Functional MRI Mapping of the Human Auditory Cortex

Mapping the human auditory cortex with standard functional imaging techniques is difficult because of its small size and angular position along the Sylvian fissure. As a result, the exact number and location of auditory cortex areas in the human remains unknown. In a first experiment, we measured the two largest tonotopic areas of primary auditory cortex (PAC, Al and R) using high-resolution functional MRI at 7 Tesla relative to the underlying anatomy of Heschl's gyrus (HG). The data reveals a clear anatomical- functional relationship that indicates the location of PAC across the range of common morphological variants of HG (single gyri, partial duplication and complete duplication). Human PAC tonotopic areas are oriented along an oblique posterior-to-anterior axis with mirror-symmetric frequency gradients perpendicular to HG, as in the macaque. In a second experiment, we tested whether these primary frequency-tuned units were modulated by selective attention to preferred vs. non-preferred sound frequencies in the dynamic manner needed to account for human listening abilities in noisy environments, such as cocktail parties or busy streets. We used a dual-stream selective attention experiment where subjects attended to one of two competing tonal streams presented simultaneously to different ears. Attention to low-frequency tones (250 Hz) enhanced neural responses within low-frequency-tuned voxels relative to high (4000 Hz), and vice versa when at-tention switched from high to low. Human PAC is able to tune into attended frequency channels and can switch frequencies on demand, like a radio. In a third experiment, we investigated repetition suppression effects to environmental sounds within primary and non-primary early-stage auditory areas, identified with the tonotopic mapping design. Repeated presentations of sounds from the same sources, as compared to different sources, gave repetition suppression effects within posterior and medial non-primary areas of the right hemisphere, reflecting their potential involvement in semantic representations. These three studies were conducted at 7 Tesla with high-resolution imaging. However, 7 Tesla scanners are, for the moment, not yet used for clinical diagnosis and mostly reside in institutions external to hospitals. Thus, hospital-based clinical functional and structural studies are mainly performed using lower field systems (1.5 or 3 Tesla). In a fourth experiment, we acquired tonotopic maps at 3 and 7 Tesla and evaluated the consistency of a tonotopic mapping paradigm between scanners. Mirror-symmetric gradients within PAC were highly similar at 7 and 3 Tesla across renderings at different spatial resolutions. We concluded that the tonotopic mapping paradigm is robust and suitable for definition of primary tonotopic areas, also at 3 Tesla. Finally, in a fifth study, we considered whether focal brain lesions alter tonotopic representations in the intact ipsi- and contralesional primary auditory cortex in three patients with hemispheric or cerebellar lesions, without and with auditory complaints. We found evidence for tonotopic reorganisation at the level of the primary auditory cortex in cases of brain lesions independently of auditory complaints. Overall, these results reflect a certain degree of plasticity within primary auditory cortex in different populations of subjects, assessed at different field strengths. - La cartographie du cortex auditif chez l'humain est difficile à réaliser avec des techniques d'imagerie fonctionnelle standard, étant donné sa petite taille et position angulaire le long de la fissure sylvienne. En conséquence, le nombre et l'emplacement exacts des différentes aires du cortex auditif restent inconnus chez l'homme. Lors d'une première expérience, nous avons mesuré, avec de l'imagerie par résonance magnétique à haute intensité (IRMf à 7 Tesla) chez des sujets humains sains, deux larges aires au sein du cortex auditif primaire (PAC; Al et R) avec une représentation spécifique des fréquences pures préférées - ou tonotopie. Nos résultats ont démontré une relation anatomico- fonctionnelle qui définit clairement la position du PAC à travers toutes les variantes du gyrus d'Heschl's (HG). Les aires tonotopiques du PAC humain sont orientées le long d'un axe postéro-antérieur oblique avec des gradients de fréquences spécifiques perpendiculaires à HG, d'une manière similaire à celles mesurées chez le singe. Dans une deuxième expérience, nous avons testé si ces aires primaires pouvaient être modulées, de façon dynamique, par une attention sélective pour des fréquences préférées par rapport à celles non-préférées. Cette modulation est primordiale lors d'interactions sociales chez l'humain en présence de bruits distracteurs tels que d'autres discussions ou un environnement sonore nuisible (comme par exemple, dans la circulation routière). Dans cette étude, nous avons utilisé une expérience d'attention sélective où le sujet devait être attentif à une des deux voies sonores présentées simultanément à chaque oreille. Lorsque le sujet portait était attentif aux sons de basses fréquences (250 Hz), la réponse neuronale relative à ces fréquences augmentait par rapport à celle des hautes fréquences (4000 Hz), et vice versa lorsque l'attention passait des hautes aux basses fréquences. De ce fait, nous pouvons dire que PAC est capable de focaliser sur la fréquence attendue et de changer de canal selon la demande, comme une radio. Lors d'une troisième expérience, nous avons étudié les effets de suppression due à la répétition de sons environnementaux dans les aires auditives primaires et non-primaires, d'abord identifiées via le protocole de la première étude. La présentation répétée de sons provenant de la même source sonore, par rapport à de sons de différentes sources sonores, a induit un effet de suppression dans les aires postérieures et médiales auditives non-primaires de l'hémisphère droite, reflétant une implication de ces aires dans la représentation de la catégorie sémantique. Ces trois études ont été réalisées avec de l'imagerie à haute résolution à 7 Tesla. Cependant, les scanners 7 Tesla ne sont pour le moment utilisés que pour de la recherche fondamentale, principalement dans des institutions externes, parfois proches du patient mais pas directement à son chevet. L'imagerie fonctionnelle et structurelle clinique se fait actuellement principalement avec des infrastructures cliniques à 1.5 ou 3 Tesla. Dans le cadre dune quatrième expérience, nous avons avons évalués la cohérence du paradigme de cartographie tonotopique à travers différents scanners (3 et 7 Tesla) chez les mêmes sujets. Nos résultats démontrent des gradients de fréquences définissant PAC très similaires à 3 et 7 Tesla. De ce fait, notre paradigme de définition des aires primaires auditives est robuste et applicable cliniquement. Finalement, nous avons évalués l'impact de lésions focales sur les représentations tonotopiques des aires auditives primaires des hémisphères intactes contralésionales et ipsilésionales chez trois patients avec des lésions hémisphériques ou cérébélleuses avec ou sans plaintes auditives. Nous avons trouvé l'évidence d'une certaine réorganisation des représentations topographiques au niveau de PAC dans le cas de lésions cérébrales indépendamment des plaintes auditives. En conclusion, nos résultats démontrent une certaine plasticité du cortex auditif primaire avec différentes populations de sujets et différents champs magnétiques

Neural Representations of Visual Motion Processing in the Human Brain Using Laminar Imaging at 9.4 Tesla

During natural behavior, much of the motion signal falling into our eyes is due to our own movements. Therefore, in order to correctly perceive motion in our environment, it is important to parse visual motion signals into those caused by self-motion such as eye- or head-movements and those caused by external motion. Neural mechanisms underlying this task, which are also required to allow for a stable perception of the world during pursuit eye movements, are not fully understood. Both, perceptual stability as well as perception of real-world (i.e. objective) motion are the product of integration between motion signals on the retina and efference copies of eye movements. The central aim of this thesis is to examine whether different levels of cortical depth or distinct columnar structures of visual motion regions are differentially involved in disentangling signals related to self-motion, objective, or object motion. Based on previous studies reporting segregated populations of voxels in high level visual areas such as V3A, V6, and MST responding predominantly to either retinal or extra- retinal (‘real’) motion, we speculated such voxels to reside within laminar or columnar functional units. We used ultra-high field (9.4T) fMRI along with an experimental paradigm that independently manipulated retinal and extra-retinal motion signals (smooth pursuit) while controlling for effects of eye-movements, to investigate whether processing of real world motion in human V5/MT, putative MST (pMST), and V1 is associated to differential laminar signal intensities. We also examined motion integration across cortical depths in human motion areas V3A and V6 that have strong objective motion responses. We found a unique, condition specific laminar profile in human area V6, showing reduced mid-layer responses for retinal motion only, suggestive of an inhibitory retinal contribution to motion integration in mid layers or alternatively an excitatory contribution in deep and superficial layers. We also found evidence indicating that in V5/MT and pMST, processing related to retinal, objective, and pursuit motion are either integrated or colocalized at the scale of our resolution. In contrast, in V1, independent functional processes seem to be driving the response to retinal and objective motion on the one hand, and to pursuit signals on the other. The lack of differential signals across depth in these regions suggests either that a columnar rather than laminar segregation governs these functions in these areas, or that the methods used were unable to detect differential neural laminar processing. Furthermore, the thesis provides a thorough analysis of the relevant technical modalities used for data acquisition and data analysis at ultra-high field in the context of laminar fMRI. Relying on our technical implementations we were able to conduct two high-resolution fMRI experiments that helped us to further investigate the laminar organization of self-induced and externally induced motion cues in human high-level visual areas and to form speculations about the site and the mechanisms of their integration

IMAGING EMOTIONAL SOUNDS PROCESSING AT 7T

Emotional sounds and their localization are influential stimuli that we need to process all along our life. Affective information contained in sounds is primordial for the human social communications and interactions. Their accurate localization is important for the identification and reaction to environmental events. This thesis investigate the encoding of emotional sounds within auditory areas and the amygdala (AMY) using 7 Tesla fMRI. In a first experiment, we studied the encoding of emotion and vocalization and their integration in early-stage auditory areas, the voice area (VA) and the AMY. We described that the response of the early-stage auditory areas was modulated by the vocalization and by the affective content of the sounds, and that this affective modulation is independent of the category of sounds. In contrast, AMY process only the emotional part, while VA is responsible for the processing of the emotional valence specifically for the human vocalization (HV) categories. Finally, we described a functional correlation between VA and AMY in the right hemisphere for the positive vocalizations only. In a second experiment, we investigated how the spatial origin of an emotional sound (HV or non- vocalizations) modulated its processing within early-stage auditory areas and VA. We highlighted a left hemispace preference for the positive vocalizations encoded bilaterally in the primary auditory cortex (PAC). Moreover, comparison with the first study indicated that the saliency of emotional valence could be increased by spatial cues, but that the encoding of vocalization is not impacted by the spatial context. Finally, we examined the functional correlations between early-stage auditory areas and VA and how they are modulated by the sound category, the valence and the lateralization. We documented a strong coupling between VA and early-stage auditory areas during the presentation of emotional HV, but not for other environmental sounds. The category of sound modulated strongly the functional correlations between VA, PAC and auditory belt areas, while the spatial positioning induced only a weak modulation and no modulation was caused by the affective content. Overall, these studies demonstrate that the affective load modulates the processing of sounds within VA only for HV, and that this preference for vocalizations impacts the functional correlations of VA with other auditory regions. This strengthens the importance of VA as a computation hub for the processing of emotional vocalizations. -- Les sons émotionnels ainsi que leur localisation sont des stimuli importants que nous devons traiter tout au long de notre vie. L’information affective contenue dans les sons est primordiale pour les communications et interactions sociales. Leur localisation correcte est importante pour l’identification et la réaction par rapport aux événements nous entourant. Cette thèse étudie l’encodage des sons émotionnels dans les aires auditives et l’amygdale (AMY) en utilisant l’IRM fonctionnel à 7 Tesla. Dans une première expérience, nous avons étudié l’encodage des émotions et des vocalisations, ainsi que leur intégration dans les aires auditives primaires et non-primaires, dans l’aire des voix (VA) et dans AMY. Nous avons décrit que la réponse des aires auditives primaires et non-primaires étaient modulées par les vocalisations ainsi que par le contenu affectif des sons, et que cette modulation affective était indépendante de la catégorie sonore. En revanche, AMY traite uniquement la partie émotionnelle, tandis que la VA est responsable du traitement de la valence émotionnelle spécifiquement pour les vocalisations humaines (HV). Finalement, nous avons décrit une corrélation fonctionnelle entre VA et AMY dans l’hémisphère droit pour les vocalisations positives uniquement. Dans une seconde expérience, nous avons cherché à comprendre de quelle manière l’origine spatiale d’un son émotionnel (HV et non-vocalisations) modulait son traitement dans les aires auditives, primaires et non-primaires, et VA. Nous avons mis en évidence une préférence de l’hémi-champ gauche pour les vocalisations positive encodées bilatéralement dans le cortex auditif primaire (PAC). De plus, une comparaison avec la première étude a indiqué que l’importance de la valence émotionnelle pourrait être augmentée grâce aux indices spatiaux, mais que l’encodage des vocalisations n’étaient pas impacté par le contexte spatial. Finalement, nous avons examiné les corrélations fonctionnelles entre les aires auditives primaires, non-primaires et VA afin d’évaluer de quelle manière elles étaient modulées par la catégorie sonore, la valence et la latéralisation. Nous avons mis en évidence un fort couplage entre VA et les aires auditives primaires et non-primaires durant la présentation des HV émotionnelles, mais cet effet n’était pas présent pour les autres sons environnementaux. La catégorie sonore modulait fortement les corrélations fonctionnelles entre VA, PAC et les régions auditives latérales, alors que le positionnement spatial n’influençait que faiblement leur modulation. De plus, il n’y avait pas de modulation causée par le contenu affectif. En résumé, ces études démontrent que le contenu affectif module le traitement des sons dans VA uniquement pour les HV, et que cette préférence pour les vocalisations a un impact sur les corrélations fonctionnelles de cette région avec les autres régions auditives. Cela souligne l’importance de VA comme centre computationnel pour le traitement des vocalisations émotionnelles

Frontoparietal networks underlying saccadic eye movements in the common marmoset

Common marmosets (Callithrix jacchus) are small-bodied New World primates that are increasingly popular as model animals for neuroscience research. Their lissencephalic cortex provides substantial advantages for the application of high-density electrophysiological techniques to enhance our understanding of local cortical circuits and their cognitive and motor functions. The oculomotor circuitry underlying saccadic eye movements has been a popular system to study cognitive control. Most of what we know about this system, comes from electrophysiological studies on macaques, but most of their cortical oculomotor areas are buried within sulci and harder to access for high-density recordings. In contrast, marmosets provide greater advantages for studies of the oculomotor system, since critical areas of this network such as the frontal eye fields (FEF) and lateral intraparietal area (LIP) are easily accessible at the cortical surface. In contrast to the well-established macaques, little is known about functional connectivity patterns of common marmosets. In this thesis, we used resting-state ultra-high-field fMRI on anesthetized marmosets and macaques along with awake human subjects, to examine and compare the functional organization of the brain, with emphasis on the saccade system. Independent component analysis revealed homologous resting-state networks in marmoset to those in macaques and humans, including a distributed frontoparietal network. Seed-region analyses of the marmoset superior colliculus (SC) revealed the strongest frontal functional connectivity with area 8aD bordering area 6DR. This frontal region exhibited a similar functional connectivity pattern to the FEF in macaques and humans. The results supported an evolutionarily preserved frontoparietal system and provided a starting point for invasive neurophysiological studies in the marmoset saccade system. We started by investigating the function of the marmoset posterior parietal cortex with electrical microstimulation. We implanted 32-channel Utah arrays at the location of area LIP as identified from our resting-state fMRI study and applied microstimulation while animals watched videos. Similar to macaque studies, stimulation evoked fixed-vector and goal-directed saccades, staircase saccades, and eyeblinks in marmosets. These findings demonstrated that the marmoset area LIP plays a role in the regulation of eye movements and is potentially homologous to that of the macaque. Next, we recorded the neuronal activity in marmoset areas LIP and 8aD using linear electrode arrays while animals performed a pro/antisaccade task. The antisaccade task is a popular paradigm to probe executive control. In this task, participants suppress a prepotent stimulus-driven response in favor of a less potent response away from the stimulus. Our behavioral findings indicated that area 8aD neurons were significantly more active for correct than errorenous antisaccades in contralateral directions, with respect to the recording site. We found neurons with significant stimulus-related activity in area LIP and significant saccade-related neurons in both areas 8aD and LIP. These findings provided further evidence on the role of marmoset frontal and parietal oculomotor areas in oculomotor control, supporting marmosets as alternative primate models of the oculomotor system

The invisible body:the neural mechanisms of non-conscious and conscious processing of emotional bodies

How do we process emotions expressed by bodies when we don’t realize we are looking at them? This research made body postures invisible for participants by using the “continuous flash suppression” method. It turned out that processing bodily emotions is very different from processing faces, and is different across emotions (e.g. neutral, fearful, angry), both when participants consciously see them and when they see them outside their awareness. The research also looked in detail at the brain activity with the 7T MRI scanner, and found that understanding bodily actions involves a large network across the brain. This research provides insights in the way we understand actions and emotions

Functional and Structural Brain Reorganization After Unilateral Prefrontal Cortex Lesions In Macaques

Visually exploring the surrounding environment relies on attentional selection of behaviourally relevant stimuli for further processing. The prefrontal cortex contributes to target selection as part of a frontoparietal network that controls shifts of gaze and attention towards relevant stimuli. Evidence from stroke patients and nonhuman primate lesion studies have shown that unilateral damage to the prefrontal cortex commonly impairs the ability to allocate attention toward stimuli in the contralesional visual hemifield. Although these impairments often exhibit a gradual improvement over time, the neural plasticity that underlies recovery of function remains poorly understood. The main objective of this dissertation was to study the relationship between large-scale network reorganization and the recovery of lateralized target selection deficits. To that aim, endothelin-1 was used to produce unilateral ischemic lesions in the caudal lateral prefrontal cortex of four rhesus macaques. Longitudinal behavioural and neuroimaging data were collected before and after the lesions, including eye-tracking while monkeys performed free-choice and visually guided saccades, resting-state fMRI, and diffusion-weighted imaging. Chapter 2 investigated the effects of unilateral prefrontal cortex lesions on saccade target selection and oculomotor parameters to disentangle attentional and motor impairments in the lasting contralesional target selection deficit. Chapter 3 examined the resting-state functional reorganization in a frontoparietal network during recovery of contralesional target selection. Finally, Chapter 4 investigated microstructural changes in cortical white matter tracts from diffusion-weighted imaging after behavioural recovery compared to pre-lesion. In general, spatiotemporal patterns of functional and structural network reorganization differed based on the extent of prefrontal damage. Altogether, these studies characterized the recovery of lateralized target selection deficits in a macaque model of focal cerebral ischemia and demonstrated involvement of both contralesional and ipsilesional networks throughout behavioural recovery. The broad implication of this research is that a network perspective is fundamental to understanding compensatory mechanisms of brain reorganization underlying recovery of function