Dr Elizabeth Shumbayawonda

This study focuses on the resting state network analysis of the brain, as well as how these networks change both in topology and location throughout life. The magnetoencephalogram (MEG) background activity from 220 healthy volunteers (age 7-84 years), was analysed combining complex network analysis principles of graph theory with both linear and non-linear methods to evaluate the changes in the brain. Granger Causality (GC) (linear method) and Phase Slope Index (PSI) (non-linear method) were used to observe the connectivity in the brain during rest, and as a function of age by analysing the degree, clustering coefficient, efficiency, betweenness, modularity and maximised modularity of the observed complex brain networks. Our results showed that GC showed little linear causal activity in the brain at rest, with small world topology, while PSI showed little information flow in the brain, with random network topology. However, both analyses produced complementary results pertaining to the resting state of the brain.

The characterisation of healthy ageing of the brain could help create a fingerprint of normal ageing that might assist in the early diagnosis of neurodegenerative conditions. This study examined changes in resting state MEG permutation entropy due to age and gender in a sample of 220 healthy participants (98 males and 122 females, ages ranging between 7 and 84). Entropy was quantified using normalised permutation entropy and modified permutation entropy, with an embedding dimension of 5 and a lag of 1 as the input parameters for both algorithms. Effects of age were observed over the 5 regions of the brain i.e. anterior, central, posterior, and left and right lateral, with the anterior and central regions containing the highest permutation entropy. Statistically significant differences due to age were observed in the different brain regions for both genders, with the evolutions described using the fitting of polynomial regressions. Nevertheless, no significant differences between the genders were observed across all ages. These results suggest that the evolution of entropy in the background brain activity, quantified with permutation entropy algorithms, might be considered an alternative illustration of a ?nominal? physiological rhythm.

This paper investigates the energy transmitted to and harvested by a camera pill travelling along the gastrointestinal tract. It focuses on the transmitted electromagnetic (EM) energy in the frequency range of 0.18 to 2450 MHz and compares it to the mechanical energy due to the motion of the pill and the force exerted from the intestine in its peristalsis onto the pill, and the electrochemical energy due to the change of pH along the path of the pill. A comprehensive multilayer EM power transmission model is constructed and implemented in a numerical code, including power attenuation through each layer and multi-reflections at material interfaces. Computer simulations of EM power transmission through a multilayer abdomen to a pill travelling in the intestine are presented for the human abdominal cavity as well as phantom organs and phantom environments, coupled with corresponding experimental studies using these phantom components and environments. Two types of phantom abdomen are investigated: a ballistic gel and a multilayer duck breast. Phantom small intestine involves gelatin gel layers with embedded phantom chyme. Due to limitations related to the energy safety limit of skin exposure and energy losses in the transmission through the abdomen and intestines, inductive range frequencies are recommended which may yield energy harvesting of 10-50 mWh during 8 hours of pill journey, complemented by about 10 mWh of mechanical energy and 10 mWh of electrochemical energy harvesting, in addition to about 330 mWh typically stored in the coin batteries of a camera pill.

Maturation and ageing, which can be characterised by the dynamic changes in brain morphology, can have an impact on the physiology of the brain. As such, it is possible that these changes can have an impact on the magnetic activity of the brain recorded using magnetoencephalography. In this study changes in the resting state brain (magnetic) activity due to healthy ageing were investigated by estimating the complexity of magnetoencephalogram (MEG) signals. The main aim of this study was to identify if the complexity of background MEG signals changed significantly across the human lifespan for both males and females. A sample of 177 healthy participants (79 males and 98 females aged between 21 and 80 and grouped into 3 categories i.e., early-, mid- and late-adulthood) was used in this investigation. This investigation also extended to evaluating if complexity values remained relatively stable during the 5 min recording. Complexity was estimated using permutation Lempel-Ziv complexity, a recently introduced complexity metric, with a motif length of 5 and a lag of 1. Effects of age and gender were investigated in the MEG channels over 5 brain regions, i.e., anterior, central, left lateral, posterior, and, right lateral, with highest complexity values observed in the signals recorded by the channels over the anterior and central regions of the brain. Results showed that while changes due to age had a significant effect on the complexity of the MEG signals recorded over 5 brain regions, gender did not have a significant effect on complexity values in all age groups investigated. Moreover, although some changes in complexity were observed between the different minutes of recording, due to the small magnitude of the changes it was concluded that practical significance might outweigh statistical significance in this instance. The results from this study can contribute to form a fingerprint of the characteristics of healthy ageing in MEGs that could be useful when investigating changes to the resting state activity due to pathology.

The brain is a very delicate, but sophisticated and complex organ of the body. During life, the brain grows and develops, matures, and then ages like all other organs of the body. This maturation and ageing comes with various physiological and anatomical changes which have an impact on the background activity of the brain. Brain activity can be recorded using various techniques including magnetoencephalography and magnetic resonance imaging, and these recordings combined with signal processing can be useful to characterise the changes in the brain that can be a result of the ageing process. By analysing various aspects of the brain, such as functional and effective connectivity, entropy and complexity, the state of the resting brain at different ages can be understood with greater detail. Furthermore, these analyses can be used to investigate the resting state brain networks that are present in the brain, as well as their topology. This information can be combined with network analysis techniques such as graph theory and used to understand the manner in which the brain both matures and ages.

This research made use of two magnetoencephalogram (MEG) databases recorded from both males and females. The first, containing resting state MEGs (rMEGs) from 220 healthy volunteers (aged 7-84), was used as the main database in this thesis to investigate the effects of age on rMEG signals throughout life. The aim of this research was to make use of rMEG signals and signal processing techniques to determine the effects of healthy ageing on the brain throughout life. It was hypothesised that the effects of age are identifiable using advanced signal processing techniques. Thus, the effects of age on linear interactions, causality, synchronisation, information flow, entropy and complexity, were investigated in the 148 MEG channels lying over 5 brain regions (anterior, central, left lateral, posterior, and, right lateral) using multiple linear and non-linear analysis techniques (namely: Pearson?s correlation, coherence, Granger causality, phase slope index, rho index, transfer entropy, synchronisation likelihood, Lempel-Ziv complexity, permutation Lempel-Ziv complexity, permutation entropy, and, modified permutation entropy). Additionally, graph theory principles were used to evaluate different network components such as integration (global efficiency), segregation (clustering coefficient and modularity), centrality (betweenness), and resilience (strength and assortativity) so as to obtain an understanding of the construct of the resting brain network. Moreover, complex network analysis was also used to determine the overall network topology of the brain network and how this changed at different stages in life. Gender effects were also studied so as to identify if there were any significant differences between males and females at different stages of life. Results from these analyses showed that the healthy resting brain has low effective and functional connectivity, relatively low complexity and entropy, as well as no significant detectable direction of information flow. Therefore this showed that there is very little synchronous or simultaneously occurring information in the rMEG time series. Thus, during rest, the brain resembles a system in limbo/phase transition, with low effective and functional connectivity, relatively low complexity and entropy, and no significant detectable direction of information flow.

The second database used in this research project was obtained during a collaboration visit to the Cognitive and Computational Neuroscience laboratory at the Centre for Biomedical Technology- Universidad Politécnica de Madrid (CTB-UPM). This database was made up of rMEGs recorded from 199 healthy volunteers (aged 60-80), and the focus of this additional set of analyses was to identify differences between the rMEG signals recorded from healthy individuals, those with subjective cognitive decline as well as those with

The analysis of resting-state brain activity recording in magnetoencephalograms (MEGs) with new algorithms of symbolic dynamics analysis could help obtain a deeper insight into the functioning of the brain and identify potential differences between males and females. Permutation Lempel-Ziv complexity (PLZC), a recently introduced non-linear signal processing algorithm based on symbolic dynamics, was used to evaluate the complexity of MEG signals in source space. PLZC was estimated in a broad band of frequencies (2?45 Hz), as well as in narrow bands (i.e., theta (4?8 Hz), alpha (8?12 Hz), low beta (12?20 Hz), high beta (20?30 Hz), and gamma (30?45 Hz)) in a sample of 98 healthy elderly subjects (49 males, 49 female) aged 65?80 (average age of 72.71 ± 4.22 for males and 72.67 ± 4.21 for females). PLZC was significantly higher for females than males in the high beta band at posterior brain regions including the precuneus, and the parietal and occipital cortices. Further statistical analyses showed that higher complexity values over highly overlapping regions than the ones mentioned above were associated with larger hippocampal volumes only in females. These results suggest that sex differences in healthy aging can be identified from the analysis of magnetoencephalograms with novel signal processing methods.

Objective

To analyse magnetoencephalogram (MEG) signals with Lempel-Ziv Complexity (LZC) to identify the regions of the brain showing changes related to cognitive decline and AlzheimeUs Disease (AD).

Methods

LZC was used to study MEG signals in the source space from 99 participants (36 male, 63 female, average age: 71.82 ± 4.06) in three groups (33 subjects per group): healthy (control) older adults, older adults with subjective cognitive decline (SCD), and adults with mild cognitive impairment (MCI). Analyses were performed in broadband (2?45 Hz) and in classic narrow bands (theta (4?8 Hz), alpha (8?12 Hz), low beta (12?20 Hz), high beta (20?30 Hz), and, gamma (30?45 Hz)).

Results

LZC was significantly lower in subjects with MCI than in those with SCD. Moreover, subjects with MCI had significantly lower MEG complexity than controls and SCD subjects in the beta frequency band. Lower complexity was correlated with smaller hippocampal volumes.

Conclusions

Brain complexity ? measured with LZC ? decreases in MCI patients when compared to SCD and healthy controls. This decrease is associated with a decrease in hippocampal volume, a key feature in AD progression.

Significance

This is the first study to date characterising the changes of brain activity complexity showing the specific spatial pattern of the alterations as well as the morphological correlations throughout preclinical stages of AD.