Cognitive deficits in brain tumor patients: A functional MRI perspective

Abstract

Cognitive deficits frequently occur in brain tumor patients, regardless of tumor type or location, and have a significant impact on their quality of life. To date, unfortunately, the underlying cause of these overarching cognitive deficits still remains largely unknown. In this dissertation we are therefore specifically interested in what brain mechanism causes these overarching cognitive impairments that cannot be pinpointed to dysfunction of a specific affected brain region. Therefore, we focused on this problem from a functional MRI perspective and we investigated the cognitive impairments of brain tumor patients from a more global (or network) view. In doing so, we focused on two important networks that are associated with cognitive performance, being: central executive network (CEN) and default mode network (DMN). When healthy individuals perform a cognitive task, these networks either increase (CEN) or decrease (DMN) their brain activity compared to a situation where no task is performed. We investigated cognitive brain activity in healthy individuals to get more insight into the representation of cognition, using an alertness task and a verbal working memory task. Subsequently, we developed a working memory task that was suitable for brain tumor patients. By comparing preoperative brain activity of glioma and meningioma patients to brain activity of healthy controls, we found normal CEN activity in patients, while DMN inhibition was reduced during cognitive task performance compared to healthy individuals. These results indicate that the DMN plays an important role in cognitive deficits in brain tumor patients. While CEN activity is typically associated with task execution, activity in the DMN has been associated with processes that are performed during rest. Deactivation of the DMN is therefore a normal neurophysiological process and is considered to be a necessary inhibition of brain processes that may otherwise interfere with cognitive task performance. When patients have a pathologically reduced capacity to inhibit the DMN, it may be harder to achieve the brain state that is necessary for normal cognitive performance. Considering the normal CEN activity found in the patients, cognitive deficits appear not to be related to deficits in brain regions associated with task execution, but rather to a reduced ability to adapt the state of the brain for optimal cognitive function. Another important factor that can cause decline in cognitive performance is age. In this dissertation, we show that the influence of age on cognitive brain activity is different in meningioma patients than in healthy controls. Meningioma patients, in fact, show a stronger deterioration in the ability to normally deactivate the DMN. This dissertation provides insight into the underlying mechanism of cognitive deficits in brain tumor patients and shows that fMRI can be of added value for more comprehensive cognitive evaluation of these patients. Additionally, this dissertation provides more insight into the effect of surgery in meningioma patients and indicates that surgery may not necessarily cause additional changes in brain activity in the first three months after surgery. The gained insights contribute to further improvement of patient counseling and the optimization of expectation management and clinical decision making.