202 research outputs found
Multivariate assessment of linear and non-linear causal coupling pathways within the central-autonomic-network in patients suffering from schizophrenia
Im Bereich der Zeitreihenanalyse richtet sich das Interesse zunehmend darauf, wie Einblicke in die Interaktions- und Regulationsprozesse von pathophysiologischen- und physiologischen Zuständen erlangt werden können. Neuste Fortschritte in der nichtlinearen Dynamik, der Informationstheorie und der Netzwerktheorie liefern dabei fundiertes Wissen über Kopplungswege innerhalb (patho)physiologischer (Sub)Systeme. Kopplungsanalysen zielen darauf ab, ein besseres Verständnis dafür zu erlangen, wie die verschiedenen integrierten regulatorischen (Sub)Systeme mit ihren komplexen Strukturen und Regulationsmechanismen das globale Verhalten und die unterschiedlichen physiologischen Funktionen auf der Ebene des Organismus beschreiben. Insbesondere die Erfassung und Quantifizierung der Kopplungsstärke und -richtung sind wesentliche Aspekte für ein detaillierteres Verständnis physiologischer Regulationsprozesse. Ziel dieser Arbeit war die Charakterisierung kurzfristiger unmittelbarer zentral-autonomer Kopplungspfade (top-to-bottom und bottom to top) durch die Kopplungsanalysen der Herzfrequenz, des systolischen Blutdrucks, der Atmung und zentraler Aktivität (EEG) bei schizophrenen Patienten und Gesunden. Dafür wurden in dieser Arbeit neue multivariate kausale und nicht-kausale, lineare und nicht-lineare Kopplungsanalyseverfahren (HRJSD, mHRJSD, NSTPDC) entwickelt, die in der Lage sind, die Kopplungsstärke und -richtung, sowie deterministische regulatorische Kopplungsmuster innerhalb des zentralen-autonomen Netzwerks zu quantifizieren und zu klassifizieren. Diese Kopplungsanalyseverfahren haben ihre eigenen Besonderheiten, die sie einzigartig machen, auch im Vergleich zu etablierten Kopplungsverfahren. Sie erweitern das Spektrum neuartiger Kopplungsansätze für die Biosignalanalyse und tragen auf ihre Weise zur Gewinnung detaillierter Informationen und damit zu einer verbesserten Diagnostik/Therapie bei. Die Hauptergebnisse dieser Arbeit zeigen signifikant schwächere nichtlineare zentral-kardiovaskuläre und zentral-kardiorespiratorische Kopplungswege und einen signifikant stärkeren linearen zentralen Informationsfluss in Richtung des Herzkreislaufsystems auf, sowie einen signifikant stärkeren linearen respiratorischen Informationsfluss in Richtung des zentralen Nervensystems in der Schizophrenie im Vergleich zu Gesunden. Die detaillierten Erkenntnisse darüber, wie die verschiedenen zentral-autonomen Netzwerke mit paranoider Schizophrenie assoziiert sind, können zu einem besseren Verständnis darüber führen, wie zentrale Aktivierung und autonome Reaktionen und/oder Aktivierung in physiologischen Netzwerken unter pathophysiologischen Bedingungen zusammenhängen.In the field of time series analysis, increasing interest focuses on insights gained how the coupling pathways of regulatory mechanisms work in healthy and ill states. Recent advances in non-linear dynamics, information theory and network theory lead to a new sophisticated body of knowledge about coupling pathways within (patho)physiological (sub)systems. Coupling analyses aim to provide a better understanding of how the different integrated physiological (sub)systems, with their complex structures and regulatory mechanisms, describe the global behaviour and distinct physiological functions at the organism level. In particular, the detection and quantification of the coupling strength and direction are important aspects for a more detailed understanding of physiological regulatory processes. This thesis aimed to characterize short-term instantaneous central-autonomic-network coupling pathways (top-to-bottom and bottom to top) by analysing the coupling of heart rate, systolic blood pressure, respiration and central activity (EEG) in schizophrenic patients and healthy participants. Therefore, new multivariate causal and non-causal linear and non-linear coupling approaches (HRJSD, mHRJSD, NSTPDC) that are able to determine the coupling strength and direction were developed. Whereby, the HRJSD and mHRJSD approaches allow the quantification and classification of deterministic regulatory coupling patterns within and between the cardiovascular- the cardiorespiratory system and the central-autonomic-network were developed. These coupling approaches have their own unique features, even as compared to well-established coupling approaches. They expand the spectrum of novel coupling approaches for biosignal analysis and thus contribute in their own way to detailed information obtained, and thereby contribute to improved diagnostics/therapy. The main findings of this thesis revealed significantly weaker non-linear central-cardiovascular and central-cardiorespiratory coupling pathways, and significantly stronger linear central information flow in the direction of the cardiac- and vascular system, and a significantly stronger linear respiratory information transfer towards the central nervous system in schizophrenia in comparison to healthy participants. This thesis provides an enhanced understanding of the interrelationship of central and autonomic regulatory mechanisms in schizophrenia. The detailed findings on how variously-pronounced, central-autonomic-network pathways are associated with paranoid schizophrenia may enable a better understanding on how central activation and autonomic responses and/or activation are connected in physiology networks under pathophysiological conditions
Multimodal assessment of emotional responses by physiological monitoring: novel auditory and visual elicitation strategies in traditional and virtual reality environments
This doctoral thesis explores novel strategies to quantify emotions and listening effort through monitoring of physiological signals. Emotions are a complex aspect of the human experience, playing a crucial role in our survival and adaptation to the environment. The study of emotions fosters important applications, such as Human-Computer and Human-Robot interaction or clinical assessment and treatment of mental health conditions such as depression, anxiety, stress, chronic anger, and mood disorders. Listening effort is also an important area of study, as it provides insight into the listeners’ challenges that are usually not identified by traditional audiometric measures. The research is divided into three lines of work, each with a unique emphasis on the methods of emotion elicitation and the stimuli that are most effective in producing emotional responses, with a specific focus on auditory stimuli. The research fostered the creation of three experimental protocols, as well as the use of an available online protocol for studying emotional responses including monitoring of both peripheral and central physiological signals, such as skin conductance, respiration, pupil dilation, electrocardiogram,
blood volume pulse, and electroencephalography. An emotional protocol was created for the study of listening effort using a speech-in-noise test designed to be short and not induce fatigue. The results revealed that the listening effort is a complex problem that cannot be studied with a univariate approach, thus necessitating the use of multiple physiological markers to study different physiological dimensions. Specifically, the findings demonstrate a strong association between the level of auditory exertion, the amount of attention and involvement directed towards stimuli that are readily comprehensible compared to those that demand greater exertion. Continuing with the auditory domain, peripheral physiological signals were studied in order to discriminate four emotions elicited in a subject who listened to music for 21 days, using a previously designed and publicly available protocol. Surprisingly, the processed physiological signals were able to clearly separate the four emotions at the physiological level, demonstrating that music, which is not typically studied extensively in the literature, can be an effective stimulus for eliciting emotions. Following these results, a flat-screen protocol was created to compare physiological responses to purely visual, purely auditory, and combined audiovisual emotional stimuli. The results show that auditory stimuli are more effective in separating emotions at the physiological level. The subjects were found to be much more attentive during the audio-only phase. In order to overcome the limitations of emotional protocols carried out in a laboratory environment, which may elicit fewer emotions due to being an unnatural setting for the subjects under study, a final emotional elicitation protocol was created using virtual reality. Scenes similar to reality were created to elicit four distinct emotions. At the physiological level, it was noted that this environment is more effective in eliciting emotions. To our knowledge, this is the first protocol specifically designed for virtual reality that elicits diverse emotions. Furthermore, even in terms of classification, the use of virtual reality has been shown to be superior to traditional flat-screen protocols, opening the doors to virtual reality for the study of
conditions related to emotional control
EEG Correlates of Learning From Speech Presented in Environmental Noise
How the human brain retains relevant vocal information while suppressing irrelevant
sounds is one of the ongoing challenges in cognitive neuroscience. Knowledge of
the underlying mechanisms of this ability can be used to identify whether a person
is distracted during listening to a target speech, especially in a learning context. This
paper investigates the neural correlates of learning from the speech presented in a noisy
environment using an ecologically valid learning context and electroencephalography
(EEG). To this end, the following listening tasks were performed while 64-channel EEG
signals were recorded: (1) attentive listening to the lectures in background sound, (2)
attentive listening to the background sound presented alone, and (3) inattentive listening
to the background sound. For the first task, 13 lectures of 5 min in length embedded
in different types of realistic background noise were presented to participants who were
asked to focus on the lectures. As background noise, multi-talker babble, continuous
highway, and fluctuating traffic sounds were used. After the second task, a written exam
was taken to quantify the amount of information that participants have acquired and
retained from the lectures. In addition to various power spectrum-based EEG features
in different frequency bands, the peak frequency and long-range temporal correlations
(LRTC) of alpha-band activity were estimated. To reduce these dimensions, a principal
component analysis (PCA) was applied to the different listening conditions resulting in the
feature combinations that discriminate most between listening conditions and persons.
Linear mixed-effect modeling was used to explain the origin of extracted principal
components, showing their dependence on listening condition and type of background
sound. Following this unsupervised step, a supervised analysis was performed to explain
the link between the exam results and the EEG principal component scores using
both linear fixed and mixed-effect modeling. Results suggest that the ability to learn
from the speech presented in environmental noise can be predicted by the several
components over the specific brain regions better than by knowing the background
noise type. These components were linked to deterioration in attention, speech envelope
following, decreased focusing during listening, cognitive prediction error, and specific
inhibition mechanisms
Imaging fascicular organisation in mammalian vagus nerve for selective VNS
Nerves contain a large number of nerve fibres, or axons, organised into bundles known as fascicles. Despite the somatic nervous system being well understood, the organisation of the fascicles within the nerves of the autonomic nervous system remains almost completely unknown. The new field of bioelectronics medicine, Electroceuticals, involves the electrical stimulation of nerves to treat diseases instead of administering drugs or performing complex surgical procedures. Of particular interest is the vagus nerve, a prime target for intervention due to its afferent and efferent innervation to the heart, lungs and majority of the visceral organs. Vagus nerve stimulation (VNS) is a promising therapy for treatment of various conditions resistant to standard therapeutics. However, due to the unknown anatomy, the whole nerve is stimulated which leads to unwanted off-target effects. Electrical Impedance Tomography (EIT) is a non-invasive medical imaging technique in which the impedance of a part of the body is inferred from electrode measurements and used to form a tomographic image of that part. Micro-computed tomography (microCT) is an ex vivo method that has the potential to allow for imaging and tracing of fascicles within experimental models and facilitate the development of a fascicular map. Additionally, it could validate the in vivo technique of EIT. The aim of this thesis was to develop and optimise the microCT imaging method for imaging the fascicles within the nerve and to determine the fascicular organisation of the vagus nerve, ultimately allowing for selective VNS. Understanding and imaging the fascicular anatomy of nerves will not only allow for selective VNS and the improvement of its therapeutic efficacy but could also be integrated into the study on all peripheral nerves for peripheral nerve repair, microsurgery and improving the implementation of nerve guidance conduits. Chapter 1 provides an introduction to vagus nerve anatomy and the principles of microCT, neuronal tracing and EIT. Chapter 2 describes the optimisation of microCT for imaging the fascicular anatomy of peripheral nerves in the experimental rat sciatic and pig vagus nerve models, including the development of pre-processing methods and scanning parameters. Cross-validation of this optimised microCT method, neuronal tracing and EIT in the rat sciatic nerve was detailed in Chapter 3. Chapter 4 describes the study with microCT with tracing, EIT and selective stimulation in pigs, a model for human nerves. The microCT tracing approach was then extended into the subdiaphragmatic branches of the vagus nerves, detailed in Chapter 5. The ultimate goal of human vagus nerve tracing was preliminarily performed and described in Chapter 6. Chapter 7 concludes the work and describes future work. Lastly, Appendix 1 (Chapter 8) is a mini review on the application of selective vagus nerve stimulation to treat acute respiratory distress syndrome and Appendix 2 is morphological data corresponding to Chapter 4
Measuring spectrally resolved information processing in neural data
Background:
The human brain, an incredibly complex biological system comprising billions of neurons and trillions of synapses, possesses remarkable capabilities for information processing and distributed computations. Neurons, the fundamental building blocks, perform elementary operations on their inputs and collaborate extensively to execute intricate computations, giving rise to cognitive functions and behavior.
Notably, distributed information processing in the brain heavily relies on rhythmic neural activity characterized by synchronized oscillations at specific frequencies.
These oscillations play a crucial role in coordinating brain activity and facilitating communication between different neural circuits [1], effectively acting as temporal windows that enable efficient information exchange within specific frequency ranges.
To understand distributed information processing in neural systems, breaking down its components, i.e., —information transfer, storage, and modification can be helpful, but requires precise mathematical definitions for each respective component. Thankfully, these definitions have recently become available [2]. Information theory is a natural choice for measuring information processing, as it offers a mathematically
complete description of the concept of information and communication. The fundamental information-processing operations, are considered essential prerequisites for achieving universal information processing in any system [3]. By quantifying and analyzing these operations, we gain valuable insights into the brain’s complex computation and cognitive abilities. As information processing in the brain is intricately tied to rhythmic behavior, there is a need to establish a connection between information theoretic measures and frequency components. Previous attempts to achieve frequency-resolved information theoretic measures have mostly relied on narrowband filtering [4], which comes with several known issues of phase shifting and high false positive rate results [5],
or simplifying the computation to few variables [6], that might result in missing important information in the analysed brain signals. Therefore, the current work aims to establish a frequency-resolved measure of two crucial components of information processing: information transfer and information storage. By proposing methodological advancements, this research seeks to shed light on the role of neural oscillations in information processing within the brain. Furthermore, a more comprehensive investigation was carried out on the communication between two critical brain regions responsible for motor inhibition in the frontal cortex (right Inferior Frontal gyrus (rIFG) and pre-Supplementary motor cortex (pre-SMA)). Here, neural oscillations in the beta band (12 − 30 Hz) have been proposed to have a pivotal role in response inhibition. A long-standing question in the field was to disentangle which of these two brain areas first signals the stopping process and drives the other
[7]. Furthermore, it was hypothesized that beta oscillations carry the information transfer between these regions.
The present work addresses the methodological problems and investigates spectral information processing in neural data, in three studies.
Study 1 focuses on the critical role of information transfer, measured by transfer entropy, in distributed computation. Understanding the patterns of information transfer is essential for unraveling the computational algorithms in complex systems, such as the brain. As many natural systems rely on rhythmic processes for distributed computations, a frequency-resolved measure of information transfer becomes highly valuable. To address this, a novel algorithm is presented, efficiently
identifying frequencies responsible for sending and receiving information in a network.
The approach utilizes the invertible maximum overlap discrete wavelet transform (MODWT) to create surrogate data for computing transfer entropy, eliminating issues associated with phase shifts and filtering. However, measuring frequency-resolved information transfer poses a Partial information decomposition problem [8] that is yet to be fully resolved. The algorithm’s performance is validated using simulated data and applied to human magnetoencephalography (MEG) and ferret
local field potential recordings (LFP). In human MEG, the study unveils a complex spectral configuration of cortical information transmission, showing top-down information flow from very high frequencies (above 100Hz) to both similarly high frequencies and frequencies around 20Hz in the temporal cortex. Contrary to the current assumption, the findings suggest that low frequencies do not solely send information to high frequencies. In the ferret LFP, the prefrontal cortex demonstrates
the transmission of information at low frequencies, specifically within the range of 4-8 Hz. On the receiving end, V1 exhibits a preference for operating at very high frequency > 125 Hz. The spectrally resolved transfer entropy promises to deepen our understanding of rhythmic information exchange in natural systems, shedding light on the computational properties of oscillations on cognitive functions.
In study 2, the primary focus lay on the second fundamental aspect of information processing: the active information storage (AIS). The AIS estimates how much information in the next measurements of the process can be predicted by examining its paste state. In processes that either produce little information (low entropy) or that are highly unpredictable, the AIS is low, whereas processes that are predictable but visit many different states with equal probabilities, exhibit high AIS [9]. Within this context, we introduced a novel spectrally-resolved AIS. Utilizing intracortical recordings of neural activity in anesthetized ferrets before and after loss of consciousness (LOC), the study reveals that the modulation of AIS by anesthesia is highly specific to different frequency bands, cortical layers, and brain regions. The findings reveal that the effects of anesthesia on AIS are prominent in the supragranular
layers for the high/low gamma band, while the alpha/beta band exhibits the strongest decrease in AIS at infragranular layers, in accordance with the predictive coding theory. Additionally, the isoflurane impacts local information processing in a frequency-specific manner. For instance, increases in isoflurane concentration lead to a decrease in AIS in the alpha frequency but to an increase in AIS in the delta frequency range (<2Hz). In sum, analyzing spectrally-resolved AIS provides valuable insights into changes in cortical information processing under anesthesia.
With rhythmic neural activity playing a significant role in biological neural systems, the introduction of frequency-specific components in active information storage allows a deeper understanding of local information processing in different brain areas and under various conditions.
In study 3, to further verify the pivotal role of neural oscillations in information processing, we investigated the neural network mechanisms underlying response inhibition. A long-standing debate has centered around identifying the cortical initiator of response inhibition in the beta band, with two main regions proposed: the right rIFG and the pre-SMA. This third study aimed to determine which of these regions is activated first and exerts a potential information exchange on the other.
Using high temporal resolution magnetoencephalography (MEG) and a relatively large cohort of subjects. A significant breakthrough is achieved by demonstrating that the rIFG is activated significantly earlier than the pre-SMA. The onset of beta band activity in the rIFG occurred at around 140 ms after the STOP signal. Further analyses showed that the beta-band activity in the rIFG was crucial for successful stopping, as evidenced by its predictive value for stopping performance. Connectivity
analysis revealed that the rIFG sends information in the beta band to the pre-SMA but not vice versa, emphasizing the rIFG’s dominance in the response inhibition process. The results provide strong support for the hypothesis that the rIFG initiates stopping and utilizes beta-band oscillations for this purpose. These findings have significant implications, suggesting the possibility of spatially localized oscillation based
interventions for response inhibition.
Conclusion:
In conclusion, the present work proposes a novel algorithm for uncovering the frequencies at which information is transferred between sources and targets in the brain, providing valuable insights into the computational dynamics of neural processes. The spectrally resolved transfer entropy was successfully applied to experimental neural data of intracranial recordings in ferrets and MEG recordings of humans. Furthermore, the study on active information storage (AIS) analysis
under anesthesia revealed that the spectrally resolved AIS offers unique additional insights beyond traditional spectral power analysis. By examining changes in neural information processing, the study demonstrates how AIS analysis can deepen the understanding of anesthesia’s effects on cortical information processing. Moreover,
the third study’s findings provide strong evidence supporting the critical role of beta oscillations in information processing, particularly in response inhibition. The research successfully demonstrates that beta oscillations in the rIFG functions as the key initiator of the response inhibition process, acting as a top-down control mechanism. The identification of beta oscillations as a crucial factor in information
processing opens possibilities for further research and targeted interventions in neurological disorders. Taken together, the current work highlights the role of spectrally-resolved information processing in neural systems by not only introducing novel algorithms, but also successfully applying them to experimental oscillatory neural activity in relation to low-level cortical information processing (anesthesia)
as well as high-level processes (cognitive response inhibition)
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Large-scale Investigation of Memory Circuits
The human brain relies on the complex interactions of distinct brain regions to support cognitive processes. The interplay between the hippocampus and neocortical regions plays a key role in the formation, storage, and retrieval of long-term episodic memories. Oscillatory activities during sleep are a fundamental mechanism that binds distributed neuronal networks into functionally coherent ensembles. However, the large-scale hippocampal-neocortical oscillatory mechanisms that support flexible modulation of long-term memory remain poorly understood.
Furthermore, alterations to physiologic spatiotemporal patterns that are essential for intact memory function can result in pathophysiology in brain disorders such as focal epilepsy. Investigating how epileptic network activity disrupts connectivity in distributed networks and the organization of oscillatory activity are additional crucial areas that require further research. Our experiments on rodents and human patients with epilepsy have provided valuable insights into these mechanisms. In rodents, we used high-density microelectrode arrays in tandem with hippocampal probes to analyze intracranial electroencephalography (iEEG) from multiple cortical regions and the hippocampus.
We identified key hippocampal-cortical oscillatory biomarkers that were differentially coordinated based on the age, strength, and type of memory. We also analyzed iEEG from patients with focal epilepsy and demonstrated how individualized pattern of pathologic-physiologic coupling can disrupt large-scale memory circuits. Our findings may offer new opportunities for therapies aimed at addressing distributed network dysfunction in various neuropsychiatric disorders
Deep brain stimulation for disorders of consciousness and diminished motivation:A search for awakenings
This thesis deals with patients who are amongst the most severely affected after severe brain injury: those with permanent disorders of consciousness or diminished motivation. The research in this thesis is an attempt to improve consciousness and the general behavioral performance of these patients with the use of experimental interventions, including medication (such as zolpidem), and more invasive procedures, such as deep brain stimulation (DBS). The thesis contains extensive descriptions of the role of the intralaminar thalamus in the arousal regulation system, the importance of recognizing and treating secondary complications after brain injury, such as hydrocephalus, as well as a pathophysiological elaboration on akinetic mutism: a severe disorder of diminished motivation. Moreover, it describes the neurophysiological changes that accompany the paradoxical effects of zolpidem, a sleeping pill that temporarily induces ‘awakenings’ in some patients with severe brain injury. Further, it describes the first clinical and neurophysiological results of an N=6 trial of DBS in patients with a minimally conscious state and shows the importance of recognizing pathological changes from the brain’s ‘physiological baseline’ that seem to disturb normal brain functions. The thesis concludes with a description of the use of moral case deliberation in dealing with research dilemmas in patients with loss of autonomy after severe brain injury
The Varieties of Contemplative Experiences and Practices
While the diverse contemplative techniques are employed across a plethora of traditions around the world, contemplative research over the years has not reflected this variety. Despite growing interest in research on meditation, studies in contemplative science have largely focused on a narrow selection of practices (e.g., mindfulness, compassion, etc.) and traditions (i.e. Buddhism, Transcendental Meditation etc.). By choosing this topic, we hope to broaden the scope of contemplative science
Local field potentials and single unit dynamics in motor cortex of unconstrained macaques during different behavioral states
Different sleep stages have been shown to be vital for a variety of brain functions, including learning, memory, and skill consolidation. However, our understanding of neural dynamics during sleep and the role of prominent LFP frequency bands remain incomplete. To elucidate such dynamics and differences between behavioral states we collected multichannel LFP and spike data in primary motor cortex of unconstrained macaques for up to 24 h using a head-fixed brain-computer interface (Neurochip3). Each 8-s bin of time was classified into awake-moving (Move), awake-resting (Rest), REM sleep (REM), or non-REM sleep (NREM) by using dimensionality reduction and clustering on the average spectral density and the acceleration of the head. LFP power showed high delta during NREM, high theta during REM, and high beta when the animal was awake. Cross-frequency phase-amplitude coupling typically showed higher coupling during NREM between all pairs of frequency bands. Two notable exceptions were high delta-high gamma and theta-high gamma coupling during Move, and high theta-beta coupling during REM. Single units showed decreased firing rate during NREM, though with increased short ISIs compared to other states. Spike-LFP synchrony showed high delta synchrony during Move, and higher coupling with all other frequency bands during NREM. These results altogether reveal potential roles and functions of different LFP bands that have previously been unexplored
25th Annual Computational Neuroscience Meeting: CNS-2016
Abstracts of the 25th Annual Computational Neuroscience
Meeting: CNS-2016
Seogwipo City, Jeju-do, South Korea. 2–7 July 201
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