399 research outputs found
Analytical validation of innovative magneto-inertial outcomes: a controlled environment study.
peer reviewe
Relationship between Anxiety and Freezing of Gait
Parkinson’s disease (PD) is the second most common neurodegenerative and a large percentage of PD patients develop freezing of gait (FOG) leading to an overall reduced quality of life. The overarching aim of the thesis is to investigate the relationship between anxiety and freezing of gait, to extend current research on this topic and produce findings that could facilitate more adequate treatment methods for this symptom.
The first study validated the seated functional MRI-compatible version of the walking threat paradigm that was previously found to induce anxiety and FOG. This would enable future studies to examine the neural correlates behind anxiety-induced freezing of gait. The second study investigated the effect of anxiety on the utilisation of body-related visual feedback in the form of an avatar in the virtual environment to improve FOG. The third study investigated the effects of Levodopa on the fronto-striato-limbic circuitry in PD Freezers at rest in their ‘ON’ and ‘OFF’ dopaminergic state.
Findings suggest that the VR seated threat paradigm is an adequate behavioural surrogate for the VR walking threat paradigm, eliciting comparable amounts of anxiety and freezing of gait as the walking version. Anxiety was also found to interfere with the utilisation of sensory feedback to improve FOG, where in highly threatening situations Freezers lack the capacity to process visual feedback for gait. Finally, dopaminergic medication was also found to partially modulate the frontoparietal-limbic-striatal circuitry in PD Freezers, where baseline anxiety levels influence the impact of Levodopa on the frontoparietal (FPN)- limbic connectivity, and the FPN-putamen connectivity.
In conclusion, the current thesis suggests that anxiety contributes to freezing of gait, which may present a barrier to treatment and could be a key factor in the heterogeneity observed in response to medication and sensory cueing
Water and Brain Function: Effects of Hydration Status on Neurostimulation and Neurorecording
Introduction: TMS and EEG are used to study normal neurophysiology, diagnose, and treat clinical neuropsychiatric conditions, but can produce variable results or fail. Both techniques depend on electrical volume conduction, and thus brain volumes. Hydration status can affect brain volumes and functions (including cognition), but effects on these techniques are unknown. We aimed to characterize the effects of hydration on TMS, EEG, and cognitive tasks. Methods: EEG and EMG were recorded during single-pulse TMS, paired-pulse TMS, and cognitive tasks from 32 human participants on dehydrated (12-hour fast/thirst) and rehydrated (1 Liter oral water ingestion in 1 hour) testing days. Hydration status was confirmed with urinalysis. MEP, ERP, and network analyses were performed to examine responses at the muscle, brain, and higher-order functioning. Results: Rehydration decreased motor threshold (increased excitability) and shifted the motor hotspot. Significant effects on TMS measures occurred despite being re-localized and re-dosed to these new parameters. Rehydration increased SICF of the MEP, magnitudes of specific TEP peaks in inhibitory protocols, specific ERP peak magnitudes and reaction time during the cognitive task. Rehydration amplified nodal inhibition around the stimulation site in inhibitory paired-pulse networks and strengthened nodes outside the stimulation site in excitatory and CSP networks. Cognitive performance was not improved by rehydration, although similar performance was achieved with generally weaker network activity. Discussion: Results highlight differences between mild dehydration and rehydration. The rehydrated brain was easier to stimulate with TMS and produced larger responses to external and internal stimuli. This is explainable by the known physiology of body water dynamics, which encompass macroscopic and microscopic volume changes. Rehydration can shift 3D cortical positioning, decrease scalp cortex distance (bringing cortex closer to stimulator/recording electrodes), and cause astrocyte swelling-induced glutamate release. Conclusions: Previously unaccounted variables like osmolarity, astrocyte and brain volumes likely affect neurostimulation/neurorecording. Controlling for and carefully manipulating hydration may reduce variability and improve therapeutic outcomes of neurostimulation. Dehydration is common and produces less excitable circuits. Rehydration should offer a mechanism to macroscopically bring target cortical areas closer to an externally applied neurostimulation device to recruit greater volumes of tissue and microscopically favor excitability in the stimulated circuits
Behavior quantification as the missing link between fields: Tools for digital psychiatry and their role in the future of neurobiology
The great behavioral heterogeneity observed between individuals with the same
psychiatric disorder and even within one individual over time complicates both
clinical practice and biomedical research. However, modern technologies are an
exciting opportunity to improve behavioral characterization. Existing
psychiatry methods that are qualitative or unscalable, such as patient surveys
or clinical interviews, can now be collected at a greater capacity and analyzed
to produce new quantitative measures. Furthermore, recent capabilities for
continuous collection of passive sensor streams, such as phone GPS or
smartwatch accelerometer, open avenues of novel questioning that were
previously entirely unrealistic. Their temporally dense nature enables a
cohesive study of real-time neural and behavioral signals.
To develop comprehensive neurobiological models of psychiatric disease, it
will be critical to first develop strong methods for behavioral quantification.
There is huge potential in what can theoretically be captured by current
technologies, but this in itself presents a large computational challenge --
one that will necessitate new data processing tools, new machine learning
techniques, and ultimately a shift in how interdisciplinary work is conducted.
In my thesis, I detail research projects that take different perspectives on
digital psychiatry, subsequently tying ideas together with a concluding
discussion on the future of the field. I also provide software infrastructure
where relevant, with extensive documentation.
Major contributions include scientific arguments and proof of concept results
for daily free-form audio journals as an underappreciated psychiatry research
datatype, as well as novel stability theorems and pilot empirical success for a
proposed multi-area recurrent neural network architecture.Comment: PhD thesis cop
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Conformable transistors for bioelectronics
The diversity of network disruptions that occur in patients with neuropsychiatric disorders creates a strong demand for personalized medicine. Such approaches often take the form of implantable bioelectronic devices that are capable of monitoring pathophysiological activity for identifying biomarkers to allow for local and responsive delivery of intervention. They are also required to transmit this data outside of the body for evaluation of the treatment’s efficacy.
However, the ability to perform these demanding electronic functions in the complex physiological environment with minimum disruption to the biological tissue remains a big challenge. An optimal fully implantable bioelectronic device would require each component from the front-end to the data transmission to be conformable and biocompatible. For this reason, organic material-based conformable electronics are ideal candidates for components of bioelectronic circuits due to their inherent flexibility, and soft nature.
In this work, first an organic mixed-conducting particulate composite material (MCP) able to form functional electronic components and non-invasively acquire high–spatiotemporal resolution electrophysiological signals by directly interfacing human skin is presented. Secondly, we introduce organic electrochemical internal ion-gated transistors (IGTs) as a high-density, high-amplification sensing component as well as a low leakage, high-speed processing unit.
Finally, a novel wireless, battery-free strategy for electrophysiological signal acquisition, processing, and transmission that employs IGTs and an ionic communication circuit (IC) is introduced. We show that the wirelessly-powered IGTs are able to acquire and modulate neurophysiological data in-vivo and transmit them transdermally, eliminating the need for any hard Si-based electronics in the implant
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