Changes in neural activity in major depressive disorder following a traumatic brain injury

2017-02-28T02:55:53Z (GMT) by Bailey, Neil
Rates of major depressive disorder (MDD) are significantly higher following a traumatic brain injury (TBI) than in the general population. Major Depression following a TBI (TBI-MDD) results in significant personal suffering, and poorer recovery outcomes. Although there are a number of psychosocial factors that can contribute to the development of TBI-MDD, evidence suggests that neural changes are also involved. However, very little research has directly examined changes in brain function in TBI-MDD. Understanding the composition and mechanisms of such changes may lead to methods to identify, treat, and possibly even prevent TBI-MDD. This thesis constitutes the first comprehensive exploration of neural changes associated with TBI-MDD. There are a number of areas of cognition which are impacted by both TBI and MDD; these changes are considered integral to both the sequalae of TBI and the development/maintenance of MDD. These cognitive changes are associated with changes in neural activity and as such are an ideal target for investigation of neural changes associated with TBI-MDD. In this thesis a series of studies were undertaken comparing electroencephalographic (EEG) measures of neural activity underlying a number of relevant cognitive processes across four different groups: a TBI group, an MDD group, an MDD following TBI group (TBI-MDD), and a healthy control group. The comparisons of neural activity between groups allowed characterisation of which processes were affected by TBI and MDD, and how this was modulated by the combination of both. Comparisons also permitted inferences to be drawn with regard to which affliction may be responsible for the lingering symptoms experienced by those with TBI-MDD. The between group differences also provided indirect evidence about the aetiology of TBI-MDD. In order to control for the heterogeneity that focal lesions would introduce to neural activity measures, only individuals with closed injuries of mild to moderate TBI severity were included. The four different groups were compared across response inhibition event related EEG potentials, and error related processes. Band activity and connectivity was also measured during working memory and at rest in these groups. The results revealed a reduction in neural activity in the MDD and TBI-MDD groups during response inhibition, error processing, and working memory. The TBI only group did not differ from healthy controls on these measures. The results also suggested that individuals with TBI-MDD show a maladaptive increase in inter-hemispheric connectivity during working memory, a finding specific to TBI-MDD. This pattern of results suggests that it is the occurrence of MDD more than the TBI that is responsible for the lingering cognitive symptoms that individuals with TBI-MDD experience. The lack of differences between individuals with TBI only and healthy controls also suggests that in the absence of MDD, full recovery might be the expected outcome in the majority of mild to moderate TBIs. Lastly, in combination with previous literature, the results provide evidence of potential causal mechanisms leading to TBI-MDD, involving aberrant functional connectivity.