Spatial attention and neglect: parietal, frontal and cingulate contributions to the mental representation and attentional targeting of salient extrapersonal events M.-Marsel Mesulam Cognitive Neurology and Alzheimer's Disease Center,The Northwestern Cognitive Brain Mapping Group, Departments of Neurology and Psychiatry and Behavioral Sciences, Northwestern University Medical School, 320 East Superior Street, 11-450 Chicago, IL 60611, USA ([email protected]) CONTENTS PAGE 1. Introduction 1326 2. The neuropsychology of neglect 1326 (a) Representational (perceptual) component of neglect: extinction, line bisection, covert shifts of attention 1326 (b) Motor-exploratory aspects of unilateral neglect: visual and tactile search 1328 (c) Motivational aspects of unilateral neglect 1329 (d) The gating in neglect is central not peripheral 1329 3. Determinants of neglect: the cost of being on the left 1330 (a) Egocentric coordinates 1330 (b) Allocentric factors and relative leftness 1330 (c) E¡ect of eye movements: the global and focal work-spaces 1330 (d) World- and object-based coordinates 1331 (e) Segmentation and conceptualization e¡ects 1331 (f ) Far-space versus near-space 1331 4. Right hemisphere dominance for spatial attention 1331 5. Functional anatomy of unilateral neglect 1333 (a) The parietal component of the attentional network 1333 (b) The temporo-occipito-parietal area, the superior temporal sulcus and the encoding of visual motion 1335 (c) The frontal connection in neglect 1336 (d) The limbic connection in neglect 1337 (e) Subcortical neglect 1337 6. Dissociations and subtypes: is there parietal versus frontal neglect 1338 7. A neural network for the distribution of spatial attention 1339 8. Overlap with other networks: eye movements, working memory and temporal expectation 1339 9. Overview and conclusions 1341 References 1341 The syndrome of contralesional neglect re£ects a lateralized disruption of spatial attention. In the human, the left hemisphere shifts attention predominantly in the contralateral hemispace and in a contraversive direction whereas the right hemisphere distributes attention more evenly, in both hemispaces and both directions. As a consequence of this asymmetry, severe contralesional neglect occurs almost exclusively after right hemisphere lesions. Patients with left neglect experience a loss of salience in the mental representation and conscious perception of the left side and display a reluctance to direct orientating and exploratory behaviours to the left. Neglect is distributed according to egocentric, allocentric, world-centred, and object-centred frames of reference. Neglected events can continue to exert an implicit in£uence on behaviour, indicating that the attentional ¢ltering occurs at the level of an inter- nalized representation rather than at the level of peripheral sensory input. The unilateral neglect syndrome is caused by a dysfunction of a large-scale neurocognitive network, the cortical epicentres of which are located in posterior parietal cortex, the frontal eye ¢elds, and the cingulate gyrus. This network coordinates all aspects of spatial attention, regardless of the modality of input or output. It helps Phil. Trans. R. Soc. Lond. B(1999)354,1325^1346 1325 & 1999 The Royal Society 1326 M.-M. Mesulam Spatial attention and neglect to compile a mental representation of extrapersonal events in terms of their motivational salience, and to generate `kinetic strategies' so that the attentional focus can shift from one target to another. Keywords: sensorimotor integration; limbic; cognition; neural networks so that the clinical examples below will be con¢ned to 1. INTRODUCTION patients with left neglect. When neglect is severe, the Nearly 25 centuries ago, Empedocles re£ected on the patient may behave almost as if one-half of the universe nature of God and likened it to `a circle of which the had abruptly ceased to exist in any meaningful form. centre is everywhere and the circumference nowhere'.The One patient may shave, groom, and dress only the right omnipresence that Empedocles envisaged would have side of the body; another may fail to eat food placed on engendered an all-encompassing awareness: nothing the left side of the tray; another may omit to read the would be ignored, nothing could be brought into sharper left half of each sentence or even the left side of every focus, all events would be registered in parallel, every- word printed anywhere on the page; still another may thing would have full access to instantaneous action, and fail to copy detail on the left side of a drawing and may the global would be identical to the focal. Anything short show a curious tendency to leave an uncommonly wide of such omnipresence creates the need for choosing which margin on the left side of the paper when asked to of many suitable mental or external events will have write. Even without speci¢c stimulation, some patients preferential access to the narrow portals of consciousness display a tonic rotation towards the right side of the and action. `Attention' is a generic term that can be used bed, as if responding to the irresistible magnetism of to designate the entire family of processes that mediate everything that is on the right. Hemianopia and gaze these choices. At the psychological level, attention implies paresis are neither necessary nor su¤cient for the a preferential allocation of the limited processing emergence of visual neglect (¢gure 2). Manual explora- resources and response channels to events that have tion of the left side is impaired even when the intact become behaviourally relevant. At the neural level, atten- right limb is used, indicating that hemiparesis is not an tion refers to reversible modulations in the selectivity, essential factor either. Neuropsychological tests help to intensity and duration of neuronal responses to such classify neglect behaviours into sensory-representational, events. motor-exploratory and limbic-motivational components No neuron is exclusively dedicated to attention, and (Mesulam 1985). Although, no test is absolutely speci¢c yet nearly every neuron displays some attentional for assessing a single component of neglect, each test modulation. Such modulations are least noticeable in emphasizes one component more than the others. primary sensory areas and become increasingly more prominent in downstream association, heteromodal and (a) Representational (perceptual) component of limbic cortices (Mesulam 1998). Conceptually, atten- neglect: extinction, line bisection, covert shifts of tional modulations can be divided into those that are attention domain-speci¢c and domain-independent. Visual neurons, Patients with unilateral neglect behave as if sensory for example, mediate domain-speci¢c attentional responses events within the left extrapersonal hemispace have lost to visual stimuli, face neurons to faces, posterior parietal their salience, especially when competing events are neurons to spatial targets, Wernicke's area to words, and concurrently occurring on the right side. This aspect of so on (Spitzer et al. 1988; McCarthy & Nobre 1993; Treue neglect can be probed with tests of extinction, line & Maunsell 1997; Wojciulik et al. 1998). Domain- bisection, and covert attentional shifts. Extinction is said independent modulations are exerted predominantly to exist when patients who respond accurately to uni- through the bottom-up in£uence of the ascending lateral stimulation from either the left or the right side, reticular activating system (ARAS) and the top-down consistently ignore the stimulation on the left under in£uence of the cerebral cortex, especially the frontal conditions of bilateral simultaneous stimulation. If lobes and the limbic system. Through the in£uence of extinction occurs in only one modality, it can conceivably these channels, domain-speci¢c modulations become re£ect a subtle disruption of relevant sensory pathways or responsive to variations in arousal levels, motivational even a callosal disconnection syndrome (Sparks & valence and cognitive state (¢gure 1). The domain- Geschwind 1968; Eidelberg & Schwartz 1971). Multi- independent attentional functions of the ARAS, frontal modal extinction, however, almost always re£ects the lobe, and limbic system have been discussed elsewhere representational aspect of neglect. Extinction can be (Mesulam 1998).This review focuses on a domain-speci¢c cross-modal. For example, contralesional tactile extinc- attentional system which directs attention to behaviour- tion in the hand may be elicited by ipsilesional visual ally relevant targets in the extrapersonal space. stimulation, especially if the visual stimulation is presented close to the hand (Di Pellegrino et al. 1997). In the traditional version of the line bisection task, 2. THE NEUROPSYCHOLOGY OF NEGLECT patients are asked to mark the midpoint of a horizontal The syndrome of contralesional neglect re£ects a line drawn on a sheet of paper. Neurologically intact severe disruption in spatial attention and is caused by subjects tend to place the bisection mark slightly left of lesions which damage the dorsal parieto-frontal streams the true centre. Patients with left hemineglect tend to of sensory processing. Severe contralesional neglect place their mark substantially rightward of centre, occurs almost exclusively after right hemisphere lesions suggesting that the representational impact of the left side Phil. Trans. R. Soc. Lond. B(1999) Spatial attention and neglect M.-M. Mesulam 1327 top-down modulation from prefrontal,