Development of High Angular Resolution Diffusion Imaging Analysis Paradigms for the Investigation of Neuropathology

Diffusion weighted magnetic resonance imaging (DW-MRI), provides unique insight into the microstructure of neural white matter tissue, allowing researchers to more fully investigate white matter disorders. The abundance of clinical research projects incorporating DW-MRI into their acquisition protocols speaks to the value this information lends to the study of neurological disease. However, the most widespread DW-MRI technique, diffusion tensor imaging (DTI), possesses serious limitations which restrict its utility in regions of complex white matter. Fueled by advances in DW-MRI acquisition protocols and technologies, a group of exciting new DW-MRI models, developed to address these concerns, are now becoming available to clinical researchers. The emergence of these new imaging techniques, categorized as high angular resolution diffusion imaging (HARDI), has generated the need for sophisticated computational neuroanatomic techniques able to account for the high dimensionality and structure of HARDI data. The goal of this thesis is the development of such techniques utilizing prominent HARDI data models. Specifically, methodologies for spatial normalization, population atlas building and structural connectivity have been developed and validated. These methods form the core of a comprehensive analysis paradigm allowing the investigation of local white matter microarcitecture, as well as, systemic properties of neuronal connectivity. The application of this framework to the study of schizophrenia and the autism spectrum disorders demonstrate its sensitivity sublte differences in white matter organization, as well as, its applicability to large population DW-MRI studies

Physiological and psychological assessment of schizophrenia and affective disorders

The study examined data on the physiological and psychological changes which occur in schizophrenia and the affective disorders. The main physiological variable studied was the P3, a component of Event Related Potentials (ERPs), which has been hypothesized to reflect a manifestation of information processing involving the matching of incoming stimuli with the subject's cognitive set. Information processing deficits have also been implicated in schizophrenia and in the affective disorders.The specific aims were:a) to compare the P3 components of the ERPs in clinical groups (schizophrenia, bipolar depression and unipolar depression) and non - patient groups (normal controls and relatives of schizophrenic patients)b) to identify dysfunctional cognitive styles which correlate with abnormalities in P3 latency and amplitudec) to consider whether the cognitive and physiological abnormalities correlate with structural change measured by Magnetic Resonance Imaging (MRI) in the schizophrenic patientsd) to consider whether another physiological variable (Eye Tracking Dysfunction, ETD) which is also involved in information processing differentiates the groups and correlates with cognitive function and structural change.Three studies were conducted. In the first study, physiological responses (P3 and ETD) and psychological performance related to the formation and use of cognitive sets were identified in 24 schizophrenic, 10 bipolar manic, 10 bipolar depressed, 10 unipolar depressed and 24 control subjects. P3 latencies were found to be significantly different in the schizophrenic and bipolar groups compared with the control subjects. Deficits in cognitive function in these patient groups correlated significantly with increased P3 latencies, indicating that schizophrenic and bipolar subjects experience dysfunctions in cognitive set which are reflected in their physiological funtioning. Two sub -groups were identified in the schizophrenic population: one group showed a strong correlation between P3 latency and tests which are sensitive to frontal lobe function, and the other group showed a significant correlation between P3 latency and performance in verbal recall.In the second test, MRI measures of structural change were correlated with physiological and cognitive scores, to validate the specific deficits identified in the schizophrenic population. Thirty schizophrenic patients and thirty control subjects were assessed. The data indicated that the schizophrenic subjects who showed physiological abnormalities had frontal lobe or hippocampal impairment or both. A decline in IQ with illness was found in the sub -group which showed most frontal lobe impairment. The same psychological tests were applied to schizophrenic patients' relatives (n =30). Relatives with prolonged P3 latencies showed deficits in frontal lobe and hippocampal function which were similar to those found in the patients.The third study compared the P3 amplitude and latency of visual ERPs to emotive stimuli in 15 depressed, 15 recovered depressed and 15 control subjects. The physiological data were correlated with ratings of severity of depression, depressogenic attitudes and personality variables. Significant differences were found between the depressed and control subjects in the physiological and psychological data. A significant relationship between the physiological and psychological measures was established. The study supported cognitive theories of depression by showing a negative set in information processing.The results from the three studies supported the hypothesis that P3 abnormalities reflect dysfunctions in cognitive set

Neurobehavioural outcome in traumatic brain injury in relation to neuropsychological performance and computed tomography data

The present study sought to determine whether information attained from computed tomography (CT) imaging and neuropsychological evaluation can predict degree of apathy, disinhibition, and executive cognitive dysfunction at one to five years following mild complicated, moderate, or severe traumatic brain injury (TBI). Furthermore, it examined the level of concordance between reports made by individuals with TBI and informants regarding these domains of neurobehavioural disturbance in daily life. Results showed that CT data collected in the acute post-injury stage was not predictive of the degree of neurobehavioural disturbance reported by either TBI survivors or informants one to five years later. While concurrent performance on neuropsychological testing was not predictive of self-reported difficulties in daily life in any of the three domains of interest, performance was predictive of informant-reported executive cognitive dysfunction. Finally, informants reported higher levels of disturbance than did the survivors themselves, with the greatest discrepancy present for level of executive cognitive dysfunction

Electrocortical correlates of autism / by Stephanie Powers Whitmont.

A review of the autism literature identified basic concepts of disorder and main issues associated with the historical emergence of an organic approach to etiology. A critical review of the electrocortical studies in this literature revealed several problems, which collectively challenge the validity and reliability of many conclusions drawn about EEG variables in autism. Major problems were sample heterogeneity, motor artefacts, failure to control for cognitive ability, and confused interpretation of experimental outcome

A STUDY OF MINOR PHYSICAL ANOMALIES IN TWIN PAIRS AGE 5-12 YEARS: A PREDICTOR OF BEHAVIORAL VARIATION?

Minor physical anomalies (MPA) are defined as unusual morphological features found in less than 4% of the general population, but with no serious medical or cosmetic significance to the bearer. An increase in MPA has been associated with irritability in newborns, hyperactivity, and adult-onset schizophrenia and bipolar disorders. In our study, we wish to determine whether minor physical anomalies serve as a predictor for behavioral variation and whether certain regions of the body are more likely to manifest anomalies related to behavioral problems. To determine the combination of MPA most predictive of behavioral variation, we performed a meta-analysis of existing literature examining the relationship between schizophrenia and MPA. Additionally, we sought to determine the heritability of this trait in a twin design. Twin pairs were recruited from Twinsburg, Ohio during the 2005 annual Twin's Day Festival and from the Pittsburgh Registry of Infant Multiplets (PRIM). The only inclusion criterion was that twin pairs were between 5 and 12 years of age. The Stroop Task and the Continuous Performance test were administered to assess attention and impulsiveness in the twin pairs. A 15-20 minute assessment for minor physical anomalies using an expanded version of the standardized Waldrop Physical Anomaly Scale was performed by two investigators. We determined, via meta-analysis, the subset of MPA that is most predictive of schizophrenia. Using a twin design, we estimated the intraclass correlations and heritability of these MPA in a set of 50 twin pairs. We determined that MPA may not be useful as predictors for behavioral variations but may be more useful in specific psychotic populations, specifically schizophrenia. This study has implications for public health because research into the biological etiology of MPA could identify risk factors that would enable early detection and prevention of later psychosis

Is There Chronic Brain Damage in Retired NFL Players? Neuroradiology, Neuropsychology, and Neurology Examinations of 45 Retired Players

BACKGROUND: Neuropathology and surveys of retired National Football League (NFL) players suggest that chronic brain damage is a frequent result of a career in football. There is limited information on the neurological statuses of living retired players. This study aimed to fill the gap in knowledge by conducting in-depth neurological examinations of 30- to 60-year-old retired NFL players. HYPOTHESIS: In-depth neurological examinations of 30- to 60-year-old retired players are unlikely to detect objective clinical abnormalities in the majority of subjects. STUDY DESIGN: A day-long medical examination was conducted on 45 retired NFL players, including state-of-the-art magnetic resonance imaging (MRI; susceptibility weighted imaging [SWI], diffusion tensor imaging [DTI]), comprehensive neuropsychological and neurological examinations, interviews, blood tests, and APOE (apolipoprotein E) genotyping. LEVEL OF EVIDENCE: Level 3. METHODS: Participants\u27 histories focused on neurological and depression symptoms, exposure to football, and other factors that could affect brain function. The neurological examination included Mini-Mental State Examination (MMSE) evaluation of cognitive function and a comprehensive search for signs of dysarthria, pyramidal system dysfunction, extrapyramidal system dysfunction, and cerebellar dysfunction. The Beck Depression Inventory (BDI) and Patient Health Questionnaire (PHQ) measured depression. Neuropsychological tests included pen-and-paper and ImPACT evaluation of cognitive function. Anatomical examination SWI and DTI MRI searched for brain injuries. The results were statistically analyzed for associations with markers of exposure to football and related factors, such as body mass index (BMI), ethanol use, and APOE4 status. RESULTS: The retired players\u27 ages averaged 45.6 +/- 8.9 years (range, 30-60 years), and they had 6.8 +/- 3.2 years (maximum, 14 years) of NFL play. They reported 6.9 +/- 6.2 concussions (maximum, 25) in the NFL. The majority of retired players had normal clinical mental status and central nervous system (CNS) neurological examinations. Four players (9%) had microbleeds in brain parenchyma identified in SWI, and 3 (7%) had a large cavum septum pellucidum with brain atrophy. The number of concussions/dings was associated with abnormal results in SWI and DTI. Neuropsychological testing revealed isolated impairments in 11 players (24%), but none had dementia. Nine players (20%) endorsed symptoms of moderate or severe depression on the BDI and/or met criteria for depression on PHQ; however, none had dementia, dysarthria, parkinsonism, or cerebellar dysfunction. The number of football-related concussions was associated with isolated abnormalities on the clinical neurological examination, suggesting CNS dysfunction. The APOE4 allele was present in 38% of the players, a larger number than would be expected in the general male population (23%-26%). CONCLUSION: MRI lesions and neuropsychological impairments were found in some players; however, the majority of retired NFL players had no clinical signs of chronic brain damage. CLINICAL RELEVANCE: These results need to be reconciled with the prevailing view that a career in football frequently results in chronic brain damage

Neuroimaging - Clinical Applications

Modern neuroimaging tools allow unprecedented opportunities for understanding brain neuroanatomy and function in health and disease. Each available technique carries with it a particular balance of strengths and limitations, such that converging evidence based on multiple methods provides the most powerful approach for advancing our knowledge in the fields of clinical and cognitive neuroscience. The scope of this book is not to provide a comprehensive overview of methods and their clinical applications but to provide a "snapshot" of current approaches using well established and newly emerging techniques

UWOMJ Volume 7, No 4, 1937

Schulich School of Medicine & Dentistryhttps://ir.lib.uwo.ca/uwomj/1127/thumbnail.jp