Symptomatology after damage to the angular gyrus through the lenses of modern lesion-symptom mapping

Brain-behavior relationships are complex. For instance, one might know a brain region's function(s) but still be unable to accurately predict deficit type or severity after damage to that region. Here, I discuss the case of damage to the angular gyrus (AG) that can cause left-right confusion, finger agnosia, attention deficit, and lexical agraphia, as well as impairment in sentence processing, episodic memory, number processing, and gesture imitation. Some of these symptoms are grouped under AG syndrome or Gerstmann's syndrome, though its exact underlying neuronal systems remain elusive. This review applies recent frameworks of brain-behavior modes and principles from modern lesion-symptom mapping to explain symptomatology after AG damage. It highlights four major issues for future studies: (1) functionally heterogeneous symptoms after AG damage need to be considered in terms of the degree of damage to (i) different subdivisions of the AG, (ii) different AG connectivity profiles that disconnect AG from distant regions, and (iii) lesion extent into neighboring regions damaged by the same infarct. (2) To explain why similar symptoms can also be observed after damage to other regions, AG damage needs to be studied in terms of the networks of regions that AG functions with, and other independent networks that might subsume the same functions. (3) To explain inter-patient variability on AG symptomatology, the degree of recovery-related brain reorganisation needs to account for time post-stroke, demographics, therapy input, and pre-stroke differences in functional anatomy. (4) A better integration of the results from lesion and functional neuroimaging investigations of AG function is required, with only the latter so far considering AG function in terms of a hub within the default mode network. Overall, this review discusses why it is so difficult to fully characterize the AG syndrome from lesion data, and how this might be addressed with modern lesion-symptom mapping.