The impact of etiology in lesion-symptom mapping - A direct comparison between tumor and stroke.

INTRODUCTION: Lesion-symptom mapping is a key tool in understanding the relationship between brain structures and behavior. However, the behavioral consequences of lesions from different etiologies may vary because of how they affect brain tissue and how they are distributed. The inclusion of different etiologies would increase the statistical power but has been critically debated. Meanwhile, findings from lesion studies are a valuable resource for clinicians and used across different etiologies. Therefore, the main objective of the present study was to directly compare lesion-symptom maps for memory and language functions from two populations, a tumor versus a stroke population. METHODS: Data from two different studies were combined. Both the brain tumor (N = 196) and stroke (N = 147) patient populations underwent neuropsychological testing and an MRI, pre-operatively for the tumor population and within three months after stroke. For this study, we selected two internationally widely used standardized cognitive tasks, the Rey Auditory Verbal Learning Test and the Verbal Fluency Test. We used a state-of-the-art machine learning-based, multivariate voxel-wise approach to produce lesion-symptom maps for these cognitive tasks for both populations separately and combined. RESULTS: Our lesion-symptom mapping results for the separate patient populations largely followed the expected neuroanatomical pattern based on previous literature. Substantial differences in lesion distribution hindered direct comparison. Still, in brain areas with adequate coverage in both groups, considerable LSM differences between the two populations were present for both memory and fluency tasks. Post-hoc analyses of these locations confirmed that the cognitive consequences of focal brain damage varied between etiologies. CONCLUSION: The differences in the lesion-symptom maps between the stroke and tumor population could partly be explained by differences in lesion volume and topography. Despite these methodological limitations, both the lesion-symptom mapping results and the post-hoc analyses confirmed that etiology matters when investigating the cognitive consequences of lesions with lesion-symptom mapping. Therefore, caution is advised with generalizing lesion-symptom results across etiologies.

Cortical and subcortical contributions to saccade latency in the human brain.

An important property of our motor system is the ability to either perform or inhibit an automatic goal-directed reaction. Imagine, for example, how easily we can catch a ball, while at the same time we would never grasp a stinging insect approaching us. The oculomotor system provides a good model to study this ability. Monkey midbrain superior colliculus neurons are responsible for automatic visually evoked saccades, whereas the frontal eye fields can prevent reflexive glances. Little is known about human superior colliculus or the competition between the midbrain and frontal areas controlling saccades. In the present functional magnetic resonance study we used the gap paradigm, where a stimulus fixated with the eyes is removed 200 ms prior to saccade target onset. Subjects were required to either look at the target or prevent an eye movement. From what is known from non-human primate neurophysiology, it is expected that the gap will result in enlarged neuronal activity in the human superior colliculus, disinhibiting the oculomotor system and enhancing automatic reactions. Importantly, we demonstrate that the human superior colliculus homologue is indeed activated by the removal of a fixation target, in either task. The frontal eye fields show a reverse pattern when saccades were suppressed. Furthermore, magnitude of responses in the superior colliculus correlated negatively with saccade latency, and in the frontal eye fields positively. These findings confirm for the first time that the human superior colliculus generates automatic goal-directed saccades, whereas the frontal eye fields can exert volitional control over automatic orienting.