Chronic Traumatic Encephalopathy (CTE) is a neurodegenerative disorder that is associated with repetitive head injury (RHI), which includes both traumatic and subclinical brain injuries. Early CTE is a tauopathy that has patchy distribution of hyperphosphorylated tau within the depths of sulci which progressively spreads. Recent studies of RHI show that deep areas of the brain are most affected during head impacts, with strain due to shearing forces peaking at deep brain regions on the midline. The anterior cingulate cortex (ACC), which is directly on the midline, is likely one of the first regions to be affected by shearing forces yet there have been few studies of the cellular irregularities in the ACC at early stages of CTE. The present study investigated the proportions of inhibitory to excitatory neurons in a midline ACC area, Area 25 (A25), in neurotypical and stage II CTE cases using immunohistochemistry and Nissl staining to investigate neuronal subpopulation densities. Inhibitory neuron subpopulations in the human cortex can be labeled by three calcium binding proteins: parvalbumin (PV), calbindin (CB), and calretinin (CR). CB and PV interneurons differentially inhibit excitatory neurons while CR neurons in the upper cortical layers inhibit other inhibitory neurons, resulting in a disinhibitory effect. The results showed that the density of CB neurons significantly decreased in stage II CTE. In addition, CR neuron density may also be reduced but results for PV neurons were inconclusive. The disruption of inhibitory neurons in A25 may be an early change and may contribute to the early clinical presentation of CTE. A25 of the ACC is known to be involved in affective disorders and specifically is overactive in major depressive disorder, which is also experienced by individuals in the early stages of CTE. / 2026-09-26T00:00:00Z

Diffusion tensor imaging (DTI) is a specialist MRI modality that can identify microstructural changes or abnormalities in the brain. It can also be used to show fibre tract pathways. Both of these features were used in this thesis. Firstly, standard imaging analysis techniques were used to study the effects of mild, repetitive closed head injury on a group of professional boxers. Such data is extremely rare, so the findings of regions of brain abnormalities in the boxers are important, adding to the body of knowledge about more severe traumatic brain injury. The author developed a novel multivariate analysis technique which was used on the same data. This new technique proved to be more sensitive than the standard univariate methods commonly used. An important part of diagnosing and monitoring brain damage involves the use of biomarkers. A novel investigation of whether diffusion parameters obtained from DTI data could serve as bio-markers of cognitive impairment in Parkinson's disease was conducted. This also involved developing a multivariate approach, which displayed increased sensitivity compared with any of the component parameters used singly, and suggested these diffusion measures could be robust bio-markers of cognitive impairment. Fibre tract connectivity between regions of the brain is also a potentially valuable measure for diagnosis and monitoring brain integrity. The feasibility of this was investigated in a multi-modal MRI study. Functional MRI (fMRI) identifies regions of activation associated with a particular task. DTI can then find the pathway of the fibre bundles connecting these regions. The feasibility of using regional connectivity to interrogate brain integrity was investigated using a single healthy volunteer. Fibre pathways between regions activated and deactivated by a working memory paradigm were determined. Though the results are only preliminary, they suggest that this line of research should be continued.

Diffusion tensor imaging (DTI) is a specialist MRI modality that can identify microstructural changes or abnormalities in the brain. It can also be used to show fibre tract pathways. Both of these features were used in this thesis. Firstly, standard imaging analysis techniques were used to study the effects of mild, repetitive closed head injury on a group of professional boxers. Such data is extremely rare, so the findings of regions of brain abnormalities in the boxers are important, adding to the body of knowledge about more severe traumatic brain injury. The author developed a novel multivariate analysis technique which was used on the same data. This new technique proved to be more sensitive than the standard univariate methods commonly used. An important part of diagnosing and monitoring brain damage involves the use of biomarkers. A novel investigation of whether diffusion parameters obtained from DTI data could serve as bio-markers of cognitive impairment in Parkinson's disease was conducted. This also involved developing a multivariate approach, which displayed increased sensitivity compared with any of the component parameters used singly, and suggested these diffusion measures could be robust bio-markers of cognitive impairment. Fibre tract connectivity between regions of the brain is also a potentially valuable measure for diagnosis and monitoring brain integrity. The feasibility of this was investigated in a multi-modal MRI study. Functional MRI (fMRI) identifies regions of activation associated with a particular task. DTI can then find the pathway of the fibre bundles connecting these regions. The feasibility of using regional connectivity to interrogate brain integrity was investigated using a single healthy volunteer. Fibre pathways between regions activated and deactivated by a working memory paradigm were determined. Though the results are only preliminary, they suggest that this line of research should be continued.

The study of high-contact sport athletes and the implications of repetitive head injury (RHI) associated with these sports has been at the forefront of traumatic brain injury (TBI) research for the last decade. The present study represents a quasi-experimental study exploring whether an experimental group (N=39) consisting of amateur and professional competitive mixed martial arts (MMA) athletes differ in three operations of executive functioning ability (shifting, updating and inhibition) when compared to a control group (N=44) of non-contact sports athletes. Participants completed a self-report measure of executive functioning ability as well as six computerized executive function (EF) tasks. The results from the study demonstrated no statistically significant differences between the experimental group and the control group on the performance of each executive functioning operation. A moderate negative correlation was found between the number of years competing and performance on shifting and updating in the experimental group. A moderate negative correlation between the number of reported competitive fights and all three EF operations within the experimental group was also reported. The results also showed a statistically significant difference in the beliefs of executive functioning abilities between the experimental group and the control group.  The experimental group reported a higher level of belief in poorer executive functioning ability than that of the control group. These findings provide evidence that while competing in MMA does have implications on executive functioning abilities, they are not in line with previous research done on other high-contact sports athletes. / Att studera hur utövare av fullkontaktsporter påverkas av upprepade huvudskador (RHI), associerat med utövandet av sporten, har varit ett fokusområde för forskningsfältet inom traumatiska huvudskador (TBI). Denna uppsats utgör en kvasi-experimentell studie som undersöker huruvida en experimentell grupp (N=39) bestående av amatörer och professionella ’mixed martial arts’ (MMA)- atleter skiljer sig i sin förmåga inom tre typer av exekutiva funktioner (skiftning, uppdatering och inhibition) jämfört med en kontrollgrupp (N=44) som inte utövar fullkontaktsport. Deltagarna fick först fylla i ett formulär där de skattade sin egen förmåga inom exekutiva funktioner, varpå de slutförde sex digitala test som gav ett mått på deras exekutiva funktioner. Studien påvisade ingen signifikant skillnad mellan de två grupperna för någon av de testade exekutiva förmågorna. Däremot fann studien en moderat negativ korrelation mellan antal år av tävlan och prestation på skifte och uppdatering, liksom en moderat negativ korrelation mellan antal tävlingstillfällen och de tre måtten på exekutiva funktioner, för den experimentella gruppen. Resultaten visade även en signifikant skillnad i självskattningen av exekutiv förmåga, mellan den experimentella gruppen och kontrollgruppen där experimentgruppen rapporterade sämre upplevda exekutiva förmågor, jämfört med kontrollgruppen. Dessa fynd indikerar att tävlan inom MMA har implikationer för exekutiva förmågor, även om de inte är i linje med tidigare forskning gjord på utövare av andra fullkontaktsporter.