Spiroperidol reinstates asymmetries in neglect in rats recovered from left or right dorsomedial prefrontal cortex lesions

The role of dopaminergic mechanisms in spontaneous behavioral recovery from cortical neglect was examined in rats that received lesions of either the left or the right dorsomedial prefrontal cortex (PCm, also referred to as AGm). Neglect was assessed by rating the degree of head orientation to visual, auditory, or tactile stimuli. Following behavioral recovery, separate groups received 0.03, 0.05, 0.07, or 0.10 mg/kg spiroperidol or the vehicle. In accordance with the lateralization of neglect typically seen postsurgery, spiroperidol dose-dependently reinstated contralesional neglect in left PCm operates and ipsilesional neglect in right PCm operates. Neglect was reinstated by spiroperidol in right PCm operates at lower doses than in left PCm operates. Also, only right PCm operates demonstrated asymmetrical bilateral dose-dependent neglect. Spiroperidol did not produce neglect in unilaterally brain-damaged control subjects. The results indicate that dopaminergic mechanisms may underlie spontaneous recovery from cortical neglect and that these mechanisms are asymmetrical in left and right PCm operates.     

Influence of the side of brain damage on postural upper-limb control including the scapula in stroke patients

Following stroke, control of both the contralesional (paretic) and ipsilesional (less affected) arms is altered. The purpose of this study was to analyse the consequences of stroke on joint rotations of both shoulder girdles, that is, glenohumeral (GH) and scapula motion. Because of hemispheric specialization, we hypothesized that changes would relate to the side of hemisphere damage. Nine stroke patients with left, and 9 with right hemisphere damage (LHD and RHD) and 9 healthy subjects were included. Reaching movements to targets positioned close, far and high in three directions were recorded using an electromagnetic system. Initial and final postures of the scapula, GH and elbow joint were evaluated. Inter-joint rotations throughout the movements were analysed using principal component analysis (PCA). The main finding was that initial and final postures of the contralesional and ipsilesional shoulders differed depending on the side of brain lesion. On the contralesional side, there was less scapula protraction and GH lateral rotation for both groups. Scapula tilt was less anterior in LHD patients, and GH elevation was greater in RHD patients. On the ipsilesional side, GH lateral rotation was reduced in both groups, and scapula protraction was reduced only for LHD patients. PCA confirmed that postures of both shoulders of the LHD group were substantially different to the healthy subjects, while only the contralesional arm of the RHD subjects differed. These results add to existing knowledge of hemispheric specialization, suggesting that the left hemisphere plays a greater role in bilateral joint postures than the right hemisphere.     

Anti-extinction Following Unilateral Parietal Damage

Following unilateral damage to the parietal cortex, extinction of sensory events on the side of space opposite the lesion frequently occurs: A contralesional event is detected when it occurs alone, but missed when it is accompanied by an ipsilesional event. We describe a patientwith left visuospatial neglect subsequent to a right parietal infarct, who shows the opposite of this typical extinction pattern: On brief visual presentations, he consistently shows better detection and identification of contralesional targets when they appear simultaneously with an ipsilesional target, compared to when the contralesional target appears alone. This benefitfor contralesional targets on simultaneous presentation is found most clearly when the same task is performed with both contra- and ipsilesional items. These findings first provide a very clear demonstration of neglect in the absence of extinction. Second, our results demonstrate that visuospatial neglect can be mitigated by non-perceptual task variables.     

Bimanual coordination and perceptual grouping in a patient with motor neglect

Motor neglect refers to the underutilisation of a limb contralateral to a brain lesion in the absence of primary motor and sensory deficits. The related problem of motor extinction refers to a contralesional motor deficit that worsens or only becomes apparent when bilateral actions are required. We present a single case (MM) of a patient with motor neglect who also demonstrates a form of motor extinction that is influenced by visual grouping between stimuli. The comparisons of unimanual and bimanual reach to grasp movements towards one or two objects in Experiment 1 showed that MM made relatively normal unimanual contralesional movements but impaired contralesional movements under bimanual action conditions. Experiment 2 demonstrated that motor extinction was improved by asking MM to make bimanual movements towards a single object. In Experiment 3, the effects of object coding on bimanual movement were replicated across conditions that varied the distance between end points for the movements. MM did not show overt visual extinction. We suggest that MM demonstrates a late-acting attentional bias that is expressed in terms of competitive motor activity. Normally, the contralesional limb "loses" the competition for action, but this can be modulated by visual grouping between targets.     

Bimanual coordination and perceptual grouping in a patient with motor neglect

Motor neglect refers to the underutilisation of a limb contralateral to a brain lesion in the absence of primary motor and sensory deficits. The related problem of motor extinction refers to a contralesional motor deficit that worsens or only becomes apparent when bilateral actions are required. We present a single case (MM) of a patient with motor neglect who also demonstrates a form of motor extinction that is influenced by visual grouping between stimuli. The comparisons of unimanual and bimanual reach to grasp movements towards one or two objects in Experiment 1 showed that MM made relatively normal unimanual contralesional movements but impaired contralesional movements under bimanual action conditions. Experiment 2 demonstrated that motor extinction was improved by asking MM to make bimanual movements towards a single object. In Experiment 3, the effects of object coding on bimanual movement were replicated across conditions that varied the distance between end points for the movements. MM did not show overt visual extinction. We suggest that MM demonstrates a late-acting attentional bias that is expressed in terms of competitive motor activity. Normally, the contralesional limb “loses” the competition for action, but this can be modulated by visual grouping between targets.     

Underestimation of contralateral space in neglect: a deficit in the “where” task

Space perception was investigated in right brain damaged patients with ( N=13) and without neglect ( N=5; control group). Patients were requested to localise a target tachistoscopically flashed at various eccentricities along the horizontal meridian. All patients had an intact visual field and spared ability to manually point to a target. To segregate magno- and parvo-pathway activity, stimuli modulated in either luminance or chromatic contrast were used. Patients were required to verbally report the stimulus position (verbal task) or to manually point to the stimulus (pointing task). Neglect patients reported the stimuli in the left visual field closer to the centre than they actually were. In the verbal test, underestimation was about 7 deg at the most eccentric position tested (20 deg), and decreased linearly for smaller eccentricities. The effect was similar but less marked in the pointing task. No difference was found for stimuli with luminance or chromatic contrast. Space underestimation was confined to the contralesional space; no evidence of misperception was detected in the ipsilesional hemifield. The present findings are consistent with the view that contralesional space representation is compressed in neglect patients.     

Effect of limb movements on orienting of attention in right-hemisphere stroke

A deficit disengaging attention from the ipsilesional space in order to re-orient toward the contralesional space has been reported after right-hemisphere stroke (disengage deficit) and has been related to the severity of visuospatial neglect. Neglect rehabilitation studies have shown that left limb movements improve leftward orienting; the effect, however, is variable, and the mechanism of improvement is uncertain. Thus, this study examined whether limb movements specifically reduce the underlying disengage deficit of attention after right-hemisphere stroke. The effects of active and passive limb movements (vs. no limb movement) on orienting were examined using a covert exogenously cued orienting task in groups of right-hemisphere stroke patients with and without a significant disengage deficit (DD+, DD?) and healthy older adults. As previously seen, disengage deficit scores of stroke patients were positively correlated with the severity of neglect. The leftward disengage deficit was not affected by either active or passive limb movements, however, although movements did have both alerting and distracting effects on other aspects of orienting. Thus, our results suggest that the benefits of limb movements may not be related to changes in the underlying disengage deficit, but may impact other processes that underlie left-sided orienting (e.g., arousal and voluntary strategies).     

Difference of neural connectivity for motor function in chronic hemiparetic stroke patients with intracerebral hemorrhage

Difference of neural connectivity for motor function had been studied by observation of neural activity within gray matter and nucleus using functional neuroimaging techniques. Diffusion tensor imaging (DTI) by a probabilistic tracking is useful for exploration of structural connectivity in the brain. We attempted to investigate difference of neural connectivity for motor function of the affected hand in chronic hemiparetic patients with intracerebral hemorrhage (ICH). Forty-four patients with ICH and 31 normal control subjects were recruited. Diffusion tensor imaging was acquired using a sensitivity-encoding head coil at 1.5 T. Motor function was evaluated using the motricity index (MI) for hand and Modified Brunnstrom Classification (MBC). The presence or absence of a connection was confirmed between the precentral knob of the affected hemisphere and seven areas. Compared with healthy subjects, the patient group showed lower connectivity to the contralesional primary motor cortex, ipsilesional basal ganglia, ipsilesional thalamus, contralesional cerebellum, and ipsilesional medullary pyramid in the affected hemisphere (p < 0.05). Connections to the ipsilesional basal ganglia, ipsilesional thalamus, and ipsilesional medullary pyramid showed positive correlation with MI and MBC (p < 0.05). We found difference of neural connectivity for motor function between chronic hemiparetic patients with ICH and control subjects. Our results suggest that the motor function of the stroke patient is related to neural connectivity between the ipsilesional M1 and the ipsilesional medullary pyramid, ipsilesional basal ganglia, and ipsilesional thalamus.     

Contralateral cerebellar damage impairs imperative planning but not updating of aimed arm movements in humans

The specific motor control processes supported by the cerebellum and impaired with cerebellar damage remain unclear. The cerebellum has been implicated in both planning and updating of accurate movements. Previously, we used a statistical model to parcel aiming performance that was constrained by a timed-response paradigm into contributions attributed to a specified plan and feedforward updating. Here, we apply this procedure to determine the putative role of the cerebellum in planning and updating goal-directed aiming by comparing the performance of subjects with unilateral cerebellar stroke to controls. Subjects rapidly moved to targets in predictable or unpredictable conditions and cerebellar subjects used the contralesional limb to control for ipsilesional motor execution deficits. Displacement-derived movement velocity was used in the statistical model to determine the effect of planning and updating on accuracy. Compared to controls, the cerebellar group demonstrated errors in final position that were primarily determined by planning deficits. This finding is manifest in four ways: Cerebellar subjects (1) were less accurate than controls in both predictable and unpredictable conditions; (2) they showed minimal benefit from increased preparation time for target amplitude specification; (3) with ample time to plan direction, wrong direction response frequency was greater; and (4) final position was minimally determined by the plan. Because these deficits were found contralesional to the moving limb, the cerebellum’s role in planning is not lateralized to one hemisphere but rather our findings suggest that cerebellar output affects motor planning for both upper limbs. Indeed, a lesion analysis showed that the dentate nucleus, an area implicated in planning motor strategies and the primary cerebellar output nucleus, was the only common region affected by our patient group with contralateral cerebellar strokes.     

Visual neglect: Is there a relationship between impaired spatial working memory and re-cancellation?

In visual search tasks, neglect patients tend to explore and repeatedly re-cancel stimuli on the ipsilesional side, as if they did not realize that they had previously examined the rightward locations favoured by their lateral bias. The aim of this study was to explore the hypothesis that a spatial working memory deficit explains these ipsilesional re-cancellation errors in neglect patients. For the first time, we evaluated spatial working memory and re-cancellation through separate and independent tasks in a group of patients with right hemisphere damage and a diagnosis of left neglect. Results showed impaired spatial working memory in neglect patients. Compared to the control group, neglect patients cancelled fewer targets and made more re-cancellations both on the left side and on the right side. The spatial working memory deficit appears to be related to re-cancellations, but only for some neglect patients. Alternative interpretations of re-exploration of space are discussed.     

Effects of illusory spatial anisometry in unilateral neglect

Patients with visuospatial neglect tend to underestimate horizontal magnitudes in contralesional space. It has been recently hypothesised that this behaviour might be due to anisometry of space perception, by which horizontal stimuli would be progressively underestimated proceeding from the ipsi towards the contralesional side of space. We investigated the effects of modulating space perception through the Oppel-Kundt illusion (i.e. a filled space is perceived as more expanded than an empty space) on the behaviour of 28 neglect patients and 28 normal subjects. The two groups bisected lines on backgrounds of vertical lines evenly spaced or unevenly spaced, with distances which decreased progressively from one side of the page to the other. On the same backgrounds, they extended segments to the left or to the right so as to double them. Patients also had to cancel targets, the density of which was evenly distributed or horizontally increased from one side of the page to the other. Both groups were prone to the illusion. Neglect bias was modulated by the illusion in the expected direction. It was reduced when the illusion induced a perceptual distortion opposite to that thought to underlie neglect. On bisection and cancellation tasks, illusory effects were greater in patients with higher values of response bias on the Milner Landmark task. These findings, taken together with patients anatomical data, suggest that a modulation of neglect through a visual illusion can normally be induced in patients with relatively intact visual input processes.     

Deficits in movements of the wrist ipsilateral to a stroke in hemiparetic subjects

We examined step-tracking movements of the wrist and associated EMG activity in seven patients (age range, 27-73 yr) and in seven normal subjects that were matched to patients in age, sex, and handedness. All patients exhibited a hemiparesis that resulted from a unilateral cerebrovascular accident (CVA) that included motor areas in the frontal lobe or their efferents. The lesion in three patients was in their dominant hemisphere. The patients were tested 1-48 mo following their CVA. They had great difficulty in performing or were unable to perform step-tracking movements with the contralesional wrist. In addition, the patients displayed striking deficits in wrist movements and muscle activity of the ipsilesional wrist. These movements were >50% slower than those of controls. The initial movement step routinely undershot the target and was only 63% as large as that of controls. The patients made wrist movements with marked directional errors requiring corrective responses. These errors were due largely to inappropriate temporal sequencing of muscle activity. The deficits in movement and muscle activity in the wrist ipsilesional to a CVA were marked, regardless of whether the lesion was in the dominant or nondominant hemisphere. These observations indicate that unilateral lesions can have significant bilateral effects on the generation and control of distal limb movements.     

Deficits in feature-based control of attention in a patient with a right fronto-temporal lesion

Three experiments examined feature-based top-down control of search in a patient with right frontal-temporal lobe brain damage (YW), in comparison with normal control participants. In Experiment 1, YW showed normal search functions for single-feature targets. However, he showed abnormal search functions relative to normal control participants when a singleton distractor irrelevant to the target-defining feature was presented. YW showed longer RTs when a target was presented in the contralesional visual field and a singleton distractor was in the ipsilesional visual field (Experiment 1), or when both were presented in the contralesional visual field (Experiment 2). These results suggest that YW's difficulty is due to a failure of selectivity for targets based on top-down control of target-defining features. Experiment 3 compared singleton detection tasks and feature detection tasks. YW showed no deficits on the singleton detection tasks, where no knowledge of target-defining features was required. However, on the feature detection tasks, YW showed long RTs when targets were presented in the contralesional visual field where knowledge of target-defining features was required. We concluded that YW's difficulty in visual search with singleton distractors was due to deficits in feature-based control. We discuss the role of fronto-temporal regions in feature-based control of attention.     

Can imagined whole-body rotations improve vestibular compensation?

Unilateral damage to the labyrinth and the vestibular nerve cause rotational vertigo, postural imbalance, oculomotor disorders and spatial disorientation. Electrophysiological investigations in animals revealed that such deficits are partly due to imbalanced spontaneous activity and sensitivity to motion in neurons located in the ipsilesional and contralesional vestibular nuclei. Neurophysiological reorganizations taking place in the vestibular nuclei are the basis of the decline of the symptoms over time, a phenomenon known as vestibular compensation. Vestibular compensation is facilitated by motor activity and sensory experience, and current rehabilitation programs favor physical activity during the acute stage of a unilateral vestibular loss. Unfortunately, vestibular-defective patients tend to develop strategies in order to avoid movements causing imbalance and nausea (in particular body movements towards the lesioned side), which impedes vestibular compensation. Neuroanatomical evidence suggests a cortical control of postural and oculomotor reflexes based on corticofugal projections to the vestibular nuclei and, therefore, the possibility to manipulate vestibular functions through top-down mechanisms. Based on evidence from neuroimaging studies showing that imagined whole-body movements can activate part of the vestibular cortex, we propose that mental imagery of whole-body rotations to the lesioned and to the healthy side will help rebalancing the activity in the ipsilesional and contralesional vestibular nuclei. Whether imagined whole-body rotations can improve vestibular compensation could be tested in a randomized controlled study in such patients beneficiating, or not, from a mental imagery training. If validated, this hypothesis will help developing a method contributing to reduce postural instability and falls in vestibular-defective patients. Imagined whole-body rotations thus could provide a simple, safe, home-based and self-administered therapeutic method with the potential to overcome the inconvenience related to physical movements.     

Deficits in feature-based control of attention in a patient with a right fronto-temporal lesion

Three experiments examined feature-based top-down control of search in a patient with right frontal-temporal lobe brain damage (YW), in comparison with normal control participants. In Experiment 1, YW showed normal search functions for single-feature targets. However, he showed abnormal search functions relative to normal control participants when a singleton distractor irrelevant to the target-defining feature was presented. YW showed longer RTs when a target was presented in the contralesional visual field and a singleton distractor was in the ipsilesional visual field (Experiment 1), or when both were presented in the contralesional visual field (Experiment 2). These results suggest that YW's difficulty is due to a failure of selectivity for targets based on top-down control of target-defining features. Experiment 3 compared singleton detection tasks and feature detection tasks. YW showed no deficits on the singleton detection tasks, where no knowledge of target-defining features was required. However, on the feature detection tasks, YW showed long RTs when targets were presented in the contralesional visual field where knowledge of target-defining features was required. We concluded that YW's difficulty in visual search with singleton distractors was due to deficits in feature-based control. We discuss the role of fronto-temporal regions in feature-based control of attention.     

Sensory and response contributions to visual awareness in extinction

Brain-damaged patients may extinguish contralesional stimuli when ipsilesional stimuli are presented simultaneously. Most theories of extinction postulate that stimuli compete for pathologically limited attentional resources with a bias to process ipsilesional over contralesional stimuli. Implicit in this view is the idea that responses follow the outcome of an earlier competition between inputs. In the current study of two patients, we used signal detection analyses to test the hypothesis that response criteria and response modalities also contribute to visual awareness. We found that identification was more sensitive than detection in uncovering deficits of contralesional awareness. Extinction was worse with bilateral stimuli when the ipsilesional stimulus was identical or similar to the target than when it was dissimilar. This diminished awareness was more likely to reflect a shift towards more conservative responses rather than diminished discrimination of contralesional stimuli. By contrast, one patient was better able to discriminate contralesional stimuli when using his contralesional limb to indicate awareness of targets than when using his ipsilesional limb. These data indicate that the nature of stimuli can modulate response criteria and the motor response can affect the sensory discriminability. Sensory discrimination and response output are not organized in a simple serial manner. Rather, input and output parameters interact in complicated ways to produce visual awareness. Visual awareness itself appears to be the outcome of two bottlenecks in processing, one having to do with sensory processing that may be covert and the other having to do with decision making, which by definition is overt. Finally, we advocate the use of signal detection analyses in studies of extinction, a method that has been surprisingly neglected in this line of research.     

Minimal forced use without constraint stimulates spontaneous use of the impaired upper extremity following motor cortex injury

The purpose of this study was to determine if recovery of neurologically impaired hand function following isolated motor cortex injury would occur without constraint of the non-impaired limb, and without daily forced use of the impaired limb. Nine monkeys (Macaca mulatta) received neurosurgical lesions of various extents to arm representations of motor cortex in the hemisphere contralateral to the preferred hand. After the lesion, no physical constraints were placed on the ipsilesional arm/hand and motor testing was carried out weekly with a maximum of 40 attempts in two fine motor tasks that required use of the contralesional hand for successful food acquisition. These motor tests were the only “forced use” of the contralesional hand. We also tested regularly for spontaneous use of the contralesional hand in a fine motor task in which either hand could be used for successful performance. This minimal intervention was sufficient to induce recovery of the contralesional hand to such a functional level that eight of the monkeys chose to use that hand on some trials when either hand could be used. Percentage use of the contralesional hand (in the task when either hand could be used) varied considerably among monkeys and was not related to lesion volume or recovery of motor skill. These data demonstrate a remarkable capacity for recovery of spontaneous use of the impaired hand following localized frontal lobe lesions. Clinically, these observations underscore the importance of therapeutic intervention to inhibit the induction of the learned nonuse phenomenon after neurological injury.     

Preattentive and attentive visual search in individuals with hemispatial neglect

Preattentive and attentive visual processing was examined in patients with hemispatial neglect, hemispatial neglect with hemianopia, and control participants. In the preattentive search task, targets possessed a unique feature that was not shared by distractors. In the attentive search task, targets lacked a feature that was present in the distractors. Preattentive search was normal in 3 neglect patients with cortical lesions but not in 2 neglect patients with hemianopia. A 4th neglect patient without hemianopia with a subcortical infarct abnormally used serial search mechanisms in the preattentive task. Neglect patients were characteristically impaired in the contralesional field in the attentive search task. This study demonstrates preserved explicit detection of visual features in cases of hemispatial neglect.     

Oculographic analysis of word reading in hemispatial neglect

Neglect dyslexia is a disorder in which individuals misread text appearing on the contralateral side of space following an acquired lesion, usually to the right parietal lobe. This disorder is generally attributed to an impairment in representing spatial information. To determine whether the spatial representations underlying reading differ from those mediating other forms of visual behavior, we investigated the co-occurrence of neglect dyslexia with that of neglect, which manifests on tasks such as line bisection or line cancellation. We also examined the correlation between neglect dyslexia, when present, and eye movements in order to characterize the neglect dyslexia disorder further. Whereas there is no clear relationship between the reading disorder and other symptoms of visuospatial neglect, suggesting segregated spatial representations, there is a direct correspondence between the oculomotor performance of patients with neglect dyslexia and their reading behavior. This latter result suggests that the reading deficit may well arise from the failure to register and perceive the contralesional information.     

Simulating and testing visual exploration in spatial neglect based on a new model for cortical coordinate transformation

Most studies of object and space perception have focused on neural representations of either object-centered or egocentric coordinate systems. But daily life requires interactions of both kinds of coordinates. We have recently proposed an 'integrated space-object (ISO-) map' combining both coordinate systems in one representation. Based on a lesioned version of this model, here we present results from visual search simulations demonstrating that the model accounts for contralesional neglect during space-centered and object-centered exploration tasks. Interestingly, the model simulations also predicted an amelioration of neglect symptoms during exploration with more ipsilesional object positions. By measuring the eye movements of neglect patients during different exploratory tasks, we confirmed all model predictions. These results corroborate the view that the brain might combine coordinates for object and space perception in an integrated coordinate system as suggested by the ISO-map model.