BackgroundNeuronal network hyperexcitability and related alterations in the excitation‐inhibition... more BackgroundNeuronal network hyperexcitability and related alterations in the excitation‐inhibition balance hold promise as early functional biomarkers of network dysfunction and as prodromal indicators of Alzheimer’s disease (AD) pathogenesis. However, the translational validity of hyperexcitability as found in some AD pathology animal models seems restricted by their limited capacity to encompass the complexity of clinical AD.MethodA comparison was made between different AD pathology mouse models with respect to the development of neuronal network hyperexcitability (LFPs) and epileptiform EEG. To this end, amyloid APP‐KI and APP/PS1 mice were assessed with and without hippocampal seeding of (human‐derived) pathological tau conformers at different ages (3‐6 months) and post‐seeding periods (1‐5 months) concerning alterations in amyloid and tau pathology in relation to hyperexcitability‐related, vigilance‐controlled neurophysiological changes.ResultsAnimals from both AD models progres...
In classification problems where the predictor variables are longitudinal, classical linear dis-c... more In classification problems where the predictor variables are longitudinal, classical linear dis-criminant analysis (LDA) is not appropriate, since the correlation between different time points will be ignored. For this particular case, where only one longitudinal predictor variable is to be used, functional linear discriminant analysis as proposed by James and Hastie [1] can be ap-plied. They proposed a method for generalizing linear discriminant analysis to functional data, which possesses all the usual LDA tools, including a low-dimensional graphical summary of the data, and classification of new curves. In this paper, we propose an extension of this method for the case where several longitudinal profiles are recorded for the same individual. When dealing with more than one longitudinal variable, we have to take the correlation between these variables into account in our classifi-cation. A full multivariate model would be the natural choice, but given the complexity of the data, c...
Neurophysiological studies have indicated that the passage of sensory information through the spe... more Neurophysiological studies have indicated that the passage of sensory information through the specific nuclei of the thalamus depends on the sleepwake state. The ‘transfer ratio’ concept implies that the ratio between the thalamic input from the sense organs and the thalamic output to the sensory cortex is equal to one during wakefulness, whereas it is reduced to 0.4 during slow wave sleep. This is due to partial closing of the ‘thalamic gate’ [1]. The question arises whether this ‘sensory gating’ mechanism influences information processing during slow wave sleep [2,3]. The rationale of the present two experiments was to test this phenomenon in rats in a behavioural/neuropsychological way. Two paradigms were applied: a conditioned suppression paradigm and a preexposure paradigm. In the conditioned suppression paradigm it is hypothesised that presentations of an auditory stimulus during wakefulness and during slow wave sleep would differentially attenuate a previously established ton...
Over the last two decades, awareness of the negative repercussions of flaws in the planning, cond... more Over the last two decades, awareness of the negative repercussions of flaws in the planning, conduct and reporting of preclinical research involving experimental animals has been growing. Several initiatives have set out to increase transparency and internal validity of preclinical studies, mostly publishing expert consensus and experience. While many of the points raised in these various guidelines are identical or similar, they differ in detail and rigour. Most of them focus on reporting, only few of them cover the planning and conduct of studies. The aim of this systematic review is to identify existing experimental design, conduct, analysis and reporting guidelines relating to preclinical animal research. A systematic search in PubMed, Embase and Web of Science retrieved 13 863 unique results. After screening these on title and abstract, 613 papers entered the full-text assessment stage, from which 60 papers were retained. From these, we extracted unique 58 recommendations on th...
Alzheimer’s disease (AD) is a progressive, neurodegenerative disease characterized by loss of syn... more Alzheimer’s disease (AD) is a progressive, neurodegenerative disease characterized by loss of synapses and disrupted functional connectivity (FC) across different brain regions. Early in AD progression, tau pathology is found in the locus coeruleus (LC) prior to amyloid-induced exacerbation of clinical symptoms. Here, a tau-seeding model in which preformed synthetic tau fibrils (K18) were unilaterally injected into the LC of P301L mice, equipped with multichannel electrodes for recording EEG in frontal cortical and CA1-CA3 hippocampal areas, was used to longitudinally quantify over 20 weeks of functional network dynamics in (1) power spectra; (2) FC using intra- and intersite phase-amplitude theta-gamma coupling (PAC); (3) coherence, partial coherence, and global coherent network efficiency (Eglob) estimates; and (4) the directionality of functional connectivity using extended partial direct coherence (PDC). A sustained leftward shift in the theta peak frequency was found early in t...
ObjectiveWithin the last years, there has been growing awareness of the negative repercussions of... more ObjectiveWithin the last years, there has been growing awareness of the negative repercussions of unstandardized planning, conduct and reporting of preclinical and biomedical research. Several initiatives have set the aim of increasing validity and reliability in reporting of studies and publications, and publishers have formed similar groups. Additionally, several groups of experts across the biomedical spectrum have published experience and opinion-based guidelines and guidance on potential standardized reporting. While all these guidelines cover reporting of experiments, an important step prior to this should be rigours planning and conduction of studies. The aim of this systematic review is to identify and harmonize existing experimental design, conduct and analysis guidelines relating to internal validity and reproducibility of preclinical animal research. The review will also identify literature describing risks of bias pertaining to the design, conduct and analysis of preclin...
BackgroundNeuronal network hyperexcitability and related alterations in the excitation‐inhibition... more BackgroundNeuronal network hyperexcitability and related alterations in the excitation‐inhibition balance hold promise as early functional biomarkers of network dysfunction and as prodromal indicators of Alzheimer’s disease (AD) pathogenesis. However, the translational validity of hyperexcitability as found in some AD pathology animal models seems restricted by their limited capacity to encompass the complexity of clinical AD.MethodA comparison was made between different AD pathology mouse models with respect to the development of neuronal network hyperexcitability (LFPs) and epileptiform EEG. To this end, amyloid APP‐KI and APP/PS1 mice were assessed with and without hippocampal seeding of (human‐derived) pathological tau conformers at different ages (3‐6 months) and post‐seeding periods (1‐5 months) concerning alterations in amyloid and tau pathology in relation to hyperexcitability‐related, vigilance‐controlled neurophysiological changes.ResultsAnimals from both AD models progres...
In classification problems where the predictor variables are longitudinal, classical linear dis-c... more In classification problems where the predictor variables are longitudinal, classical linear dis-criminant analysis (LDA) is not appropriate, since the correlation between different time points will be ignored. For this particular case, where only one longitudinal predictor variable is to be used, functional linear discriminant analysis as proposed by James and Hastie [1] can be ap-plied. They proposed a method for generalizing linear discriminant analysis to functional data, which possesses all the usual LDA tools, including a low-dimensional graphical summary of the data, and classification of new curves. In this paper, we propose an extension of this method for the case where several longitudinal profiles are recorded for the same individual. When dealing with more than one longitudinal variable, we have to take the correlation between these variables into account in our classifi-cation. A full multivariate model would be the natural choice, but given the complexity of the data, c...
Neurophysiological studies have indicated that the passage of sensory information through the spe... more Neurophysiological studies have indicated that the passage of sensory information through the specific nuclei of the thalamus depends on the sleepwake state. The ‘transfer ratio’ concept implies that the ratio between the thalamic input from the sense organs and the thalamic output to the sensory cortex is equal to one during wakefulness, whereas it is reduced to 0.4 during slow wave sleep. This is due to partial closing of the ‘thalamic gate’ [1]. The question arises whether this ‘sensory gating’ mechanism influences information processing during slow wave sleep [2,3]. The rationale of the present two experiments was to test this phenomenon in rats in a behavioural/neuropsychological way. Two paradigms were applied: a conditioned suppression paradigm and a preexposure paradigm. In the conditioned suppression paradigm it is hypothesised that presentations of an auditory stimulus during wakefulness and during slow wave sleep would differentially attenuate a previously established ton...
Over the last two decades, awareness of the negative repercussions of flaws in the planning, cond... more Over the last two decades, awareness of the negative repercussions of flaws in the planning, conduct and reporting of preclinical research involving experimental animals has been growing. Several initiatives have set out to increase transparency and internal validity of preclinical studies, mostly publishing expert consensus and experience. While many of the points raised in these various guidelines are identical or similar, they differ in detail and rigour. Most of them focus on reporting, only few of them cover the planning and conduct of studies. The aim of this systematic review is to identify existing experimental design, conduct, analysis and reporting guidelines relating to preclinical animal research. A systematic search in PubMed, Embase and Web of Science retrieved 13 863 unique results. After screening these on title and abstract, 613 papers entered the full-text assessment stage, from which 60 papers were retained. From these, we extracted unique 58 recommendations on th...
Alzheimer’s disease (AD) is a progressive, neurodegenerative disease characterized by loss of syn... more Alzheimer’s disease (AD) is a progressive, neurodegenerative disease characterized by loss of synapses and disrupted functional connectivity (FC) across different brain regions. Early in AD progression, tau pathology is found in the locus coeruleus (LC) prior to amyloid-induced exacerbation of clinical symptoms. Here, a tau-seeding model in which preformed synthetic tau fibrils (K18) were unilaterally injected into the LC of P301L mice, equipped with multichannel electrodes for recording EEG in frontal cortical and CA1-CA3 hippocampal areas, was used to longitudinally quantify over 20 weeks of functional network dynamics in (1) power spectra; (2) FC using intra- and intersite phase-amplitude theta-gamma coupling (PAC); (3) coherence, partial coherence, and global coherent network efficiency (Eglob) estimates; and (4) the directionality of functional connectivity using extended partial direct coherence (PDC). A sustained leftward shift in the theta peak frequency was found early in t...
ObjectiveWithin the last years, there has been growing awareness of the negative repercussions of... more ObjectiveWithin the last years, there has been growing awareness of the negative repercussions of unstandardized planning, conduct and reporting of preclinical and biomedical research. Several initiatives have set the aim of increasing validity and reliability in reporting of studies and publications, and publishers have formed similar groups. Additionally, several groups of experts across the biomedical spectrum have published experience and opinion-based guidelines and guidance on potential standardized reporting. While all these guidelines cover reporting of experiments, an important step prior to this should be rigours planning and conduction of studies. The aim of this systematic review is to identify and harmonize existing experimental design, conduct and analysis guidelines relating to internal validity and reproducibility of preclinical animal research. The review will also identify literature describing risks of bias pertaining to the design, conduct and analysis of preclin...
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Papers by Wilhelmus Drinkenburg