Dynamic Complexity and Causality Analysis of Scalp EEG for Detection of Cognitive Deficits

This dissertation explores the potential of scalp electroencephalography (EEG) for the detection and evaluation of neurological deficits due to moderate/severe traumatic brain injury (TBI), mild cognitive impairment (MCI), and early Alzheimer’s disease (AD). Neurological disorders often cannot be accurately diagnosed without the use of advanced imaging modalities such as computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET). Non-quantitative task-based examinations are also used. None of these techniques, however, are typically performed in the primary care setting. Furthermore, the time and expense involved often deters physicians from performing them, leading to potential worse prognoses for patients. If feasible, screening for cognitive deficits using scalp EEG would provide a fast, inexpensive, and less invasive alternative for evaluation of TBI post injury and detection of MCI and early AD. In this work various measures of EEG complexity and causality are explored as means of detecting cognitive deficits. Complexity measures include eventrelated Tsallis entropy, multiscale entropy, inter-regional transfer entropy delays, and regional variation in common spectral features, and graphical analysis of EEG inter-channel coherence. Causality analysis based on nonlinear state space reconstruction is explored in case studies of intensive care unit (ICU) signal reconstruction and detection of cognitive deficits via EEG reconstruction models. Significant contributions in this work include: (1) innovative entropy-based methods for analyzing event-related EEG data; (2) recommendations regarding differences in MCI/AD of common spectral and complexity features for different scalp regions and protocol conditions; (3) development of novel artificial neural network techniques for multivariate signal reconstruction; and (4) novel EEG biomarkers for detection of dementia

Direction-Dependent Responses To Traumatic Brain Injury In Pediatric Pigs

Traumatic brain injury (TBI) in children is a costly and alarmingly prevalent public health concern. Children (4-11 years of age) in the US have the highest rate of TBI-related emergency department visits. The plane of head rotation significantly affects neurocognitive deficits and pathophysiological responses such as axonal injury, but is largely ignored in TBI literature. In Chapter 1, an outline of existing research is provided, including the lack of attention to diagnosis, treatment, and prevention in children, who exhibit distinct biomechanical and neuropathological responses to TBI. Additionally, we hypothesize that the plane of head rotation in TBI induces a) region-specific changes in axonal injury, which lead to acute and chronic changes in electrophysiological responses; b) changes to event-related potentials and resting state electroencephalography (EEG) and c) tract-oriented strain and strain rate alterations in the white matter. All work in this dissertation is based on a well-established piglet model of TBI. In Chapter 2, we assess a novel rotational head kinematic metric, rotational work (RotWork), which incorporates head rotation rate, direction, and brain shape, as a predictor of acute axonal injury. This metric provides an improvement over existing metrics and could be useful in the development of effective child safety equipment used in recreation or transportation. In Chapter 3, we generate functional networks from auditory event-related potentials and use the patterns of change to distinguish injured brains from non-injured; the resulting algorithm showed an 82% predictive accuracy. In Chapter 4, we find elevations in network nodal strength, modularity and clustering coefficient after TBI across all frequency bands relative to baseline, whereas both metrics were reduced in shams. We report the first study using resting state EEG to create functional networks in relation to pediatric TBI, noting that this work may assist in the development of TBI biomarkers. In Chapter 5, we use a high-resolution finite element model to examine the effects of head rotation plane on the distribution of regional strains and strain rates. Sagittal rapid head rotations induced significantly larger volume fraction of damaged brainstem than axial and coronal rotations. We also found that local tissue deformation and histopathology were head direction- and region- dependent but poorly correlated at a local scale. Finally, in Chapter 6, we conclude that the work presented in this dissertation is novel and contributes valuable knowledge to the study of pediatric TBI, and that consideration of the plane of head rotation is critical to the understanding and accurate prediction of pediatric functional and region-dependent responses to TBI

An investigation into the effects of commencing haemodialysis in the critically ill

<b>Introduction:</b> We have aimed to describe haemodynamic changes when haemodialysis is instituted in the critically ill. 3 hypotheses are tested: 1)The initial session is associated with cardiovascular instability, 2)The initial session is associated with more cardiovascular instability compared to subsequent sessions, and 3)Looking at unstable sessions alone, there will be a greater proportion of potentially harmful changes in the initial sessions compared to subsequent ones. <b>Methods:</b> Data was collected for 209 patients, identifying 1605 dialysis sessions. Analysis was performed on hourly records, classifying sessions as stable/unstable by a cutoff of >+/-20% change in baseline physiology (HR/MAP). Data from 3 hours prior, and 4 hours after dialysis was included, and average and minimum values derived. 3 time comparisons were made (pre-HD:during, during HD:post, pre-HD:post). Initial sessions were analysed separately from subsequent sessions to derive 2 groups. If a session was identified as being unstable, then the nature of instability was examined by recording whether changes crossed defined physiological ranges. The changes seen in unstable sessions could be described as to their effects: being harmful/potentially harmful, or beneficial/potentially beneficial. <b>Results:</b> Discarding incomplete data, 181 initial and 1382 subsequent sessions were analysed. A session was deemed to be stable if there was no significant change (>+/-20%) in the time-averaged or minimum MAP/HR across time comparisons. By this definition 85/181 initial sessions were unstable (47%, 95% CI SEM 39.8-54.2). Therefore Hypothesis 1 is accepted. This compares to 44% of subsequent sessions (95% CI 41.1-46.3). Comparing these proportions and their respective CI gives a 95% CI for the standard error of the difference of -4% to 10%. Therefore Hypothesis 2 is rejected. In initial sessions there were 92/1020 harmful changes. This gives a proportion of 9.0% (95% CI SEM 7.4-10.9). In the subsequent sessions there were 712/7248 harmful changes. This gives a proportion of 9.8% (95% CI SEM 9.1-10.5). Comparing the two unpaired proportions gives a difference of -0.08% with a 95% CI of the SE of the difference of -2.5 to +1.2. Hypothesis 3 is rejected. Fisher’s exact test gives a result of p=0.68, reinforcing the lack of significant variance. <b>Conclusions:</b> Our results reject the claims that using haemodialysis is an inherently unstable choice of therapy. Although proportionally more of the initial sessions are classed as unstable, the majority of MAP and HR changes are beneficial in nature

Novel models to predict elevated intracranial pressure during intensive care and long-term neurological outcome after TBI

status: publishe

Does tight glycemic control positively impact on patient mortality?

peer reviewe