Quantification of neural substrates of vergence system via fMRI

Vergence eye movement is one of the oculomotor systems which allow depth perception via disconjugate movement of the eyes. Neuroimaging methods such as functional magnetic resonance imaging (fMRI) measure neural activity changes activity in the brain while subjects perform experimental tasks. A rich body of primate investigations on vergence is already established in the neurophysiology literature; on the other hand, there are a limited number of fMRI studies on neural mechanisms behind the vergence system. The results demonstrated that vergence system shares neural sources and also shows differentiation within the boundaries of frontal eye fields (FEF) and midbrain of the brainstem in comparison to saccadic, rapid conjugate eye movements, system with application of simple tracking experiment. Functional activity within the FEF was located anterior to the saccadic functional activity (z \u3e 2.3; p \u3c 0.03). Functional activity within the midbrain was observed as a result of application of vergence task, but not for the saccade data set. The novel memory-guided vergence experiment also showed a relationship between posterior parahippocampal area and memory where two other experiments were implemented for comparison of memory load in this region. Significant percent change in the functional activity was observed for the posterior parahippocampal area. Furthermore, an increase in the interconnectivity was observed for vergence tasks via utilization of Granger-Causality Analysis. When prediction was involved the increase in the number of causal interactions was statistically significant (p\u3c 0.05). The comparison of the number of influences between prediction-evoked vergence task and simple tracking vergence task was also statistically significant for these two experimental paradigms, p \u3c 0.0001. Another result observed in this dissertation was the application of hierarchical independent component analysis from to the fronto-parietal and cerebellar components within saccade and vergence tasks. Interestingly, cerebellar component showed delayed latency in the group level signal in comparison to fronto-parietal group level signals, which was evaluated to determine why segregation existed between the components acquired from the implementation of independent component analysis. Lastly, region of interet (ROI) based analysis in comparison to global (whole) brain analysis indicated more sensitive results on frontal, parietal, brainstem and occipital areas at both individual and group levels. Overall, the purpose of this dissertation was to investigate neural control of vergence movements by 1-spatial mapping of vergence induced functional activity, 2- applying different signal processing methods to quantify neural correlates of the vergence system at causal functional connectivity, underlying sources and region of interests (ROI) based levels. It was concluded that quantification of vergence movements via fMRI can build a synergy with behavioral investigations and may also shed light on neural differentiation between healthy individuals and patients with neural dysfunctions and injuries by serving as a biomarker

Frequency-domain analysis of fNIRS fluctuations induced by rhythmic mental arithmetic

Functional near-infrared spectroscopy (fNIRS) is an increasingly used technology for imaging neural correlates of cognitive processes. However, fNIRS signals are commonly impaired by task-evoked and spontaneous hemodynamic oscillations of non-cerebral origin, a major challenge in fNIRS research. In an attempt to isolate the task-evoked cortical response, we investigated the coupling between hemodynamic changes arising from superficial and deep layers during mental effort. For this aim, we applied a rhythmic mental arithmetic task to induce cyclic hemodynamic fluctuations suitable for effective frequency-resolved measurements. Twenty university students aged 18–25 years (eight males) underwent the task while hemodynamic changes were monitored in the forehead using a newly developed NIRS device, capable of multi-channel and multi-distance recordings. We found significant task-related fluctuations for oxy-and deoxy-hemoglobin, highly coherent across shallow and deep tissue layers, corroborating the strong influence of surface hemodynamics on deep fNIRS signals. Importantly, after removing such surface contamination by linear regression, we show that the frontopolar cortex response to a mental math task follows an unusual inverse oxygenation pattern. We confirm this finding by applying for the first time an alternative method to estimate the neural signal, based on transfer function analysis and phasor algebra. Altogether, our results demonstrate the feasibility of using a rhythmic mental task to impose an oscillatory state useful to separate true brain functional responses from those of non-cerebral origin. This separation appears to be essential for a better understanding of fNIRS data and to assess more precisely the dynamics of the neuro-visceral link

High-resolution CBV-fMRI allows mapping of laminar activity and connectivity of cortical input and output in human M1

Layer-dependent fMRI allows measurements of information flow in cortical circuits, as afferent and efferent connections terminate in different cortical layers. However, it is unknown to what level human fMRI is specific and sensitive enough to reveal directional functional activity across layers. To answer this question, we developed acquisition and analysis methods for blood-oxygen-level-dependent (BOLD) and cerebral-blood-volume (CBV)-based laminar fMRI and used these to discriminate four different tasks in the human motor cortex (M1). In agreement with anatomical data from animal studies, we found evidence for somatosensory and premotor input in superficial layers of M1 and for cortico-spinal motor output in deep layers. Laminar resting-state fMRI showed directional functional connectivity of M1 with somatosensory and premotor areas. Our findings demonstrate that CBV-fMRI can be used to investigate cortical activity in humans with unprecedented detail, allowing investigations of information flow between brain regions and outperforming conventional BOLD results that are often buried under vascular biases

Influence of Early Bilingual Exposure in the Developing Human Brain.

190 p.La adquisición del lenguaje es un proceso que ese encuentra determinado tanto por mecanismos de desarrollo cognitivo, como por la experiencia lingüística durante los primeros años de vida. Aunque se trata de un proceso relativamente complejo, los bebés muestran una gran habilidad para el aprendizaje del lenguaje. Un entorno de aprendizaje lingüístico bilingüe podría considerarse aun más complejo, ya que los bebés están expuestos a las características lingüísticas de dos lenguas simultáneamente. En primer lugar, los bebés que crecen en un entorno bilingüe tienen que ser capaces de darse cuenta de que están expuestos a dos lenguas diferentes, y posteriormente deben separar y aprender las características especificas de cada una de ellas; por ejemplo, los distintos fonemas, palabras o estructuras gramaticales. Aunque la exposición lingüística total de los bebés bilingües debería ser comparable a la de los bebés monolingües, es probable que la exposición a cada una de las lenguas de su entorno sea menor, ya que tienen que dividir su tiempo de exposición entre ambas. Si bien los bebés bilingües parecen no tener problemas para enfrentarse a un contexto de aprendizaje potencialmente más complejo, ya que alcanzan las distintas etapas de adquisición del lenguaje a un ritmo similar a los bebés monolingües, sí se han observado adaptaciones a nivel conductual y a nivel de funcionamiento cerebral que podrían producirse como consecuencia de este contexto.Basque Center on cognition, brain and languag

Exploring the combined use of electrical and hemodynamic brain activity to investigate brain function

This thesis explored the relationship between electrical and metabolic aspects of brain functioning in health and disease, measured with QEEG and NIRS, in order to evaluate its clinical potential. First the limitations of NIRS were investigated, depicting its susceptibility to different types of motion artefacts and the inability of the CBSI-method to remove them from resting state data. Furthermore, the quality of the NIRS signals was poor in a significant portion of the investigated sample, reducing clinical potential. Different analysis methods were used to explore both EEG and NIRS, and their coupling in an eyes open eyes closed paradigm in healthy participants. It could be reproduced that during eyes closed blocks less HbO2 (p = 0.000), more Hbb (p = 0.008), and more alpha activity (p = 0.000) was present compared to eyes open blocks. Furthermore, dynamic cross correlation analysis reproduced a positive correlation between alpha and Hbb (r: 0.457 and 0.337) and a negative correlation between alpha and HbO2 (r: -0.380 and -0.366) with a delayed hemodynamic response (7 to 8s). This was only possible when removing all questionable and physiological illogical data, suggesting that an 8s hemodynamic delay might not be the golden standard. Also the inability of the cross correlation to take non-linear relationships into account may distort outcomes. Therefore, In chapter 5 non-linear aspects of the relationship were evaluated by introducing the measure of relative cross mutual information. A newly suggested approach and the most valuable contribution of the thesis since it broadens knowledge in the fields of EEG, NIRS and general time series analysis. Data of two stroke patients then showed differences from the healthy group between the coupling of EEG and NIRS. The differences in long range temporal correlations (p= 0.000 for both cases), entropy (p< 0.040 and p =0.000), and relative cross mutual information (p < 0.003 and p < 0.013) provide the proof of principle that these measures may have clinical utility. Even though more research is necessary before widespread clinical use becomes possible

Influence of Early Bilingual Exposure in the Developing Human Brain.

190 p.La adquisición del lenguaje es un proceso que ese encuentra determinado tanto por mecanismos de desarrollo cognitivo, como por la experiencia lingüística durante los primeros años de vida. Aunque se trata de un proceso relativamente complejo, los bebés muestran una gran habilidad para el aprendizaje del lenguaje. Un entorno de aprendizaje lingüístico bilingüe podría considerarse aun más complejo, ya que los bebés están expuestos a las características lingüísticas de dos lenguas simultáneamente. En primer lugar, los bebés que crecen en un entorno bilingüe tienen que ser capaces de darse cuenta de que están expuestos a dos lenguas diferentes, y posteriormente deben separar y aprender las características especificas de cada una de ellas; por ejemplo, los distintos fonemas, palabras o estructuras gramaticales. Aunque la exposición lingüística total de los bebés bilingües debería ser comparable a la de los bebés monolingües, es probable que la exposición a cada una de las lenguas de su entorno sea menor, ya que tienen que dividir su tiempo de exposición entre ambas. Si bien los bebés bilingües parecen no tener problemas para enfrentarse a un contexto de aprendizaje potencialmente más complejo, ya que alcanzan las distintas etapas de adquisición del lenguaje a un ritmo similar a los bebés monolingües, sí se han observado adaptaciones a nivel conductual y a nivel de funcionamiento cerebral que podrían producirse como consecuencia de este contexto.Basque Center on cognition, brain and languag

Brain tissue temperature dynamics during functional activity and possibilities for optical measurement techniques

Regional tissue temperature dynamics in the brain are determined by the balance of the metabolic heat production rate and heat exchange with blood flowing through capillaries embedded in the brain tissue, the surrounding tissues and the environment. Local changes in blood flow and metabolism during functional activity can upset this balance and induce transient temperature changes. Invasive experimental studies in animal models have estab- lished that the brain temperature changes during functional activity are observable and a definitive relationship exists between temperature and brain activity. We present a theoreti- cal framework that links tissue temperature dynamics with hemodynamic activity allowing us to non-invasively estimate brain temperature changes from experimentally measured blood- oxygen level dependent (BOLD) signals. With this unified approach, we are able to pinpoint the mechanisms for hemodynamic activity-related temperature increases and decreases. In addition to these results, the potential uses and limitations of optical measurements are dis- cussed

Depth-Dependent Physiological Modulators of the BOLD Response in the Human Motor Cortex

This dissertation proposes a set of methods for improving spatial localization of cerebral metabolic changes using functional magnetic resonance imaging (fMRI). Blood oxygen level dependent (BOLD) fMRI estabilished itself as the most frequently used technique for mapping brain activity in humans. It is non-invasive and allows to obtain information about brain oxygenation changes in a few minutes. It was discovered in 1990 and, since then, it contributed enormously to the developments in neuroscientific research. Nevertheless, the BOLD contrast suffers from inherent limitations. This comes from the fact that the observed response is the result of a complex interplay between cerebral blood flow (CBF), cerebral blood volume (CBV) and cerebral metabolic rate of oxygen consumption (CMRO2) and has a strong dependency on baseline blood volume and oxygenation. Therefore, the observed response is mislocalized from the site where the metabolic activity takes place and it is subject to high variability across experiments due to normal brain physiology. Since the peak of BOLD changes can be as much as 4 mm apart from the site of metabolic changes, the problem of spatial mislocalization is particularly constraining at submillimeter resolution. Three methods are proposed in this work in order to overcome this limitation and make data more comparable. The first method involves a modification of an estabilished model for calibration of BOLD responses (the dilution model), in order to render it applicable at higher resolutions. The second method proposes a model-free scaling of the BOLD response, based on spatial normalization by a purely vascular response pattern. The third method takes into account the hypothesis that the cortical vasculature could act as a low-pass filter for BOLD fluctuations as the blood is carried downstream, and investigates differences in frequency composition of cortical laminae. All methods are described and tested on a depth-dependent scale in the human motor cortex

Detection of Human Vigilance State During Locomotion Using Wearable FNIRS

Human vigilance is a cognitive function that requires sustained attention toward change in the environment. Human vigilance detection is a widely investigated topic which can be accomplished by various approaches. Most studies have focused on stationary vigilance detection due to the high effect of interference such as motion artifacts which are prominent in common movements such as walking. Functional Near-Infrared Spectroscopy is a preferred modality in vigilance detection due to the safe nature, the low cost and ease of implementation. fNIRS is not immune to motion artifact interference, and therefore human vigilance detection performance would be severely degraded when studied during locomotion. Properly treating and removing walking-induced motion artifacts from the contaminated signals is crucial to ensure accurate vigilance detection. This study compared the vigilance level detection during both stationary and walking states and confirmed that the performance of vigilance level detection during walking is significantly deteriorated (with a