Functional magnetic resonance imaging (fMRI) studies performed to date have focused on brain structures rostral to the thalamus, although the first level of sensory information and pain transmission occurs at the spinal cord (SC). The primary goal of this project is to map activity using fMRI, from the entire cervical SC and brainstem following innocuous and noxious stimuli before and after peripheral sensitization in normal human volunteers. This study is unique in that it determines functional activity throughout the lower neural axis in response to mechanical stimuli that are perceived as painful only after sensitization. Functional MRI studies of the SC were carried out in 18 healthy individuals in a 3T Siemens Magnetom Trio. Innocuous touch and brush (n=8), and noxious touch (n=10) stimuli were applied before and after peripheral sensitization. Peripheral sensitization was induced by topical application of capsaicin. Functional image data spanned from the C7/T1 disc to the superior edge of the thalamus and analyzed using a general linear model to discriminate signal intensity changes from physiological motion. Normalized results were combined to demonstrate the number of volunteers showing activity at each location on a voxel-by-voxel basis. Areas of activity were superimposed onto anatomical transverse drawings and identified visually with comparison to several stereotaxic atlases. The results from this study confirm previous reports that a non-noxious stimulus translates into a pain response after peripheral sensitization. The brush stimulus, before sensitization activated areas in the ipsilateral dorsal horn (DH), gracile and cuneate nuclei in the medulla and areas surrounding the dorsal column medial lemniscal pathway. Peripheral sensitization produced activity in the contralateral ventral horn (VH), typical of a pain response. The innocuous von Frey stimulus produced activity in typical sensory centres in the DH and brainstem before sensitization, and areas more consistent with a noxious response after sensitization. When examining equi-nociceptive stimuli in a control versus sensitized state, the noxious touch stimuli showed similar activation patterns even though the force of the filaments were different. In all experiments there was indication of descending modulation as activity was observed in the periaqueductal gray, midbrain red nuclei and pontine reticular formation. This study demonstrates how non-painful and pain information is transmitted from the dorsal spinal horn to the brain in healthy individuals and how peripheral sensitization induces changes in non-noxious stimuli that correlate with pain sensory transmission. / Thesis (Master, Neuroscience Studies) -- Queen's University, 2008-09-24 20:13:08.655

In functional magnetic resonance imaging (fMRI) studies, inter-subject anatomical variability of the human brain has been a major challenge in finding reliable functional/anatomical correspondences. Assessment of brain-behavior relations involves a series of geometrical/statistical operations on brain images to minimize such inter-subject variability, so that group maps of brain activity relative to brain anatomy can be developed. Various methods of image registration, segmentation, and analysis have been proposed for mapping functional activity on to anatomical atlases of the brain. The two most common techniques that have been widely accepted and used by neuroimaging scientists are volume-based (VB) analysis using group registration methods and region-of-interest (ROI)-based methods using automated segmentation algorithms or macro/microanatomical probabilistic atlases for labeling. Nevertheless, the analysis results based on these techniques are significantly affected by the accuracy of the selected segmentation and/or registration methods. Furthermore, conventional fMRI data analysis techniques (VB, and ROI-based methods) mainly rely on the assumption that brain processes are common and universal among individual humans; however, besides anatomical differences, there also exist cognitive and behavioral variability among individuals due to differential engagement of brain networks even when performing an identical cognitive task. In this thesis, I have assessed the impact of anatomy-based alignment techniques (VB, and ROI-based methods) on sensitivity of fMRI data group analysis. I evaluated the effect of the type of inter-subject registration used and related factors on sensitivity of group-level fMRI data analysis. Furthermore, I have also assessed the goodness of fit of probabilistic maps by proposing an evidence-based framework for evaluation of probabilistic maps. As a test model, I have selected the human auditory cortex. Auditory cortex is an interesting yet challenging case with substantial inter-individual functional/anatomical variability. For the sake of ROI-based method of analysis, I have proposed a novel approach for automatic segmentation of Heschl's gyrus, which is the landmark for primary auditory cortex. Finally, in order to assess the impact of inter-subject variability in anatomy on functional organization, I analyze data from an fMRI study, which demonstrates that the degree to which anatomical registration compensates for functional variability depends on the brain region activated. / Thesis (Ph.D, Computing) -- Queen's University, 2010-04-29 07:07:55.77

To date, most studies investigating the neural signature of pain in humans have focused on the brain, and those studies concerned with more caudal areas (such as the spinal cord (SC) or brainstem) have used only experimental models of pain. The objectives of this study were 1) to determine the neural activity in the human brainstem and SC that is caused by a noxious mechanical stimulus and 2) to compare the neural response to noxious stimuli in healthy controls and a patient population diagnosed with peripheral neuropathic pain. The SC and brainstem contain important synaptic points in several major pain pathways, and comparing the neural response between a control and patient population in these areas provides a more complete picture of healthy and pathological pain processing. Functional MRI studies of the SC and brainstem were carried out in healthy control subjects and patients diagnosed with carpal tunnel syndrome (CTS) in a 3T Siemens Magnetom Trio. Subjects reported the point at which the pressure (in mmHg, applied to the wrist at the location of the median nerve) corresponded to a pain level of 2, 4, and 6 on a numerical 11 point pain scale. Spatially normalized group results superimposed on anatomical templates in the axial orientation were visually identified using several stereotaxic atlases. We observed consistent signal intensity change in areas implicated in the transmission and modulation of pain in both control and CTS groups. Both groups showed a similar decrease in signal change with increasing pain, as results at pain level 2 are predominantly positive signal change and at pain level 6 are typically negative. This may indicate a reduction in the tonic inhibition of painful sensations. Differences between groups were readily visible in regions anatomically consistent with the dorsal horn (DH) of the cervical SC, rostral ventromedial medulla (RVM), dorsolateral pontine tegmentum (DLPT), and midbrain periaqudectal gray (PAG). The anatomical variation in signal change between groups may represent, for the first time, a visualization of the functional difference between healthy and pathological pain processing in the SC and brainstem using spinal fMRI. / Thesis (Master, Neuroscience Studies) -- Queen's University, 2010-08-03 14:46:01.7

Many studies of ‘executive control’ have focused on the prefrontal cortex (PFC), which contains the neuronal functional properties, modulatory neurotransmitters, and network connections with sensory and motor regions to make this large brain area a candidate region to provide all the necessary elements to voluntarily control behavior. However, like the motor and premotor cortex, the PFC is integrated with the basal ganglia (BG) in such a similar fashion, that it is impossible not to consider that the PFC might depend on the BG to implement executive control effectively. This thesis draws on knowledge of PFC and BG function, and combines studies that require the instantaneous top-down control over motor behavior with a neurological patient group with primarily BG dysfunction (Parkinson’s disease), to provide for a new understanding of prefrontal-BG networks sub-serving executive control. The tasks performed by subjects consist of antisaccades (generate a voluntary eye-movement away from a visual stimulus) and those dealing with task switching (change behavior after an alternate was previously required). Numerous neural and functional imaging studies have identified key areas of the prefrontal cortex and BG that are critical to antisaccade generation, and studies in task switching have implicated similar neural mechanisms that are involved in overriding one behavior with another. By combining task switching with antisaccades, this thesis specifically examines the neural mechanisms related to suddenly changing behavior, under conditions where one behavior is easier to perform than the other. The methods utilize on-line eye-tracking in healthy young adults and older adults with, and without, Parkinson’s disease, to develop theories of a role of the BG in executive control, and to search for specific neural correlates of executive control signals in the PFC, premotor cortex and BG using functional magnetic resonance imaging (fMRI). Together, the conclusions drawn from this thesis point to an important role of the BG in overriding more automatic behavior with behavior that is more difficult to perform. This thesis also suggests that this overriding mechanism occurs through the boosting of cortical executive control signals via net excitatory feedback from the BG. / Thesis (Ph.D, Neuroscience Studies) -- Queen's University, 2010-09-09 12:17:46.904

The most common and natural human behaviours are often the most computationally difficult to understand. This is especially true of spoken language comprehension considering the acoustic ambiguities inherent in a speech stream, and that these ambiguities are exacerbated by the noisy and distracting listening conditions of everyday life. Nonetheless, the human brain is capable of rapidly and reliably processing speech in these situations with deceptive ease – a feat that remains unrivaled by state-of-the-art speech recognition technologies. It has long been known that supportive context facilitates robust speech perception, but it remains unclear how the brain integrates contextual information with an acoustically degraded speech signal. The four studies in this dissertation utilize behavioural and functional magnetic resonance imaging (fMRI) methods to examine how the normally functioning human brain uses context to support the perception of degraded speech. First, I have observed that text presented simultaneously with distorted sentences results in an illusory experience of perceptually clearer speech, and that this illusion depends on the amount of distortion in the bottom-up signal, and on the relative timing between the visual and auditory stimuli. Second, fMRI data indicate that activity in the earliest region of primary auditory cortex is sensitive to the perceived clarity of speech, and that this modulation of activity likely comes from left frontal cortical regions that probably support higher-order linguistic processes. Third, conscious awareness of the visual stimulus appears to be necessary to increase the intelligibility of degraded speech, and thus attention might also be required for multisensory integration. Finally, I have demonstrated that attention greatly enhances the processing of degraded speech, and this enhancement is (again) supported by the recruitment of higher-order cortical areas. The results of these studies provide converging evidence that brain uses prior knowledge to actively predict the form of a degraded auditory signal, and that these predictions are projected through feedback connections from higher- to lower-order order areas. These findings are consistent with a predictive coding model of perception, which provides an elegant mechanism in which accurate interpretations of the environment are constructed from ambiguous inputs in way that is flexible and task dependent. / Thesis (Ph.D, Neuroscience Studies) -- Queen's University, 2012-09-25 10:48:50.73

Magnetic resonance imaging (MRI) has revolutionized the field of cognitive neuroscience as it allows researchers to noninvasively map brain function in response to stimulus or task demands. However, the acquisition of MR images generates substantial acoustic noise, so that imaging studies of speech, language and hearing are problematic. One proven solution for reducing acoustic noise in MRI scanners is the use of micro-perforated panels placed in the bore of the scanner. They can be applied to existing scanners with minimal cost and are suitable for sterile environments. Although these panels result in quantifiably lower noise levels, measured with microphones in an empty MRI, the improvement has not been quantified with a patient in the scanner bore, which dramatically affects the acoustic noise field. This thesis tested the reduction of noise inside the MRI environment using a previously designed micro-perforated acoustic absorber panel. These panels resulted in quantifiably lower noise levels with a volunteer in the scanner bore, however the reduction was not sufficient for significant differences in volunteer perceptions. Volunteers were generally unable to perceive a difference in noise between scans with and without absorbers and no reduction of fatigue was observed. Also no significant change in cortical activity was found between scans done with and without absorbers during an auditory function MRI study. Further testing could include designing a micro-perforated acoustic absorber for a specific scan sequence for maximum attenuation. / Thesis (Master, Mechanical and Materials Engineering) -- Queen's University, 2012-09-25 16:54:41.118

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Investigating the Neural Correlates of Crossmodal Facilitation as a Result of Attentional Cueing: An Event-Related fMRI Study. Degree of Masters of Science, 2008 Zainab Fatima Institute of Medical Science, University of Toronto ABSTRACT Attentional cueing modulated neural processes differently depending on input modality. I used event-related fMRI to investigate how auditory and visual cues affected reaction times to auditory and visual targets. Behavioural results showed that responses were faster when: cues appeared first compared to targets and cues were auditory versus visual. The first result was supported by an increase in BOLD percent signal change in sensory cortices upon cue but not target presentation. Task-related activation patterns showed that the auditory cue activated auditory and visual cortices while the visual cue activated the visual cortices and the fronto-polar cortex. Next, I computed brain-behaviour correlations for both cue types which revealed that the auditory cue recruited medial visual areas and a fronto-parietal attentional network to mediate behaviour while the visual cue engaged a posterior network composed of lateral visual areas and subcortical structures. The results suggest that crossmodal facilitation occurs via independent neural pathways depending on cue modality.

This thesis gives an overview on how to estimate changes in functional brain networks using graph theoretical measures. It explains the assessment and definition of functional brain networks derived from fMRI data. More explicitly, this thesis provides examples and newly developed methods on the measurement and visualization of changes due to pathology, external electrical stimulation or ongoing internal thought processes. These changes can occur on long as well as on short time scales and might be a key to understanding brain pathologies and their development. Furthermore, this thesis describes new methods to investigate and visualize these changes on both time scales and provides a more complete picture of the brain as a dynamic and constantly changing network.

<p>The goal of this dissertation is to characterize goal directed proactive behavioral responses to threat as well as reactive responses to threat exposure, and to identify the neural and personality correlates of individual differences in these responses. Three specific studies are reported wherein participants completed a novel shock avoidance paradigm while concurrent measures of behavioral, muscular, and sympathetic autonomic activity were collected; self-report was used to measure mood and trait personality; and blood oxygen-level dependent functional magnetic resonance imaging (BOLD fMRI) was used to measure individual differences in threat-related amygdala reactivity and intrinsic connectivity within the corticolimbic circuit.</p><p>Results from Study 1 demonstrate that during threat exposure, participants exhibit increased avoidance behavior, faster reaction times, and increased muscular and sympathetic activity. Moreover, results demonstrate that two broad patterns characterize individual differences in how participants respond during avoidance: 1) a generalized tendency to exhibit magnified threat responses across domains; and 2) a tendency to respond either with proactive behavioral responses or reactive autonomic responses. Heightened state anxiety during the shock avoidance paradigm, and increased trait anxiety were both associated with the generalized tendency to exhibit magnified threat responses. However, gender moderated the relationship between trait anxiety and generalized increases in threat responses during avoidance, such that only male participants exhibited a positive relationship between these two factors. Study 2 demonstrates that intrinsic connectivity between the dorsomedial prefrontal cortex and centromedial region of the amygdala prospectively predicts whether participants will respond proactively or reactively during active avoidance. Finally, Study 3 provides evidence that responses to threat-related facial expressions within the centromedial region of the amygdala are associated with more reactive and less proactive responses during avoidance. </p><p>These results demonstrate that patterns observed in animal models of avoidance, specifically the competition between proactive and reactive responses to threat cues, extend to human participants. Moreover, our results suggest that while anxious mood during performance and heightened trait anxiety are associated with a generalized facilitation of threat responses across domains, measures of neural circuit function within the corticolimbic system predict whether individuals will exhibit increased proactive or reactive responses during active avoidance. In addition to facilitating the search for the neural processes underlying how the brain responds dynamically to threat, these results have the potential to aide researchers in characterizing the symptoms and neural processes underlying anxiety disorders.</p> / Dissertation