Contralateral Neglect Research Articles

Large Subcortical Hemispheric Infarctions

A specific form of large subcortical hemispheric infarction on computed tomography was identified in 24 of 2198 (1%) stroke registry patients. Combined with 13 cases from earlier literature reports, a characteristic neurologic picture developed. Severe face plus arm plus leg weakness at onset (76%), corticallike features of aphasia and/or contralateral neglect (68%), and premonitory transient ischemic attacks (24%) were frequent. Twenty-two patients (59%) had large vessel arterial occlusive disease. Eight patients (22%) had primary embolic occlusion in the middle cerebral artery territory. During an average follow-up of 16 months, five patients (14%) suffered recurrent stroke or death. The clinical presentation and prognostic features of this distinct stroke subtype are described.

Small lateral suprasylvian cortex lesions produce visual neglect and decreased visual activity in the superior colliculus.

Previous experiments in cats have shown that complete contralateral visual neglect is produced by removing all known visual cortex on one side of the brain, which can then be reversed by damaging the opposite superior colliculus. Presumably, descending facilitatory influences from the visual cortex to the ipsilateral superior colliculus are counterbalanced by intercollicular inhibition (Sprague: Science 153:1544-1546, '66). However, not all of visual cortex or all of the superior colliculus needs to be involved in this circuit. It is the deep rather than the superficial laminae of the superior colliculus that are primarily involved in visual attentive and orientation behaviors, and these laminae are largely independent of primary visual cortex. However, they do depend on corticotectal influences from a comparatively small extraprimary visual area of the posterior region of the lateral suprasylvian cortex (PSSC-Ogasawara et al: J. Neurophysiol. 52:1226-1245, '84). The present experiments demonstrate that lesions only a few millimeters in diameter in this corticotectal zone of the PSSC can produce profound visual neglect. While damage to this area has little, if any, effect on superficial laminae visual activity, it produces a dramatic decrease in the visual activity of the deep laminae. These cats with PSSC lesions fail to orient to a visual stimulus that is introduced suddenly into the contralateral visual field, yet they respond on nearly 100% of the trials to this same stimulus when it is presented in the ipsilateral visual field. The lesion-induced visual neglect produced by PSSC lesions is long-lasting but can be abruptly ameliorated by a midbrain lesion that primarily involves, or undercuts, the deep laminae of the contralateral superior colliculus. Thus, 1) visual neglect can be produced by depriving the deep laminae of the superior colliculus of visual inputs from the cortex, even when the principal visual cortical regions (17, 18, and 19) and their target structures are intact, and 2) visually guided behavior can be restored by eliminating afferents originating in, or passing through, the deep laminae of the contralateral superior colliculus.

Lateral neglect in a head movement task: More impairment with unilateral than bilateral lesions of the superior colliculus in the rat

Unilateral lesions of the superior colliculus produce contralateral neglect. This study determined if bilateral lesions would impair head orientation in a way expected from the summation of two contralateral neglects. Rats were trained to make various head movements to get water at a 3 × 3 array of holes, each with a recessed water-baited dipper. On each of 20 trials in a session, a water-deprived subject approached and sampled the array by orienting its head and inserting its snout in the holes in a self-determined sequence. The measures recorded for each position and for each trial were: the order in which a baited position was sampled (selection order), the number of times it was not sampled (misses), and the number of times it was sampled when dry (perseverations). Radio-frequency lesions were made and testing was resumed after 3 days. Large unilateral lesions of the superior colliculus produced a neglect of contralateral positions and increased perseverations to ipsilateral positions. Center positions were also neglected but to a lesser extent. Bilateral lesions of the superior colliculus produced only a moderate increase in lateral misses and no increase in lateral perseverations. Bilateral lesions did produce a neglect of upper positions on both sides. The results indicate that a major contributor to contralateral neglect produced by a unilateral lesion is an antagonistic process that promotes orientation to the side ipsilateral to the lesion.

Efferent Connections of the Rostral Portion of Medial Agranular Cortex in Rats

This study of the rostral part of medial agranular cortex (AGm) was undertaken with two principal aims in mind. First, to delineate the efferent connections of AGm and compare these with the pattern of afferents defined by us in a previous study. Second, to provide a firmer basis for anatomical and functional comparisons with cortical regions in monkeys. Autoradiographic, horseradish peroxidase, and fiber degeneration techniques were used. Rostral AGm has a variety of corticocortical connections—with lateral agranular motor cortex (AGI); visual, auditory, and somatic sensory regions; and limbic/paralimbic areas including orbital, insular, perirhinal, entorhinal, retrosplenial and presubicular fields. The projections to orbital, perirhinal and entorhinal cortices are bilateral. Thalamic projections of rostral AGm are concentrated in the ventral lateral, central lateral, paracentral, mediodorsal and ventromedial nuclei. Moderate terminal fields are consistently seen in the reticular, anteromedial, central medial, gelatinosus, parafascicular, and posterior nuclei. More caudal projections reach the central gray, superior colliculus and pontine gray. The efferents of the adjacent AGI were also examined. Although many of these overlapped those of rostral AGm, there were no efferents to visual or auditory cortex and limbic/paralimbic projections were reduced. Thalamic projections were more focused in the ventral lateral and posterior nuclei and there were no terminal fields in the central gray or superior colliculus. Based on its afferent and efferent connections, role in contralateral neglect, and the results of microstimulation studies, rostral AGm can be viewed as a multimodal association area with strong ties to the motor system. On these structural and functional grounds, rostral AGm bears certain striking resemblances to the frontal eye field, supplementary motor, and arcuate premotor areas of monkey cortex.

Right cerebral dominance in spatial attention. Further evidence based on ipsilateral neglect.

Tasks based on visuomotor scanning and tactile exploration were used to quantitate neglect behavior in patients with unilateral brain damage and in normal control subjects. The results confirm previous observations that contralateral neglect is markedly more severe following right-hemisphere injury and that it is independent of the modality of sensory input or motor output. In addition, patients with right-hemisphere injury also showed multimodal neglect for targets in the hemisphere ipsilateral to the brain lesion. The emergence of both contralateral and ipsilateral neglect in these patients strongly supports a model of right-hemispheric dominance for the distribution of attention within the extrapersonal space.

Environmental enrichment and recovery from contralateral sensory neglect in rats with large unilateral neocortical lesions.

Previous investigations of the potential value of postoperative environmental enrichment in enhancing functional recovery in brain-lesioned rats have yielded contradictory results. The present study sought to resolve some of the contradictions by drawing a clear distinction between the contribution of environmental enrichment to the processes of compensation for sensory loss and recovery per se. By using unilateral lesions, thus avoiding total loss in any sensory modality, and examining a behavioural deficit not anyway thought to be, primarily, a consequence of sensory loss, it was hoped to arrive at an experimental test in which reinstatement of preoperative performance would necessarily reflect recovery rather than compensation. Recovery from the effects of large unilateral neocortical removals on performance on the 'bracelets' test, recently proposed by Schallert and Whishaw, Behavioural Neuroscience, 1984, 98: 518-540, as a model of simultaneous extinction in humans, was investigated. Lesions significantly impaired bracelet removal from the contralateral paw and a degree of recovery from this impairment was observed. However, recovery was not enhanced by postoperative environmental enrichment. The reasons for this were discussed and possible explanations of the recovery that did occur were considered. Implications for Schallert and Whishaw's model were also discussed. It was concluded that the present results were consistent with the view that any restorative value that postoperative environmental enrichment may have lies in facilitating compensation rather than recovery.

Parietal and frontal eye field neglect in the rat

Rats were given unilateral aspiration lesions of parietal, medial frontal, or dorsolateral frontal (motor) cortex and then tested for visual, auditory and tactile neglect, and for circling. All medial frontal lesion animals showed contralateral neglect in each modality and circled ipsiversively. The parietal lesion rats initially displayed contralateral visual and auditory neglect as severe as that in the medial frontal group. Three weeks after the lesions, the parietal group had a smaller residual deficit on the visual test than the medial frontal group. In the first week, parietal animals responded less than the medial frontals to stroking the vibrissae but were more responsive to mild pinching of a toe contralateral to the lesion side. In striking contrast to the medial frontal animals, the parietal group circled strongly to the contralateral side. No rat with a motor cortex lesion neglected or circled preferentially. Like medial frontal cortex, unilateral parietal lesions also produce neglect and circling, but there are important features distinguishing unilateral lesion effects in these two regions.

Four-year prognosis of stroke patients with visuospatial inattention

The four-year prognosis of patients with visuospatial inattention in a stroke register (altogether 255 patients) was studied. Sixty-six surviving patients under the age of 65 were examined neurologically and neuropsychologically after 3 months and 1 year from stroke. Fifty-two of these 66 patients were still reexamined after 4 years from onset. Twelve patients with ischaemic brain infarction had visuospatial inattention: 7 had a clear-cut and contralateral neglect and 5 had milder and less lateralized inattention. The recovery of these 12 patients was poorer in ADL than the other 54 patients. Even when hemiparesis was taken into account, the difference still existed in ADL. The recovery of the 7 neglect patients was poorer than that of the 5 inattention patients. During the follow-up the visuospatial neglect persisted in all 7 cases and the visuospatial inattention disappeared in only one case.

Transplantation of embryonic ventral forebrain neurons to the neocortex of rats with lesions of nucleus basalis magnocellularis—II. Sensorimotor and learning impairments

The cholinergic projection from the nucleus basalis magnocellularis to the neocortex has been implicated in normal memory function and in the dementia of Alzheimer's disease. In order to investigate functions of this cholinergic system of the forebrain, rats with unilateral ibotenic acid lesions of the nucleus basalis magnocellularis have been compared with normal animals and with rats given cortically-placed transplants, either of cholinergic-rich embryonic ventral forebrain cells or of control noncholinergic cells taken from embryonic hippocampus. In the first experiment, lesions of the nucleus basalis magnocellularis led to impairments in step-through passive avoidance and Morris' water-maze tasks, and to locomotor hyperactivity attributable to a reduction in within-trial habituation. The ventral forebrain grafts, but not the noncholinergic hippocampal grafts, significantly ameliorated the deficits of passive avoidance retention, and of water-maze spatial accuracy, but had no effect on the acquisition impairments in either task, nor on the habituation deficit in locomotor activity of the nucleus basalis magnocellularis lesioned rats. In the second experiment, the lesions induced contralateral sensory neglect and ipsilateral turning biases, which were also partially ameliorated by the ventral forebrain grafts. The results support the hypothesis that the basal forebrain-neocortical cholinergic system contributes to certain memory processes, but suggest a more general role for this system in other cortical functions also.

Quantitation of a mass action of dopaminergic neurones regulating temporal damping of linear electrocortical waves

We have previously proposed that electrocortical waves are linear waves, subject to regulation by mesotelencephalic dopaminergic neurones. As a further means to test this theory, selective unilateral lesions of varying extent were made in the nucleii of origin of the dopaminergic mesotelencephalic tract. Changes in the electrocortical power spectrum were assessed by a repeated measure, between hemispheres comparison of ratio changes in power. With increasing unilateral dopamine cell damage, the animals showed increasing contralateral sensorimotor neglect. Curve fitting the ratio changes in power attributable to lesion, showed that estimates of the power of driving signals and the temporal damping moved in reverse directions with increasing extent of lesion, as expected from the theory. A further test was undertaken, to determine whether equal estimates for a transformation of surface signals were obtained from each side. Equality would not be expected if the equation for relative power were invalid. Left and right equality was found for three grades of unilateral lesion.

Deficits in visual discrimination performance following neglect-producing unilateral lateral hypothalamic lesions in the albino rat

Adult male albino rats were trained with water reinforcement on a lateralized visual discrimination task. For six rats the correct head turn—nose poke response was to the side as the discriminative stimulus (Turn Towards group). For six others the correct response was to the side opposite from the discriminative stimulus (Turn Away group). Immediately after a rat had mastered its task, a unilateral electrolytic lesion was made under ether anesthesia through a stainless steel electrode previously implanted in the lateral hypothalamus (LH). Discrimination training continued until the rat's performance returned to criterion. The lesions produced contralateral neglect as demonstrated by deficits in turning and orientation contralateral to the lesion. The lesions also disrupted all measures of discrimination performace (% correct, latency, and duration of observing response) for trials on which responses contralateral to the lesion were correct, regardless of whether the discriminative stimulus was also contralateral (Turn Towards group) or was ipsilateral (Turn Away group). These data are interpreted as showing that contralateral neglect following LH lesions is associated with a deficit in initiating instrumental responses contralateral to the lesion. They also confirm previous results from a similar task using tactile discriminative stimuli.

Development of the Superior Colliculus

Reference is often made to a study by Adamiik (1872) to illustrate how long we have known that the superior colliculus (SC) plays a role in eye movements. The interest in the involvement of the SC in eye movements has not waned, but has actually increased as a result of recent work describing the activity of SC cells in behaving animals (for comprehensive discussions, see Sparks & Pol­ lack 1977 , Goldberg & Robinson 1978, and Wurtz & Albano 1980). In striking contrast to the decades of exploration of the role the SC plays in eye move­ ments, and in vision in general, is the comparative recency of our appreciation of its multisensory roles. It is even difficult to point to a specific date when this began, because the view of the SC as a structure persisted even after anatomical studies demonstrated that it received nonvisual afferents (e. g. Marburg & Warner 1947, Poirier & Bertrand 1955, Anderson & Berry 1959, Mehler et aI1960). As late as 1962, the deep portion of the SC was described as containing . . . cells that respond to extraoptic stimulation of unknown origin (Altman & Malis 1962). Soon thereafter, however, demonstrations that SC cells could respond to nonvisual stimuli began to accumulate (Bell et aI1964, Jassik-Gerschenfeld 1965, Hom & Hill 1966), and now the involvement of the SC in auditory and somatosensory as well as visual functions is firmly estab­ lished. Many of the early studies that mention the SC do so in passing; seldom was it the major focus of attention. However, an upsurge of interest in the SC took place during the 1960s and has continued unabated since. Of considerable importance in initiating this interest was the description of the profound contralateral sensory neglect that occurred after destruction of the SC in cats

Sensorimotor impairment and elevated levels of dopamine metabolites in the neostriatum occur rapidly after intranigral injection of 6-hydroxydopamine or gamma-hydroxybutyrate in awake rats

The unilateral injection of 6-hydroxydopamine (8 μg) into the ventral tegmental area of awake rats produced a rapidly developing and irreversible sensory neglect to contralateral tactile stimuli. This neglect developed in a caudal to rostral direction on the affected body surface and coincided with significant elevation in the concentrations of dopamine and two of its metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the ipsilateral neostriatum. The unilateral injection of procaine or gamma-hydroxybutyric acid (GHB) into the substantia nigra of awake animals also produced a contralateral neglect that developed in a caudal to rostral direction, but the behavioral effect of these drugs diminished within 1 hr. Concentrations of dopamine, dihydroxyphenylacetic acid and homovanillic acid in the neostriatum were markedly elevated during continuous infusions of procaine or gammahydroxybutyric acid. The extent of sensory neglect and changes in dopamine metabolism in the neostriatum varied according to the amount of gamma-hydroxybutyric acid injected into the nigra and according to the proximity of injections of gamma-hydroxybutyric acid to the pars compacta. The rapid onset of sensory neglect following microinjections of 6-hydroxydopamine, procaine or gamma-hydroxybutyric acid is consistent with the ability of each of these drugs to block the conduction of impulses in mesostriatal neurons and suggests that concomitant increases in levels of dopamine, dihydroxyphenylacetic acid and homovanillic acid in the neostriatum resulted from decreases in the release of dopamine coupled with increased synthesis of dopamine. These findings also indicate that the catabolism of dopamine to dihydroxyphenylacetic acid or homovanillic acid may originate intraneuronally, without prior release of dopamine and its recapture by mesostriatal terminals, if the flow of impulses in this pathway has been blocked.

Visual experience, unilateral cortical lesions, and lateralization of function in rats.

The effects of early visual experience and later unilateral neocortical lesions on the behavior of male hooded rats were measured on an open-field, 17-arm spatial maze, and a visual field or perimetry test. The comparison of behavior observed in the open field revealed that light-reared (LR) rats that suffered a right hemispheric lesion were more active and reared more than any of their dark-reared (DR) counterparts as well as LR animals that had left hemispheric or sham operations. On the radial maze task in which 8 of 17 arms were baited, the rats with unilateral lesions performed less effectively than did the sham-operated animals. The effect of the lesions was significantly greater for LR rats than their DR counterparts. The perimetry testing revealed that although the operated animals did react to stimuli throughout their visual field, some contralateral neglect was evident in the case of both LR and DR rats. The lesions did have a much greater impact on orientational behavior of operated LR rats. However, as was the case with respect to performance on the radial maze, no evidence emerged of any functional asymmetry following the unilateral cortical lesions. The results are discussed in terms of Denenberg's (1981) hypothesis about cerebral and functional asymmetry in the rat.

Posture-independent sensorimotor analysis of inter-hemispheric receptor asymmetries in neostriatum

Nigrostriatal dopaminergic neurons are thought to be critically important for somato-sensorimotor behavior. Following unilateral irreversible elimination of these neurons, an animal shows an ipsiversive postural bias and permanently fails to orient its head toward tactile stimuli placed on the contralateral side of the body. In response to apomorphine, a dopamine agonist, these rats display contraversive circling. This effect is thought to reflect denervation-induced proliferation of dopamine receptors in the ipsilateral striatum. We have developed a sensitive procedure that measures sensorimotor function independent of postural and circling biases. We record the latencies to remove small pieces of adhesive stimuli placed onto the snout or radial surface of the forelimbs. The stimuli are placed symmetrically and simultaneously, which is analogous to tactile-extinction procedures used clinically. In the first study we found that rats with unilateral 6-hydroxydopamine (6-OHDA)-induced lesions of the nigrostriatal pathway showed a contralateral sensorimotor bias in response to doses of apomorphine below those necessary to produce contraversive circling. In a second study, unilateral striatal microinjections of kainic acid (KA) were used to destroy the neurons on which the postsynaptic dopaminergic receptors of the nigrostriatal system are contained. Compared to 6-OHDA, KA produced unexpected results in standard orientation tests. None of the KA-treated rats showed contralateral neglect, and some even showed ipsilateral deficits. However, the standard orientation tests are confounded by postural asymmetries, which were irregular in the KA-treated group. Using again the posture-independent sensorimotor procedure, we found that all KA-treated rats, like the 6-OHDA-treated rats, uniformly displayed ipsilateral sensorimotor biases. Sensorimotor function relating to inter-striatal asymmetries may be more specifically assessed with the bilateral-adhesive tests.

Lateralized loss of biting attack-patterned reflexes following induction of contralateral sensory neglect in the cat: A possible role for the striatum in centrally elicited aggressive behaviour

A syndrome of ‘contralateral sensory neglect’ was induced by hypothalamic knife cuts in 6 of 10 cats in which quiet biting attack behaviour could be elicited by lateral hypothalamic stimulation. The contralateral sensory neglect in the 6 affected cats was accompanied by a loss on the ‘neglected’ side of the body of the patterned reflexes which mediate positioning of the head to bite and the jaw-opening component of biting. As a result, when these cats were stimulated in the lateral hypothalamus, although they continued to approach and even make tactile contact with the rat, they generally failed to bite it. Analysis of the histological and behavioural data suggested that damage to the nigrostriatal and/or striato/pallidonigral fibre systems provided the likely basis for both the induction of the contralateral sensory neglect and the lateralized patterned reflex loss. It was suggested, with respect to these specific patterned reflex components of the attack, that an important contribution may be made by the striatum.

Brain and conscious representation of outside reality

Right brain-damaged patients with contralateral neglect proved unable to describe accurately the left half of recollected images. Analogical brain processes seem therefore to underlie these representations. It is suggested that the left half of the spatial framework of visual representations is impaired in these patients. The alternative explanation based on the unilateral involvement of a hypothetical scanning of inner images is criticized.

Visual-evoked response in lateral hypothalamic neglect

Visual-evoked responses were recorded bilaterally from the occipitoparietal region of six split-brain cats, before and 2 days after a unilateral hypothalamic lesion had produced a contralateral sensorimotor neglect syndrome. No consistent change in each visual-evoked response was detected, but there was an average increase in voltage in slow components on the side of the lesion compared to changes on the intact side. It is concluded that sensorimotor neglect is not associated with reduction of sensory input, and that the changed cortical synchrony accompanying this syndrome therefore reflects disruption of a nonsensory mechanism.

Conditioning compensates the neglect due to unilateral 6-OHDA lesions of substantia nigra in rats

The degree of the contralateral sensory neglect in rats with unilateral 6-OHDA lesions of substantia nigra was assessed by a conditioning procedure, employing lateralized CS. In the first experiment visual neglect (revealed by failure of the visually elicited placing reaction contralateral to the lesion) was shown to be accompanied by slower acquisition of a brightness discrimination task. The impairment was due to ipsilateral turning tendency rather then to visual deficit, however, since monocular relearning yielded equal savings with the ipsilateral and contralateral eyes. The second experiment showed that rats anesthetized with urethane reacted to noxious skin stimulation contralateral to the lesion with shorter-lasting EEG arousal than to ipsilateral stimulation of the same intensity. The electrophysiological asymmetry could be compensated by classical conditioning, i.e. by pairing habituated tactile stimuli with noxious tail shock. The conditioned arousal reaction could be elicited with the same efficiency from the neglected and intact body surface. It is concluded that neglect is due neither to a sensory nor to a motor failure, but that 6-OHDA lesions of substantia nigra in one hemisphere reduce the arousing efficiency of unconditioned stimuli and interfere with sensorimotor integrating mechanisms on the side contralateral to the lesion. Compensation of the neglect by conditioning indicates that the role of the nigrostriatal system can be partly substituted by other circuits.

Limbic and prefrontal contributions to somesthetic learning in monkeys

Monkeys with forebrain commissurotomies and either lateral temporal, medial temporal, dorsal prefrontal, or ventral prefrontal removals from the right hemisphere were compared with control animals in learning tactual discriminations and reversal with the left hand. The lateral temporal removal yielded no effect, confirming the modality-specific roles of this sector in audition (superior temporal gyrus) and vision (inferior temporal gyrus). The dorsal prefrontal removal yielded a deficit in discrimination learning, possibly as a result of the contralateral sensory neglect or the spatial disorder produced by this lesion. Each of the two remaining lesions, medial temporal and ventral prefrontal, yielded deficits in both discrimination learning and reversal; and the effects of combined removal of these two limbic sectors appeared to be additive. Taken together with earlier findings in vision and audition, the results indicate that the two limbic sectors contribute to learning in all sensory modalities, and that they do so through cortico-cortical interaction with the sensory systems.