Neglect Syndrome


Short Description or Definition

The neglect syndrome (or more simply, neglect) is a fascinating and multifaceted neurological disorder. Patients with neglect act as if portions of their world do not exist. In addition to spatial neglect, they may appear unconcerned about their hemi-paresis and even deny ownership of a limb on the neglected side of their body. A widely cited operational definition states that persons with neglect fail to report, respond, or orient to external stimulation (or mental representations of sensory events) located contralateral to a brain lesion (i.e., contralesional) when the failure cannot be attributed to a primary sensory or motor deficit such as hemianopia or paralysis (Heilman, Watson, & Valenstein, 1985). Not surprisingly, neglect has and continues to inspire ideas about how humans perceive, attend, and respond to their world. Unfortunately, neglect is also an extremely debilitating disorder and a leading predictor of poor outcome following rehabilitation (Chatterjee & Mennemeier, 1998; Mark, 2003). While neglect is responsive to different types of pharmacological and behavioral interventions, no widely efficacious treatment for neglect currently exists (Pierce & Buxbaum, 2002). This chapter provides an overview of the neglect syndrome. The reader is referred to the Chapter Visual Neglect in this volume, for more information on assessment and the spatial dimensions of neglect. Several books on neglect are recommended for further readings (Karnath, Milner, & Vallar, 2002; Robertson & Halligan, 1999; Robertson & Marshall, 1993).


Neglect is a heterogeneous disorder with many variations, similar to the way that language disorders (i.e., aphasia) include many subtypes. Neglect is most commonly attributed to a disorder of spatial attention, but it involves other types of disorders as well, including deficits of intention, a disinclination to move in and toward neglected space; deficits in arousal, which limit the capacity of attention and sensory integration; deficits in spatial working memory that impair visual and manual search; and alterations of psychophysical processing that may explain how much of something is neglected (Chatterjee & Mennemeier, 1998; Heilman et al., 1985; Husain & Rorden, 2003; McIntosh & Milner, 2005). In general, neglect involves a combination of these disorders, and one disorder alone may be insufficient to cause a recognizable neglect syndrome. Lesions that cause neglect, such as cerebral infarction, are typically large and involve several cortical areas specialized for processing different types of information. Understanding and classifying one patient's neglect is further complicated by the fact that signs and symptoms of neglect may change over time (Hamilton, Coslett, Buxbaum, Whyte, & Ferraro, 2008).

Elements of the neglect syndrome include hemi-inattention, extinction to double simultaneous stimulation, hemiakinesia, allesthesia, and hemispatial neglect (Heilman et al., 1985). Hemi-inattention refers to a failure to report, respond, or orient to stimulation on the contralesional side of the body. An important feature of hemi-inattention is that it can be observed across multiple sensory modalities. Extinction to double simultaneous stimulation may have several causes including hemi-inattention. In this procedure, patients are asked first to report a touch, a visual stimulus, or a sound delivered unilaterally to each side of the body. Second, they are asked to report the same stimuli delivered either to one side of the body or simultaneously to both sides of the body. After confirming that a patient can detect unilateral stimulation on both sides of the body, failure to report stimulation delivered to one side of the body when both sides are stimulated simultaneously confirms extinction and may indicate hemi-inattention.

Hemiakinesia refers to failure or disinclination to use the contralesional limbs and even to extinguish movement with the contralesional limb when both sides of the body are tested for movement at the same time. Allesthesia refers to a misperception of which side of the body has been stimulated. Specifically, stimulation on the contralesional side of the body can evoke a response similar to stimulation on the ipsilesional side. For example, a patient may look for someone on the ipsilesional side when touched on the contralesional shoulder.

Hemispatial neglect denotes the consistency with which neglect occurs on one side of space as defined by the midline of the body. Hemispatial is not synonymous with the sensory hemifields. Rather, each cerebral hemisphere is presumed to direct attention and movement in contralateral hemispace independent of the sensory hemifields or of the extremity used to operate in hemispace. In other words, the hemispheres are organized hemispatially with regard to attention and intention. Although neglect typically occurs on the contralesional side of the body, it is important to recognize that patients can also exhibit ipsilesional neglect - neglect on the same side as their brain lesion - and even exhibit neglect for stimuli in the middle of a display. Ipsilesional neglect may be caused by biases in attention or intention occurring in response to brain lesions in specific areas (Kim et al., 1999). Alternatively, instructions and stimulus features can promote ipsilesional neglect. Ipsilesional neglect often occurs when attention is actively directed toward stimuli in contralesional space (Robertson & Marshall, 1993). Additionally, lines may be bisected on the contralesional or ipsilesional side of true center depending on their length (Mennemeier et al., 2005).

Neglect for external stimulation, such as that described above, has been called perceptual neglect; however, neglect also occurs for mental images of a visual scene or object (Bisiach & Luzzatti, 1978). This type of neglect is called representational neglect (Chapter on Visual Neglect for more detail). Perceptual and representational neglect may represent different processes or different levels of severity because they are dissociable (not everyone who has perceptual neglect also has representational neglect) and because representational neglect without perceptual neglect is relatively rare (Bartolomeo, D'Erme, & Gainotti, 1994; Coslett, 1997).

Associated features of neglect include performance deficits that are lateralized primarily to one side of space and deficits that cause behavioral impairment which is not necessarily worse on one side of the body (i.e., nonlateralized features of neglect) (Husain & Rorden, 2003). Lateralized and nonlateralized deficits are functionally different. They contribute to different aspects of neglect behavior and in combination they may exacerbate the overall picture of neglect. Nonlateralized deficits are not specific to neglect but they may be more pronounced in patients with neglect than in patients without neglect. Nonlateralized deficits appear to diminish a patient's prospects for functional recovery even when lateralized symptoms of neglect have resolved (see below). Examples of nonlateralized deficits in neglect include: (1) Delayed attentional blink, or an increase in the time required by the visual system to detect a new stimulus after it has attended to a previous stimulus. Delayed attentional blinks occur in patients with and without neglect following lesions of the inferior parietal and superior temporal cortex. (2) Poor sustained attention which can greatly exacerbate neglect on behavioral tasks. (3) Impairment of spatial working memory, which may explain the observation that some neglect patients repeatedly explore the same spatial locations during visual search tasks (McIntosh & Milner, 2005). Deficits in spatial working memory may interact with lateralized biases in spatial orientation to cause recursive searching of ipsilesional locations.

Whereas the vast majority of neglect research focuses on where neglect occurs in space, an equally interesting and important question concerns how much of a stimulus is neglected (Chatterjee & Mennemeier, 1998). Quantitative features of neglect are determined, in part, by the total amount of stimuli presented to a subject, such as the number of items on a cancellation test or the length of a line presented for bisection. This observation implies that neglect patients may initially process all of the information in a display but, when asked to report or act on the stimuli, they neglect a proportion based on the total amount presented to them (Chatterjee & Mennemeier, 1998). For example, one patient with left neglect after a right hemisphere stroke omitted targets on the left side of a cancellation test. When instructed to perform the same test in an alternating fashion, first canceling one target on the left and then one on the right, she neglected targets in the middle of the page (Chatterjee, Mennemeier, & Heilman, 1992b). Furthermore, the number of neglected targets was precisely predicted by the number of targets presented (Chatterjee, Mennemeier, & Heilman, 1992a). Similar observations have been made in neglect with regard to line bisection (Mennemeier et al., 2005) and reading tests (Chatterjee, 1995). These observations defy classical theories of neglect that were predicated solely on contralesional inattention. They indicate that how much of something is neglected may be due to a fundamental alteration of psychophysical processes relating objective measures and subjective estimates of stimulus intensity. Altered psychophysical function may be viewed as a nonlateralized deficit because it is not specific to neglect and operates independent of where neglect occurs in space (Mennemeier et al., 2005).


Neglects is usually a consequence of stroke, brain tumors, or head trauma and more commonly associated with damage to the right than left hemisphere (Chatterjee & Mennemeier, 1998) but neglect following left hemisphere injury is not uncommon. A study of 1,281 patients with acute stroke found signs of neglect in 43% of patients with right and 20% of patients with left hemisphere lesions (Ringman, Saver, Woolson, Clarke, & Adams, 2004). At 3 months neglect was still present in 17% of the patients with right and 5% of patients with left hemisphere lesions. Neglect follows damage to similar areas of the right and left hemispheres; however, aphasia can either mask or cause difficulty in assessing neglect in patients with left hemisphere injury. Additionally, the intact right hemisphere may compensate to some degree for left hemisphere damage, because the right hemisphere possesses a greater functional ability than the left to attend to both sides of the body and both sides of space. This situation leaves the left sides of the body and space relatively unattended following damage to the right hemisphere.

Natural History, Prognostic Factors, Outcomes

Supramodal cortex receives converging input from multiple unimodal and polymodal processing areas. Neglect is classically associated with cortical lesions to supramodal processing areas in the right cerebral hemisphere (Heilman, Watson, & Valenstein, 1994; Vallar & Perani, 1987). This association is consistent with the observation that neglect is not simply due to a sensory deficit and that it can affect processing across sensory modalities. Damage to the inferior parietal lobule is the characteristic lesion that causes neglect, although, it can also occur following isolated damage to the dorsolateral frontal and anterior cingulate cortices. More recently, the superior temporal cortex of the right hemisphere has been postulated to be a critical location for lesions resulting in neglect (Karnath, Ferber, & Himmelbach, 2001; McIntosh & Milner, 2005). This area undoubtedly contributes to neglect both in humans and in monkeys, but it's exact contribution may depend upon how neglect is assessed. For example, neglect on cancellation testing may be more likely following a lesion of the superior temporal cortex, whereas neglect on line bisection may be more likely when a lesion involves the inferior parietal lobe. Regardless, lesion studies have shown that neglect follows damage to a distributed cortical system. Subcortical lesions of the thalamus, basal ganglia, and midbrain also produce neglect and, in animals, lesions to the reticular formation are known to result in neglect. Involvement of these subcortical structures is consistent with the idea that neglect involves disorders of movement and arousal as well as attention.

Neglect is especially important to consider during rehabilitation, as it has been associated with impaired functional recovery more often than any other cognitive disorder (Mark, 2003). Neglect predicts poor rehabilitation outcome in terms of activities of daily living (Stone et al., 1991), and also increases a patient's risk for falls (Nyberg & Gustafson, 1997). A key contributor to the functional limitations associated with neglect is a decreased awareness of deficits and a lack of concern. Poor awareness places patients at risk because they may attempt unsafe activities for them such as getting out of bed. Decreased awareness also makes patients less able to protect themselves, such as failing to guard a paretic limb from injury. Diminished concern or frank indifference to a deficit diminishes a patient's motivation to improve their condition. Patients with lateralized symptoms of neglect at 6 months following stroke also showed nonlateralized deficits (Samuelsson, Hjelmquist, Jenson, Ekholm, & Blomstrand, 1998). Lateralized deficits are correlated with stroke volume and appear to resolve more quickly than nonlateralized deficits (Hier, Mondlock, & Caplan, 1983); however, persisting nonlateralized deficits may predict poor outcome even when lateralized signs of neglect have resolved (Farne et al., 2004; Kinsella & Ford, 1985; Linden, Samuelsson, Skoog, & Blomstrand, 2005; Robertson, 2001). One account suggests that neglect is fundamentally a disorder of nonlateralized attentional capacity (Robertson, 2001). Functional imbalances between the damaged and non-damaged hemispheres may initially promote the lateralized signs of neglect. These imbalances may resolve as the brain recovers. In contrast, fundamental decreases in attentional capacity may be less amenable to recovery or compensation by the remaining intact brain structure.

Neuropsychology and Psychology of the Neglect Syndrome

Neglect phenomenology is truly bizarre. Striking behavioral abnormalities that typically affect the side of the body or the surrounding space located contralateral to a brain injury can contrast sharply with preserved awareness for the opposite side (i.e., the ipsilesional side). For example, patients with neglect may fail to shave or apply makeup to the contralesional side of their face, or even fail to properly dress the contralesional half of their body (personal neglect). They may only eat from the ipsilesional side of their plate. A patient with neglect is often able to see objects within neglected regions of space when their attention is drawn there, but they may fail to notice the same objects either spontaneously or when other stimuli compete for attention. Neglect also alters mental images of the body and environment in addition to perception of external stimuli. Interestingly, neglect occurs when stimuli are processed at a conscious level of awareness. Patients with neglect are able to process stimuli implicity, at a level below conscious recognition, and this processing influences their behavior even if the patient denies awareness of such information. For example, neglect patients in one study were asked to make same/difference judgments about two pictures presented in contralesional and ipsilesional space (Volpe, Ledoux, & Gazzaniga, 1979). Their responses were accurate above a chance level of performance for the contralesional pictures even though the patients denied seeing them.

Neglect occurs in multiple perspectives, or frames of reference, and multiple axes of space (Chatterjee & Mennemeier, 1998). Neglect with regard to the viewer's eye, head, and body midline is referred to as egocentric neglect. Neglect for the intrinsic properties of objects is referred to as allocentric neglect. Neglect with reference to environmental landmarks and gravitational coordinates is referred to as environment-centered neglect. Whereas visual neglect is most commonly described along a horizontal axis of space, such as left neglect, it also occurs along a vertical axis, typically following bilateral lesions, and along an axis that radiates away from the viewer (i.e., radial neglect). The Chapter on Visual Neglect describes these dimensions in more detail.

Theories concerning neglect posit deficits in arousal, attention, motor-intention, and mental representation (Chatterjee & Mennemeier, 1998; Heilman et al., 1985). Arousal theories posit that the right hemisphere is dominant for arousal processes, and that deficits in arousal impair attention and the ability to integrate sensory information. Attentional theories postulate that left neglect following right hemisphere injury is due to either (1) an unfettered bias of the intact left hemisphere that directs attention toward the right, (2) an impairment of the right hemisphere's rather exclusive ability to direct attention to the left of the body midline, or (3) a selective impairment of disengaging attention from right-sided stimuli to allow shifting attention to the left following right parietal damage or dysfunction. Intentional theories explain hemiakinesia and motor extinction as a disinclination to initiate movements in or toward contralesional hemispace. Representational theories propose that left neglect is due to an inability to either form or attend to contralateral portions of mental representations. Each theory is validated by experimental evidence and each theory may be designed to explain different facets of the heterogeneous neglect syndrome.


Behavioral tests for neglect typically include line bisection, cancellation, drawing, and reading tests (Chatterjee & Mennemeier, 1998). Other assessments include tests for extinction (described below) and experimental tests such as chimeric faces, same/different judgments, midline pointing, saccade tasks, tests of reaction time to targets in space and many others (Robertson & Marshall, 1993). Commonly used behavioral tests are summarized briefly here. The section on Visual Neglect describes them in more detail. During line bisection, patients are simply asked to mark the center of lines typically measuring between 10 and 30 cm in length. Neglect is indicated by consistent deviations to the ipsilesional side of true center of at least 2% of the line's total length. On cancellation, patients are asked to mark out target stimuli distributed across a page (Figs. 1-3). Target omissions toward the contralesional side of the page indicate neglect. On drawing tasks, patients are asked either to make a spontaneous drawing or to copy a picture. Omitting details on the contralesional side of the page or crowding details from the contralesional side into the ipsilesional side indicates neglect. On reading tasks, patients with neglect either omit or confabulate portions of words, sentences, or paragraphs occupying a relative contralesional position. For example, they may read the word "cowboy" as "boy" or they may read only the ipsilesional half of a sentence or a paragraph.
Neglect Syndrome. Figure 1 Pronounced left neglect on a line cancellation test. Lines are cancelled only on the right side of the page. One line is cancelled twice which may indicate impairment in spatial working memory
Neglect Syndrome. Figure 2 Left neglect on a drawing test. The left-most side of the daisy is omitted
Neglect Syndrome. Figure 3 Left neglect on a clock drawing test (A). Even though the clock outline, hand and numbers are well draw, all of the numbers are crowded into the right side of the clock face. Figure 3B shows a less well drawn clock face but without evidence of neglect

Clinicians who treat neglect patients readily associate the disorder with other types of functional impairment (Mark, 2003). Whereas these disorders are not synonymous with neglect, they frequently accompany neglect and are part of the behavioral evaluation. Some of the more common functional impairments in the acute stage of illness include a strong gaze bias directed ipsilateral to brain injury that is associated with a disinclination to explore contralateral space either visually or manually; flattened affect (aprosodia); unawareness and indifference to deficit (anosognosia and anosodiaphoria, respectively); and disgust with or denial of ownership of a limb (somatoparaphrenia). Impairments in eating, dressing, grooming, and wheelchair navigation are also common.


Pharmacological treatments for neglect have attempted to increase arousal using bromocriptine, apomorphine, methylphenidate, amphetamine, and modafinil (Pierce & Buxbaum, 2002; Woods et al., 2006). These studies have invariably used open-label designs with small samples of subjects, and the results have been mixed (Pierce & Buxbaum, 2002). No pharmacological treatment has emerged as a standard of care in neglect. One behavioral study of neglect attempted to increase arousal using an auditory tone paired with a verbal command that instructed patients to attend just prior to the appearance of a stimulus in contralesional space (Robertson & Marshall, 1993). Patients were then trained to alert themselves sub-vocally. Whereas the training led to improvements in sustained attention and lateralized spatial neglect, generalization beyond treatment was not assessed.

Most behavioral studies have attempted to overcome lateralized deficits in neglect by using sensory stimulation or sensory deprivation (Chatterjee & Mennemeier, 1998; Pierce & Buxbaum, 2002). Activation of the contralesional hand or limb improves performance during walking, reading, and cancellation tests in patients with neglect. Irrigating the contralesional ear canal with cold water (cold caloric stimulation), which causes a vestibular-induced nystagmus, has a dramatic ameliorative effect on neglect lasting 5-10 min. Similarly, inducing nystagmus by moving a striped pattern in front of the subject's eyes (optokinetic stimulation) tends to decrease neglect during stimulation. Strong vibrations of the neck muscles on the contralesional side of the body can improve contralesional target detection in some patients with neglect. Rotating the trunk into contralesional space improved reaction time to detect contralesional targets. Several treatment studies have attempted to improve contralesional orientation and attention with some success by stimulating the ipsilesional superior colliculus with flashes of light delivered to the contralesional eye. Other studies achieved the same behavioral results by patching the ipsilesional eye in order to suppress stimulation of the contralesional superior colliculus. Both strategies achieved short term benefits, but these gains often fail to generalize to other tasks and experimental settings.

Finally, prism lenses that displace the visual field toward the right have been used to treat neglect. Prisms initially cause subjects to misreach for objects toward the right, but eventually subjects learn to correct the reach trajectory following a period of training known as prism adaptation. Twenty-minute sessions of prism adaptation delivered twice per day for 2 weeks led to improved performance in patients with neglect. Improvement lasted for up to 17 weeks. Follow-up studies indicate that prism adaptation may facilitate recovery after treatment ends and that gains may generalize to other activities of daily living.

Cross References

References and Readings

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