Cerebellar tumors of childhood - impact on cognition and functional connectivity

The traditional teaching assumes the cerebellum to be a pure motor control organ. This view is based on the concept of a rigid brain organization in fixed eloquent areas. Recent advances in neuroscience have provided a new perception of the brain being organized as a complex large-scale, and dynamic global network. Early findings of neuroanatomic connectivity works that identified multiple fibers connecting the cerebellum with association areas of the cerebrum, as well as hodology and clinical data lead to the concept that the cerebellum effects specific network configurations, thereby influencing cognitive processing. Functional neuroimaging studies have catalyzed the understanding of the overall organization of the brain networks and the exploration of functional connectivity in the human brain. Functional connectivity, i.e. the level of functional communication, of large-scale functional systems is defined as the temporal dependence of neuronal activity patterns of anatomically separated brain regions and can be examined as the level of coactivation of functional MRI BOLD series measured during rest, called resting-state fMRI. Resting state fMRI has been used to map multiple brain systems linked to sensory, motor, and cognitive functions like primary visual network, auditory network, attention control network, memory network, executive control network and other higher-order cognitive networks. Recently, several studies on healthy subjects identified common cerebellar contributions to this previously identified connectivity networks involved in executive control, episodic memory/selfreflection, salience detection, and sensomotoric function. Furthermore, in neuropsyciatric disorders investigators elucidated a correlation between behavioural performance and emotional measures and functional connectivity results assed by rsfMRI. In children after cerebellar tumor surgery long term studies have identified distinct neuropsychological deficits reflecting the possible impairment in higher-order cognitive networks. In detail, they had statistically significant lower scores on verbal intelligence, sustained attention, speed, long-term visual-spatial memory, executive functioning and naming. These results fit with the data derived from rsfMRI analysis showing that the cerebellum is involved in cognition networks involved in executive control, episodic memory/selfreflection and salience detection. Our aim is to investigate the effect of cerebellar tumor surgery on the resting state functional connectivity level in the known higher order cognition networks and to correlate these results with the neuropsychological performance of the children. As children with brain tumors now have the potential for long term survival and neuropsychological testing has been increasingly incorporated into the standard of care, rsfMRI could serve as a novel adjunctive outcome measure.

The traditional teaching assumes the cerebellum to be a pure motor control organ. This view is based on the concept of a rigid brain organization into fixed areas. Recent advances in imaging and neuroscience have provided a new perception of the brain being organized as a complex large-scale, and dynamic global network with the cerebellum that contributes to cognition networks. Functional fMRI is a magnetic resonance imaging method that is able to visualize these networks and that can be used as an indirect measuring tool. The stronger the network connection, the better the underlying function and the more efficient the brain is working. A more direct way to measure the potential contribution of the cerebellum to cognition is the conduction of neuropsychological testing in patients with isolated cerebellar damage. In children after surgery for a tumor of the cerebellum distinct neuropsychological deficits have been described, but a correlation of this clinical testing and the indirect imaging method hasnt been performed yet. For these reasons our aim was to investigate the effect of surgery for tumors of the cerebellum on the functional brain networks and to correlate these results with the neuropsychological performance of the children. As children with brain tumors now have the potential for long-term survival and the neuropsychological outcome has become one of the main focuses in research, functional MRI could serve as a novel adjunctive outcome measure. Our study shows marked differences between the 13 patients and 16 healthy subjects after a median follow-up time of 15 years in the overall intelligence quotient and distinct neuropsychological measures related to working memory, attention and information processing speed. We succeeded in correlating this result with two different fMRI methods (task-based and resting state). This strongly supports the concept that the cerebellum, apart from being a motor control organ, has significant impact on cognition. The successful correlation may be the basis for the future effort to implement rsfMRI as a surrogate measure for cognitive outcome assessment in this patient population and neurooncolgy patients in general. This effort seems worthwhile; i) as fMRI has been established as a valuable surrogate marker in other conditions like Alzheimers disease, schizophrenia, depression and traumatic brain injury; ii) comprehensive neuropsychological assessments are a large financial and time related effort and differences in the applied neuropsychological methods make a direct comparison difficult. A next step would be to implement fMRI in the preoperative and postoperative imaging schedule to gain more insight into this promising imaging tool.