Lesion-symptom mapping (LSM) is an increasingly utilized method in the VCI research field. The concept of LSM is that it examines relationships between the location of brain injury – usually at the level of individual voxels or regions of interest – and behavioral measures such as cognition. This is commonly done through statistical comparisons of patients with and without a lesion for individual voxels, or by associating regional lesion volumes with cognition. LSM studies have identified strategic lesion locations for acute infarcts and small vessel disease.
A growing number of scientific publications and lesion analysis methods have emerged over the past decades. Yet, most LSM studies are hampered by incomplete lesion coverage of the brain. This is important, because the cognitive impact of damage to a particular brain region can only be addressed in the statistical analyses if this region is damaged in a sufficient number of patients. Because vascular lesions are not distributed randomly across the brain, some regions are commonly affected, but others that may be relevant for cognition – such as the orbitofrontal lobes in anterior cerebral artery territory infarction – are rarely affected. As a consequence, previous studies found that even with several hundred subjects, large regions of the brain were not affected by vascular lesions and could therefore not be considered in LSM analyses. Thus it remains difficult to obtain a comprehensive picture of strategic lesion locations for cognitive dysfunction.