Does function fit structure? A ground truth for non-invasive neuroimaging.

There are now a number of non-invasive methods to image human brain function in-vivo. However, the accuracy of these images remains unknown and can currently only be estimated through the use of invasive recordings to generate a functional ground truth. Neuronal activity follows grey matter structure and accurate estimates of neuronal activity will have stronger support from accurate generative models of anatomy. Here we introduce a general framework that, for the first time, enables the spatial distortion of a functional brain image to be estimated empirically. We use a spherical harmonic decomposition to modulate each cortical hemisphere from its original form towards progressively simpler structures, ending in an ellipsoid. Functional estimates that are not supported by the simpler cortical structures have less inherent spatial distortion. This method allows us to compare directly between magnetoencephalography (MEG) source reconstructions based upon different assumption sets without recourse to functional ground truth

Optimising experimental design for MEG resting state functional connectivity measurement

The study of functional connectivity using magnetoencephalography (MEG) is an expanding area of neuroimaging, and adds an extra dimension to the more common assessments made using fMRI. The importance of such metrics is growing, with recent demonstrations of their utility in clinical research, however previous reports suggest that whilst group level resting state connectivity is robust, single session recordings lack repeatability. Such robustness is critical if MEG measures in individual subjects are to prove clinically valuable. In the present paper, we test how practical aspects of experimental design affect the intra-subject repeatability of MEG findings; specifically we assess the effect of co-registration method and data recording duration. We show that the use of a foam head-cast, which is known to improve co-registration accuracy, increased significantly the between session repeatability of both beamformer reconstruction and connectivity estimation. We also show that recording duration is a critical parameter, with large improvements in repeatability apparent when using ten minute, compared to five minute recordings. Further analyses suggest that the origin of this latter effect is not underpinned by technical aspects of source reconstruction, but rather by a genuine effect of brain state; short recordings are simply inefficient at capturing the canonical MEG network in a single subject. Our results provide important insights on experimental design and will prove valuable for future MEG connectivity studies

Moving magnetoencephalography towards real-world applications with a wearable system

Imaging human brain function with techniques such as magnetoencephalography1 (MEG) typically requires a subject to perform tasks whilst their head remains still within a restrictive scanner. This artificial environment makes the technique inaccessible to many people, and limits the experimental questions that can be addressed. For example, it has been difficult to apply neuroimaging to investigation of the neural substrates of cognitive development in babies and children, or in adult studies that require unconstrained head movement (e.g. spatial navigation). Here, we develop a new type of MEG system that can be worn like a helmet, allowing free and natural movement during scanning. This is possible due to the integration of new quantum sensors2,3 that do not rely on superconducting technology, with a novel system for nulling background magnetic fields. We demonstrate human electrophysiological measurement at millisecond resolution whilst subjects make natural movements, including head nodding, stretching, drinking and playing a ball game. Results compare well to the current state-of-the-art, even when subjects make large head movements. The system opens up new possibilities for scanning any subject or patient group, with myriad applications such as characterisation of the neurodevelopmental connectome, imaging subjects moving naturally in a virtual environment, and understanding the pathophysiology of movement disorders

High Precision Anatomy for MEG

Magnetoencephalography (MEG) is a non-invasive brain imaging method with high temporal resolution but relatively poor spatial resolution as compared to some other non-invasive techniques. This thesis examines how the spatial resolution of MEG can be improved using new recording paradigms in which the subject’s head position is fixed and known in advance. This is accomplished by using subject-specific head casts made using a combination of structural MRI and 3D printing technology. The resulting high-precision spatial models allow one to make inference at spatial scales of the order of cortical laminae. This thesis outlines the design of the head casts and examines the potential theoretical and empirical advances they offer. Specifically I outline simulation and then empirical investigations showing it is possible to non-invasively distinguish between electrophysiological signals in different layers of the cortex

Source Modelling of the Human Hippocampus for MEG

Magnetoencephalography (MEG) is a neuroimaging technique which gives direct non-invasive measurements of neuronal activity with high temporal resolution. Given its increasing use in cognitive and clinical research, it is important to characterize, and ideally improve upon, its advantages and limitations. For example, it is conventionally assumed to be insensitive to deep structures because of their distance from the sensors. Consequently, knowledge about their signal contribution is limited. One deep structure of particular interest is the hippocampus which plays a key role in memory and learning, and in organising temporal flow of information across regions. A large body of rodent studies have demonstrated quantifiable oscillatory underpinnings of these functions, now waiting to be addressed in humans. Due to its high temporal resolution, MEG is ideally suited for doing so but faces technical challenges. Firstly, the source-to-sensor distance is large, making it difficult to obtain sufficiently high signal-to-noise ratio (SNR) data. Secondly, most generative models (which describe the relationship between sensors and signal) include only the cortical surface. Thirdly, errors in co-registering data to an anatomical image easily obstruct or blur hippocampal sources. This thesis tested the hypotheses that a) identification and optimisation of acquisition parameters which improve the SNR, b) inclusion of the hippocampus in the generative model, and c) minimisation of co-registration error, together enable reliable inferences about hippocampal activity from MEG data. We found the most important empirical factor in detecting hippocampal activity using the extended generative model to be co-registration error; that this can be minimised using flexible head-casts; and that combining anatomical modelling, head-casts, and a spatial memory task, allows hippocampal activity to be reliably observed. Hence the work confirmed the overall hypothesis to be valid. Additionally, simulation results revealed that for a new generation of MEG sensors, ~5-fold sensitivity improvements can be obtained but critically depend on low sensor location errors. These findings set down a new basis for time-resolved examination of hippocampal function