Hemispatial neglect, balance and eye-movement control Paresh Malhotra, Elizabeth Coulthard and Masud Husain Purpose of review Introduction Disorders of spatial awareness and balance following The neglect syndrome is a common disorder following stroke are common but often under-diagnosed. They lead to stroke, particularly prominent and severe after right- poor outcome and frequently coexist. Here we focus on hemisphere lesions. Patients with hemispatial neglect recent progress in the understanding of the mechanisms often fail to be aware of or acknowledge objects or people underlying these disorders and potential therapeutic on their contralesional side (the left side for patients with advances. right brain damage), attending instead to ipsilesional Recent findings items (the right side for right-hemisphere stroke Right-hemisphere networks are important for both spatial patients). Many such patients have intact visual fields attention and postural awareness. Neglect patients show and can initiate eye or limb movements contralesionally. multiple oculomotor impairments including reduced But despite this they appear selectively to attend to items saccade amplitude and difficulty retaining spatial locations on their ipsilesional side. across saccades. There has been controversy regarding the brain regions associated with neglect, although most From a clinical perspective hemispatial neglect repre- studies show the right inferior parietal lobe to be crucial and sents an important disorder because enduring neglect is new imaging modalities have provided insight into neglect associated with a poor functional outcome following caused by subcortical stroke. The ‘pusher syndrome’ is a stroke [1]. In addition to its clinical importance, neglect poorly understood balance disorder where patients push has also attracted a great deal of interest because of the towards their paretic side, resulting in falls. It may involve insights it provides into the brain networks that underlie impairment of subjective verticality but experimental studies spatial awareness and cognition [2,3], as well as non- have reported diverse findings. Advances in treatment for spatial functions such as the ability to sustain vigilant neglect include the successful use of prism adaptation and attention [4]. Here we review recent studies that have pilot data suggesting noradrenergic stimulation may begun to investigate the relationship and impact of the improve search in selected patients. cognitive deficits in neglect with eye movement and Summary balance control in these patients. In addition, we consider New experimental techniques have provided insight into the recent controversies regarding the anatomical basis of the debilitating disorders of spatial and postural awareness that neglect syndrome, the relationship of these findings to often follow stroke. There are currently no widely used current knowledge about the cortical control of balance therapies for neglect but both new behavioural techniques and eye movements, the clinical impact of neglect on and pharmacological methods are promising. patients and novel treatments for the disorder. More general recent reviews of neglect are also available for Keywords the interested reader [5–8]. parietal lobe, pusher syndrome, stroke, unilateral neglect, vestibular Eye-movement studies Oculomotor studies in neglect have tended to concen- Curr Opin Neurol 19:14–20. ß 2006 Lippincott Williams & Wilkins. trate on lateralized saccadic impairments, but more Institute of Cognitive Neuroscience, UCL, Queen Square, London WC1N 3AR, UK recently there has been interest in a failure to update and Imperial College, Division of Neuroscience, Charing Cross Hospital, London W6 8RF, UK representations of space across saccades, leading to recur- Correspondence to Paresh Malhotra, Institute of Cognitive Neuroscience, UCL, sive search in patients with neglect. Queen Square, London WC1N 3AR, UK Tel: +44 (0)207 679 5499; fax: +44 (0)207 916 8517; e-mail: [email protected] Contralesional saccades in neglect Current Opinion in Neurology 2006, 19:14–20 Patients with hemispatial neglect often spontaneously Abbreviations fail to explore contralesional space in everyday life, confining their eye movements instead to their ipsi- IPL inferior parietal lobe IPS intraparietal sulcus lesional side. It is vital to understand though that the SPV subjective postural verticality demarcation between the neglected and the non- STG superior temporal gyrus SVV subjective visual verticality neglected ‘field’ of vision need not be neatly through TPJ temporoparietal junction the vertical meridian of the visual field, or the midline of the search display (see Fig. 1). The degree of neglect, as ß 2006 Lippincott Williams & Wilkins 1350-7540 assessed for example by fixation patterns [9], varies 14 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Hemispatial neglect, eye movements and balance Malhotra et al. 15 Figure 1 Eye-movement scan path of a right-hemisphere patient stimuli [17]. The authors argued that paying attention to with neglect searching for letter Ts embedded among distractor an item at central fixation leads to shrinkage of the letter Ls effective visual field, worse to the contralesional side. Thus when searching a display with high attentional demands, right-hemisphere patients with neglect may have a constricted effective field of vision, accounting for the generally small-amplitude saccades they make. Saccade amplitudes to the left may be particularly reduced under some circumstances, as demonstrated by Niemeier and Karnath [18]. These researchers used two interesting variants of a visual search paradigm on right-hemisphere patients with and without neglect. In the first task subjects freely searched for the letter A in a random array of letters. The subjects’ scan paths when performing this task were recorded and used to generate the second ‘replay’ condition. In this second task, partici- pants viewed the same display but had to follow a red Black dots show fixations and white lines denote saccades. Note that neglect of the left side of the array is not strictly down the vertical square, which took exactly the same path as the fixations meridian of the display. In this case the patient found some Ts well to the made by subjects in the previous task, thus replaying it. left of centre in the upper part of the screen. The figure also vividly In the first (free search) condition, neglect patients illustrates how such patients with neglect often refixate locations they have already searched on the right, at the expense of exploring the left of tended to search on the right side of array and ignore the array. Such recursive ipsilesional search may, in some patients, be the left, but there was no major discrepancy between due to a failure to keep track of spatial locations that have already been leftward and rightward saccade amplitude or frequency. explored (from [10]). However, in the replay task, saccades were of reduced amplitude, particularly when leftward, despite the pre- between patients, and even within the same patient scribed eye movements being identical to the first task. depending upon the task and stimulus characteristics This finding suggests the contralesional saccadic deficit [10]. Thus a greater degree of contralesional neglect in neglect may be most prominent for stimulus-driven or is often found when patients are asked to search a dense, reflexive saccades (replay task) than for volitional move- cluttered visual scene compared to a non-cluttered one ments (free search condition). [10]. Moreover, there is often a gradient of neglect, such that the probability of finding a target in contralesional Spatial working memory and saccadic control space falls off gradually with distance, rather than When searching a visual scene, neglect patients not only patients demonstrating an abrupt failure to detect targets fail to explore contralesional space, they often keep at the midline [9,10]. Even in the dark, the resting refixating items on their ipsilesional side [9] (for example, position of gaze of right-hemisphere patients with neglect see Fig. 1). Many of these refixations are associated with a is far to the right of the midline [11]. failure to keep track of spatial locations across saccades, with patients revisiting locations they have previously When asked to shift their gaze contralesionally, neglect visited, unaware that they have looked there before patients demonstrate a variety of impairments, often [10,16,19]. Mannan and colleagues [10] monitored being slower to initiate saccades in that direction or eye movements while patients searched for target letter making small, multistep saccades [12–14]. When search- Ts among distractors. Subjects were asked to click a ing a visual scene, they do not necessarily make fewer response button to indicate whenever they identified a saccades in the contralesional direction [15,16], but their new target T (one they had not previously found). Right- eye movements are generally of small amplitude [15]. hemisphere neglect patients with lesions involving either This behaviour may be related to constriction of the the intraparietal sulcus (IPS) or the inferior frontal gyrus ‘effective field of vision’ when searching a dense array frequently misjudged targets on the right as new when for small targets among distractors. A recent study of they had in fact fixated and clicked on them before. In right-hemisphere-lesioned patients who had recovered neglect patients