Based on electrophysiological data from nonhuman primates and other species, models of visual attention predict that, in humans, the midbrain superior colliculus (SC) represents the last downstream structure of a large fronto-subcortical attentional network.1 This view is partly supported by human case studies showing that visuospatial inattention, often referred to as visual neglect, can occur after extensive brain lesions affecting, among others, the SC.1 Here, we show the rare case of a patient with a small lesion solely confined to the SC, confirming the models’ prediction and demonstrating that, in humans, an isolated SC lesion may result in contralesional visual neglect.
The SC receives retinal input predominantly from the contralateral visual hemifield, striate cortex, prefrontal cortex, frontal eye field, and parietal cortex.1 It processes visual input and controls the orientation of head and eye movements in response to visual stimuli. Experiments in animals have shown that the SC is also implicated in attentional mechanisms. For instance, inactivation of the SC in monkeys or cats results in neglect-like signs to targets presented in the contralateral visual field.1 However, a review of the PubMed database revealed that, to date, no direct evidence exists to show that an isolated lesion of the SC produces contralateral visual neglect in humans.
A woman in her 40s presented with a small abscess confined to the right SC (Figure 1).2 She was otherwise healthy. Because the data measured were part of a routine clinical examination and not a study, institutional board review approval did not apply. The patient gave explicit written consent for the use of her clinical data for research purposes and publication. The data of the 15 healthy control individuals were acquired as part of another study on free visual exploration, which was approved by the Ethics Committee Nordwest and Zentralschweiz, Switzerland.
The unilateral involvement of the SC enabled us to observe an asymmetry in visual attention deployment, directly demonstrating the role of this structure in the latter. Our experimental protocol used a free visual exploration paradigm,3 quantifying visual attention deployment in the left and right hemispace by means of the horizontal distribution of visual fixations. We predicted that the mean number of fixations and the cumulative fixation duration would be decreased within the left contralesional and increased within the right ipsilesional hemispace. In addition, as previous data showed an ipsilesional bias in early attentional orientation in neglect,3 we also tested the hypothesis that the first saccade would be less frequently directed toward the contralesional left hemispace. 2-sided P values were statistically significant at P < .05. Analyses were done using Singlims.4
Three months after diagnosis and medical treatment, the analysis of the free visual exploration behavior revealed a mean gaze position of 2.143° visual angle, above the cutoff of 1.333°, indicating neglect.3 Statistical analyses4 (Figure 2), comparing the patient’s oculomotor data against those derived from 15 age- and sex-matched healthy controls (HC), confirmed our hypothesis of a leftward neglect, with significantly fewer fixations (patient: 5.208; HC: mean [SD], 10.858 [1.422]; t = −3.848; P = .002) and lower cumulative fixation duration (patient: 1512 milliseconds; HC: mean [SD], 2815  milliseconds; t = −6.450; P < .001) within the left contralesional hemispace, and significantly more fixations (patient: 14.125; HC: mean [SD], 11.223 [1.265]; t = 2.222; P = .04) and higher cumulative fixation duration (patient: 4114 milliseconds; HC: mean [SD], 2982  milliseconds; t = 3.573; P = .003) within the right ipsilesional hemispace. Also, the patient’s first saccade was significantly less often directed toward the contralesional left hemispace (patient: 8.333%; HC: mean [SD], 61.677% [22.426%]; t = −2.304; P = .04). No difference was found in mean fixation duration (patient: left, 290 milliseconds and right, 291 milliseconds; HC: mean [SD], left, 263  milliseconds; t = 0.765; P = .46 and right, 268  milliseconds; t = 0.641; P = .53). A follow-up measurement, performed 9 months after diagnosis, showed an improvement of neglect in terms of mean gaze position (0.978°), but the persistence of pathological findings in other parameters (cumulative fixation duration: left, 2151 milliseconds; t = −3.288; P = .005; right, 3743 milliseconds; t = 2.401; P = .03; early orientation left, 8.333%; t = −2.304; P = .04).
The investigation of this rare case provides direct evidence for the role of the SC in directing visual attention and the eyes toward the contralateral hemispace, supporting the view that, in humans, the SC is not merely a node in the descending visual attention pathway, but is in fact a crucial neural substrate of visual attention control itself. Furthermore, the fact that this patient still had evidence of neglect after months is consistent with the view that monkeys have a more developed subcortical visual pathway than humans.5
Corresponding Author: Thomas Nyffeler, MD, Gerontechnology and Rehabilitation Group, ARTORG Center for biomedical engineering research, University of Bern, Murtenstrasse 50, Bern 3008, Switzerland (firstname.lastname@example.org).
Accepted for Publication: August 27, 2021.
Published Online: October 25, 2021. doi:10.1001/jamaneurol.2021.3863
Author Contributions: Drs Kaufman and Cazzoli had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: All authors.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: All authors.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Kaufmann, Cazzoli.
Obtained funding: Nyffeler, Cazzoli.
Administrative, technical, or material support: Cazzoli.
Supervision: Nyffeler, Cazzoli.
Conflict of Interest Disclosures: Drs Nyffeler, Kaufmann, and Cazzoli report grants from the Swiss National Science Foundation (grant 320030_169789 to Dr Nyffeler, P2BEP3_195283 to Dr Kaufmann, and Z00P3_154714/1 to Dr Cazzoli).
Additional Contributions: We thank the patient for granting permission to publish this information and the editor and the reviewers for their helpful comments.