Imaging and lesion studies have led to valuable insights into the functional anatomy of the brain, and localization principles are vital to the clinical neurologist. As outlined in the introduction, however, localization-based perspectives often fail to explain the complex interrelationship between neurodegenerative pathology and clinical symptoms. Even ‘focal’ lesions like stroke (e.g. ‘strategic’ infarction), brain tumour or traumatic brain injury can cause widespread disturbance of functional connectivity and unexpected cognitive symptoms that can be explained by a variety of lesion locations.45-47 There is also increasing evidence that local damage can change the overall network structure in a way that can lead to pathological hypersynchronization and epilepsy.48 In an elegant simulation study,49 the effect of focal brain lesions on the patterns of functional connectivity was investigated by simulating lesions at different brain locations. The study showed that focal lesions located in the precuneus, medial anterior cingulate cortex, temporo-parietal junction, or superior frontal cortex produced widespread and pronounced changes in functional connectivity with intra-hemispheric and contralateral regions. Conversely, lesions to the visual or motor cortex had limited effects on global connectivity.49 Neurodegenerative
