Teses / dissertações sobre o tema "R-fMRI"

The designs of two functional magnetic resonance imaging-compatible electronic interfaces for use in neuropsychological studies involving musical tasks are presented. The devices, a two-button response box in the form of a computer mouse and a piano keyboard, were designed for rhythmic tapping and piano performance tasks, respectively. In order to correlate changes in neural activation acquired through magnetic resonance imaging (MRI) with task performance, the electronic collection of behavioural data, such as the timing of button or key presses was required. These behavioural measures were captured electronically and communicated to a host computer for synchronization with feedback, stimuli, and the MRI scanner itself. As well, data was logged for offline analysis. Due to the intense and volatile electromagnetic fields, most commercially-available electronic interfaces do not function properly and can even pose a serious safety hazard within the MRI scanner environment. Therefore these custom-designed interfaces were free of ferromagnetic parts and all electronic components were relegated to the control room outside of the scanner environment. Acquisition of button and key presses was accomplished using fibre optic sensors, which are immune to electromagnetic interference. The devices performed successfully within the scanner, and MRI scans showed no image artifacts caused by the prototypes. Sensing of key and button transition velocity was sufficient after extensive calibration. Next generation prototypes are planned and will implement more robust and tighter tolerance manufacturing, improved sensing techniques, the acquisition of isometric forces, and an auto-calibration scheme.

In the early stages of visual processing (primary visual cortex) shapes are sampled by discrete, localized, visual filters. The integration of the outputs of these local filters allows us to detect global shape information. Although this integration process is critical for visual processing beyond the primary visual cortex, it remains poorly understood. This thesis investigates what limits the performance of the mechanisms used to detect global structure. In particular, we asked four questions: (1) What information is important for detecting global form? (2) How well can we detect shape defined by changes in contrast? (3) Do the spatial properties of detectors that process global shape change across the visual field? (4) What cortical areas are involved in global shape processing?
We used psychophysical methods and functional magnetic resonance imaging (fMRI) to study the integration of local filters for global shape processing in normal adult observers. All our stimuli were spatially bandpass and contained global circular structure.
Overall, our findings suggest that the visual system combines the outputs of local detectors both across the visual field and over different stimulus attributes (e.g. contrast, spatial frequency, spatial position, polarity, contrast-defined information). Our excellent sensitivity to these globally structured patterns suggests the involvement of higher-order mechanisms optimized for global processing. However, these higher-order mechanisms are not localized in an individual retinotopic area nor is there a systematic hierarchical increase in activity throughout the ventral processing pathway in response to globally structured stimuli. In conclusion, significant processing of shapes occurs at both the local and the global level.

The technique of functional magnetic resonance imaging (fMRI) is rapidly developing from one of technical interest to wide clinical application. fMRI exploits the fact that brain neural activity produces a change in blood oxygenation level dependent (BOLD) response which is recorded at each point in the brain. In a typical experiment, a subject is given a stimulus or cognitive task, and the statistical question is to relate it to the BOLD response, usually via a linear model. The BOLD response is not instantaneous; it is delayed and smoothed by about 6 seconds. In this thesis we propose a rapid method of estimating and making inference about this delay. Our method is compared to other alternatives, and validated on an fMRI data set from an experiment in pain perception.

Our visual world contains both luminance- (first-order) and contrast-defined (second-order) information. Distinct mechanisms underlying the perception of first-order and second-order motion have been proposed from electrophysiological, psychophysical and neurological studies. In this thesis psychophysical and human brain imaging (fMRI) experiments are described that support the notion of distinct mechanisms, but extend the previous studies by providing evidence for a functional dissociation and a relative cortical specialization for first- and second-order motion.
Using psychophysical methods, a directional anisotropy was found for second-order but not first-order motion in peripheral vision. This anisotropy is interpreted as a functional dissociation implicating the second-order mechanism in optic flow processing.
Identification of early visual cortical areas is a prerequisite to any functional assessment of these visual areas. To this aim a novel human brain mapping method has been developed which automatically segments early human retinotopic visual areas. Unlike previous methods this procedure does not depend on a cortical surface reconstruction and thereby greatly simplifies the analysis.
In a combined psychophysical and fMRI study, distinct cortical regions, in occipital and parietal lobes, were preferentially activated by either first- or second-order motion. These results provide evidence for the idea that first-order motion is computed in V1 and second-order motion in later occipital visual areas. In addition the results suggest a functional dissociation of the two kinds of motion beyond the occipital lobe consistent with a role for the second-order mechanism in optic flow analysis.

Functional magnetic resonance imaging (fMRI) is a technique allowing the study of hemodynamic changes in the brain. Having a number of advantages over positron emission tomography (PET), the current gold standard, fMRI appears like an attractive alternative to study brain function. However, the measurements obtained with fMRI have not been rigorously validated.
This thesis describes a study comparing cerebral blood flow (CBF) changes measured using a flow-sensitive alternating inversion recovery (FAIR) fMRI perfusion method, to the ones obtained using PET. We scanned 10 healthy normal volunteers under identical experimental conditions during presentation of 4 levels of visual stimulation and one level of hypercapnia. The CBF changes were compared in 4 regions-of-interest.
Good correspondence was found in the locations of the CBF changes. FAIR CBF changes had a higher signal-to-noise ratio and presented a monotonic increase with stimulation intensity, absent in PET measurements. FAIR measurements were correlated to PET but slightly lower. Statistical analysis of the data did not show that FAIR measurements were significantly different from PET ones.

Recent neuroimaging studies have found greater left and right prefrontal cortex (PFC) activity during spatial source and temporal recency tasks, respectively. It is unclear whether these findings result from inherent differences in PFC contributions to spatial vs. temporal memory retrieval or to differences in task difficulty and/or structure. To address this issue, I used event-related functional magnetic resonance imaging to assess healthy adults while they performed spatial and temporal memory tasks for faces, matched for structure and difficulty. Findings show greater left-lateralized activity during both spatial and temporal context retrieval tasks, with a greater degree of recruitment during spatial tasks. A response number manipulation, designed to identify regions related to selection, activated the left-inferior PFC. After controlling for task structure, such that both spatial and temporal retrieval tasks required more categorical versus continuous processing, we only observed left-lateralized PFC activations; rather than previously reported laterality effects in PFC during spatial vs. temporal context retrieval. We interpret these activations as reflecting left PFC involvement in domain-general cognitive control processes that are important for categorically based memory retrieval; such as, response selection and covert verbalization of stimuli.
Des études récentes de neuro-imagerie ont trouvé une plus grande activité du cortex préfrontal (CPF) gauche et droit lors de tâche de mémoire spatiale et de récence temporelle, respectivement. Il n'est pas clair si ces résultats sont dus à une différence inhérente de la contribution du CPF aux tâches de remémoration spatiale et temporelle, ou s'il s'agit de différences dans la difficulté et/ou la structure des tâches. Pour répondre à cette question, j'ai utilisé l'imagerie par résonance magnétique fonctionnelle pour évaluer la performance d'adultes en santé lors de tâches de mémoire spatiale et temporelle pour les visages, en appariant les tâches au niveau de leur structure et de leur difficulté. Les résultats démontrent une plus grande activité latéralisée à gauche durant toutes les tâches, en plus de démontrer un plus grand degré de recrutement lors des tâches spatiales, qui sont de nature catégorique. De plus, une manipulation du nombre de réponse, conçue pour déterminer quelles régions se rapportent à la sélection des réponses et à la mémoire de travail verbal, activa le CPF inférieur gauche. Ces résultats suggèrent une contribution latéralisée à gauche du CPF pour les réseaux favorisant les tâches de mémoire catégorique ainsi que les tâches de traitement exécutif général, plutôt que spécifiquement pour l'information spatiale ou temporelle.

The world around us contains a variety of visual information, both first-order (luminance-defined) and second-order (defined by characteristics other than luminance). Previous studies suggest that the human visual cortex employs distinct mechanisms for segregating regions whose borders are defined by modulations of first- and second-order properties. This study uses a new approach of human psychophysics and fMRI experiments to explore the brain responses to both first-order and second-order (orientation, spatial frequency and contrast) texture borders. The results reveal differential activation among these modulations both in known retinotopic areas and in higher occipital/parietal regions. Orientation modulated textures elicit significantly different responses compared to modulations of other properties; whereas spatial frequency and contrast modulated textures produce similar responses. These findings suggest that higher visual cortical areas are heavily involved in texture processing, with a functional dissociation between segregating textures with modulations of (a) orientation, (b) spatial frequency or contrast and (c) luminance.

Feeding behavior is a complex phenomenon involving homeostatic signals, and non-homeostatic inputs such as visual cues. In primates, exposure to food-related sensory cues has been shown to elicit cephalic phase responses as well as trigger central appetitive processing, in a motivationally-dependent manner. Neural structures consistently implicated in such responses and/or in the regulation of ingestive behavior in general, in both monkeys and in humans, include the amygdala, insula, striatum, hypothalamus, and frontal and occipital cortices. In humans however, the cerebral response to visual food stimulation remains minimally explored.
Functional Magnetic Resonance Imaging (fMRI) provides information about state-dependent changes in local neuronal activity in vivo. Using fMRI, the present dissertation examined changes in human brain activity to food and nonfood pictures following the pharmacological induction of hunger with the orexigenic hormone ghrelin (Study 1), and following manipulation of the cognitive state of food expectation (Study 2).
Our data reinforce the involvement of a distributed frontal-limbic-paralimbic circuit in the central processing of food imagery, under both experimental conditions. The first study revealed that intravenous ghrelin administration potently modulated food-associated neural responses III areas involved in reward, motivation, memory, and attention (amygdala, insula, orbitofrontal cortex, striatum, hippocampus, midbrain, visual areas). This suggests that metabolic signals such as ghrelin may promote food consumption by enhancing the appetitive response to food cues via engagement of the hedonic network.
The second study revealed that brain regions activated in the 'expectant' state (i.e. when subjects were anticipating food reward) were at least partially dissociable from those in the 'not expectant' state. In particular, recruitment of the dorsolateral prefrontal cortex, a principal component in the cognitive control network, exclusively in the 'not expectant' condition, may signal an attempt to suppress appetite in the absence of food expectation. Areas of convergence were observed in the amygdala and insula.
Obesity is rapidly becoming the major cause of excess mortality worldwide; therefore, understanding how the central nervous system controls appetite and nutrient consumption is of considerable interest. The projects in this thesis offer significant insights regarding the effects two select factors (one intrinsic and the other extrinsic) on the neural reaction to visual food stimuli, in healthy male participants.

Distinct brain regions process innocuous vibration and cutaneous heat pain. The role of these areas in the perception of pain is still a matter of debate; and the role of these areas in the mediation of memory of somatosensory stimuli is uncertain and has not been studied with brain imaging in healthy human volunteers. All experiments described here, involved an experimental design, which included a delayed-discrimination paradigm and functional magnetic resonance imaging (fMRI). In manuscript #1, we aimed at unraveling the cerebral correlates of attention and spatial localization of innocuous vibrotactile stimuli applied to the right volar surface of the forearm. In this study, we report that increased degrees of attention to the vibrotactile stimuli were associated with heightened levels of activation in several brain areas. In manuscript #2, we investigated the short-term memory for sensory aspects (intensity and location) of cutaneous heat pain delivered to two areas (thenar and hypothenar eminences) of the palm of the right hand. In this experiment, the memory and control trials were presented in blocks, whereby the subjects could predict what trials were going to follow. This study revealed that the presentation of painful stimuli evoked activation in different brain regions than those activated during the online maintenance (interstimulus interval or ISI) of the intensity and spatial features of those stimuli; a process, which I will refer to short-term memory. In manuscript #3, we investigated again short-term memory for sensory aspects of heat pain (as in manuscript #2), but in this case, the memory and control trials were presented in a randomized order. In this study, we found that the perception and short-term memory of pain were processed by a comparable network of areas. The predictability of the memory and control trials may have contributed to these findings.
La vibration inoffensive ainsi que la chaleur douloureuse cutanée sont traitées pardifférentes régions du cerveau. Le rôle de ces régions dans la perception de la douleurest controversé; et le rôle de ces régions dans la mémoire des stimuli somatosensorielsest incertain et n'a jamais encore été étudié en imagerie cérébrale chez des sujetshumains sains. Le design expérimental de toutes les études décrites ici comprenait unparadigme de 'delayed-discrimination' et l'imagerie par résonance magnétiquefonctionnelle (IRMf). L'étude #1 visait à élucider les corrélats cérébraux de l'attention etde la localisation spatiale des stimuli vibrotactiles inoffensifs présentés à la faceantérieure de l'avant-bras droit. Dans cette étude, nous avons trouvé que des degrésélevés d'attention portée aux stimuli vibrotactiles étaient associés à des niveaux accrusd'activation dans plusieurs zones du cerveau. Dans l'étude #2, nous avons enquêté surla mémoire à court-terme des caractéristiques sensorielles (intensité et emplacement)de la chaleur douloureuse cutanée présentée à deux endroits (éminences thénar ethypothénar) de la paume de la main droite. Dans cette étude, les essais mémoire etcontrôle étaient présentés en bloc, ou de sorte que les participants pouvaient prévoir dequel type serait le prochain essai. Cette étude a révélé que la présentation des stimulidouloureux a évoqué une activation de différentes régions cérébrales que celles quiétaient activées lors de la rétention de l'intensité et de l'emplacement des stimulationsdurant l'intervalle inter-stimuli (liS); un processus que je qualifierai de mémoire à courtterme.Dans l'étude #3, nous avons également enquêté sur la 'mémoire à court-termedes aspects sensoriels de la chaleur douloureuse (tout comme dans l'étude #2), maisdans ce cas, les essais mémoire et contrôle étaient présentés de façon aléatoire. Danscette étude, nous avons trouvé que la perception de la douleur ainsi que la mémoire àcourt-terme de la douleur étaient traitées par un réseau de régions semblable. Laprévisibilité des essais mémoire et contrôle peut avoir contribué à ce résultat.

This study was designed to clarify some of the issues surrounding the nature of hemispheric contributions to the processing of emotional and linguistic prosody, as well as to examine the relative contribution of different sensory modalities in processing prosodic structures. Ten healthy young participants were presented with semantically neutral sentences expressing affective or linguistic prosody solely through the use of non-verbal cues (intonation, facial expressions) while undergoing tMRI. The sentences were presented under auditory, visual, as well as audio-visual conditions. The emotional prosody task required participants to identify the emotion of the utterance (happy or angry) and the linguistic prosody task required participants to identify the type of utterance (question or statement). Core peri-sylvian, frontal and occipital areas were activated bilaterally in all conditions suggesting that processing of affective and linguistic prosodic structures is supported by overlapping networks. The strength of these activations may, in part, be modulated by task and modality of presentation.

Abstract Neuropsychiatric illnesses usually become overtly manifest in adolescence and early adulthood. A critical long-term aim is to be able to prevent the development of such illnesses, which requires instruments to identify subjects at high risk of illness and to offer them effective interventions. There is an indisputable need for more sophisticated methods to enable more precise detection of adolescents and young adults who are at high risk of developing psychosis. Abnormal function in brain networks has been reported in people with schizophrenia and other psychotic disorders. Similar abnormalities have been found also in people at risk for developing psychosis, but it is not known whether this applies also to spontaneous resting state activity in young people with a familial risk for psychosis. We conducted resting-state functional MRI (R-fMRI) in 72 (29 male) young adults with a history of psychosis in one or both parents (FR) but without psychosis themselves, and 72 (29 male) similarly healthy control subjects without familial risk for psychosis. Both groups in the Oulu Brain and Mind study were drawn from the Northern Finland Birth Cohort 1986. All volunteers were 20–25 years old. Parental psychosis was established using the Care Register for Health Care. R-fMRI data was pre-processed using independent component analysis (ICA). A dual regression technique was used to detect between-group differences with p < 0.05 threshold corrected for multiple comparisons at voxel level. FR subjects demonstrated significantly decreased activity compared to control subjects in the default mode network and in the central executive network and increased activity in the cerebellum. The findings clarify previously controversial literature on the subject. The finding suggests that abnormal activity in these brain networks in rest may be associated with increased vulnerability to psychosis. The findings maybe helpful in developing more precise methods for detecting young people at highest risk for developing psychosis
Tiivistelmä Psykoottisiin häiriöihin sairastutaan yleensä nuoruudessa tai varhaisaikuisuudessa. Psykoositutkimuksen tavoitteena on löytää uusia menetelmiä, joiden avulla kyettäisiin tunnistamaan suurimmassa psykoosiriskissä olevat nuoret, jotta heille voitaisiin tarjota sairautta ennaltaehkäiseviä hoitokeinoja. Skitsofreniaan ja muihin psykoottisiin häiriöihin sairastuneilla on havaittu aivotoiminnan poikkeavuuksia. Samankaltaisia aivotoiminnan poikkeavuuksia on havaittu myös nuorilla, jotka ovat vaarassa sairastua psykoosiin. Toistaiseksi on ollut epäselvää, onko psykoosiin sairastuneiden henkilöiden lapsilla aivohermoverkkojen toiminnan poikkeavuuksia lepotilassa. Suoritimme aivojen lepotilan MRI-tutkimuksen (R-fMRI) 72:lle (29 miestä) nuorelle aikuiselle, joiden jompikumpi vanhempi oli sairastunut psykoosin sekä 72:lle (29 miestä) nuorelle aikuiselle, joiden vanhemmat eivät olleet sairastaneet psykoosia. Molemmat tutkimusryhmät tässä Oulu Brain and Mind -tutkimuksessa olivat Pohjois-Suomen 1986 syntymäkohortin jäseniä. Tutkittavat olivat 20–25 vuoden iässä. Lepotilan toiminnallinen magneettikuvaus suoritettiin 1.5 Teslan Siemensin magneettikuvantamislaitteella. Tutkimuskohteiksi valittiin lepotilan toiminnallinen aivohermoverkko, toiminnan ohjauksesta vastaava aivohermoverkko ja pikkuaivot. Kuvantamisdataan sovellettiin itsenäisten komponenttien analyysia aivohermoverkkojen määrittämistä varten. Ryhmien välisen eron havaitsemiseen käytettiin ei-parametristä permutaatiotestiä, joka kynnystettiin tilastollisesti merkitsevään tasoon (p < 0.05). Lepotilan oletushermoverkossa ja toiminnanohjauksesta vastaavassa aivohermoverkoissa havaittiin vähäisempää aktiivisuutta ja pikkuaivoissa kohonnutta aktiivisuutta perinnöllisessä psykoosiriskissä olevilla nuorilla aikuisilla verrattuna verrokkeihin. Tutkimustulokset selkeyttivät aiempaa ristiriitaista kirjallisuutta tutkimusaiheesta. Tutkimuksessa havaittujen aivoalueiden poikkeava toiminta lepotilassa voi liittyä kohonneeseen psykoosin puhkeamisriskiin. Tutkimuslöydösten avulla voidaan todennäköisesti edesauttaa parempien kuvantamismenetelmien kehittämistä suurimmassa psykoosiriskissä olevien nuorten tunnistamiseen

In recent years, although a number of functional neuroimaging studies have demonstrated a relationship between activity in the prefrontal cortex and memory retrieval, it has been difficult to relate specific aspects of retrieval processing to specific regions of the prefrontal cortex. The present event-related fMRI study focuses on the role of the mid-ventrolateral prefrontal cortex in active retrieval processes, leading to the dissociation of different aspects of mnemonic information. Thirteen normal volunteers were scanned with a 1.5-T Siemens Vision Scanner. Functional images sensitive to the blood oxygenation level dependent (BOLD) signal were acquired in an event-related fashion. In the experimental condition one of four different faces was briefly presented at one of four different locations on the screen. This encoding phase was followed by a question phase during which a cue in the center of the screen instructed the subjects to either retrieve the particular face of the initially presented stimulus or its location. After a delay, a test stimulus was presented and the subjects had to decide whether it corresponded to the aspect of the encoded stimulus instructed by the cue (i.e. the particular face or location). In the recognition control condition for the same sequence of events the subjects had simply to recall the encoded stimulus in order to recognize it in the test phase. The subtraction method was used to compare the signal between these two conditions. Correlation maps computed for the group revealed, relative to the recognition condition, selective increases in activity in the mid-ventrolateral prefrontal cortex when subjects were involved in active retrieval processes both for visual spatial (i.e. location) and visual non-spatial (i.e. face) material. These results support the hypothesis that the mid-ventrolateral prefrontal cortical region is selectively involved in active mnemonic retrieval.

Changes in cerebral venous blood volume (DCBVv) is a critical component of the BOLD fMRI signal (instead of total DCBV), but its role has remained relatively unexplored, predominantly because measuring CBVv non-invasively is challenging. Motivated by this challenge, this thesis focuses on the development and use of the venous refocusing for volume estimation (VERVE) technique to non-invasively measure DCBVv. Driven by the substantial signal-to-noise (SNR) gain at high field, VERVE was re-designed for 3 T. This technique is strongly field-dependent through its reliance on venous blood transverse relaxation (T2) variations as a function of the Carr-Purcell Meiboom-Gill (CPMG) refocusing interval and blood oxygenation. To characterize this dependence, human whole blood T2 relaxometry was performed at 3 T. The results reveal significantly enhanced blood T2 dependence relative to 1.5 T, one best modelled as a diffusion process. In addition, human grey and white matter T2 relaxometry results support venous blood T2 variation being the predominant source of VERVE contrast at 3 T. The subsequent design of VERVE was based on the blood relaxometry results. Also, to minimize signal biases due to gradient-echo BOLD effects, greatly amplified at 3 T, a turbo spin-echo approach was adopted, further boosting SNR. VERVE was then used with arterial spin labeling (ASL) to assess the steady-state venous flow-volume relationship in humans under visual and sensorimotor stimulation. The results demonstrated a spatially-invariant flow-volume relationship characterized by a power-law coefficient (a) of 0.23, significantly lower than Grubb’s value of 0.38 (derived using total DCBV). The assumption of the latter in calibrated BOLD introduced a significant underestimation in cerebral oxygen metabolism changes (DCMRO2). Finally, the interactions giving rise to the controversial BOLD post-stimulus undershoot were examined with respect to the prevalent biomechanical, metabolic and neuron
Les changements du volume sanguin cérébral veineux (DCBVv) est un élément essentiel du signal BOLD (par opposition à l’ensemble de DCBV). Pourtant, jusqu'ici le rôle du CBVv est resté relativement inexploré, et ce du aux difficultés liées aux mesures non-invasives du CBVv. Motivée par ce défi, cette thèse se rapporte sur le développement et l'utilisation de la méthode VERVE (refocalisation veineuse pour l’estimation du volume), qui permet l’estimation non-invasive de DCBVv. D’abord, l’augmentation importante du rapport signal-sur-bruit (SNR) aux champs magnétiques élevés a mené à réviser VERVE pour 3 T. Le contraste VERVE est basé sur les variations du temps de relaxation transversale (T2) sanguin veineux en fonction de l’intervalle de refocalisation Carr-Purcell Meiboom-Gill (CPMG) et de l’oxygénation sanguine. Pour caractériser cette dépendance, qui dépend fortement du champ magnétique, une étude relaxométrique du sang humain a été réalisé à 3 T. Les résultats indiquent que la dépendance du T2 sanguin est amplifiée de façon importante entre 1.5 T et 3 T. Un modèle de diffusion décrit le mieux cette dépendance. D’autre part, une étude relaxométrique de la matière grise et blanche a été réalisée, confirmant la dominance de l’effet T2 sanguin dans le contraste VERVE. La composition de VERVE se rapporte aux résultats relaxométriques sanguins. En plus, afin de minimiser l’effet de l’écho de gradient, amplifié à 3 T, une approche turbo spin-écho a été adoptée. VERVE est ensuite utilisée avec le marquage des spins artériels (ASL) pour mesurer les changements du CBVv et du débit sanguin cérébral (CBF) chez les sujets sains lors de stimulations visuelles et sensorimotrices. Les résultats démontrent une relation débit-volume invariante à travers le cortex, caractérisée par a = 0.23, inférieure à la valeur de Grubb (0.38, calculée a partir du CBV total). En employant cett

Multiple memory systems are involved in processing information during navigation. A hippocampus-dependent "spatial" navigation system requires learning the relationships between environmental landmarks to build a cognitive map, while habit-based "response" learning involves the automatization of patterns of behavioral responses and is mediated by the caudate nucleus. Studies have demonstrated that people will spontaneously use one or the other of these two alternative strategies with almost equal frequency to solve a given navigation task (Iaria et al., 2003) and that strategy selection correlates with grey matter density (Bohbot et al., 2007). While there is evidence for experience modulating grey matter in the hippocampus (Maguire et al., 2000), genetic contributions may also play an important role in the hippocampus and caudate nucleus. Recently, the Brain-derived neurotrophic factor (BDNF) val66met polymorphism has emerged as a possible inhibitor of hippocampal function. Here we investigate a role for this polymorphism in strategy selection and functional magnetic resonance imaging (fMRI) activity during human virtual navigation tasks as well as an effect of this genotype on human brain morphology.
Plusieurs systèmes de mémoire sont impliqués dans le traitement des informations durant la navigation. Un système de navigation « spatiale », qui dépend de l'hippocampe, exploite les liens entre les points de repère pour construire une carte cognitive, tandis que l'apprentissage par réponse, basé sur la répétition et le renforcement est dirigé par le noyau caudé. Des études ont démontré qu'une proportion quasi égale de gens utilisent spontanément l'une ou l'autre de ces stratégies pour résoudre une tâche de navigation donnée (Iaria et al., 2003), et que la sélection d'une stratégie est corrélée avec la densité de la matière grise l'hippocampe et aux noyaux caudés (Bohbot et al., 2007). Bien qu'il ait été démontré que l'expérience en navigation module la matière grise a l'hippocampe (Maguire et al., 2000), des contribution génétiques peuvent aussi y jouer un rôle. Plus récemment, le polymorphisme val66met du FNDC se fait candidat comme inhibiteur potentiel de la fonction hippocampique. Nous avons examiné le rôle de ce polymorphisme dans la sélection d'une stratégie et dans l'activité neuronale par IRMf pendant des tâches de navigation virtuelle, ainsi que l'effet du génotype sur la morphologie du cerveau humain.

Positron emission tomography (PET) studies of the human brain reveal pain-related activation in several regions of the cerebral cortex. Nevertheless, patterns of activation vary among studies. This study used the more sensitive method, functional magnetic resonance imaging (fMRI), to assess variability between and within subjects, for both pain and tactile-related activation. Four subjects participated in two fMRI sessions each. Thermal and tactile stimuli were applied to the skin on separate runs. Activation maps were generated comparing painful to neutral heat and tactile to rest.
Group analysis revealed pain- and tactile-related activation consistent with the majority of PET studies. Comparison of activation sites across subjects revealed differences in the location of peaks corresponding to anatomical variability in sulcal position. Comparing across sessions for each subject revealed differences in the intensity but not the location of peaks.
These results indicate that pain and touch evoke reliable patterns of cortical activation. Intensity-related differences and intersubject variability could explain the variable results of PET studies.

Recent brain imaging studies have shed light on the effects of nicotine on human cognition. However, few efforts have investigated how changes in brain connectivity may engender nicotine-induced cognitive modulation. Recent studies have also examined the effects of drug cues in addicts; however, little has been established about the influence of perceived drug availability on these responses and the resulting changes in brain connectivity. Using functional magnetic resonance imaging (fMRI), we investigated the effects of nicotine on brain connectivity during a verbal and visual working memory (WM) task. We have shown that nicotine modulates connectivity in a cortico-striatal-thalamic loop during the verbal WM task in which nicotine also improved behavioural performance. In a second inquiry using a cue reactivity paradigm and fMRI, we showed that smoking cue-dependent functional connectivity was significantly greater in subjects that were in a state of expectation to smoke.

Emotion can exert a modulatory role on declarative memory. Several studies have shown that emotional stimuli (e.g., words, pictures) are better remembered than neutral ones. Although facial expressions are powerful emotional stimuli and have been shown to influence perception and attention processes, little is known about their effect on memory. We conducted an event-related fMRI study in 18 healthy individuals (9 men) to investigate the effects of expression on recognition memory for faces. During the encoding phase, participants viewed 84 faces of different individuals, depicting happy, fearful or neutral expressions. Subjects were asked to perform a gender discrimination task and remember the faces for later. In the recognition part subjects performed an old/new decision task on 168 faces (84 new). Both runs were scanned. Our findings highlight the importance of the amygdala, hippocampus and prefrontal cortex on the formation and retrieval of memories with emotional content.

Introduction. The use of Functional Magnetic Resonance Imaging (fMRI) in studying central auditory pathways expanded our knowledge of the neurophysiology of hearing. In various studies, an array of diverse auditory stimuli has been used, including pure tones and words, in a "Block" design. Few studies, thus far, have been performed using an event-related design. None of these has used pure tone stimulation.
Subjects and methods. In eight out of 13 subjects enrolled and scanned in this project, data have been acquired and processed. Binaural pure tone stimulation at 2kHz and one higher frequency at 6, 8, or 12 kHz, at 90 dB SPL was presented to all subjects, using a stroboscopic design in an attempt to eliminate cortical response to scanning noise. In addition, an unusually long time of repetition (TR) interval of 10 seconds was utilized. The aim in data processing was to generate: (a) a Peak Height Map (PHM) with selection of areas of stimulation based on the maximal response; (b) a statistical map from the raw data of the images.
Results. No consistent morphology was detected in the BOLD event-related curves, corresponding to the percentage change from baseline over time. Such curves revealed significant oscillation with marked dips below baseline, highly suggestive of an irregular noise pattern. Comparing the curves to each other, no discernible shape or similarities were noted.
Conclusion. Attempting to extract both the temporal and spatial characteristics of the cortical response to pure tone stimuli resulted in a dispersal of data over many parameters, therefore "diluting" it. This, in turn, yielded a negative result where the responses were "drowned" revealing but a noise pattern.

The role of primary somatosensory cortex (S1) in pain perception remains uncertain. Human imaging studies have had variable success in showing pain-related activation in S1, and single-unit recordings in primate S1 have revealed few nociceptors. This study assessed the fMRI time course of S1 activity in humans during noxious heat and innocuous tactile stimulation to determine if temporal differences in the perception of these stimuli would be reflected by temporal differences in S1 activation.
Four normal subjects participated in three fMRI sessions each. Thermal (painful heat 45--46°C; neutral heat 35--36°C) and tactile stimuli (brushing at 2Hz) were applied to the left leg on separate runs. Activation maps were generated comparing painful to neutral heat and tactile to rest. Directed searches were performed on identified S1 regions reliably activated by brush and noxious heat stimuli, from which regions of interest (ROI) were selected in each subject. Time course for each stimulus modality was extracted from these ROIs, and data were further averaged to examine the mean time course of activation per stimulus cycle.
Both brushing and noxious heat produced significant activation within contralateral S1 which could be differentiated by the time course of activation relative to the onset of stimulation. These data indicate that S1 cortex is involved in the processing of nociceptive information. The data are consistent with other indications that this structure has a role in the perception of pain intensity.

Several clinical populations (e.g. Schizophrenia, Alzheimer's disease, frontal lobe damage, and healthy aging with memory decline) display memory deficits which may be related to a failure to engage efficient memory encoding strategies. However, these groups often show improved memory performance when cued towards the use of efficient encoding strategies, suggesting the deficits are related to self-initiating elaborative encoding processes. At present, little is know about the neural correlates of self-initiating elaborative encoding strategies in episodic memory. The purpose of this thesis was to better understand the process of initiating elaborative encoding strategies. We hypothesized that the left dorsolateral prefrontal cortex (DLPFC) was involved in self-initiating elaborative encoding strategies. Experiment 1 was an fMRI study in which we presented conditions in which participants were either cued to use an efficient encoding strategy (semantic analysis) or were not cued to do so (a self-initiated condition), while presenting stimuli with variable semantic relatedness. We observed activity in the left DLPFC and bilateral supramarginal gyrus in response to semantic relatedness in the non-semantic (self-initiated) encoding condition. In experiment 2, we attempted to confirm the role of the left DLPFC in self-initiating elaborative encoding using transcranial magnetic stimulation (TMS), a method in which we can transiently disrupt neural activity in a limited cortical area. We performed stimulation of the left DLPFC and a control site (the vertex) during a memory encoding task. We observed a significant correlation in a subsequent cued recall task (a measure of encoding success) between the effects of TMS during encoding and participant's use of memory strategies during encoding only in the condition in which self-initiated elaborative encoding was beneficial to memory performance. This suggests a causative role for the DLPFC in self-initiating elaborative encoding. Experiment 3 was a concurrent TMS-fMRI study. Participants performed an encoding task (similar to the self-initiated condition in experiment 1) while we measured brain activity using fMRI. TMS stimulation was presented for 300ms on ¾ of trials. The onset of stimulation was varied, starting at 200ms, 600ms, or 1000ms after stimulus onset. We observed time-specific changes in neural activity in response to TMS stimulation, suggesting that concurrent TMS-fMRI can be used to measure time-varying interactions between the DLPFC and distal brain regions These three experiment provide evidence o f the role of the left DLPFC in self-initiating elaborative encoding strategies, and the utility of TMS and fMRI (separately or combined) as research techniques to address these techniques. These studies also demonstrate the utility of our selected paradigms to directly address the issue of self-initiating elaborative encoding (rather than correlating activity to specific encoding strategies).
Plusieurs populations cliniques (ex. schizophrénie, maladie d'Alzheimer, lésions du lobe frontal, vieillissement normal avec déclin de mémoire) démontrent des déficits de mémoire qui peuvent être reliés à une incapacité d'initier des stratégies efficaces d'encodage de mémoire. Cependant, ces groupes démontrent souvent une amélioration de leur performance lorsqu'on les aide à choisir une stratégie d'encodage efficace, suggérant que les déficits seraient reliés à l'utilisation spontanée de stratégies d'encodage élaborées. A ce jour, nous savons très peu de choses à propos des corrélats neuronaux de l'utilisation spontanée de stratégies d'encodage élaborées. Le but de cette thèse est de mieux comprendre les processus de l'initiation de stratégies d'encodage élaborées. Nous émettons l'hypothèse que le cortex préfrontal dorsolatéral (DLPFC) est impliqué dans l'utilisation spontanée de stratégies d'encodage élaborées. L'expérience 1 consiste en une étude d'IRMf dans laquelle nous avons présenté des conditions dans lesquelles les participants étaient guidés à utiliser une stratégie d'encodage efficace (analyse sémantique) ou non guidés d'utiliser cette stratégie (condition auto-initiée), en présentant des stimuli de relations sémantiques variées. Nous avons observé une activité dans le DLPFC gauche et le gyrus supramarginal bilatéral en réponse à la relation sémantique dans la condition d'encodage non-sémantique (auto-initiée). Dans l'expérience 2, nous avons tenté de confirmer le rôle du DLPFC gauche dans l'utilisation spontanée de stratégies d'encodage élaborées en utilisant la stimulation magnétique transcrânienne (SMT), une méthode avec laquelle nous pouvons perturber l'activité neuronale de façon transitoire dans une aire corticale limitée. Nous avons performé une stimulation du DLPFC gauche et d'un site contrôle (le vertex) durant une tâche d'encodage de mémoire. Nous avons observé une corrélation significative dans la tâche de reconnaissance subséquente (une mesure de la réussite de l'encodage) entre les effets de la SMT durant l'encodage et l'utilisation de stratégies de mémoire du participant pendant l'encodage seulement dans la condition où l'utilisation spontanée de stratégies d'encodage élaborées était bénéfique pour la performance de mémoire. Ceci suggère un rôle causal du DLPFC dans l'utilisation spontanée de stratégies d'encodage élaborées. L'expérience 3 était une étude simultanée de SMT-IRMf. Les participants devaient faire une tâche d'encodage (similaire à la condition auto-initiée de l'expérience 1) pendant que l'on mesurait l'activité du cerveau avec l'IRMf. Une SMT était faite pendant 300ms sur les trois-quarts des essais. Le début de la stimulation était varié, commençant à 200ms, 600ms ou 1000ms après le début du stimulus. Nous avons observé des changements spécifiques au temps dans l'activité neuronale en réponse à la stimulation SMT, indiquant que l'utilisation simultanée de SMT-IRMf peut être utilisée pour mesurer l'interaction en fonction du temps entre le DLPFC et les régions distales du cerveau. Ces trois expériences apportent des évidences du rôle du DLPFC gauche dans l'utilisation spontanée de stratégies d'encodage élaborées et l'utilité de la SMT et de l'IRMf (séparément ou combinées) comme techniques de recherche pour étudier ces processus. Ces études démontrent aussi l'utilité de nos paradigmes pour étudier directement l'utilisation spontanée de stratégies d'encodage élaborées (au lieu de corréler l'activité à des stratégies d'encodage spécifique).

Recent studies using brain imaging have begun to reveal the neural systems that underlie the response to drug cues in human addicts, however, little is known about how they are affected by perceived drug availability and degree of abstinence in the user. Using functional magnetic resonance imaging (fMRT) and a cue reactivity paradigm in cigarette smokers, we have investigated, for the first time, the neural correlates of expectancy and abstinence on the drug user's response to stimuli associated with drug use. Exposure to smoking cues induced a subjective craving response and elicited activation of a distributed neural system involved in the cognitive and emotional processing of salient stimuli. We showed that in a state of anticipation to smoke, this neural response was heightened, notably in the prefrontal cortex, whereas it was absent during a state of non-expectancy. In addition, we showed that this cue-induced response was disrupted during acute withdrawal from smoking.

A complex physiological system, composed of central and peripheral signals, balances energy intake and expenditure. Among these signals, the enteric and orexigenic hormone ghrelin is a regulator of energy balance with several uncharacterized functions. Although much research has accumulated regarding ghrelin's effects on metabolic parameters, little is known about its other behavioural and cognitive effects. Consequently, this study, using functional magnetic resonance imaging, showed that ghrelin administered intravenously to healthy volunteers increased the neural response to food pictures, as well as faces of fear and disgust, in brain areas regulating the hedonic and incentive evaluation of visual stimuli, such as the amygdala. Moreover, ghrelin exhibited memory enhancing effects for both food pictures and faces of fear and disgust. These findings suggest that ghrelin's activation of the amygdala may serve as a magnitude signal for value judgments of visually-presented food and non-food stimuli, thus engaging critical feeding, emotional and cognitive responses.

Human cognitive processes, such as learning and memory, are particularly vulnerable to the effects of cortisol, the human stress hormone. In the field of magnetic resonance imaging (MRI) the different cortisol characteristics are neither controlled nor accounted for. This study will aim to investigate, by means of functional MRI, the effects of morning and afternoon cortisol levels on neural activation changes in response to a working memory task in young males. We hypothesized a significant difference between morning and afternoon subjects' cortisol levels and neural activation patterns in relation to the task. Nineteen young males were recruited, 9 for the morning group and 10 for the afternoon group. Cortisol levels, neuronal activation, and behavioural measurements (correct percentage of hits and reaction time) were assessed during the task. Six saliva samples were taken during the experiment at various time intervals. As expected, morning cortisol levels were higher than afternoon cortisol levels. Results indicate that the afternoon group had significantly slower reaction time on the frontal task compared to the morning group, whilst the percentage of correct hits did not differ. Furthermore, we observed an increased range of neural activation in the morning group compared to the afternoon group. This study demonstrates the impact of time of day of testing (i.e. different cortical levels) on neural activation in functional MRI experiments. It is important for investigators using this technique to be aware of and control for this variable.