Bi-hemispheric transcranial direct current stimulation for upper-limb hemiparesis in acute stroke: a randomized, double-blind, sham-controlled trial.

BACKGROUND AND PURPOSE: Neuromodulation is a promising approach to increasing motor recovery in stroke; however, to date, there is a scarcity of evidence documenting the clinical potential of transcranial direct current stimulation (tDCS) administered in the acute phase of stroke. The present study aims to examine the clinical effects of a treatment involving the application of tDCS in the acute stage post-stroke. METHODS: This was a randomized, double-blind, sham-controlled trial. A cohort of 32 stroke patients with severe motor impairment underwent 5 days of treatment with real or sham bi-hemispheric tDCS over the motor cortex. During the treatment, tDCS was applied twice per day (two daily applications each of 15 min), starting 48 to 72 h after stroke onset. RESULTS: We found statistically significant improvements after both real and sham tDCS treatments in primary (hand grip strength, Motricity Index) and secondary (National Institutes of Health Stroke Scale score, Barthel Index) outcomes. Patients receiving real tDCS showed a larger improvement of upper-limb muscle strength at the end of treatment phase; this advantage was no longer present after 6 months. CONCLUSIONS: Transcranial direct current stimulation may be used to accelerate the rate of upper-limb motor recovery during the spontaneous recovery period.

Supercalifragilisticexpialidocious: how the brain learns words never heard before.

Vocabulary acquisition is such a major aspect of language learning in children, but also in adults when learning a foreign language, that a dedicated vocabulary learning device may exist within the language organ. To identify the relevant brain systems, we performed regional cerebral blood flow measurements in normal subjects while they were learning a list of neologisms or a list of word-nonword pairs. Structures implicated in phonological short-term memory (Broca's area, left temporo-parietal junction) were steadily activated during nonwords learning, while the left temporal lobe neocortical and paralimbic structures (parahippocampal region), associated with long-term memory, contributed to learning in a time-dependent manner, with maximal activation at the beginning of the process. The neural system specifically activated when learning new vocabulary was strongly lateralized to the left hemisphere. This evidence refines current models of memory function and supports theories which emphasise the importance of phonological competence in hemispheric dominance for language.

Spatial hemineglect in humans.

The term `spatial hemineglect' refers collectively to disorders of spatial cognition, which concern specific sectors of space with reference to a given coordinate system. Patients with cerebral lesions involving the posterior-inferior parietal and the premotor cortex, most often in the right hemisphere, sometimes fail to explore the extra-personal and personal sectors of space contralateral to the side of the lesion, are not aware of stimuli presented in these portions of space, or of contralateral body parts and their disordered function. In addition to these negative signs patients may also show positive pathological manifestations, such as avoidance or withdrawal from the contralateral side of space, and delusional views concerning contralateral body parts. The many varieties of this disorder can occur in dissociated forms, suggesting a multifaceted organization of the internal representation of space, of spatial attention, and of their neural correlates. Many manifestations of hemineglect are modulated in a similar fashion by specific sensory stimulation that also affects visuo-motor processes in normal subjects. This ongoing sensory modulation might update the internal representations of space in a continuously changing environment, and contribute to the formation, around the vertical orientation of gravity, of our subjective unitary experience of space.

Metabolic impairment in human amnesia: a PET study of memory networks.

Human amnesia is a clinical syndrome exhibiting the failure to recall past events and to learn new information. Its "pure" form, characterized by a selective impairment of long-term memory without any disorder of general intelligence or other cognitive functions, has been associated with lesions localized within Papez's circuit and some connected areas. Thus, amnesia could be due to a functional disconnection between components of this or other neural structures involved in long-term learning and retention. To test this hypothesis, we measured regional cerebral metabolism with 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) and positron emission tomography (PET) in 11 patients with "pure" amnesia. A significant bilateral reduction in metabolism in a number of interconnected cerebral regions (hippocampal formation, thalamus, cingulate gyrus, and frontal basal cortex) was found in the amnesic patients in comparison with normal controls. The metabolic impairment did not correspond to alterations in structural anatomy as assessed by magnetic resonance imaging (MRI). These results are the first in vivo evidence for the role of a functional network as a basis of human memory.

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.

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.

Hemianesthesia, sensory neglect, and defective access to conscious experience.

We report a patient with an ischemic stroke in the vascular territory of the right middle cerebral artery who had left spatial neglect and left hemianesthesia. The patient showed a dissociation between defective verbal reporting of somatosensory stimuli delivered to the left hand and physiologic evidence from an autonomic index. This indicates that there was processing of undetected stimuli without the patient's awareness, and suggests that the hemianesthesia was due, at least in part, to somesthetic hemi-inattention.

Hemianopia, hemianesthesia, and spatial neglect: a study with evoked potentials.

We recorded somatosensory or visual evoked potentials (SEPs, VEPs) to stimuli contralateral and ipsilateral to the lesion in three right-brain-damaged patients with left spatial hemineglect and in three left-brain-damaged patients without evidence of neglect, as assessed by visual exploratory tasks. All patients had contralateral homonymous hemianopia or hemianesthesia. The three neglect patients showed normal SEPs or VEPs to stimuli delivered to the left half-field or to the left hand, without conscious perception and verbal report of the stimulation. By contrast, the three left-brain-damaged patients without neglect showed no recognizable cortical evoked response to contralateral visual or somatosensory stimuli. In all patients, the cortical evoked responses to ipsilateral stimulation were normal. In patients with spatial hemineglect, hemianopia and hemianesthesia may be manifestations of the neglect syndrome (visual and somatosensory hemi-inattention), rather than representing primary sensory deficit. Visual and somatosensory hemi-inattention may be due to defective access to the neural processes subserving conscious perception by information that has undergone early sensory processing.

The anatomy of unilateral neglect after right-hemisphere stroke lesions. A clinical/CT-scan correlation study in man.

The anatomical correlates of extrapersonal visual neglect were investigated in 110 right-handed stroke patients with lesions confined to the right hemisphere. Neglect is much more frequently associated with retrorolandic damage, as compared with frontal lesions. The inferior parietal lobule appears to be the area most frequently involved in patients with cortical lesions showing signs of neglect. When the cerebral lesion is confined to deep structures, neglect occurs much more frequently when grey nuclei such as the thalamus and the basal ganglia are damaged; a remarkable number of negative cases were, however, found. Conversely, lesions limited to the subcortical white matter are rarely associated with neglect. The relevance of these results to anatomophysiological models of directed attention and neglect is discussed.

Processing of illusion of length in spatial hemineglect: a study of line bisection.

Bisection of horizontal lines and of the Brentano form of the Müller-Lyer illusion was investigated in six right brain-damaged patients with left spatial hemineglect, and in six control subjects. Patients bisected the lines to the right of the objective mid-point. Comparable illusory effects on line bisection were however found in both patients and control subjects. Relative to the baseline condition, in both groups the subjective midpoint was displaced towards the side expanded by the illusion, both leftwards and rightwards. By contrast, line length and spatial position of the stimulus had differential effects. In neglect patients, the rightward bisection error increased disproportionately with line length, and when the stimulus was located in the left, neglected, side of egocentric space. Control subjects showed no such effects. The suggestion is made that the visual, non-egocentric, processes underlying these illusory effects of length may be spared in patients with left spatial neglect. The possible neural basis of this dissociation is discussed.

Left hemisphere contribution to motor programming of aphasic speech: a reaction time experiment in aphasic patients.

Simple reaction time to lateralized visual dot stimuli was studied in 10 fluent and 10 nonfluent right-handed chronic aphasics with left hemisphere lesions. As well as the standard simple reaction time condition, the patients were given a concomitant verbal task, requiring overt articulation while reacting to the visual stimuli. Compared with the control condition, in both aphasic groups the verbal task produced an overall lengthening of latencies, with a significant slowing down of responses to the stimuli located in the right visual half-field. According to these results the verbal concurrent activity appears to involve the left hemisphere as in normal subjects, suggesting that the undamaged regions of the left hemisphere have a role to play in the motor programming of aphasic speech. As a collateral finding, the difference between latencies to stimuli ipsilateral and contralateral to the responding hand--a measure of interhemispheric transmission time--is greatly increased in patients with motor deficits. This is consistent with the view that, in simple visuo-motor reaction time, interhemispheric transfer takes place between anterior regions of the brain.

Selective visual interference with right hemisphere performance in verbal recall. A divided field study.

Three experiments were performed in normal subjects to find out whether interhemispheric functional asymmetries in oral recall of meaningless trigrams of consonants, laterally presented through a tachistoscope, were affected by the subsequent presentation and the immediate recall of visual (verbal and geometrical) vs auditory information. It was shown that the visual presentation of after-target information brought about a right hemisphere disadvantage, which did not occur when the additional information was presented auditorily. The results are consistent with the view that, as to visually presented letters, the right hemisphere processing systems run along a physical code.

Deficits of position sense, unilateral neglect and optokinetic stimulation.

The effects of optokinetic stimulation on position sense disorders were investigated in a series of 30 patients with unilateral vascular lesions (10 right brain-damaged patients with visuospatial hemineglect, 10 right brain-damaged patients without visuo-spatial hemineglect, 10 left brain-damaged patients), and 10 control subjects. The position sense deficit was more severe in right brain-damaged patients with neglect, where both the contralateral and the ipsilateral arm were involved. Optokinetic stimulation was effective only in right brain-damaged patients with neglect: stimulation with a leftward movement (contralateral to the side of the hemispheric lesion) improved the position sense deficit, while stimulation with a rightward (ipsilateral) movement produced a worsening of the performance level. These findings suggest that in right brain-damaged patients with neglect the position sense deficit has a nonsensory component, related to neglect, which may be affected by optokinetic stimulation. The role of the derangement of sensory and perceptual-egocentric representations of the body and of extrapersonal space in producing position sense disorders is discussed.

Unilateral neglect: personal and extra-personal.

Ninety-seven right brain-damaged patients were given two tasks aimed at assessing unilateral neglect in personal and in extra-personal space. The frequency of the two aspects of neglect, as well as their patterns of association with each other and with more elementary neurological disorders are reported and discussed. The results suggest a non-unitary frame of spatial reference for unilateral neglect, which may tentatively be interpreted in terms of a personal vs extra-personal dichotomy.

Remission of somatoparaphrenic delusion through vestibular stimulation.

The effects of vestibular stimulation on somatoparaphrenic delusion were investigated in a patient suffering from a fronto-temporo-parietal infarction located in the right hemisphere. Transitory remission of the patient's delusional belief was consistently observed during unilateral vestibular activation obtained by means of cold-water irrigation of the left (contralesional) ear.

Remission of hemineglect and anosognosia during vestibular stimulation.

The effects of vestibular stimulation on extrapersonal and personal neglect and on awareness of disease were investigated in four patients with severe neglect and anosognosia. Neglect phenomena improved in all patients, while an effect on anosognosia was found in two cases. These preliminary findings indicate a possible role of vestibular stimulation on hemispheric activation.

Language and verbal memory after right hemispheric stroke: a clinical-CT scan study.

The performances on language and verbal memory tests of 26 right-hemisphere damaged subjects (RHD) have been compared with normal controls and 11 non-aphasic left-hemisphere damaged subjects. While phonological and syntactic performance was unimpaired, a small subgroup of RHD patients, with CT scan evidence of subcortical lesion, was mildly impaired in naming tasks. The performance of RHD patients on free recall was characterized by a reduced recency effect. The implications of these findings for theories about the participation of the right hemisphere in linguistic functions are discussed.

Left and right hemisphere contribution to recovery from neglect after right hemisphere damage--an [18F]FDG pet study of two cases.

A 2-[18F]-Fluoro-2-Deoxy-D-Glucose ([18F]FDG) and positron emission tomography (PET) study was performed in the acute and chronic phase of stroke in one patient with unilateral neglect due to a right hemispheric lesion. In the acute phase, severe neglect, as well as hypometabolism in both the right and in the left unaffected cerebral hemisphere, was demonstrated. At follow-up evaluation the patient showed an almost complete recovery from unilateral neglect. This was associated with a return of left hemisphere metabolism to normal values and partial metabolic recovery in the right hemisphere, where frontal and parietal areas remained functionally impaired. Another patient with an extensive right cerebral ischaemic lesion on CT and severe unilateral neglect was studied by PET in chronic phase. A severe metabolic depression in the left unaffected hemisphere and in the right cerebral areas spared by the lesion, was found. These data suggest that the remission of unilateral neglect might be associated to a functional metabolic recovery in both the undamaged left hemisphere and the unaffected regions of the right hemisphere.

Challenging current accounts of unilateral neglect.

Two left-neglect patients were asked (i) to bisect a 15 cm line, (ii) to bisect the empty space between the endpoints of a 15 cm virtual line, and (iii) to set the endpoints of a 15 cm virtual line, given its midpoint. With one patient, the subjective midpoint of the virtual line was found to be displaced leftwards with respect to the subjective midpoint of the real line, whereas with the other it was found to be displaced rightwards. However, in condition (iii) both patients significantly underestimated the distance from the centre of the rightmost point of the virtual line while relatively overestimating that from the centre to the left endpoint. This latter result challenges current accounts of unilateral neglect.