A Study of Brain Networks Associated With Motor Sequence Learning Foot Tapping Tasks

Understanding the learning behavior of brain functional connectivity within motor sequence learning of foot tapping tasks is of great importance to help improving walking quality of elderly people. It is also of great interest to clinical and scientific communities. The role of functional connectivity in brain function has not yet been well understood. This study comprises of two parts; the first part is to investigate brain signal stationarity, while the other will look into brain interactions while performing motor learning sequence task. Functional magnetic resonance imaging (fMRI) was utilized to acquire data from twelve healthy adult participants to study brain functional connectivity and interactions during a sequence of motor learning foot tapping tasks. Tasks were divided into: two different learning blocks, two control blocks, and five blocks of resting states. In this condition, 90 percent of the subjects developed awareness of the sequence. The stationarity of fMRI time series needs to be understood as it has important implications on the choice of appropriate approaches for the analysis of complex brain networks. The reverse arrangement test RAT was utilized to investigate the time series stationarity. Our analysis showed some non-stationary signals with a time varying first moment as a major source of non-stationarity. Next, we choose to apply psycho-physiological interactions (PPI) approach to our data and we revealed some information about the degree to which components of large-scale neural systems were functionally coupled together to achieve and perform the designed learning sequence task. In this work, we will introduce the idea of psycho-physiological interaction (PPI), which explains the responses in one cortical region in terms of an interaction between the effects of other regions and learning task parameter. We have found that the Thalamus was mostly involved and modulated with our predesigned motor learning task. We also found that the Middle frontal Gyrus and Left pre-central Gyrus were the most interacting regions with the above mentioned cluster. This interaction can only be related to the interactions that are based on the experimental factors which are the psychological and physiological interactions. The current results have also supported PPI as a potential tool for understanding learning mechanism during foot tapping tasks

Diffusion-adapted spatial filtering of fMRI data for improved activation mapping in white matter

Brain activation mapping using fMRI data has been mostly focused on finding detections in gray matter. Activations in white matter are harder to detect due to anatomical differences between both tissue types, which are rarely acknowledged in experimental design. However, recent publications have started to show evidence for the possibility of detecting meaningful activations in white matter. The shape of the activations arising from the BOLD signal is fundamentally different between white matter and gray matter, a fact which is not taken into account when applying isotropic Gaussian filtering in the preprocessing of fMRI data. We explore a graph-based description of the white matter developed from diffusion MRI data, which is capable of encoding the anisotropic domain. Based on this representation, two approaches to white matter filtering are tested, and their performance is evaluated on both semi-synthetic phantoms and real fMRI data. The first approach relies on heat kernel filtering in the graph spectral domain, and produced a clear increase in both sensitivity and specificity over isotropic Gaussian filtering. The second approach is based on spectral decomposition for the denosing of the signal, and showed increased specificity at the cost of a lower sensitivity.Novel approach to white matter filtering We introduced new advanced methods for filtering brain scans. Using them, we managed to improve the detection of activity in the white matter of the brain

Choosing Wavelet Methods, Filters, and Lengths for Functional Brain Network Construction

Wavelet methods are widely used to decompose fMRI, EEG, or MEG signals into time series representing neurophysiological activity in fixed frequency bands. Using these time series, one can estimate frequency-band specific functional connectivity between sensors or regions of interest, and thereby construct functional brain networks that can be examined from a graph theoretic perspective. Despite their common use, however, practical guidelines for the choice of wavelet method, filter, and length have remained largely undelineated. Here, we explicitly explore the effects of wavelet method (MODWT vs. DWT), wavelet filter (Daubechies Extremal Phase, Daubechies Least Asymmetric, and Coiflet families), and wavelet length (2 to 24) - each essential parameters in wavelet-based methods - on the estimated values of network diagnostics and in their sensitivity to alterations in psychiatric disease. We observe that the MODWT method produces less variable estimates than the DWT method. We also observe that the length of the wavelet filter chosen has a greater impact on the estimated values of network diagnostics than the type of wavelet chosen. Furthermore, wavelet length impacts the sensitivity of the method to detect differences between health and disease and tunes classification accuracy. Collectively, our results suggest that the choice of wavelet method and length significantly alters the reliability and sensitivity of these methods in estimating values of network diagnostics drawn from graph theory. They furthermore demonstrate the importance of reporting the choices utilized in neuroimaging studies and support the utility of exploring wavelet parameters to maximize classification accuracy in the development of biomarkers of psychiatric disease and neurological disorders.Comment: working pape

Network approaches to understanding the functional effects of focal brain lesions

Complex network models of functional connectivity have emerged as a paradigm shift in brain mapping over the past decade. Despite significant attention within the neuroimaging and cognitive neuroscience communities, these approaches have hitherto not been extensively explored in neurosurgery. The aim of this thesis is to investigate how the field of connectomics can contribute to understanding the effects of focal brain lesions and to functional brain mapping in neurosurgery. This datasets for this thesis include a clinical population with focal brain tumours and a cohort focused on healthy adolescent brain development. Multiple network analyses of increasing complexity are performed based upon resting state functional MRI. In patients with focal brain tumours, the full complement of resting state networks were apparent, while also suggesting putative patterns of network plasticity. Connectome analysis was able to identify potential signatures of node robustness and connections at risk that could be used to individually plan surgery. Focal lesions induced the formation of new hubs while down regulating previously established hubs. Overall these data are consistent with a dynamic rather than a static response to the presence of focal lesions. Adolescent brain development demonstrated discrete dynamics with distinct gender specific and age-gender interactions. Network architecture also became more robust, particularly to random removal of nodes and edges. Overall these data provide evidence for the early vulnerability rather than enhanced plasticity of brain networks. In summary, this thesis presents a combined analysis of pathological and healthy development datasets focused on understanding the functional effects of focal brain lesions at a network level. The coda serves as an introduction to a forthcoming study, known as Connectomics and Electrical Stimulation for Augmenting Resection (CAESAR), which is an evolution of the results and methods herein.MGH is funded by the Wellcome Trust Neuroscience in Psychiatry Network with additional support from the National Institute for Health Research Cambridge Biomedical Research Centre

Dynamic brain networks explored by structure-revealing methods

The human brain is a complex system able to continuously adapt. How and where brain activity is modulated by behavior can be studied with functional magnetic resonance imaging (fMRI), a non-invasive neuroimaging technique with excellent spatial resolution and whole-brain coverage. FMRI scans of healthy adults completing a variety of behavioral tasks have greatly contributed to our understanding of the functional role of individual brain regions. However, by statistically analyzing each region independently, these studies ignore that brain regions act in concert rather than in unison. Thus, many studies since have instead examined how brain regions interact. Surprisingly, structured interactions between distinct brain regions not only occur during behavioral tasks but also while a subject rests quietly in the MRI scanner. Multiple groups of regions interact very strongly with each other and not only do these groups bear a striking resemblance to the sets of regions co-activated in tasks, but many of these interactions are also progressively disrupted in neurological diseases. This suggests that spontaneous fluctuations in activity can provide novel insights into fundamental organizing principles of the human brain in health and disease. Many techniques to date have segregated regions into spatially distinct networks, which ignores that any brain region can take part in multiple networks across time. A more natural view is to estimate dynamic brain networks that allow flexible functional interactions (or connectivity) over time. The estimation and analysis of such dynamic functional interactions is the subject of this dissertation. We take the perspective that dynamic brain networks evolve in a low-dimensional space and can be described by a small number of characteristic spatiotemporal patterns. Our proposed approaches are based on well-established statistical methods, such as principal component analysis (PCA), sparse matrix decompositions, temporal clustering, as well as a multiscale analysis by novel graph wavelet designs. We adapt and extend these methods to the analysis of dynamic brain networks. We show that PCA and its higher-order equivalent can identify co-varying functional interactions, which reveal disturbed dynamic properties in multiple sclerosis and which are related to the timing of stimuli for task studies, respectively. Further we show that sparse matrix decompositions provide a valid alternative approach to PCA and improve interpretability of the identified patterns. Finally, assuming an even simpler low-dimensional space and the exclusive temporal expression of individual patterns, we show that specific transient interactions of the medial prefrontal cortex are disturbed in aging and relate to impaired memory

The iso-response method

Throughout the nervous system, neurons integrate high-dimensional input streams and transform them into an output of their own. This integration of incoming signals involves filtering processes and complex non-linear operations. The shapes of these filters and non-linearities determine the computational features of single neurons and their functional roles within larger networks. A detailed characterization of signal integration is thus a central ingredient to understanding information processing in neural circuits. Conventional methods for measuring single-neuron response properties, such as reverse correlation, however, are often limited by the implicit assumption that stimulus integration occurs in a linear fashion. Here, we review a conceptual and experimental alternative that is based on exploring the space of those sensory stimuli that result in the same neural output. As demonstrated by recent results in the auditory and visual system, such iso-response stimuli can be used to identify the non-linearities relevant for stimulus integration, disentangle consecutive neural processing steps, and determine their characteristics with unprecedented precision. Automated closed-loop experiments are crucial for this advance, allowing rapid search strategies for identifying iso-response stimuli during experiments. Prime targets for the method are feed-forward neural signaling chains in sensory systems, but the method has also been successfully applied to feedback systems. Depending on the specific question, “iso-response” may refer to a predefined firing rate, single-spike probability, first-spike latency, or other output measures. Examples from different studies show that substantial progress in understanding neural dynamics and coding can be achieved once rapid online data analysis and stimulus generation, adaptive sampling, and computational modeling are tightly integrated into experiments