This thesis explores the role of what has traditionally been considered as neural “noise”, specifically BOLD signal variability and aperiodic neural activity, in human cognitive functions,... Show moreThis thesis explores the role of what has traditionally been considered as neural “noise”, specifically BOLD signal variability and aperiodic neural activity, in human cognitive functions, particularly in metacontrol. The metacontrol model assumes that individuals vary in their cognitive styles between "persistence" and "flexibility." Persistence emphasizes focused goal pursuit, while flexibility allows for easy task switching and consideration of diverse possibilities. Through three empirical studies, this thesis investigates the relationship between two specific forms of neural "noise" – BOLD signal variability and aperiodic neural activity – and metacontrol biases (i.e., persistence vs. flexibility). Chapter 2 emphasizes the importance of resting-state BOLD signal variability in understanding individualized cognitive control styles. Chapter 3 highlights the importance of the aperiodic component of the EEG power spectrum in reflecting demand-specific metacontrol states. Notably, Chapter 4 illuminates the functional significance of aperiodic activity in creative thinking. Overall, the research presented in this thesis highlights the importance of resting-state BOLD signal variability and aperiodic activity in the EEG power spectrum for understanding the neural underpinnings of cognitive functions. Show less
To cope with environmental changes, humans need to adjust their cognitive control states to meet different challenges. Two important cognitive control states are cognitive persistence and cognitive... Show moreTo cope with environmental changes, humans need to adjust their cognitive control states to meet different challenges. Two important cognitive control states are cognitive persistence and cognitive flexibility. Persistence is a state of maintaining stable attention, while flexibility is a state where attention can switch freely. These two states are antagonistic to each other; one cannot switch attention flexibly while being focused, and one cannot focus on a single stimulus while switching attention flexibly. Our understanding of the neural mechanisms underlying these cognitive control states is still limited. Therefore, in this dissertation, we used two brain science research techniques, EEG and fMRI, to study brain activities associated with these two states. To induce these states, the dissertation employed two creative thinking tasks, namely convergent thinking and divergent thinking, and two meditation techniques, focused attention meditation and open monitoring meditation. The results discuss EEG and fMRI indicators related to these states, providing preliminary evidence for research in this field. Show less
The entire healthcare system is grappling with shortages of personnel that are likely to grow. There are increasingly more people in need of care, but the number of people providing care cannot... Show moreThe entire healthcare system is grappling with shortages of personnel that are likely to grow. There are increasingly more people in need of care, but the number of people providing care cannot keep up.This thesis examines whether the assessment of long-term EEG registrations (4 – 90 hours) in adults can be partially taken over by an algorithm, referred to as automated spike and seizure detection software in the thesis. This is done without compromising the quality of the assessment.We evaluated the performance of three commercially available software packages (Persyst, Encevis, and BESA) to determine if they perform as well as human experts. We looked at both interictal and ictal abnormalities (epileptic seizures).In conclusion, the software detects interictal abnormalities as well as human experts do. However, epileptic seizures are not detected as well as by human experts, especially for seizures with short duration (less than 10 seconds) or subtle EEG abnormalities. Overall, the Persyst software package performs the best.Furthermore, this thesis includes a new method in which automatic detection is combined with sampled visual assessment. We compared this new assessment method with the conventional assessment method (based on complete visual assessment) and found no difference in conclusion. Show less
Placebo and nocebo effects, positive and negative effects experienced after both real and sham interventions, putatively due to positive or negative outcome expectancies, can shape our sensory... Show morePlacebo and nocebo effects, positive and negative effects experienced after both real and sham interventions, putatively due to positive or negative outcome expectancies, can shape our sensory experience. Although placebo and nocebo effects are known to occur reliably in many individuals for sensations like pain and itch, our understanding of psychological learning processes and methodological factors that influence these effects remains limited. Chapters 2, 3, and 4 investigate this topic with meta-analysis, narrative review, and a behavioral study. Similarly, our characterization of the neural markers of nocebo effects is incomplete. A better grasp of how these effects form is necessary to contextualize them within the larger framework of bottom-up and top-down integration. Chapters 5, 6, and 7 investigate this topic in a series of EEG and fMRI studies. Advancing both psychological and neural accounts of placebo and nocebo effects will aid in applying findings from this field of study to everyday life; particularly in clinical settings, and potentially any setting in which expectations regarding one’s future experiences come into play. Show less
PurposeEarly recognition of seizures in neonates secondary to pathogenic variants in potassium or sodium channel coding genes is crucial, as these seizures are often resistant to commonly used anti... Show morePurposeEarly recognition of seizures in neonates secondary to pathogenic variants in potassium or sodium channel coding genes is crucial, as these seizures are often resistant to commonly used anti-seizure medications but respond well to sodium channel blockers. Recently, a characteristic ictal amplitude-integrated electroencephalogram (aEEG) pattern was described in neonates with KCNQ2-related epilepsy. We report a similar aEEG pattern in seizures caused by SCN2A- and KCNQ3-pathogenic variants, as well as conventional EEG (cEEG) descriptions.MethodsInternational multicentre descriptive study, reporting clinical characteristics, aEEG and cEEG findings of 13 neonates with seizures due to pathogenic SCN2A- and KCNQ3-variants. As a comparison group, aEEGs and cEEGs of neonates with seizures due to hypoxic-ischemic encephalopathy (n = 117) and other confirmed genetic causes affecting channel function (n = 55) were reviewed.ResultsIn 12 out of 13 patients, the aEEG showed a characteristic sequence of brief onset with a decrease, followed by a quick rise, and then postictal amplitude attenuation. This pattern correlated with bilateral EEG onset attenuation, followed by rhythmic discharges ending in several seconds of post-ictal amplitude suppression. Apart from patients with KCNQ2-related epilepsy, none of the patients in the comparison groups had a similar aEEG or cEEG pattern.DiscussionSeizures in SCN2A- and KCNQ3-related epilepsy in neonates can usually be recognized by a characteristic ictal aEEG pattern, previously reported only in KCNQ2-related epilepsy, extending this unique feature to other channelopathies. Awareness of this pattern facilitates the prompt initiation of precision treatment with sodium channel blockers even before genetic results are available. Show less
Objective: Automated detection of spikes and seizures has been a subject of research for several decades now. There have been important advances, yet automated detection in EMU (Epilepsy Monitoring... Show moreObjective: Automated detection of spikes and seizures has been a subject of research for several decades now. There have been important advances, yet automated detection in EMU (Epilepsy Monitoring Unit) settings has not been accepted as standard practice. We intend to implement this software at our EMU and so carried out a qualitative study to identify factors that hinder ('barriers') and facilitate ('enablers') implementation.Method: Twenty-two semi-structured interviews were conducted with 14 technicians and neurologists involved in recording and reporting EEGs and eight neurologists who receive EEG reports in the outpatient department. The study was reported according to the Consolidated Criteria for Reporting Qualitative Studies (COREQ).Results: We identified 14 barriers and 14 enablers for future implementation. Most barriers were reported by technicians. The most prominent barrier was lack of trust in the software, especially regarding seizure detection and false positive results. Additionally, technicians feared losing their EEG review skills or their jobs. Most commonly reported enablers included potential efficiency in the EEG workflow, the opportunity for quantification of EEG findings and the willingness to try the software. Conclusions: This study provides insight into the perspectives of users and offers recommendations for implementing automated spike and seizure detection in EMUs. Show less
Objective: To clarify the significance of any form of myoclonus in comatose patients after cardiac arrest with rhythmic and periodic EEG patterns (RPPs) by analyzing associations between myoclonus... Show moreObjective: To clarify the significance of any form of myoclonus in comatose patients after cardiac arrest with rhythmic and periodic EEG patterns (RPPs) by analyzing associations between myoclonus and EEG pattern, response to anti-seizure medication and neurological outcome.Design: Post hoc analysis of the prospective randomized Treatment of ELectroencephalographic STatus Epilepticus After Cardiopulmonary Resus-citation (TELSTAR) trial.Setting: Eleven ICUs in the Netherlands and Belgium.Patients: One hundred and fifty-seven adult comatose post-cardiac arrest patients with RPPs on continuous EEG monitoring. Interventions: Anti-seizure medication vs no anti-seizure medication in addition to standard care.Measurements and Main Results: Of 157 patients, 98 (63%) had myoclonus at inclusion. Myoclonus was not associated with one specific RPP type. However, myoclonus was associated with a smaller probability of a continuous EEG background pattern (48% in patients with vs 75% without myoclonus, odds ratio (OR) 0.31; 95% confidence interval (CI) 0.16-0.64) and earlier onset of RPPs (24% vs 9% within 24 hours after cardiac arrest, OR 3.86;95% CI 1.64-9.11). Myoclonus was associated with poor outcome at three months, but not invariably so (poor neurological outcome in 96% vs 82%, p = 0.004). Anti-seizure medication did not improve outcome, regardless of myoclonus presence (6% good outcome in the intervention group vs 2% in the control group, OR 0.33; 95% CI 0.03-3.32).Conclusions: Myoclonus in comatose patients after cardiac arrest with RPPs is associated with poor outcome and discontinuous or suppressed EEG. However, presence of myoclonus does not interact with the effects of anti-seizure medication and cannot predict a poor outcome without false positives. Show less
Struiksma, M.E.; De Mulder, H.N.M.; Van Berkum, J.J.A. 2022
Verbal insults go against a universal moral imperative not to inflict harm on others, and they also pose a threat to one’s face or reputation. As such, these “verbal slaps in the face” provide a... Show moreVerbal insults go against a universal moral imperative not to inflict harm on others, and they also pose a threat to one’s face or reputation. As such, these “verbal slaps in the face” provide a unique opportunity to explore the interface between language and emotion. We used electroencephalography (EEG) and skin conductance (SC) recordings to compare the short-term impact of verbal insults such as “Linda is an idiot” or “Paula is horrible” to that of more positive evaluations (e.g., “Linda is an angel”, “Paula is impressive”) and neutral factual descriptions (e.g., “Linda is a student”), examining how responses to these various speech acts adapt as a function of massive repetition. By using either the participant’s or somebody else’s name, we also explored how statement impact depended on who was being evaluated. Multilevel ERP analysis with three predesignated latency ranges revealed an early insult effect in P2 amplitude that was highly robust over repetition and also did not depend on who the insult was about. This P2 effect points to a very rapid and stable capture of emotional attention, plausibly triggered by the retrieval of evaluative word meaning from long-term memory. Insults also elicited a larger late positive potential (LPP), again regardless of who the insult was about, but this later effect did not withstand repetition. Skin conductance responses showed that insults did not lead to more arousal than compliments did. In all, our findings suggest that in a standard psycholinguistic comprehension experiment without real interaction between speakers, insults deliver lexical “mini-slaps in the face,” such that the strongly negative evaluative words involved (e.g., “idiot”) automatically grab attention during lexical retrieval, regardless of how often that retrieval occurs. Show less
Machine Learning is becoming a more and more substantial technology for industry. It allows to learn from previous experiences in an automated way to make decisions based on the learned behavior.... Show moreMachine Learning is becoming a more and more substantial technology for industry. It allows to learn from previous experiences in an automated way to make decisions based on the learned behavior. Machine learning enables the development of completely new products like autonomous driving or services which are purely driven by data.The development of such new data-driven products is often a long procedure. Even the application of machine learning algorithms to specific problems is mostly not straightforward. To illustrate this, a data-driven service, called Automated Damage Assessment, from the automotive industry is introduced in this work. Based on the gained experience from such data-driven service developments, this dissertation proposes a methodology to develop data-driven services in an accurate and fast manner. The Automated Damage Assessment service is based on sensor data, i.e. data recorded from vehicle on-board sensors over time. Using such time series from more than one sensor results in a multivariate time series. The existent methods to solve multivariate time series classification-problems are often complex and developed for specific problems without being scalable. To overcome this, suitable approaches with different complexities are proposed in this work. These approaches are applied on multiple publicly available data sets and on real-world data sets from medical and industrial domain with the result that especially two AutoML (Automated Machine Learning) approaches, namely GAMA and ATM, as well as one of the proposed approaches (PHCP) are most suitable to solve these particular multivariate time series problems. Show less
Perenboom, M.J.L.; Ruit, M. van de; Zielman, R.; Maagdenberg, A.M.J.M. van den; Ferrari, M.D.; Carpay, J.A.; Tolner, E.A. 2020
BackgroundMigraine is associated with altered sensory processing and cortical responsivity that may contribute to susceptibility to attacks by changing brain network excitability dynamics. To gain... Show moreBackgroundMigraine is associated with altered sensory processing and cortical responsivity that may contribute to susceptibility to attacks by changing brain network excitability dynamics. To gain better insight into cortical responsivity changes in migraine we subjected patients to a short series of light inputs over a broad frequency range ("chirp" stimulation), designed to uncover dynamic features of visual cortex responsivity.MethodsEEG responses to visual chirp stimulation (10-40 Hz) were measured in controls (n = 24) and patients with migraine with aura (n = 19) or migraine without aura (n = 20). Average EEG responses were assessed at (i) all EEG frequencies between 5 and 125 Hz, (ii) stimulation frequencies, and (iii) harmonic frequencies. We compared average responses in a low (10-18 Hz), medium (19-26 Hz) and high (27-40 Hz) frequency band.ResultsResponses to chirp stimulation were similar in controls and migraine subtypes. Eight measurements (n = 3 migraine with aura; n = 5 without aura) were assigned as "pre-ictal", based on reported headache within 48 hours after investigation. Pre-ictally, an increased harmonic response to 22-32 Hz stimulation (beta band) was observed (p = 0.001), compared to interictal state measurements.ConclusionsWe found chirp responses to be enhanced in the 48 hours prior to migraine headache onset. Visual chirp stimulation proved a simple and reliable technique with potential to detect changes in cortical responsivity associated with the onset of migraine attacks. Show less
Background: The combination of EEG and ultra-high-field (7T and above) fMRI holds the promise to relate electrophysiology and hemodynamics with greater signal to noise level and at higher spatial... Show moreBackground: The combination of EEG and ultra-high-field (7T and above) fMRI holds the promise to relate electrophysiology and hemodynamics with greater signal to noise level and at higher spatial resolutions than conventional field strengths. Technical and safety restrictions have so far resulted in compromises in terms of MRI coil selection, resulting in reduced, signal quality, spatial coverage and resolution in EEG-fMRI studies at 7 T.New method: We adapted a 64-channel MRI-compatible EEG cap so that it could be used with a closed 32-channel MRI head coil thus avoiding several of these compromises. We compare functional and anatomical as well as the EEG quality recorded with this adapted setup with those recorded with a setup that uses an open-ended 8-channel head-coil.Results: Our set-up with the adapted EEG cap inside the closed 32 channel coil resulted in the recording of good quality EEG and (f)MRI data. Both functional and anatomical MRI images show no major effects of the adapted EEG cap on MR signal quality. We demonstrate the ability to compute ERPs and changes in alpha and gamma oscillations from the recorded EEG data.Comparison with existing methods: Compared to MRI recordings with an 8-channel open-ended head-coil, the loss in signal quality of the MRI images related to the adapted EEG cap is considerably reduced.Conclusions: The adaptation of the EEG cap permits the simultaneous recording of good quality whole brain (f) MRI data using a 32 channel receiver coil, while maintaining the quality of the EEG data. Show less
It is common in life to not perform at the very top of our cognitive abilities. This phenomenon usually exacerbates when we are under high levels of stress and in people with psychiatric disorders.... Show moreIt is common in life to not perform at the very top of our cognitive abilities. This phenomenon usually exacerbates when we are under high levels of stress and in people with psychiatric disorders. Attention to negative information is considered to play a crucial role in the development and maintenance of these disorders, especially anxiety-related disorders. Attention to negative information is not necessarily bad as it is an evolutionary function to protect us from dangerous situations. However, it can be destructive when it occurs constantly or when we need to focus on an important task. There are many situations where we have to perform difficult cognitive tasks and we worry about our performance or other people’s evaluation. Trait cognitive control, the ability to control attention and maintain a goal-relevant behaviour, is suggested to play a key role in the relationships between anxiety/stress, attention to negative information, and cognitive performance. Yet, the evidence is limited and further investigation is needed. In the current thesis, the relations between anxiety/stress, attention to emotional information, and cognitive performance will be investigated in a multidisciplinary approach, synthesizing clinical and cognitive factors and neurobiological underpinnings, while focusing on the role of trait cognitive control. Show less
Son, D. van; Rover, M. de; Blasio, F.M. de; Does, W. van der; Barry, R.J.; Putman, P. 2019
Musical hallucinations are poorly understood phenomena. Their relation with epilepsy was first described over a century ago, but never systematically explored. We, therefore, reviewed the... Show moreMusical hallucinations are poorly understood phenomena. Their relation with epilepsy was first described over a century ago, but never systematically explored. We, therefore, reviewed the literature, and assessed all descriptions of musical hallucinations attributed to epileptic activity. Our search yielded 191 articles, which together describe 983 unique patients, with 24 detailed descriptions of musical hallucinations related to epilepsy. We also describe six of our own patients. Based on the phenomenological descriptions and neurophysiological data, we distinguish four subgroups of epilepsy-related musical hallucination, comprising auras/ictal, inter-ictal and post-ictal phenomena, and phenomena related to brain stimulation. The case descriptions suggest that musical hallucinations in epilepsy can be conceptualised as lying on a continuum with other auditory hallucinations, including verbal auditory hallucinations, and—notably—tinnitus. To account for the underlying mechanism we propose a Bayesian model involving top-down and bottom-up prediction errors within the auditory network that incorporates findings from EEG and MEG studies. An analysis of phenomenological characteristics, pharmacological triggers, and treatment effects suggests wider ramifications for understanding musical hallucinations. We, therefore, conclude that musical hallucinations in epilepsy open a window to understanding these phenomena in a variety of conditions. Show less
Bilderbeck, A.C.; Penninx, B.W.J.H.; Arango, C.; Wee, N. van der; Kahn, R.; Winter-van Rossum, I.; ... ; Dawson, G.R. 2019
Trans-diagnostic, domain- or symptom-focused approaches have been heralded as advancing psychiatric research, but relatively few clinical research programmes have been undertaken to leverage their... Show moreTrans-diagnostic, domain- or symptom-focused approaches have been heralded as advancing psychiatric research, but relatively few clinical research programmes have been undertaken to leverage their potential. In this manuscript we describe the approach and protocol for an exploratory study, PRISM (Psychiatric Ratings using Intermediate Stratified Markers), that will be conducted to explore the biomarkers in schizophrenia (SZ) and Alzheimer's Disease (AD) that may be related to a common symptom, social withdrawal. Patient participants (N = 72 SZ and N = 72 AD study completers), will complete a series of fMRI, EEG, and behavioural paradigms, as well as contributing blood-derived (e.g. epigenetic) and smartphone data related to social behaviour. Self- as well as caregiver- and researcher-reported assessments will be provided to characterise social withdrawal. Normative data will also be collected from a group of healthy controls (N = 48 study completers), half of whom will be matched in terms of age and gender distribution to the SZ and AD group, respectively. Thus we will explore both differentiation and cross-diagnostic overlap in the biomarkers associated with different levels of social withdrawal in SZ and AD. In this way we aim to provide a deeper understanding of the biological underpinnings of symptomatology common to both disorders, and provide insights into novel treatment targets and future drug development approaches. Show less
Wee, N.J.A. van der; Bilderbeck, A.C.; Cabello, M.; Ayuso-Mateos, J.L.; Saris, I.M.J.; Giltay, E.J.; ... ; Porcelli, S. 2019
Social withdrawal is one of the first and common signs of early social dysfunction in a number of important neuropsychiatric disorders, likely because of the enormous amount and complexity of brain... Show moreSocial withdrawal is one of the first and common signs of early social dysfunction in a number of important neuropsychiatric disorders, likely because of the enormous amount and complexity of brain processes required to initiate and maintain social relationships (Adolphs, 2009). The Psychiatric Ratings using Intermediate Stratified Markers (PRISM) project focusses on the shared and unique neurobiological basis of social withdrawal in schizophrenia, Alzheimer and depression. In this paper, we discuss the working definition of social withdrawal for this study and the selection of objective and subjective rating scales to assess social withdrawal chosen or adapted for this project. We also discuss the MRI and EEG paradigms selected to study the systems and neural circuitry thought to underlie social functioning and more particularly to be involved in social withdrawal in humans, such as the social perception and the social affiliation networks. A number of behavioral paradigms were selected to assess complementary aspects of social cognition. Also, a digital phenotyping method (a smartphone application) was chosen to obtain real-life data. Show less
This chapter describes neurolinguistic aspects of morphology, morphological theory, and especially morphological processing. It briefly mentions the main processing models in the literature and how... Show moreThis chapter describes neurolinguistic aspects of morphology, morphological theory, and especially morphological processing. It briefly mentions the main processing models in the literature and how they deal with morphological issues, i.e. full-listing models (all morphologically related words are listed separately in the lexicon and are processed individually), full-parsing or decompositional models (morphologically related words are not listed in the lexicon but are decomposed into their constituent morphemes, each of which is listed in the lexicon), and hybrid, so-called dual route, models (regular morphologically related words are decomposed, irregular words are listed). The chapter also summarizes some important findings from the literature that bear on neurolinguistic aspects of morphological processing, from both language comprehension and language production, taking into consideration neuropsychological patient studies as well as studies employing neuroimaging methods. Show less
Warren C.M., Tona K.D., Ouwerkerk L., Paridon J. van, Poletiek F., Steenbergen H. van, Bosch J.A., Nieuwenhuis S. 2018
