Neuroanatomical Dissections of Unilateral Visual Neglect Symptoms: ALE Meta-Analysis of Lesion-Symptom Mapping

Abstract

Unilateral visual neglect is commonly defined as impaired ability to attend to stimuli presented on the side of visual space contralateral to the brain lesion. However, behavioral analyses indicate that different neglect symptoms can dissociate. The neuroanatomy of the syndrome has been hotly debated. Some groups have argued that the syndrome is linked to posterior parietal cortex lesions, while others report damage within regions including the superior temporal gyrus, insula, and basal ganglia. Several recent neuroimaging studies provide evidence that heterogeneity in the behavioral symptoms of neglect can be matched by variations in the brain lesions, and that some of the discrepancies across earlier findings might have resulted from the use of different neuropsychological tests and/or varied measures within the same task for diagnosing neglect. In this paper, we review the evidence for dissociations between both the symptoms and the neural substrates of unilateral visual neglect, drawing on ALE (anatomic likelihood estimation) meta-analyses of lesion-symptom mapping studies. Specifically, we examine dissociations between neglect symptoms associated with impaired control of attention across space (in an egocentric frame of reference) and within objects (in an allocentric frame of reference). Results of ALE meta-analyses indicated that, while egocentric symptoms are associated with damage within perisylvian network (pre- and postcentral, supramarginal, and superior temporal gyri) and damage within sub-cortical structures, more posterior lesions including the angular, middle temporal, and middle occipital gyri are associated with allocentric symptoms. Furthermore, there was high concurrence in deficits associated with white matter lesions within long association (superior longitudinal, inferior fronto-occipital, and inferior longitudinal fasciculi) and projection (corona radiata and thalamic radiation) pathways, supporting a disconnection account of the syndrome. Using this evidence we argue that different forms of neglect link to both distinct and common patterns of gray and white matter lesions. The findings are discussed in terms of functional accounts of neglect and theoretical models based on computational studies of both normal and impaired attention functions.

Keywords: allocentric; egocentric; lesion-symptom mapping; spatial attention; unilateral neglect.

Figure 1

Examples of tests frequently used to diagnose heterogeneous symptoms associated with unilateral visual neglect, which can provide measure of deficits associated with impaired control of attention either (A–D) across space, i.e., egocentric frame of reference and/or (E–H) within objects, i.e., allocentric frame of reference (see Introduction for further details). Common cancelation tests: (A) star cancelation, (B) key cancelation, and (C) line crossing, all administered by asking patients to cross targets (small stars, keys, or lines respectively) evenly distributed on the centrally placed sheet of paper – deficits are measured by target omissions on either left or right side of space. (D) Clock drawing test that can be administered by either asking patients to place numbers on the face of the clock or asking patients to copy the fully drawn clock (the face of the clock or fully drawn clock are centrally presented on the sheet of paper). Gap detection tests: (E) Ota test and (F) Apples Cancelation, both administered by asking patients to cross only full targets (full circles or full apples respectively) evenly distributed on the centrally placed sheet of paper – deficits are measured by counting missing targets on either left or right side of space as well as false-positive responses, i.e., crossing objects with either left or right openings). (G) Line bisection test, which is administered by asking patients to mark middle of a series of horizontally presented lines – deficits are measured by deviation from the center of each line. (H) Scene copying task, which is administered by asking patients to copy multi-object scene consisting of several elements horizontally distributed on the centrally presented sheet of paper – deficits are measured by omissions of left or right sided elements of the scene as well as omissions of either left of right side of individual elements/objects).

Figure 2

Significant clusters identified in Analysis 1 (ALE meta-analysis, p < 0.05, FDR corrected for multiple comparisons, cluster size >200 mm³) – the convergence between results from different lesion-symptom mapping studies concerned with neuroanatomy of the unilateral visual neglect syndrome. The numbers denote indentified ALE clusters as listed in Table 2.

Figure 3

Significant clusters identified in Analyses 2, 3, 4, and 5 (ALE meta-analyses, p < 0.05, FDR corrected for multiple comparisons, cluster size >200 mm³). The concurrence in lesion sites associated with impaired control of attention either (A) across space, i.e., egocentric frame of reference (green; Analysis 2) or (B) within objects, i.e., allocentric frame of reference (blue; Analysis 3) including lesion sites associated with impaired performance on line bisection test. (C) Distribution of ALE clusters indentified in both analyses (Analysis 2 in green and Analysis 3 in blue). (D) The concurrence in lesions associated with either impaired performance on line bisection (red; Analysis 4) or impaired control of attention within objects, i.e., allocentric frame of reference as measured by various neglect diagnostic tests excluding line bisection (Analysis 5; blue). The numbers in (A,B,D) denote indentified ALE clusters as listed in Table 3.

Figure 4

Significant clusters within the white matter identified in Analyses 6, 7, and 8 (ALE meta-analysis, p < 0.05, FDR corrected for multiple comparisons, cluster size >200 mm³). (A) The convergence between results from different lesion-symptom mapping studies examining link between damage within white matter pathways and unilateral visual neglect syndrome (Analysis 6). (B) The concurrence in white matter lesions associated with impaired control of attention either across space, i.e., egocentric frame of reference (Analysis 7; green) or within objects, i.e., allocentric frame of reference (Analysis 8; blue). The numbers denote indentified ALE clusters as listed in Table 4.