Regionally Specific White Matter Disruptions of Fornix and Cingulum in Schizophrenia

Limbic circuitry disruptions have been implicated in the psychopathology and cognitive deficits of schizophrenia, which may involve white matter disruptions of the major tracts of the limbic system, including the fornix and the cingulum. Our study aimed to investigate regionally specific abnormalities of the fornix and cingulum in schizophrenia using diffusion tensor imaging (DTI). We determined the fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD) profiles along the fornix and cingulum tracts using a fibertracking technique and a brain mapping algorithm, the large deformation diffeomorphic metric mapping (LDDMM), in the DTI scans of 33 patients with schizophrenia and 31 age-, gender-, and handedness-matched healthy controls. We found that patients with schizophrenia showed reduction in FA and increase in RD in bilateral fornix, and increase in RD in left anterior cingulum when compared to healthy controls. In addition, tract-based analysis revealed specific loci of these white matter differences in schizophrenia, that is, FA reductions and AD and RD increases occur in the region of the left fornix further from the hippocampus, FA reductions and RD increases occur in the rostral portion of the left anterior cingulum, and RD and AD increases occur in the anterior segment of the left middle cingulum. In patients with schizophrenia, decreased FA in the specific loci of the left fornix and increased AD in the right cingulum adjoining the hippocampus correlated with greater severity of psychotic symptoms. These findings support precise disruptions of limbic-cortical integrity in schizophrenia and disruption of these structural networks may contribute towards the neural basis underlying the syndrome of schizophrenia and clinical symptomatology

Executive control in the anterior cingulate cortex

Converging evidence supports the hypothesis that the prefrontal cortex is critical for executive control. One prefrontal subregion, the anterior cingulate cortex has previously been shown to be active in situations involving high conflict, presentation of salient, distracting stimuli, and error processing, i.e. situations that occur when learning new response contingencies, when previously learned response strategies fail, or when a shift in attention or responding is required. These situations all involve goal-oriented monitoring of performance in order to effectively adjust cognitive processes. Several neuropsychological disorders, for instance schizophrenia, attention deficit hyperactivity disorder, and obsessive compulsive disorder, are correlated with morphological changes in the anterior cingulate cortex. Individuals with these disorders show impairments on tasks that require goal-oriented monitoring. The current studies used multiple behavioral paradigms to assess the effects of anterior cingulate cortex excitotoxic lesions in rats on executive control. Animals with anterior cingulate cortex lesions showed greater decline in cognitive capacity as tasks progressed, longer response latencies to conflicting stimuli, impaired reversal learning, impaired error processing, and impaired performance in the presence of previously relevant distractors. These results are consistent with the hypothesis that the anterior cingulate cortex is involved in executive control, specifically monitoring impairments in performance that signal the need to adjust cognitive control

The neurophysiological changes associated with motor learning in adults and adolescents

One main purpose of this dissertation was to explore how sensorimotor cortical oscillations changed after practicing a novel ankle plantarflexion target matching task. We behaviorally quantified the speed, accuracy, reaction time, velocity, and variability of the participant’s performance of the task, while collecting their neurophysiological responses with magnetoencephalography (MEG). With these data, we assessed how the motor planning and execution stages of movement during a goal directed target matching task changed after practicing a task in typically developing young adults with their non-dominant ankle. We found that the cortical oscillations in the beta frequency range that were sourced from the sensorimotor and occipital cortices were weaker after practice. These individuals also improved behaviorally, with faster speed, greater accuracy, higher velocity, and less variability. The decreased strength likely reflects a more refined motor plan, a reduction in neural resources needed to perform the task, and/or an enhancement of the processes that are involved in the visuomotor transformations that occur prior to the onset of the motor action. The second purpose was to explore how the changes of the sensorimotor cortical oscillations after practicing a novel ankle plantarflexion target matching task differ between adults and adolescents. We assessed these behavioral and neurophysiological changes in a cohort of typically developed adults and adolescents. After practice, all of the participants matched more targets, matched the targets faster, had improved accuracy, faster reaction times, and faster force production. However, the motor performance of the adults exceeded what was seen in the adolescents regardless of practice. In conjunction with the behavioral results, the strength of the beta ERD across the motor planning and execution stages was reduced after practice in the sensorimotor cortices of the adolescents, but was stronger in the adults. These outcomes suggest that there are age-dependent changes in the sensorimotor cortical oscillations after practice, which might be related to familiarity with the motor task. The third purpose was to explore how movement attenuates the somatosensory cortical oscillations and how this attenuation differs in adults and adolescents. We used MEG to address this knowledge gap by applying an electrical stimulation to the tibial nerve as adolescents and adults produced an isometric ankle plantarflexion force, or sat quietly with no motor activity. We found movement-related attenuation of the somatosensory oscillations. Attenuation of the alpha-beta ERS while producing the isometric force was greater in adolescents when compared with adults, while the adults had a greater attenuation of the beta ERD. These results imply that alterations of frequency specific somatosensory cortical oscillations may partly underlie the altered motor performance characteristics seen in adolescents

An investigation of in-vivo neuroimaging in schizophrenia, using various modalities

Schizophrenia is a devastating mental illness and a huge disease burden in terms of cost. The individual is typically affected in early adulthood, thus loosing the best years of their life. The stigma of mental illness and pattern of downward social drift also results in families and society being adversely affected. With advances in neuroscience and neuroimaging, psychiatrists can advance their understanding of schizophrenia as a disease of the brain using biological models. This thesis investigates how volumetric magnetic resonance imaging (MRI), structural MRI techniques such as magnetisation transfer imaging (MTI), diffusion tensor imaging (DTI), and novel techniques such as optical coherence tomography (OCT) and visual function testing may be used to elucidate the neuropathology of schizophrenia in-vivo, in addition to explaining the cognitive deficits that are commonly observed. . The following studies are included in this thesis: 1) A diffusion tensor imaging (DTI) study to explore white matter abnormalities in first episode psychosis and correlations with cognitive performance. 2) An exploratory study utilizing OCT to investigate whether retinal nerve fibre layer thickness varies between patients with schizophrenia and healthy controls. 3) A longitudinal study using MRI and MTI to examine structural brain changes following first episode psychosis and correlating these findings with cognitive performance. 4) An investigation of chromatic vision in schizophrenia spectrum disorders and correlations between hue discrimination ability and cognitive performance. 5) A cross-sectional comparison study of grey matter volume and associations with oculomotor function in first episode patients and healthy controls