Connectome-based lesion-symptom mapping (CLSM): A novel approach to map neurological function☆

Lesion-symptom mapping is a key tool in understanding the relationship between structure and function in neuroscience as it can provide objective evidence about which regions are crucial for a given process. Initial limitations with this approach were largely overcome by voxel-based lesion-symptom mapping (VLSM), a method introduced in the early 2000s, which allows for a whole-brain approach to study the association between damaged areas and behavioral impairment by applying an independent statistical test at every voxel. By doing so, this technique eliminated the need to predefine regions of interest or classify patients into groups based on arbitrary cutoff scores. VLSM has nonetheless its own limitations; chiefly, a bias towards recognizing cortical necrosis/gliosis but with poor sensitivity for detecting injury along long white matter tracts, thus ignoring cortical disconnection, which can per se lead to behavioral impairment. Here, we propose a complementary method that, instead, establishes a statistical relationship between the strength of connections between all brain regions of the brain (as defined by a standard brain atlas) and the array of behavioral performance seen in patients with brain injury: connectome-based lesion-symptom mapping (CLSM). Whole-brain CLSM therefore has the potential to identify key connections for behavior independently of a priori assumptions with applicability across a broad spectrum of neurological and psychiatric diseases. We propose that this approach can further our understanding of brain-structure relationships and is worth exploring in clinical and theoretical contexts.