Does outcome of neuropsychological treatment in patients with unilateral spatial neglect after stroke affect functional outcome?

BACKGROUND: Unilateral spatial neglect (USN) after stroke is associated to severe disability and to a poor rehabilitation outcome. However it is still unclear if a reduction of USN after a specific neurophsycological treatment could also favor the functional recovery. AIM: The first aim of this study was to determine if low responders to neuropsychological treatment of unilateral spatial neglect may have a worse functional prognosis for activities of daily living. The second aim was to investigate which variables can predict a low response to neuropsychological treatment. DESIGN: Observational study. SETTING: Neurorehabilitation hospital in Italy. POPULATION: Two hundred inpatients with the diagnosis of ischemic stroke were screened in this observational study. Inclusion criteria were: patients in subacute phase of first ischemic stroke in right hemisphere. Exclusion criteria were: presence of previous and/or other disabling pathologies, medical conditions contraindicating physical therapy. Data of 73 patients who performed neurorehabilitation and visual scanning training for reducing USN were analysed, while the remaining others were excluded for at least one of the following reasons: hemorrhagic lesions, presence of other chronic disabling pathologies, contraindications for therapy. METHODS: USN was evaluated using: Letter Cancellation Test, Barrage Test, Sentence Reading Test and Wundt-Jastrow Area Illusion Test. Barthel Index (BI), Beck Depression Inventory, and Canadian Neurological Scale were also administered. According to the aim of the study, forward binary logistic regressions were performed to evaluate the effects of different factors on functional recovery. RESULTS: Three factors were identified as predictors of low effectiveness in terms of BI-score: older age (odds ratio OR=9.882, P=0.002), severity of disease at admission (OR=12.594, P=0.002) and being low responders to neuropsychological treatment (OR=3.847, P=0.027). Further, the initial barrage score (OR=3.313, P=0.027) and the initial BI-score (OR=3.252, P=0.039) effectively predict the response to neuropsychological treatment. CONCLUSION: The outcome of the whole rehabilitation resulted affected by the outcome of neuropsychological treatment in patients with USN, being a low score at Barrage test at the beginning of therapy a negative predictor of USN recovery. CLINICAL REHABILITATION IMPACT: Patients with USN after stroke can benefit of a specific training for reducing USN also in terms of functional outcome. Further, the simple use of Barrage test could provide important prognostic information about recovery.

The "Altitudinal Anton's syndrome": coexistence of anosognosia, blindsight and left inattention.

We describe a 69-year-old patient with superior altitudinal hemianopia who contentiously denied having any visual impairment after stroke in the lower banks of both calcarine fissures. Although the patient did not produce intentional responses to visual stimuli in the blind fields, he showed reduced reaction times to stimuli presented in the inferior visual fields when they were primed by identical stimuli in the superior blind fields. Furthermore he showed left extinction to the double stimulation and delayed reaction times for left unprimed stimuli in the inferior fields. Based on these findings we discuss the possibility that blindsight and right hemisphere damage might be both necessary conditions for denying bilateral blindness.

Sight and sound of actions share a common neural network.

The mirror-neuron system (MNS) connects sensory information that describes an action with a motor plan for performing that action. Recently, studies using the repetition-suppression paradigm have shown that strong activation occurs in the left premotor and superior temporal areas in response to action-related, but not non-action-related, stimuli. However, few studies have investigated the mirror system by using event-related potentials (ERPs) and employing more than one sensory modality in the same sample. In the present study, we compared ERPs that occurred in response to visual and auditory action/non-action-related stimuli to search for evidence of overlapping activations for the two modalities. The results confirmed previous studies that investigated auditory MNS and extended these studies by showing that similar activity existed for the visual modality. Furthermore, we confirmed that the responses to action- and non-action-related stimuli were distinct by demonstrating that, in the case of action-related stimuli, activity was restricted mainly to the left hemisphere, whereas for non-action-related stimuli, activity tended to be more bilateral. The time course of ERP brain sources showed a clear sequence of events that subtended the processing of action-related stimuli. This activity seemed to occur in the left temporal lobe and, in agreement with findings from previous studies of the mirror-neuron network, the information involved appeared to be conveyed subsequently to the premotor area. The left temporo-parietal activity observed following a delay might reflect processing associated with stimulus-related motor preparation.

Cortical plasticity following surgical extension of lower limbs.

Human cortical plasticity has been studied after peripheral sensory alterations due to amputations or grafts, while sudden 'quasi-physiological' changes in the dimension of body parts have not been investigated yet. We examined the cortical reorganization in achondroplastic dwarfs submitted to progressive elongation (PE) of lower limbs through the Ilizarov technique. This paradigm is ideal for studying cortical plasticity because it avoids the perturbation connected with deafferentation and re-afferentation. Somatosensory evoked-potentials (SEP) and fMRI studies were performed before and after PE during foot and knee stimulation, above and below the surgical fracture. A body schema test was also performed. Following PE, cortical modifications were observed in the primary somatosensory cortex for foot stimulation and in higher order somatosensory cortices for foot and knee. The former modifications tended to decrease 6 months after the elongation ending, whereas the latter tended to persist. Results are interpreted in terms of cortical adaptation mediated by temporary disorganization.

Separate neural systems for processing action- or non-action-related sounds.

The finding of a multisensory representation of actions in a premotor area of the monkey brain suggests that similar multimodal action-matching mechanisms may also be present in humans. Based on the existence of an audiovisual mirror system, we investigated whether sounds referring to actions that can be performed by the perceiver underlie different processing in the human brain. We recorded multichannel ERPs in a visuoauditory version of the repetition suppression paradigm to study the time course and the locus of the semantic processing of action-related sounds. Results show that the left posterior superior temporal and premotor areas are selectively modulated by action-related sounds; in contrast, the temporal pole is bilaterally modulated by non-action-related sounds. The present data, which support the hypothesis of distinctive action sound processing, may contribute to recent theories about the evolution of human language from a mirror system precursor.

Development of neuropsychiatric symptoms in poststroke patients: a cross-sectional study.

OBJECTIVE: The study aimed to characterize neuropsychiatric symptomatology and its evolution in a large group of poststroke patients during their first year. METHOD: The Neuropsychiatric Inventory (NPI) was administered to a sample of 124 poststroke patients, divided into three independent groups on the basis of time from stroke (2, 6 and 12 months). The controls were 61 healthy subjects. RESULTS: A wide range of neuropsychiatric symptoms was found significant in the poststroke population: mostly depression (61%), irritability (33%), eating disturbances (33%), agitation (28%), apathy (27%) and anxiety (23%). Modifications in terms of greater depression, anxiety, irritability and eating disturbances evolved in the year following stroke. Other symptoms were significantly present depending on time from stroke. Clear relations with other clinical and demographic variables were also found. CONCLUSION: Neuropsychiatric symptoms constitute an important part of comorbidity in stroke patients; thus, suitable assessment tools may improve clinical understanding of these patients.

Spatial coding of visual and somatic sensory information in body-centred coordinates.

Because sensory systems use different spatial coordinate frames, cross-modal sensory integration and sensory-motor coordinate transformations must occur to build integrated spatial representations. Multimodal neurons using non-retinal body-centred reference frames are found in the posterior parietal and frontal cortices of monkeys. We used functional magnetic resonance imaging to reveal regions of the human brain using body-centred coordinates to code the spatial position of both visual and somatic sensory stimuli. Participants determined whether a visible vertical bar (visual modality) or a location touched by the right index finger (somatic sensory modality) lay to the left or to the right of their body mid-sagittal plane. This task was compared to a spatial control task having the same stimuli and motor responses and comparable difficulty, but not requiring body-centred coding of stimulus position. In both sensory modalities, the body-centred coding task activated a bilateral fronto-parietal network, though more extensively in the right hemisphere, to include posterior parietal regions around the intraparietal sulcus and frontal regions around the precentral and superior frontal sulci, the inferior frontal gyrus and the superior frontal gyrus on the medial wall. The occipito-temporal junction and other extrastriate regions exhibited bilateral activation enhancement related to body-centred coding when driven by visual stimuli. We conclude that posterior parietal and frontal regions of humans, as in monkeys, appear to provide multimodal integrated spatial representations in body-centred coordinates, and these data furnish the first indication of such processing networks in the human brain.

The role of unilateral spatial neglect in rehabilitation of right brain-damaged ischemic stroke patients: a matched comparison.

OBJECTIVE: To assess the specific influence of unilateral spatial neglect (USN) on rehabilitation outcome. DESIGN: A case-control study in consecutive stroke inpatients. SETTING: Rehabilitation hospital. PATIENTS: One hundred seventy-eight patients with sequelae of first stroke, enrolled in homogeneous subgroups, matched for age (within 1yr) and onset admission interval (within 3d), and difference because of the presence of USN, evaluated by a specific neuropsychologic battery. INTERVENTIONS: All patients received physical rehabilitation: physiotherapy for 60 minutes twice a day (once on Saturday), 6 days a week, within 24 hours of admission. USN-positive (USN(+)) patients received specific treatment of 5, 1-hour sessions per week, for 8 consecutive weeks: (1) visual scanning, (2) reading and copying, (3) copying of line drawings on a dot matrix, and (4) describing a scene. Patients were assessed with neurologic (Canadian Neurological Scale), neuropsychiatric (Hamilton Depression Rating Scale), neuroradiologic, and functional (Barthel Index, Rivermead Mobility Index [RMI]) examinations. MAIN OUTCOME MEASURES: Length of stay, efficiency (average daily increase in Barthel Index), effectiveness (amount of potential improvement achieved during rehabilitation) of treatment and percentage of low- and high-response patients calculated on the Barthel Index and the RMI, and percentage of urinary incontinence and return home were evaluated. Odds ratios (ORs) of dropouts and of low and high therapeutic response were also quantified. RESULTS: Compared with USN-negative patients, USN(+) patients had significantly more severe baseline neurologic and functional status at admission, less effectiveness and efficiency on activities of daily living (ADLs) and mobility, a higher percentage of low responders, longer hospitalization, a higher percentage of persistent incontinence at discharge (20.5% vs 4.9%), and a lower percentage of high responders and patients returning home. The presence of USN was incompatible with a high therapeutic response, for both ADLs (OR= 2.94, 95% confidence interval [CI]= 1.05-8.20; b +/- standard error = 1.08 +/- .52, p< .05), and mobility (OR = 7.16, 95% CI = 2.78-18.44; b = 1.97 +/- .52, p < .001) and was a relevant prognostic factor for institutional discharge (OR = 5.62, 95% CI = 1.63-19.38; b = 1.73 +/-.63, p < .01, accuracy 88.41%). CONCLUSIONS: The results of this study provide further strong evidence of the relationship between USN and disability in right brain-damaged patients and of its unfavorable impact on rehabilitation, despite the cognitive training performed by all USN(+) patients.

The contribution of functional neuroimaging to recovery after brain damage: a review.

The introduction of functional neuroimaging techniques has contributed to understanding the neural correlates of recovery of motor, sensory and cognitive functions after brain damage. In this paper, we review the literature of the past twenty years, with particular emphasis on quantitative studies of cerebral blood flow and metabolism. Studies are presented that examine recovery from hemiparesis, aphasia, spatial hemineglect and sensory disorders. The contribution of this research is critically discussed in a methodological perspective. A basic distinction is made between cerebral plasticity and recovery of functions. It is also argued that the most frequently used experimental designs do not permit directly relating changes in brain activity to functional recovery. The importance of accurate behavioural measures is underlined. Alternative experimental designs are proposed, based on correlations between behavioural performance and brain activations.

Linguistic and nonlinguistic priming in aphasia.

Studies of real-time processing in aphasia suggest that linguistic symptoms may be due to deficits in activation dynamics rather than loss of linguistic knowledge. To investigate the domain specificity of such processing deficits, we compared performance by Italian-speaking fluent aphasics, nonfluent aphasics, and normal controls in a linguistic priming task (grammatical gender) with their performance in a color-priming task that requires no verbal mediation. Normal or larger than normal color-priming effects were demonstrated in both aphasic groups. Gender priming did not reach significance in either group, even though the patients displayed above-chance sensitivity to gender class and gender agreement in their accuracy scores. The demonstration of spared gender knowledge despite impaired gender priming underscores the utility of on-line techniques in the study of aphasia. The demonstration of spared color priming suggests that priming deficits in aphasia are either (1) specific to speech and language or (2) specific only to those sensorimotor and attentional processes that language shares with other nonlinguistic systems.

Psychophysical properties of line bisection and body midline perception in unilateral neglect.

Past research associated unilateral neglect with a systematic ipsilesional shift of the perceived position of the body midline; however, this was not confirmed by recent experiments. We used the constant stimuli method to control for potential artifacts intrinsic to the techniques used in previous studies. Body midline perception was measured in the visual and proprioceptive modalities in ten patients with left unilateral neglect, ten control patients and ten normal subjects and compared with a visual line bisection task, also using the constant stimuli method. Neglect patients showed a significant rightward bias in the line bisection task, but no consistent directional bias either in the proprioceptive or in the visual body midline task. These results clearly counter the association between neglect and an ipsilesional shift of the body midline. However, in the body midline tasks neglect patients made more errors in judgement on both sides of their subjective midline, both with respect to the control groups and with respect to the line bisection task. This may imply that a specific impairment of body-centered representations is indeed present and manifests as a non directional increase in response variability, rather than as a systematic shift. It is suggested that body- and object-related tasks (such as line bisection) may be processed by independent cognitive computations. This interpretation is discussed with reference to a recent neuroimaging study investigating the same kinds of tasks.

The neural basis of egocentric and allocentric coding of space in humans: a functional magnetic resonance study.

The spatial location of an object can be represented in the brain with respect to different classes of reference frames, either relative to or independent of the subject's position. We used functional magnetic resonance imaging to identify regions of the healthy human brain subserving mainly egocentric or allocentric (object-based) coordinates by asking subjects to judge the location of a visual stimulus with respect to either their body or an object. A color-judgement task, matched for stimuli, difficulty, motor and oculomotor responses, was used as a control. We identified a bilateral, though mainly right-hemisphere based, fronto-parietal network involved in egocentric processing. A subset of these regions, including a much less extensive unilateral, right fronto-parietal network, was found to be active during object-based processing. The right-hemisphere lateralization and the partial superposition of the egocentric and the object-based networks is discussed in the light of neuropsychological findings in brain-damaged patients with unilateral spatial neglect and of neurophysiological studies in the monkey.

TENS modulates spatial reorientation in neglect patients.

The existence of separate systems for processing geometric and non-geometric spatial information was studied. Twelve neglect patients were asked to reorient themselves in a room using only geometric information or to integrate this information with relevant visual cues both in the presence and in the absence of transcutaneous electrical neural stimulation (TENS). In the absence of TENS, all patients were greatly impaired in coding geometric information, and they had difficulty in coding non-geometric information. TENS significantly improved the ability to code shape-based representation, but is ineffective with non-geometric representations (such as color). The data support previous findings on neglect patients suggesting the presence of separate, independent neural systems subserving different types of space representation.

Cortical control of optokinetic nystagmus in humans: a positron emission tomography study.

Positron emission tomography (PET) was used to address the issue of physiological changes in the cerebral cortex associated to optokinetic nystagmus (OKN) in humans. We studied regional cerebral blood flow in eight volunteers during reflexive induction of OKN by a pattern of dots moving unidirectionally (toward the left side). We used two control conditions, with subjects passively viewing either stationary or incoherently moving dots. This paradigm was designed in order to differentiate the OKN-related activations from blood flow changes related to visual motion. When compared with the stationary condition, OKN activated a set of occipital areas known to be sensitive to visual motion. Bilateral activation was found in the striate cortex (V1) and the parieto-occipital fissure, while area V5, the intraparietal sulcus, and the pulvinar were activated only in the left hemisphere. When compared with incoherent motion, OKN activated the V1 and the parieto-occipital fissure bilaterally and the right lingual gyrus, while a signal decrease was observed in the V5 region in both hemispheres. No significant signal changes were found in areas implicated in saccades or in processing vestibular information. These results indicate that processing of OKN-related information is associated with neural activity in a specific set of visual motion areas and suggest that this network can be asymmetrically activated by a strictly unidirectional stimulation. Results are also discussed in terms of the specific kinds of OKN-related information processing subserved by each area in this network.

A fronto-parietal system for computing the egocentric spatial frame of reference in humans.

Spatial orientation is based on coordinates referring to the subject's body. A fundamental principle is the mid-sagittal plane, which divides the body and space into the left and right sides. Its neural bases were investigated by functional magnetic resonance imaging (fMRI). Seven normal subjects pressed a button when a vertical bar, moving horizontally, crossed the subjective mid-sagittal plane. In the control condition, the subjects' task was to press a button when the direction of the bar movement changed, at the end of each leftward or rightward movement. The task involving the computation of the mid-sagittal plane yielded increased signal in posterior parietal and lateral frontal premotor regions, with a more extensive activation in the right cerebral hemisphere. This direct evidence in normal human subjects that a bilateral, mainly right hemisphere-based, cortical network is active during the computation of the egocentric reference is consistent with neuropsychological studies in patients with unilateral cerebral lesions. Damage to the right hemisphere, more frequently to the posterior-inferior parietal region, may bring about a neglect syndrome of the contralesional, left side of space, including a major rightward displacement of the subjective mid-sagittal plane. The existence of a posterior parietal-lateral premotor frontal network concerned with egocentric spatial reference frames is also in line with neurophysiological studies in the monkey.

Somatosensory stimulation improves imagery disorders in neglect.

A group of 9 right brain damaged patients with unilateral neglect performed a set of tasks involving mental imagery with and without a transcutaneous electrical neural stimulation (TENS) to both sides of the neck. Results showed that TENS on the left side of the neck produced significant improvements of performances on the left side of mental representations of objects (drawing, shape comparison) as well as on left side of mental images of space (description of squares). The results suggest that the modification induced by TENS may affect the imagery systems involved in objects as well as in space representation.

Recovery of neglect after right hemispheric damage: H2(15)O positron emission tomographic activation study.

BACKGROUND: The neural correlates of recovery of unilateral neglect (ULN), as well as of other consequences of focal brain damage, are largely unknown. Functional neuroimaging methods (in particular, positron emission tomography [PET]) can be applied to the in vivo study of recovery mechanisms in neurologic patients. OBJECTIVE: To evaluate the functional cerebral correlates of recovery from ULN in patients with right-sided lesions, with the use of a PET activation paradigm. METHODS: Study of 3 patients with cerebrovascular lesions that involved corticosubcortical (patient 1) or subcortical (patients 2 and 3) areas of the right hemisphere. Unilateral neglect was tested twice, before and after completion of a 2-month rehabilitation program, after which all 3 patients showed considerable improvement. Similarly, 2 PET examinations were performed, before and after recovery, during the performance of a visuospatial task requiring the patients to detect and respond to visual targets moving on a computer screen from the right to the left visual hemifield (experimental condition). The cerebral activation was compared with a baseline task in which subjects responded to a black dot flashing in a fixed position of the right hemifield. RESULTS: The brain areas activated by the performance of the visuospatial task before and after recovery were compared. In all 3 patients, the regions notably more active after recovery were almost exclusively found in right-sided cortical areas and largely overlapped with those observed in a group of 4 normal subjects performing the same task. Other areas, which have been shown to be involved in attentional and oculomotor tasks in other PET studies, were also activated in patients with ULN. CONCLUSIONS: The behavioral recovery of ULN in these patients with predominantly subcortical lesions is mainly associated with cerebral activations in cortical regions similar to those observed in normal subjects. There is some evidence of functional reorganization in individual subjects, which involves other areas related to space representation and exploration.

Evidence for separate allocentric and egocentric space processing in neglect patients.

Spatial orientation was investigated in two different conditions: (a) when the shape of the enclosure was the only available information; (b) when a clearly perceivable visual cue was added. Three groups of subjects were investigated: normal controls, right brain-damaged patients without and with hemispatial neglect. The performance of the first two groups clearly demonstrated the capacity to use the geometric properties of the environment and to integrate this information with an additional visual cue. Considered as a group, patients with hemispatial neglect were able to use the shape of the environment and, to a lesser extent, the additional visual cue. However, individual differences suggest two opposite performance patterns: two patients responded randomly when the shape of the environment was the only available information, and they improved considerably when the cue was offered; two other patients showed normal competence in dealing with the geometrical properties of the environment, but were unable to take advantage of the cue. The different lesion site in these two types of patients suggests a possible dissociation of processing based upon allocentric or egocentric coding of space in humans as well as in animals.

Motor deficits and optokinetic stimulation in patients with left hemineglect.

Optokinetic stimulation with left direction of the movement of luminous dots temporarily improved motor weakness of the left hand in two right-brain-damaged patients with left spatial hemineglect. Stimulation to the right had no effect. In two left-brain-damaged patients, optokinetic stimulation did not affect the right motor weakness, regardless of direction of the movement of the optokinetic stimuli. We suggest that in patients with left hemineglect, contralesional motor deficits have a neglect-related component, which, as other aspects of the neglect syndrome, may be improved by optokinetic stimulation. The mechanisms may include a temporary restoration of the spatial coordinates of bodily representations, pathologically distorted towards the side of the lesion.

Dissociation between position sense and visual-spatial components of hemineglect through a specific rehabilitation treatment.

Current evidence suggests an association between contralesional extra-personal hemineglect, and deficits of arm position sense in patients with damage to the right cerebral hemisphere. A unitary deficit may produce both disorders, or this association may reflect the anatomical contiguity of relevant brain structures. A rehabilitation treatment, devised for visual-spatial hemineglect, was used to investigate these hypotheses in 8 patients with damage to the right cerebral hemisphere. The treatment improved hemineglect, but not the position sense deficit. The severity of the latter was however transiently reduced by optokinetic stimulation, with effects similar to those found in visual-spatial hemineglect. These effects of rehabilitation suggest that extra-personal hemineglect and the neglect-related component of the position sense disorder of the left forearm are independent, though frequently associated, deficits. Implications for the design of rehabilitation programs are discussed.