizures. This might be achieved by a system that predicts seizure onset combined with a system that interferes with the process that leads to the onset of a seizure. Seizure prediction remains, as of yet, unresolved in absence-epilepsy, due to the sudden onset of seizures. We have developed a real-time absence seizure prediction algorithm, evaluated it and implemented it in an on-line, closed-loop brain stimulation system designed to prevent the spike-wave-discharges (SWDs), typical for absence epilepsy, in a genetic rat model. The algorithm corretly predicted 88% of the SWDs while the remaining were quickly detected. A high number of false-positive detections occurred mainly during light slow-wave-sleep. Inclusion of criteria to prevent false-positives greatly reduced the false alarm rate but decreased the sensitivity of the algoritm. Implementation of the latter version into a closed-loop brain-stimulation-system resulted in a 72% decrease in seizure activity. In contrast to long standing beliefs that SWDs are unpredictable, these results demonstrate that they can be predicted and that the development of closed-loop seizure prediction and prevention systems is a feasable step towards interventions to attain control and freedom from epileptic seizures.

Network mechanisms relevant for the generation, maintenance and termination of spike-wave discharges (SWD), the neurophysiological hallmark of absence epilepsy, are still enigmatic and widely discussed. Within the last years, however, improvements in signal analytical techniques, applied to both animal and human fMRI, EEG, MEG, and ECoG data, greatly increased our understanding and challenged several, dogmatic concepts of SWD. This review will summarize these recent data, demonstrating that SWD are not primary generalized, are not sudden and unpredictable events. It will disentangle different functional contributions of structures within the cortico-thalamo-cortical system, relevant for the generation, generalization, maintenance, and termination of SWD and will present a new "network based" scenario for these oscillations. Similarities and differences between rodent and human data are presented demonstrating that in both species a local cortical onset zone of SWD exists, although with different locations; that in both some forms of cortical and thalamic precursor activity can be found, and that SWD occur through repetitive cyclic activity between cortex and thalamus. The focal onset zone in human data could differ between patients with varying spatial and temporal dynamics; in rats the latter is still poorly investigated.

In his first description of Autism Spectrum Disorders (ASD), Kanner emphasized emotional impairments by characterizing children with ASD as indifferent to other people, self-absorbed, emotionally cold, distanced, and retracted. Thereafter, emotional impairments became regarded as part of the social impairments of ASD, and research mostly focused on understanding how individuals with ASD recognize visual expressions of emotions from faces and body postures. However, it still remains unclear how emotions are processed outside of the visual domain. This systematic review aims to fill this gap by focusing on impairments of emotional language processing in ASD. We systematically searched PubMed for papers published between 1990 and 2013 using standardized search terms. Studies show that people with ASD are able to correctly classify emotional language stimuli as emotionally positive or negative. However, processing of emotional language stimuli in ASD is associated with atypical patterns of attention and memory performance, as well as abnormal physiological and neural activity. Particularly, younger children with ASD have difficulties in acquiring and developing emotional concepts, and avoid using these in discourse. These emotional language impairments were not consistently associated with age, IQ, or level of development of language skills. We discuss how emotional language impairments fit with existing cognitive theories of ASD, such as central coherence, executive dysfunction, and weak Theory of Mind. We conclude that emotional impairments in ASD may be broader than just a mere consequence of social impairments, and should receive more attention in future research.

After the presentation of a visual stimulus, neural processing cascades from low-level sensory areas to increasingly abstract representations in higher-level areas. It is often hypothesised that a reversal in neural processing underlies the generation of mental images as abstract representations are used to construct sensory representations in the absence of sensory input. According to predictive processing theories, such reversed processing also plays a central role in later stages of perception. Direct experimental evidence of reversals in neural information flow has been missing. Here, we used a combination of machine learning and magnetoencephalography to characterise neural dynamics in humans. We provide direct evidence for a reversal of the perceptual feed-forward cascade during imagery and show that, during perception, such reversals alternate with feed-forward processing in an 11 Hz oscillatory pattern. Together, these results show how common feedback processes support both veridical perception and mental imagery.

Brain Computer Interfaces could be useful in rehabilitation of movement, perhaps also for gait. Until recently, research on movement related brain signals has not included measuring electroencephalography (EEG) during walking, because of the potential artifacts. We investigated if it is possible to measure the event Related Desynchronization (ERD) and event related spectral perturbations (ERSP) during walking. Six subjects walked on a treadmill with a slow speed, while EEG, electromyography (EMG) of the neck muscles and step cycle were measured. A Canonical Correlation Analysis (CCA) was used to remove EMG artifacts from the EEG signals. It was shown that this method correctly deleted EMG components. A strong ERD in the mu band and a somewhat less strong ERD in the beta band were found during walking compared to a baseline period. Furthermore, lateralized ERSPs were found, depending on the phase in the step cycle. It is concluded that this is a promising method to use in BCI research on walking. These results therefore pave the way for using brain signals related to walking in a BCI context.

Stroke significantly impacts the quality of life. However, the long-term cognitive evolution in stroke is poorly predictable at the individual level. There is an urgent need to better predict long-term symptoms based on acute clinical neuroimaging data. Previous works have demonstrated a strong relationship between the location of white matter disconnections and clinical symptoms. However, rendering the entire space of possible disconnection-deficit associations optimally surveyable will allow for a systematic association between brain disconnections and cognitive-behavioural measures at the individual level. Here we present the most comprehensive framework, a composite morphospace of white matter disconnections (disconnectome) to predict neuropsychological scores 1 year after stroke. Linking the latent disconnectome morphospace to neuropsychological outcomes yields biological insights that are available as the first comprehensive atlas of disconnectome-deficit relations across 86 scores-a Neuropsychological White Matter Atlas. Our novel predictive framework, the Disconnectome Symptoms Discoverer, achieved better predictivity performances than six other models, including functional disconnection, lesion topology and volume modelling. Out-of-sample prediction derived from this atlas presented a mean absolute error below 20% and allowed personalize neuropsychological predictions. Prediction on an external cohort achieved an R2 = 0.201 for semantic fluency. In addition, training and testing were replicated on two external cohorts achieving an R2 = 0.18 for visuospatial performance. This framework is available as an interactive web application (http://disconnectomestudio.bcblab.com) to provide the foundations for a new and practical approach to modelling cognition in stroke. We hope our atlas and web application will help to reduce the burden of cognitive deficits on patients, their families and wider society while also helping to tailor future personalized treatment programmes and discover new targets for treatments. We expect our framework's range of assessments and predictive power to increase even further through future crowdsourcing.

The terminology used in discussions on mental state attribution is extensive and lacks consistency. In the current paper, experts from various disciplines collaborate to introduce a shared set of concepts and make recommendations regarding future use.

Converging evidence indicates that motor deficits in cerebral palsy (CP) are related not only to problems with execution, but also to impaired motor planning. Current rehabilitation mainly focuses on alleviating compromised motor execution. Motor imagery is a promising method of training the more 'cognitive' aspects of motor behaviour, and may, therefore, be effective in facilitating motor planning in patients with CP. In this review first we present the specific motor planning problems in CP followed by a discussion of motor imagery and its use in clinical practice. Second, we present the steps to be taken before motor imagery can be used for rehabilitation of upper limb functioning in CP. Motor imagery training has been shown to be a useful addition to existing rehabilitation protocols for poststroke rehabilitation. No such study has been conducted in CP. The age at which children can reliably use motor imagery, as well as the specific way in which motor imagery training needs to be implemented, must be researched before motor imagery training can be employed in children with CP. Based on the positive results for poststroke rehabilitation, and in light of the motor problems in CP, motor imagery training may be a valuable additional tool for rehabilitation in CP.

The WAG/Rij model is a well characterized and validated genetic animal epilepsy model in which the for absence epilepsy highly characteristic spike-wave discharges (SWDs) develop spontaneously. In this review we discuss first some older and many new studies, with an emphasis on pharmacological and neurochemical studies towards the role of GABA and glutamate and the ion channels involved in the pathological firing patterns. Next, new insights and highlights from the last 5-10 years of reaearch in WAG/Rij rats are discussed. First, early environmental factors modulate SWD characteristics and antiepileptogenesis is possible. Also new is that the classically assumed association between sleep spindles and SWDs seems no longer valid as an explanatory role for the occurrence of SWDs in the genetic rodent models. A role of cortical and thalamic glial cells has been revealed, indicating a putative role for inflammatory cytokines. Neurophysiologic and signal analytical studies in this and in another rodent model (GAERS) point towards a cortical site of origin, that SWDs do not have a sudden onset, and propose a more important role for the posterior thalamus than was previously assumed. Finally it is proposed that the reticular nucleus of the thalamus might be heterogeneous with respect to its role in propagation and maintenance of SWDs. The presence of a well-established cortical region in which SWDs are elicited allows for research towards new non-invasive treatment options, such as transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS). The first results show the feasibility of this new approach.

Abstract This article adopts the production model of Levelt to discuss brain imaging studies of continuous speech. Conclusions about the involvement of brain regions in processes of language production are mainly drawn on the basis of the presence or absence of processing components of speaking in certain experimental tasks. Such conclusions are largely theory independent, because differences between current models do not concern the assumed processing levels but the exact nature of the information flow between them. In a second step, the article tests some of these conclusions by comparing the few available data on activation time courses of brain regions and independent evidence on the timing of processes in language production. It also discusses brain regions involved in word production, conceptually driven lexical selection, phonological code (word form) retrieval, phonological encoding, phonetic encoding and articulation, self-monitoring, whether the hemodynamic core areas are necessary for word production, and bilingual language production.

We introduce a practical and computationally not demanding technique for inferring interactions at various microscopic levels between the units of a network from the measurements and the processing of macroscopic signals. Starting from a network model of Kuramoto phase oscillators, which evolve adaptively according to homophilic and homeostatic adaptive principles, we give evidence that the increase of synchronization within groups of nodes (and the corresponding formation of synchronous clusters) causes also the defragmentation of the wavelet energy spectrum of the macroscopic signal. Our methodology is then applied to getting a glance into the microscopic interactions occurring in a neurophysiological system, namely, in the thalamocortical neural network of an epileptic brain of a rat, where the group electrical activity is registered by means of multichannel EEG. We demonstrate that it is possible to infer the degree of interaction between the interconnected regions of the brain during different types of brain activities and to estimate the regions' participation in the generation of the different levels of consciousness.