Studying Resting State and Stimulus Induced BOLD Activity using the Generalized Ising Model and Independent Component Graph Analysis

Although many technical advancements have been made, neuroscientists still struggle to explain the underlying behaviour of how brain regions communicate with each other to form large-scale functional networks. functional Magnetic Resonance Imaging (fMRI) has been commonly used to investigate changes between brain regions over time using the Blood Oxygen Level Dependent (BOLD) signal. The goal of this thesis is to show the applicability of novel techniques and tools, such as the generalized Ising model (GIM) and the independent component graph analysis (GraphICA), to obtain information on the functional connectivity of populations with altered perception of consciousness. The GIM was used to model brain activity in healthy brains during various stages of consciousness, as induced by an anesthetic agent, propofol, in the auditory paradigm. GraphICA, a tool that combines ICA and graph theory was used to investigate the functional connectivity of resting state networks (RSNs) in patients with altered perception caused by tinnitus and in patients with altered states of consciousness caused by severe brain injury. For the tinnitus patients, we examined whether a correlation exists between tinnitus behavioural scores and functional brain connectivity of RSNs. Moreover, for the severely brain injured patients, a multimodal neuroimaging approach with hybrid FDG-PET/MRI was implemented to study the functional connectivity changes of the RSNs. The GIM simulated with an external field was able to model the brain activity at different levels of consciousness under naturalistic stimulation, at a temperature in the super critical regime. Further, a strong correlation was observed between tinnitus distress and the connectivity pattern within and between the right executive control network and the other RSNs. This suggests that tinnitus distress is the consequence of a hyperactive attention condition. A variability was observed in the appearance and temporal/spatial patterns of RSNs among the two resting state fMRI acquisitions acquired within the same scanning session of the severely brain injured patients. This suggests the need for new strategies to be developed in order to pick the best RSN from each acquisition. Overall, this work demonstrated that the GIM and GraphICA were promising tools to investigate brain activity of populations with altered perception of consciousness and in future can be extended to investigate different neurological populations

OMCVD Gold Nanoparticles Covalently Attached to Polystyrene for Biosensing Applications

Remarkable developments and successes were witnessed in the fabrication and implementation of optical sensors based on localized surface plasmon resonance (LSPR) for the investigation of chemical and biological material quantities and to detect lethal diseases such as cancer in early stages. Gold nanoparticles (AuNPs) are ideal candidate for sensing purposes due to their chemical stability, ease of surface functionalization and strong LSPR in the visible range. Although there are several designs of sensors published, most of them are still limited to small scale research laboratory use partly due to their high cost of fabrication and waste management, in particular critical for solution based LSPR sensors. Sensors implementing immobilized AuNPs show decreased impact in waste management as they are strongly attached to the surface. In addition, sensors made from polymers are less expensive, mass producible and easier to handle in comparison to brittle glass sensors. We report on the reproducible fabrication of chemically stable surface immobilized AuNPs grown via organometallic chemical vapor deposition (OMCVD) on polystyrene (PS). Oxygen plasma and UV ozone treated PS samples depict enhanced amounts of polar –OH groups allowing for nucleation and growth of AuNPs. The optimum plasma treatment conditions, the largest shifts in the LSPR curves and the bulk sensitivity of the OMCVD grown AuNPs are discussed. It was found that the bio-sensing limit of detection of the grown AuNPs for streptavidin binding to biotin was ~ 10 ng/ml. In order to make this sensor applicable for clinical purposes, the sensitivity needs to be enhanced by building a polymer channel waveguide carrying AuNPs and increasing the interaction between the sample and the probing beam in future

Tinnitus and Dysfunctional Interactions between Distributed Resting State Networks

It is known that peripheral lesions in the cochlea or the auditory nerve produce dysfunctional input to central auditory structures and induce changes in the auditory system causing tinnitus. Recently, it has been proposed that the unified percept of tinnitus could be considered as an emergent property of multiple overlapping dynamic brain networks, each encoding a specific tinnitus characteristic. The aim of our study was to investigate the neuronal activation patterns associated with specific clinical tinnitus characteristics using fMRI. We hypothesize that tinnitus clinical characteristics could be associated with specific resting-state activity and connectivity patterns and that this could be tested by looking at the spontaneous brain activity of 135 tinnitus patients. We combine individual independent component analysis (ICA) with graph theory (GraphICA) to select the 9 components of interest (resting-state networks) and calculate the graph properties of these networks. We performed an analysis to identify the correlation between different tinnitus characteristics (age, distress, loudness, intensity, duration and hearing loss) and the graph strength of the functional connectivity pattern of these 9 different resting-state networks. Our findings provide evidence that alterations of functional interactions between key neural circuits of the brain are associated with mostly the subjective age, distress and duration of tinnitus. Specifically, the activity and connectivity patterns of the left executive control network are mostly being affected by the tinnitus distress. Further, this resting-state study indicates that longer the tinnitus is perceived, more changes are seen in the default mode network

Modeling an auditory stimulated brain under altered states of consciousness using the generalized ising model

Propofol is a short-acting medication that results in decreased levels of consciousness and is used for general anesthesia. Although it is the most commonly used anesthetic in the world, much remains unknown about the mechanisms by which it induces a loss of consciousness. Characterizing anesthesia-induced alterations to brain network activity might provide a powerful framework for understanding the neural mechanisms of unconsciousness. The aim of this work was to model brain activity in healthy brains during various stages of consciousness, as induced by propofol, in the auditory paradigm. We used the generalized Ising model (GIM) to fit the empirical fMRI data of healthy subjects while they listened to an audio clip from a movie. The external stimulus (audio clip) is believed to be at least partially driving a synchronization process of the brain activity and provides a similar conscious experience in different subjects. In order to observe the common synchronization among the subjects, a novel technique called the inter subject correlation (ISC) was implemented. We showed that the GIM—modified to incorporate the naturalistic external field—was able to fit the empirical task fMRI data in the awake state, in mild sedation, in deep sedation, and in recovery, at a temperature T* which is well above the critical temperature. To our knowledge this is the first study that captures human brain activity in response to real-life external stimuli at different levels of conscious awareness using mathematical modeling. This study might be helpful in future to assess the level of consciousness of patients with disorders of consciousness and help in regaining their consciousness

Multimodal neuroimaging approach to variability of functional connectivity in disorders of consciousness: A PET/MRI pilot study

Behavioral assessments could not suffice to provide accurate diagnostic information in individuals with disorders of consciousness (DoC). Multimodal neuroimaging markers have been developed to support clinical assessments of these patients. Here we present findings obtained by hybrid fludeoxyglucose (FDG-)PET/MR imaging in three severely brain-injured patients, one in an unresponsive wakefulness syndrome (UWS), one in a minimally conscious state (MCS), and one patient emerged from MCS (EMCS). Repeated behavioral assessment by means of Coma Recovery Scale-Revised and neurophysiological evaluation were performed in the two weeks before and after neuroimaging acquisition, to ascertain that clinical diagnosis was stable. The three patients underwent one imaging session, during which two resting-state fMRI (rs-fMRI) blocks were run with a temporal gap of about 30 min. rs-fMRI data were analyzed with a graph theory approach applied to nine independent networks. We also analyzed the benefits of concatenating the two acquisitions for each patient or to select for each network the graph strength map with a higher ratio of fitness. Finally, as for clinical assessment, we considered the best functional connectivity pattern for each network and correlated graph strength maps to FDG uptake. Functional connectivity analysis showed several differences between the two rs-fMRI acquisitions, affecting in a different way each network and with a different variability for the three patients, as assessed by ratio of fitness. Moreover, combined PET/fMRI analysis demonstrated a higher functional/metabolic correlation for patients in EMCS and MCS compared to UWS. In conclusion, we observed for the first time, through a test-retest approach, a variability in the appearance and temporal/spatial patterns of resting-state networks in severely brain-injured patients, proposing a new method to select the most informative connectivity pattern

Tinnitus distress: a paradoxical attention to the sound?

Tinnitus, the perception of sound in the absence of external stimuli, is often a disturbing symptom for which the underlying functional neuroanatomy still remains poorly understood. Most studies have focused solely on functional connectivity changes in the auditory cortex of tinnitus patients. The aim of this study was to investigate whether a correlation exists between tinnitus behavioural scores and functional brain connectivity of five resting-state networks comprising the auditory, the default mode, the external control left and right, and the salience network. For this purpose, a large sample of one hundred and thirty-five subjects underwent resting-state functional magnetic resonance imaging and their behavioural scores were obtained using clinical evaluations. Networks were extracted using independent component analysis, and functional connectivity patterns in the extracted networks were evaluated by a graph theoretical approach. The effects of tinnitus for each network were investigated by correlating the graph strength of all the regions with the tinnitus behavioural scores using stepwise fit regression analysis. Results indicated that alterations of functional interactions between key neural circuits of the brain are not limited to one single network. In particular, tinnitus distress showed a strong correlation with the connectivity pattern within and between the right executive control network and the other four resting-state networks, indicating that tinnitus distress is probably the consequence of a hyperactive attention condition. Among the behavioural scores, the strongest correlation was observed between age and hearing loss, while the tinnitus objective loudness was not correlated with any behavioural scores