Noninvasive fMRI investigation of interaural level difference processing the rat auditory subcortex

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In vivo manganese-enhanced MRI for visuotopic brain mapping

This study explored the feasibility of localized manganese-enhanced MRI (MEMRI) via 3 different routes of Mn(2+) administrations for visuotopic brain mapping of retinal, callosal, cortico-subcortical, transsynaptic and horizontal connections in normal adult rats. Upon fractionated intravitreal Mn(2+) injection, Mn enhancements were observed in the contralateral superior colliculus (SC) and lateral geniculate nucleus (LGN) by 45-60% at 1-3 days after initial Mn(2+) injection and in the contralateral primary visual cortex (V1) by about 10% at 2-3 days after initial Mn(2+) injection. Direct, single-dose Mn(2+) injection to the LGN resulted in Mn enhancement by 13-21% in V1 and 8-11% in SC of the ipsilateral hemisphere at 8 to 24 hours after Mn(2+) administration. Intracortical, single-dose Mn(2+) injection to the visual cortex resulted in Mn enhancement by 53-65% in ipsilateral LGN, 15-26% in ipsilateral SC, 32-34% in the splenium of corpus callosum and 17-25% in contralateral V1/V2 transition zone at 8 to 24 hours after Mn(2+) administration. Notably, some patchy patterns were apparent near the V1/V2 border of the contralateral hemisphere. Laminar-specific horizontal cortical connections were also observed in the ipsilateral hemisphere. The current results demonstrated the sensitivity of MEMRI for assessing the neuroarchitecture of the visual brains in vivo without depth-limitation, and may possess great potentials for studying the basic neural components and connections in the visual system longitudinally during development, plasticity, pharmacological interventions and genetic modifications.published_or_final_versio

The interaction between human vision and eye movements in health and disease

Human motor behaviour depends on the successful integration of vision and eye movements. Many studies have investigated neural correlates of visual processing in humans, but typically with the eyes stationary and fixated centrally. Similarly, many studies have sought to characterise which brain areas are responsible for oculomotor control, but generally in the absence of visual stimulation. The few studies to explicitly study the interaction between visual perception and eye movements suggest strong influences of both static and dynamic eye position on visual processing and modulation of oculomotor structures by properties of visual stimuli. However, the neural mechanisms underlying these interactions are poorly understood. This thesis uses a range of fMRI methodologies such as retinotopic mapping, multivariate analsyis techniques, dynamic causal modelling and ultra high resolution imaging to examine the interactions between the oculomotor and visual systems in the normal human brain. The results of the experiments presented in this thesis demonstrate that oculomotor behaviour has complex effects on activity in visual areas, while spatial properites of visual stimuli modify activity in oculomotor areas. Specifically, responses in the lateral geniculate nucleus and early cortical visual areas are modulated by saccadic eye movements (a process potentially mediated by the frontal eye fields) and by changes in static eye position. Additionally, responses in oculomotor structures such as the superior colliculus are biased for visual stimuli presented in the temporal rather than nasal hemifield. These findings reveal that although the visual and oculomotor systems are spatially segregated in the brain, they show a high degree of integration at the neural level. This is consistent with our everyday experience of the visual world where frequent eye movements do not lead to disruption of visual continuity and visual information is seamlessly transformed into motor behaviour

Impact of the pulvinar on the ventral pathway of the cat visual cortex

Signals from the retina are relayed to the lateral geniculate nucleus from which they are sent to the primary visual cortex. At the cortical level, the information is transferred across several visual areas in which the complexity of the processing increases progressively. Anatomical and functional evidence demonstrate the existence of two main pathways in visual cortex processing distinct features of the visual information: the dorsal and ventral streams. Cortical areas composing the dorsal stream are implicated mostly in motion processing while those comprising the ventral stream are involved in the processing of form and colour. This classic view of the cortical functional organization is challenged by the existence of reciprocal connections of visual cortical areas with the thalamic nucleus named pulvinar. These connections allow the creation of a trans-thalamic pathway that parallels the cortico-cortical communications across the visual hierarchy. The main goal of the present thesis is twofold: first, to obtain a better comprehension of the processing of light increments and decrements in an area of the cat ventral stream (area 21a); second, to characterize the nature of the thalamo-cortical inputs from the cat lateral posterior nucleus (LP) to area 21a. In study #1, we investigated the spatiotemporal response profile of neurons from area 21a to light increments (brights) and decrements (darks) using a reverse correlation analysis of a sparse noise stimulus. Our findings showed that 21a neurons exhibited stronger responses to darks with receptive fields exhibiting larger dark subfields. However, no differences were found between the temporal dynamics of brights and darks. In comparison with the primary visual cortex, the dark preference in area 21a was found to be strongly enhanced, supporting the notion that the asymmetries between brights and darks are transmitted and amplified along the ventral stream. In study #2, we investigated the impact of the reversible pharmacological inactivation of the LP nucleus on the contrast response function (CRF) of neurons from area 21a and the primary visual cortex (area 17). The thalamic inactivation yielded distinct effects on both cortical areas. While in area 17 the LP inactivation caused a slight decrease in the response gain, in area 21a a strong increase was observed. Thus, our findings suggest that the LP exerts a modulatory influence on the cortical processing along the ventral stream with stronger impact on higher order extrastriate areas. Taken together, our findings allowed a better comprehension of the functional properties of the cat ventral stream and contributed to the current knowledge on the role of the pulvinar on the cortico-thalamo-cortical processing of visual information.Les signaux provenant de la rétine sont relayés dans le corps géniculé latéral où ils sont envoyés au cortex visuel primaire. L’information passe ensuite à travers plusieurs aires visuelles où la complexité du traitement augmente progressivement. Des données tant anatomiques que fonctionnelles ont démontré l’existence de deux voies principales qui traitent différentes propriétés de l’information visuelle : les voies dorsale et ventrale. Les aires corticales composant la voie dorsale sont impliquées principalement dans le traitement du mouvement tandis que les aires de la voie ventrale sont impliquées dans le traitement de la forme et de la couleur. Cette vision classique de l’organisation fonctionnelle du cortex est toutefois remise en question par l’existence de connections réciproques entre les aires corticales visuelles et le pulvinar, un noyau thalamique. En effet, ces connections permettent la création d’une voie trans-thalamique parallèle aux connections cortico-corticales à travers la hiérarchie visuelle. Le but principal de la présente thèse consiste en deux volets : le premier est d’obtenir une meilleure compréhension du traitement des incréments et décréments de la lumière dans une aire de la voie ventrale du chat (aire 21a); le second est de caractériser la nature des inputs thalamo-corticaux du noyau latéral postérieur (LP) à l’aire 21a chez le chat. Dans l’étude #1, nous avons investigué le profil spatiotemporel des réponses des neurones de l’aire 21a aux incréments (blancs) et décréments (noirs) de lumière en utilisant l’analyse de corrélation inverse d’un stimulus de bruit épars. Les neurones de l’aire 21a ont répondu plus fortement aux stimuli noirs, en montrant des champs récepteurs avec des sous-champs noirs plus larges. Cependant, aucune différence n’a été trouvée en ce qui concerne les dynamiques temporelles des réponses aux blancs et aux noirs. En comparaison avec le cortex visuel primaire, la préférence aux stimuli noirs dans l’aire 21a s’est avérée fortement augmentée. Ces données indiquent que les asymétries entre les réponses aux blancs et aux noirs sont transmises et amplifiées à travers la voie ventrale. Dans l’étude #2, nous avons investigué l’impact de l’inactivation pharmacologique réversible du noyau LP sur la fonction de réponse au contraste (CRF) des neurones de l’aire 21a et du cortex visuel primaire (aire 17). L’inactivation a eu différents effets dans les deux aires corticales. Alors que, dans l’aire 17, l’inactivation du LP a causé une légère réduction du gain de la réponse, une forte augmentation a été observée dans l’aire 21a. Ainsi, nos résultats suggèrent que le LP exerce une influence modulatrice dans le traitement cortical à travers la voie ventrale avec un impact plus important dans des aires extrastriées de plus haut niveau. Nos résultats ont permis d’avoir une meilleure compréhension des propriétés fonctionnelles de la voie ventrale du chat et de contribuer à enrichir les connaissances actuelles sur le rôle du pulvinar dans le traitement cortico-thalamo-cortical de l’information visuelle

Functional magnetic resonance imaging of the mouse brain

Functional magnetic resonance imaging (fMRI) measuring a blood-oxygen-level dependent (BOLD) signal is the most commonly used neuroimaging tool to understand brain function in humans. As mouse models are one of the most commonly used neuroscience experimental models, and with the advent of transgenic mouse models of neurodegenerative pathologies, there has been an increasing push in recent years to apply fMRI techniques to the mouse brain. This thesis focuses on the development and implementation of mouse brain fMRI techniques, in particular to describe the mouse visual system. Multiple studies in the literature have noted several technical challenges in mouse fMRI. In this work I have developed methods which go some way to reducing the impact of these issues, and I record robust and reliable haemodynamic-driven signal responses to visual stimuli in mouse brain regions specific to visual processing. I then developed increasingly complex visual stimuli, approaching the level of complexity used in electrophysiology studies of the mouse visual system, despite the geometric and magnetic field constraints of using a 9.4T pre-clinical MRI scanner. I have also applied a novel technique for measuring high-temporal resolution BOLD responses in the mouse superior colliculus, and I used this data to improve statistical parametric mapping of mouse brain BOLD responses. I also describe the first application of dynamic causal modelling to mouse fMRI data, characterising effective connectivity in the mouse brain visual system. This thesis makes significant contributions to the reverse translation of fMRI to the mouse brain, closing the gap between invasive electrophysiological measurements in the mouse brain and non-invasive fMRI measurements in the human brain

Neural Correlates of Multisensory Enhancement in Audiovisual Narrative Speech Perception: A fMRI investigation

This fMRI study investigated the effect of seeing articulatory movements of a speaker while listening to a nat- uralistic narrative stimulus. It had the goal to identify regions of the language network showing multisensory enhancement under synchronous audiovisual conditions. We expected this enhancement to emerge in regions known to underlie the integration of auditory and visual information such as the posterior superior temporal gyrus as well as parts of the broader language network, including the semantic system. To this end we presented 53 participants with a continuous narration of a story in auditory alone, visual alone, and both synchronous and asynchronous audiovisual speech conditions while recording brain activity using BOLD fMRI. We found multi- sensory enhancement in an extensive network of regions underlying multisensory integration and parts of the semantic network as well as extralinguistic regions not usually associated with multisensory integration, namely the primary visual cortex and the bilateral amygdala. Analysis also revealed involvement of thalamic brain regions along the visual and auditory pathways more commonly associated with early sensory processing. We conclude that under natural listening conditions, multisensory enhancement not only involves sites of multisensory in- tegration but many regions of the wider semantic network and includes regions associated with extralinguistic sensory, perceptual and cognitive processing

Cognitive and Perceptual Functions of the Visual Thalamus

The thalamus is classically viewed as passively relaying information to the cortex. However, there is growing evidence that the thalamus actively regulates information transmission to the cortex and between cortical areas using a variety of mechanisms, including the modulation of response magnitude, firing mode, and synchrony of neurons according to behavioral demands. We discuss how the visual thalamus contributes to attention, awareness, and visually guided actions, to present a general role for the thalamus in perception and cognition

Long-range projections coordinate distributed brain-wide neural activity with a specific spatiotemporal profile

One challenge in contemporary neuroscience is to achieve an integrated understanding of the large-scale brain-wide interactions, particularly the spatiotemporal patterns of neural activity that give rise to functions and behavior. At present, little is known about the spatiotemporal properties of long-range neuronal networks. We examined brain-wide neural activity patterns elicited by stimulating ventral posteromedial (VPM) thalamo-cortical excitatory neurons through combined optogenetic stimulation and functional MRI (fMRI). We detected robust optogenetically evoked fMRI activation bilaterally in primary visual, somatosensory, and auditory cortices at low (1 Hz) but not high frequencies (5–40 Hz). Subsequent electrophysiological recordings indicated interactions over long temporal windows across thalamo-cortical, cortico-cortical, and interhemispheric callosal projections at low frequencies. We further observed enhanced visually evoked fMRI activation during and after VPM stimulation in the superior colliculus, indicating that visual processing was subcortically modulated by low-frequency activity originating from VPM. Stimulating posteromedial complex thalamo-cortical excitatory neurons also evoked brain-wide blood-oxygenation-level–dependent activation, although with a distinct spatiotemporal profile. Our results directly demonstrate that low-frequency activity governs large-scale, brain-wide connectivity and interactions through long-range excitatory projections to coordinate the functional integration of remote brain regions. This low-frequency phenomenon contributes to the neural basis of long-range functional connectivity as measured by resting-state fMRI

Neural measures of visual attention and suppression as biomarkers for ADHD-associated inattention

Whilst there is a wealth of literature examining neural differences in those with ADHD, few have investigated visual-associated regions. Given extensive evidence demonstrating visual-attention deficits in ADHD, it is possible that inattention problems may be associated with functional abnormalities within the visual system. By measuring neural responses across the visual system during visual-attentional tasks, we aim to explore the relationship between visual processing and ADHD-associated Inattention in the typically developed population. We first explored whether differences in neural responses occurred within the superior colliculus (SC); an area linked to distractibility and attention. Here we found that Inattention traits positively correlated with SC activity, but only when distractors were presented in the right visual field (RVF) and not the left visual field (LVF). Our later work followed up on these findings to investigate separate responses towards task-relevant targets and irrelevant, peripheral distractors. Findings showed that those with High Inattention exhibited increased responses towards distractors compared to targets, while those with Low Inattention showed the opposite effect. Hemifield differences were also observed where those with High Inattention showed increased RVF distractor-related signals compared to those with Low Inattention. No differences were observed for the LVF. Finally, we examined attention and suppression-related neural responses. Our results indicated that, while attentional responses were similar between Inattention groups, those with High Inattention showed weaker suppression responses towards the unattended RVF. No differences were found when suppressing the LVF. Findings across all studies suggest that differences in neural responses between those with High and Low levels of Inattention exist within the visual system. Such differences appear to relate to suppression of task-irrelevant distractors rather than attention towards task-relevant targets, suggesting such mechanisms are differentially affected in those with frequent Inattention problems. We also show a clear relationship between Inattention traits and visual suppression of the RVF