Individual differences and brain structure: correlates with magnetoencephalography

The work presented in this thesis aims to increase clinical capacity for magnetoencephalography (MEG) by developing an understanding of how, in healthy participants, individual differences in brain structure, personality, and demographics influence measurements of neural oscillatory responses and functional connectivity. To this end, a large cohort of normative data was acquired using MEG with additional data acquisition using high-field MRI and supplementary individual difference data collected via a psychometric battery and screening questionnaire. MEG data were analysed to elucidate both primary sensory responses to stimulation and functional connectivity within task and task-free acquisitions. Chapters two and three introduce the physiological origins of the MEG signal and the instrumentation required to record it. Chapter four describes data acquisition and preprocessing, from the methods used in the recruitment of participants to the scanning parameters employed for our MEG and MRI acquisitions. Chapters five to seven present three empirical studies. The first investigates the relationship between MEG derived measurements of functional connectivity and cortical myeloarchitecture. We demonstrate that covariation of cortical myelin is significantly predicted by MEG-derived measurements of functional connectivity both within individual frequency bands and by their linear and non-linear combination. Chapter six presents an exploratory analysis into the impact of aging and sex-differences on MEG derived measurements of sensorimotor responses and whole-brain functional connectivity. We find trends indicating increased oscillatory responses with age. Further, we find female volunteers to exhibit greater induced responses than males. Analysis of whole-brain functional connectivity revealed a near-global increase in connectivity in female participants as compared to males. The final empirical chapter assesses the shared neuronal representations between patients diagnosed with schizophrenia and healthy individuals scoring highly on a personality questionnaire measuring schizotypy. We found highly schizotypal individuals to exhibit attenuated sensorimotor responses akin to those previously observed in schizophrenia. Patients displayed reduced functional connectivity within an occipital network, identified in task and task free data. We found this aberrant network connectivity to also be present in healthy subjects scoring highly on a questionnaire assessing schizotypy. The thesis, in sum, presents work demonstrating the significant modulatory effects of individual differences ranging from sex differences to schizotypy. This work highlights the need for consideration of participant demographics and individual differences in both clinical and basic science studies. Further, the thesis presents a newly identified relationship between MEG-derived measurements of functional connectivity and cortical myeloarchitecture. Future work assessing the role of other sources of individual difference in modulating MEG measurements is required. Moreover, the framework for assessing the relationship between functional connectivity and cortical myeloarchitecture is well suited to application in clinical populations where this relationship is hypothesised to break down

Multi-channel whole-head OPM-MEG: Helmet design and a comparison with a conventional system

© 2020 The Authors Magnetoencephalography (MEG) is a powerful technique for functional neuroimaging, offering a non-invasive window on brain electrophysiology. MEG systems have traditionally been based on cryogenic sensors which detect the small extracranial magnetic fields generated by synchronised current in neuronal assemblies, however, such systems have fundamental limitations. In recent years, non-cryogenic quantum-enabled sensors, called optically-pumped magnetometers (OPMs), in combination with novel techniques for accurate background magnetic field control, have promised to lift those restrictions offering an adaptable, motion-robust MEG system, with improved data quality, at reduced cost. However, OPM-MEG remains a nascent technology, and whilst viable systems exist, most employ small numbers of sensors sited above targeted brain regions. Here, building on previous work, we construct a wearable OPM-MEG system with ‘whole-head’ coverage based upon commercially available OPMs, and test its capabilities to measure alpha, beta and gamma oscillations. We design two methods for OPM mounting; a flexible (EEG-like) cap and rigid (additively-manufactured) helmet. Whilst both designs allow for high quality data to be collected, we argue that the rigid helmet offers a more robust option with significant advantages for reconstruction of field data into 3D images of changes in neuronal current. Using repeat measurements in two participants, we show signal detection for our device to be highly robust. Moreover, via application of source-space modelling, we show that, despite having 5 times fewer sensors, our system exhibits comparable performance to an established cryogenic MEG device. While significant challenges still remain, these developments provide further evidence that OPM-MEG is likely to facilitate a step change for functional neuroimaging

Measurement of dynamic task related functional networks using MEG

The characterisation of dynamic electrophysiological brain networks, which form and dissolve in order to support ongoing cognitive function, is one of the most important goals in neuroscience. Here, we introduce a method for measuring such networks in the human brain using magnetoencephalography (MEG). Previous network analyses look for brain regions that share a common temporal profile of activity. Here distinctly, we exploit the high spatio-temporal resolution of MEG to measure the temporal evolution of connectivity between pairs of parcellated brain regions. We then use an ICA based procedure to identify networks of connections whose temporal dynamics covary. We validate our method using MEG data recorded during a finger movement task, identifying a transient network of connections linking somatosensory and primary motor regions, which modulates during the task. Next, we use our method to image the networks which support cognition during a Sternberg working memory task. We generate a novel neuroscientific picture of cognitive processing, showing the formation and dissolution of multiple networks which relate to semantic processing, pattern recognition and language as well as vision and movement. Our method tracks the dynamics of functional connectivity in the brain on a timescale commensurate to the task they are undertaking

Age-related differences in myeloarchitecture measured at 7 T

We have used the magnetisation transfer (MT) MRI measure as a primary measure of myelination in both the grey matter (GM) of the 78 cortical automated anatomical labelling (AAL) regions of the brain, and the underlying white matter in each region, in a cohort of healthy adults (aged 19 to 62 years old). The results revealed a significant quadratic trend in myelination with age, with average global myelination peaking at 42.9 years old in grey matter, and at 41.7 years old in white matter. We also explored the possibility of using the Nuclear Overhauser Enhancement (NOE) effect, which is acquired in a similar method to MT, as an additional measure of myelination. We found that the MT and NOE signals were strongly correlated in the brain and that the NOE effects displayed similar (albeit weaker) parabolic trends with age. We also investigated differences in cortical thickness with age, and confirmed a previous result of a linear decline of 4.5±1.2μm/year

Attenuated post-movement beta rebound associated with schizotypal features in healthy people

Introduction: Schizophrenia and Schizotypal Personality Disorder (SPD) lie on a single spectrum of mental illness and converging evidence suggests similarities in the etiology of the two conditions. However, schizotypy is a heterogeneous facet of personality in the healthy population and so may be seen as a bridge between health and mental illness. Neural evidence for such a continuity would have implications for the characterization and treatment of schizophrenia. Based on our previous work identifying a relationship between symptomology in Schizophrenia and abnormal movement-induced electrophysiological response (the post-movement beta rebound (PMBR)), we predicted that if subclinical schizotypy arises from similar neural mechanisms to schizophrenia, schizotypy in healthy individuals would be associated with reduced PMBR. Methods: 116 participants completed a visuomotor task whilst their neural activity was recorded by magnetoencephalography. Partial correlations were computed between a measure of PMBR extracted from left primary motor cortex and scores on the Schizotypal Personality Questionnaire (SPQ), a self-report measure of schizotypal personality. Correlations between PMBR and SPQ factor scores measuring Cognitive-Perceptual, Interpersonal and Disorganization dimensions of schizotypy were also computed. Effects of site, age, and sex were controlled for. Results: We found a significant negative correlation between total SPQ score and PMBR. This was most strongly mediated by variance shared between Interpersonal and Disorganization factor scores. Conclusion: These findings indicate a continuum of neural deficit between schizotypy and schizophrenia, with diminution of PMBR, previously reported in schizophrenia, also measurable in individuals with schizotypal features, particularly disorganization and impaired interpersonal relations

Attenuated post-movement beta rebound associated with schizotypal features in healthy people

Introduction: Schizophrenia and Schizotypal Personality Disorder (SPD) lie on a single spectrum of mental illness and converging evidence suggests similarities in the etiology of the two conditions. However, schizotypy is a heterogeneous facet of personality in the healthy population and so may be seen as a bridge between health and mental illness. Neural evidence for such a continuity would have implications for the characterization and treatment of schizophrenia. Based on our previous work identifying a relationship between symptomology in Schizophrenia and abnormal movement-induced electrophysiological response (the post-movement beta rebound (PMBR)), we predicted that if subclinical schizotypy arises from similar neural mechanisms to schizophrenia, schizotypy in healthy individuals would be associated with reduced PMBR. Methods: 116 participants completed a visuomotor task whilst their neural activity was recorded by magnetoencephalography. Partial correlations were computed between a measure of PMBR extracted from left primary motor cortex and scores on the Schizotypal Personality Questionnaire (SPQ), a self-report measure of schizotypal personality. Correlations between PMBR and SPQ factor scores measuring Cognitive-Perceptual, Interpersonal and Disorganization dimensions of schizotypy were also computed. Effects of site, age, and sex were controlled for. Results: We found a significant negative correlation between total SPQ score and PMBR. This was most strongly mediated by variance shared between Interpersonal and Disorganization factor scores. Conclusion: These findings indicate a continuum of neural deficit between schizotypy and schizophrenia, with diminution of PMBR, previously reported in schizophrenia, also measurable in individuals with schizotypal features, particularly disorganization and impaired interpersonal relations

Altered temporal stability in dynamic neural networks underlies connectivity changes in neurodevelopment

Network connectivity is an integral feature of human brain function, and characterising its maturational trajectory is a critical step towards understanding healthy and atypical neurodevelopment. Here, we used magnetoencephalography (MEG) to investigate both stationary (i.e. time averaged) and rapidly modulating (dynamic) electrophysiological connectivity, in participants aged from mid-childhood to early adulthood (youngest participant 9 years old; oldest participant 25 years old). Stationary functional connectivity (measured via inter-regional coordination of neural oscillations) increased with age in the alpha and beta frequency bands, particularly in bilateral parietal and temporo-parietal connections. Our dynamic analysis (also applied to alpha/beta oscillations) revealed the spatiotemporal signatures of 8 dynamic networks; these modulate on a ∼100 ms time scale, and temporal stability in attentional networks was found to increase with age. Significant overlap was found between age-modulated dynamic networks and inter-regional oscillatory coordination, implying that altered network dynamics underlie age related changes in functional connectivity. Our results provide novel insights into brain network electrophysiology, and lay a foundation for future work in childhood disorders

A multi-layer network approach to MEG connectivity analysis

Recent years have shown the critical importance of inter-regional neural network connectivity in supporting healthy brain function. Such connectivity is measurable using neuroimaging techniques such as MEG, however the richness of the electrophysiological signal makes gaining a complete picture challenging. Specifically, connectivity can be calculated as statistical interdependencies between neural oscillations within a large range of different frequency bands. Further, connectivity can be computed between frequency bands. This pan-spectral network hierarchy likely helps to mediate simultaneous formation of multiple brain networks, which support ongoing task demand. However, to date it has been largely overlooked, with many electrophysiological functional connectivity studies treating individual frequency bands in isolation. Here, we combine oscillatory envelope based functional connectivity metrics with a multi-layer network framework in order to derive a more complete picture of connectivity within and between frequencies. We test this methodology using MEG data recorded during a visuomotor task, highlighting simultaneous and transient formation of motor networks in the beta band, visual networks in the gamma band and a beta to gamma interaction. Having tested our method, we use it to demonstrate differences in occipital alpha band connectivity in patients with schizophrenia compared to healthy controls. We further show that these connectivity differences are predictive of the severity of persistent symptoms of the disease, highlighting their clinical relevance. Our findings demonstrate the unique potential of MEG to characterise neural network formation and dissolution. Further, we add weight to the argument that dysconnectivity is a core feature of the neuropathology underlying schizophrenia

Individual differences and brain structure: correlates with magnetoencephalography

The work presented in this thesis aims to increase clinical capacity for magnetoencephalography (MEG) by developing an understanding of how, in healthy participants, individual differences in brain structure, personality, and demographics influence measurements of neural oscillatory responses and functional connectivity. To this end, a large cohort of normative data was acquired using MEG with additional data acquisition using high-field MRI and supplementary individual difference data collected via a psychometric battery and screening questionnaire. MEG data were analysed to elucidate both primary sensory responses to stimulation and functional connectivity within task and task-free acquisitions. Chapters two and three introduce the physiological origins of the MEG signal and the instrumentation required to record it. Chapter four describes data acquisition and preprocessing, from the methods used in the recruitment of participants to the scanning parameters employed for our MEG and MRI acquisitions. Chapters five to seven present three empirical studies. The first investigates the relationship between MEG derived measurements of functional connectivity and cortical myeloarchitecture. We demonstrate that covariation of cortical myelin is significantly predicted by MEG-derived measurements of functional connectivity both within individual frequency bands and by their linear and non-linear combination. Chapter six presents an exploratory analysis into the impact of aging and sex-differences on MEG derived measurements of sensorimotor responses and whole-brain functional connectivity. We find trends indicating increased oscillatory responses with age. Further, we find female volunteers to exhibit greater induced responses than males. Analysis of whole-brain functional connectivity revealed a near-global increase in connectivity in female participants as compared to males. The final empirical chapter assesses the shared neuronal representations between patients diagnosed with schizophrenia and healthy individuals scoring highly on a personality questionnaire measuring schizotypy. We found highly schizotypal individuals to exhibit attenuated sensorimotor responses akin to those previously observed in schizophrenia. Patients displayed reduced functional connectivity within an occipital network, identified in task and task free data. We found this aberrant network connectivity to also be present in healthy subjects scoring highly on a questionnaire assessing schizotypy. The thesis, in sum, presents work demonstrating the significant modulatory effects of individual differences ranging from sex differences to schizotypy. This work highlights the need for consideration of participant demographics and individual differences in both clinical and basic science studies. Further, the thesis presents a newly identified relationship between MEG-derived measurements of functional connectivity and cortical myeloarchitecture. Future work assessing the role of other sources of individual difference in modulating MEG measurements is required. Moreover, the framework for assessing the relationship between functional connectivity and cortical myeloarchitecture is well suited to application in clinical populations where this relationship is hypothesised to break down