Increasing fMRI Sampling Rate Improves Granger Causality Estimates

Estimation of causal interactions between brain areas is necessary for elucidating large-scale functional brain networks underlying behavior and cognition. Granger causality analysis of time series data can quantitatively estimate directional information flow between brain regions. Here, we show that such estimates are significantly improved when the temporal sampling rate of functional magnetic resonance imaging (fMRI) is increased 20-fold. Specifically, healthy volunteers performed a simple visuomotor task during blood oxygenation level dependent (BOLD) contrast based whole-head inverse imaging (InI). Granger causality analysis based on raw InI BOLD data sampled at 100-ms resolution detected the expected causal relations, whereas when the data were downsampled to the temporal resolution of 2 s typically used in echo-planar fMRI, the causality could not be detected. An additional control analysis, in which we SINC interpolated additional data points to the downsampled time series at 0.1-s intervals, confirmed that the improvements achieved with the real InI data were not explainable by the increased time-series length alone. We therefore conclude that the high-temporal resolution of InI improves the Granger causality connectivity analysis of the human brain

Remembering Forward: Neural Correlates of Memory and Prediction in Human Motor Adaptation

We used functional MR imaging (FMRI), a robotic manipulandum and systems identification techniques to examine neural correlates of predictive compensation for spring-like loads during goal-directed wrist movements in neurologically-intact humans. Although load changed unpredictably from one trial to the next, subjects nevertheless used sensorimotor memories from recent movements to predict and compensate upcoming loads. Prediction enabled subjects to adapt performance so that the task was accomplished with minimum effort. Population analyses of functional images revealed a distributed, bilateral network of cortical and subcortical activity supporting predictive load compensation during visual target capture. Cortical regions – including prefrontal, parietal and hippocampal cortices – exhibited trial-by-trial fluctuations in BOLD signal consistent with the storage and recall of sensorimotor memories or “states” important for spatial working memory. Bilateral activations in associative regions of the striatum demonstrated temporal correlation with the magnitude of kinematic performance error (a signal that could drive reward-optimizing reinforcement learning and the prospective scaling of previously learned motor programs). BOLD signal correlations with load prediction were observed in the cerebellar cortex and red nuclei (consistent with the idea that these structures generate adaptive fusimotor signals facilitating cancelation of expected proprioceptive feedback, as required for conditional feedback adjustments to ongoing motor commands and feedback error learning). Analysis of single subject images revealed that predictive activity was at least as likely to be observed in more than one of these neural systems as in just one. We conclude therefore that motor adaptation is mediated by predictive compensations supported by multiple, distributed, cortical and subcortical structures

Cerebellar structural variations in subjects with different hypnotizability

Hypnotizability-the proneness to accept suggestions and behave accordingly-has a number of physiological and behavioral correlates (postural, visuomotor, and pain control) which suggest a possible involvement of cerebellar function and/or structure. The present study was aimed at investigating the association between cerebellar macro- or micro-structural variations (analyzed through a voxel-based morphometry and a diffusion tensor imaging approach) and hypnotic susceptibility. We also estimated morphometric variations of cerebral gray matter structures, to support current evidence of hypnotizability-related differences in some cerebral areas. High (highs, N = 12), and low (lows, N = 37) hypnotizable healthy participants (according to the Stanford Hypnotic Susceptibility Scale, form A) were submitted to a high field (3 T) magnetic resonance imaging protocol. In comparison to lows, highs showed smaller gray matter volumes in left cerebellar lobules IV/V and VI at uncorrected level, with the results in left lobule IV/V maintained also at corrected level. Highs showed also gray matter volumes smaller than lows in right inferior temporal gyrus, middle and superior orbitofrontal cortex, parahippocampal gyrus, and supramarginal parietal gyrus, as well as in left gyrus rectus, insula, and middle temporal cortex at uncorrected level. Results of right inferior temporal gyrus survived also at corrected level. Analyses on micro-structural data failed to reveal any significant association. The here found morphological variations allow to extend the traditional cortico-centric view of hypnotizability to the cerebellar regions, suggesting that cerebellar peculiarities may sustain hypnotizability-related differences in sensorimotor integration and emotional contro

Measuring visual stimulation and attention signals in human superior colliculus using high-resolution fMRI

textThe superior colliculus (SC) is a laminated oculomotor structure in the midbrain. In non-human primates SC has long been known to contain a retinotopically-organized map of visual stimulation in its superficial layers, which is aligned to a map of saccadic eye movements in the deeper layers. Microstimulation and electrophysiology experiments have shown that SC also plays a key role in covert visuospatial attention and suggest that attentional modulation also occurs in a retinotopic manner. Retinotopic organization of the visual field can be non-invasively mapped in humans using functional MRI with a technique called phase-encoded retinotopy. In this technique, rotating wedges and expanding rings of visual stimuli are used to map the polar angle and eccentricity dimensions of a polar coordinates system, respectively. A similar technique can also be used to map spatial attention by keeping the visual stimulus constant and cueing subjects to attend to apertures of rotating wedges and expanding rings within the stimulus. A previous study using fMRI has shown the polar angle representation of visual stimulation in human SC but was unable to find a representation of eccentricity. This work uses high-resolution fMRI along with special surface analysis techniques developed in our lab to demonstrate maps of both polar angle and eccentricity for visual stimulation. Moreover, visual attention is also shown to be topographically organized within SC and in registration with visual stimulation. Finally, in human visual cortex, fMRI is known to show activity for sustained spatial attention even in the absence of a significant visual stimulus, an attentional "base response". In this work, SC is shown to exhibit a similar sustained attention base response using a threshold-contrast detection paradigm. This base response was compared with a response for attention with visual stimulation. The peak amplitude of the base response occurred more deeply within SC tissue than the peak for attention with stimulation. It is proposed that this reflects the specific attentional enhancement of the deeper visuomotor neurons, which are hypothesized to be a direct neuronal correlate of the oculomotor theory of attention.Psycholog

Sequential Neural Processes in Abacus Mental Addition: An EEG and fMRI Case Study

Abacus experts are able to mentally calculate multi-digit numbers rapidly. Some behavioral and neuroimaging studies have suggested a visuospatial and visuomotor strategy during abacus mental calculation. However, no study up to now has attempted to dissociate temporally the visuospatial neural process from the visuomotor neural process during abacus mental calculation. In the present study, an abacus expert performed the mental addition tasks (8-digit and 4-digit addends presented in visual or auditory modes) swiftly and accurately. The 100% correct rates in this expert’s task performance were significantly higher than those of ordinary subjects performing 1-digit and 2-digit addition tasks. ERPs, EEG source localizations, and fMRI results taken together suggested visuospatial and visuomotor processes were sequentially arranged during the abacus mental addition with visual addends and could be dissociated from each other temporally. The visuospatial transformation of the numbers, in which the superior parietal lobule was most likely involved, might occur first (around 380 ms) after the onset of the stimuli. The visuomotor processing, in which the superior/middle frontal gyri were most likely involved, might occur later (around 440 ms). Meanwhile, fMRI results suggested that neural networks involved in the abacus mental addition with auditory stimuli were similar to those in the visual abacus mental addition. The most prominently activated brain areas in both conditions included the bilateral superior parietal lobules (BA 7) and bilateral middle frontal gyri (BA 6). These results suggest a supra-modal brain network in abacus mental addition, which may develop from normal mental calculation networks

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

Action execution, action perception and 'mirror' neurones

Imperial Users onl

Reconstruction de l'activité corticale à partir de données MEG à l'aide de réseaux cérébraux et de délais de transmission estimés à partir d'IRMd

White matter fibers transfer information between brain regions with delays that are observable with magnetoencephalography and electroencephalography (M/EEG) due to their millisecond temporal resolution. We can represent the brain as a graph where nodes are the cortical sources or areas and edges are the physical connections between them: either local (between adjacent vertices on the cortical mesh) or non-local (long-range white matter fibers). Long-range anatomical connections can be obtained with diffusion MRI (dMRI) tractography which yields a set of streamlines representing white matter fiber bundles. Given the streamlines’ lengths and the information conduction speed, transmission delays can be estimated for each connection. dMRI can thus give an insight into interaction delays of the macroscopicbrain network.Localizing and recovering electrical activity of the brain from M/EEG measurements is known as the M/EEG inverse problem. Generally, there are more unknowns (brain sources) than the number of sensors, so the solution is non-unique and the problem ill-posed. To obtain a unique solution, prior constraints on the characteristics of source distributions are needed. Traditional linear inverse methods deploy different constraints which can favour solutions with minimum norm, impose smoothness constraints in space and/or time along the cortical surface, etc. Yet, structural connectivity is rarely considered and transmission delays almost always neglected.The first contribution of this thesis consists of a multimodal preprocessing pipeline used to integrate structural MRI, dMRI and MEG data into a same framework, and of a simulation procedure of source-level brain activity that was used as a synthetic dataset to validate the proposed reconstruction approaches.In the second contribution, we proposed a new framework to solve the M/EEG inverse problem called Connectivity-Informed M/EEG Inverse Problem (CIMIP), where prior transmission delays supported by dMRI were included to enforce temporal smoothness between time courses of connected sources. This was done by incorporating a Laplacian operator into the regularization, that operates on a time-dependent connectivity graph. Nonetheless, some limitations of the CIMIP approach arised, mainly due to the nature of the Laplacian, which acts on the whole graph, favours smooth solutions across all connections, for all delays, and it is agnostic to directionality.In this thesis, we aimed to investigate patterns of brain activity during visuomotor tasks, during which only a few regions typically get significantly activated, as shown by previous studies. This led us to our third contribution, an extension of the CIMIP approach that addresses the aforementioned limitations, named CIMIP_OML (“Optimal Masked Laplacian”). We restricted the full source space network (the whole cortical mesh) to a network of regions of interest and tried to find how the information is transferred between its nodes. To describe the interactions between nodes in a directed graph, we used the concept of network motifs. We proposed an algorithm that (1) searches for an optimal network motif – an optimal pattern of interaction between different regions and (2) reconstructs source activity given the found motif. Promising results are shown for both simulated and real MEG data for a visuomotor task and compared with 3 different state-of-the-art reconstruction methods.To conclude, we tackled a difficult problem of exploiting delays supported by dMRI for the reconstruction of brain activity, while also considering the directionality in the information transfer, and provided new insights into the complex patterns of brain activity.Les fibres de la matière blanche permettent le transfert d’information dans le cerveau avec des délais observables en Magnétoencéphalographie et Électroencéphalographie (M/EEG) grâce à leur haute résolution temporelle. Le cerveau peut être représenté comme un graphe où les nœuds sont les régions corticales et les liens sont les connexions physiques entre celles-ci: soit locales (entre sommets adjacents sur le maillage cortical), soit non locales (fibres de la matière blanche). Les connexions non-locales peuvent être reconstruites avec la tractographie de l’IRM de diffusion (IRMd) qui génère un ensemble de courbes («streamlines») représentant des fibres de la matière blanche. Sachant les longueurs des fibres et la vitesse de conduction de l’information, les délais de transmission peuvent être estimés. L’IRMd peut donc donner un aperçu des délais d’interaction du réseau cérébral macroscopique.La localisation et la reconstruction de l’activité électrique cérébrale à partir des mesures M/EEG est un problème inverse. En général, il y a plus d’inconnues (sources cérébrales) que de capteurs. La solution n’est donc pas unique et le problème est dit mal posé. Pour obtenir une solution unique, des hypothèses sur les caractéristiques des distributions de sources sont requises. Les méthodes inverses linéaires traditionnelles utilisent différentes hypothèses qui peuvent favoriser des solutions de norme minimale, imposer des contraintes de lissage dans l’espace et/ou dans le temps, etc. Pourtant, la connectivité structurelle est rarement prise en compte et les délais de transmission sont presque toujours négligés.La première contribution de cette thèse est un pipeline de prétraitement multimodal utilisé pour l’intégration des données d’IRM, IRMd et MEG dans un même cadre, et d’une méthode de simulation de l’activité corticale qui a été utilisée comme jeu de données synthétiques pour valider les approches de reconstruction proposées. Nous proposons également une nouvelle approche pour résoudre le problème inverse M/EEG appelée «Problème Inverse M/EEG Informé par la Connectivité» (CIMIP pour Connectivity-Informed M/EEG Inverse Problem), où des délais de transmission provenant de l’IRMd sont inclus pour renforcer le lissage temporel entre les décours des sources connectées. Pour cela, un opérateur Laplacien, basé sur un graphe de connectivité en fonction du temps, a été intégré dans la régularisation. Cependant, certaines limites de l’approche CIMIP sont apparues en raison de la nature du Laplacien qui agit sur le graphe entier et favorise les solutions lisses sur toutes les connexions, pour tous les délais, et indépendamment de la directionnalité.Lors de tâches visuo-motrices, seules quelques régions sont généralement activées significativement. Notre troisième contribution est une extension de CIMIP pour ce type de tâches qui répond aux limitations susmentionnées, nommée CIMIP_OML («Optimal Masked Laplacian») ou Laplacien Masqué Optimal. Nous essayons de trouver comment l’information est transférée entre les nœuds d’un sous-réseau de régions d’intérêt du réseau complet de l’espace des sources. Pour décrire les interactions entre nœuds dans un graphe orienté, nous utilisons le concept de motifs de réseau. Nous proposons un algorithme qui 1) cherche un motif de réseau optimal- un modèle optimal d’interaction entre régions et 2) reconstruit l’activité corticale avec le motif trouvé. Des résultats prometteurs sont présentés pour des données MEG simulées et réelles (tâche visuo-motrice) et comparés avec 3 méthodes de l’état de l’art. Pour conclure, nous avons abordé un problème difficile d’exploitation des délais de l’IRMd lors l’estimation de l’activité corticale en tenant compte de la directionalité du transfert d’information, fournissant ainsi de nouvelles perspectives sur les patterns complexes de l’activité cérébrale

Effects of aging on the neural networks underlying visuomotor adaptation

Visuomotor adaptation is the ability to correct movements in response to an error and becomes increasingly important during the aging process when assistive devices may become necessary. Neuroimaging has observed age-related atrophy in several brain regions implicated with visuomotor adaptation, and the integrity of white matter connections between these regions is also known to decline. The present research is a three-part study that assessed age-related changes in brain function and structure during healthy aging. Functional magnetic resonance images (fMRI) and diffusion tensor images (DTI) were acquired from 37 neurologically healthy, right handed participants from three age groups: young (N = 12, age range = 22-39), middle-aged (N = 13, age range = 41-58), and older (N=12, age range = 65-80). During two fMRI scans, participants completed a novel moving-target task in which visual feedback of a cursor on a computer screen was manipulated in order to elicit a visuomotor response. In the first paper of this thesis, the behavioural and neural differences between the first fMRI scan (early adaptation trials) and second scan (late adaptation trials) were analyzed for the young age group. This study aimed to outline the visuomotor transformations associated with a novel task that incorporates more natural behaviours. Visuomotor behaviour was examined through measurements of the mean cursor velocity and number of reversals in cursor direction. Although the interaction between scan number and cursor type was found to be insignificant for cursor velocity along with an insignificant main effect of scan number, a repeated-measures analysis of variance (ANOVA) found a significant main effect of cursor type. Pairwise comparisons revealed significant differences between normal and x-flip cursor conditions, and x- and y-flip conditions. Following an insignificant interaction between scan and condition, a significant main effect of cursor condition (normal, x-flip, or y-flip) for the number of reversals was determined. Pairwise comparisons revealed that participants made fewer reversals during the normal cursor condition when compared to either the x- or y-flip conditions. Areas of neural activity related to visuomotor transformations were subsequently identified through fMRI using contrast to examine regions of greater signal change for distorted vs. normal cursor conditions. A random-effects General Linear Model (GLM) was then performed to examine differences in neural activity between the two fMRI scans. Frontal regions and the postcentral and anterior cingulate gyri were activated for the early adaptation trials, while the superior temporal, inferior frontal and parahippocampal gyri, as well as the putamen and parietal regions were activated for the late trials