1 Hz repetitive transcranial magnetic stimulation of the unaffected hemisphere ameliorates contralesional visuospatial neglect in humans.

The aim of the study was to investigate whether low-frequency repetitive transcranial magnetic stimulation (rTMS) over the unaffected hemisphere can ameliorate visuospatial neglect. We treated three right brain damaged patients with left neglect. 900 pulses (1 Hz frequency) were given over left posterior parietal cortex every other day for 2 weeks. Patients performed a computerized task requiring length judgement of prebisected lines, tachistoscopically presented for 150 ms. With respect to rTMS the task was given 15 days before, at the beginning, at the end and 15 days after. At these times patients performed also line bisection and clock drawing tasks. rTMS induced a significant improvement of visuo-spatial performance that remained quite unchanged 15 days after. Patients performance at Time 3 and 4 improved also as concerns line bisection and clock drawing tasks.

rTMS of the unaffected hemisphere transiently reduces contralesional visuospatial hemineglect.

To verify the role of interhemispheric influences on manifestations of neglect, the authors investigated the effects of a transient repetitive transcranial magnetic stimulation (rTMS)-induced disruption of the unaffected hemisphere on contralesional visuospatial neglect in two left- and five right-brain-damaged patients. Parietal rTMS of the unaffected hemisphere during the execution of a computerized task of bisected line's length judgment transiently decreased the magnitude of neglect as expressed in the number of errors.

Timing of right parietal and frontal cortex activity in visuo-spatial perception: a TMS study in normal individuals.

In a recent study we showed that repetitive transcranial magnetic stimulation (rTMS) with train duration of 400 ms over right frontal and right posterior parietal cortices gives rise to transitory contralateral visuo-spatial neglect in normal subjects. In the present experiment we investigated whether using single-pulse TMS it is possible to obtain information about the timing of cortical activity related to spatial cognition. Nine healthy subjects performed in baseline condition and during TMS a tachistoscopic task, requiring a forced-choice estimation of the length of the two segments of prebisected horizontal lines. Single-pulse TMS was triggered at various time intervals (150 ms, 225 ms, 300 ms) after visual stimulus onset with a focal coil over P6 and F4 (according to 10/20 EEG system). Relative transitory rightward bias was observed only when parietal TMS was delivered 150 ms after visual stimulus presentation. Frontal stimulation induced no effect on visuo-spatial perception with the time intervals explored.

Verbal-response and manual-response versions of the Milner Landmark task: normative data.

The paper reports normative data relative to a shortened form of two versions of the Milner Landmark task, involving verbal and manual response, respectively, which have been found to provide crucial information to discriminate perceptual from response bias in unilateral neglect. Normative data based on a large group of subjects were believed to be necessary because the Landmark task is held to be worth further investigation: (a) in comparison with other tasks devised for similar purposes, (b) in elucidating clinico-anatomical correlations, and (c) in planning selective remediation programmes. The results of the investigation provide criteria on the basis of which a patient's bias can be classified as being normal, borderline, or pathological.

Contralateral neglect induced by right posterior parietal rTMS in healthy subjects.

We applied repetitive transcranial magnetic stimulation (rTMS) in order to induce interference on visuo-spatial perception in 11 healthy subjects. Subjects performed a visuo-spatial task requiring judgements about the symmetry of prebisected lines. Visual stimuli consisted of symmetrically or asymmetrically transected lines, tachystoscopically presented for 50 ms on a computer-monitor. Performance was examined in basal condition and during rTMS trains of 10 stimuli at 25 Hz, delivered through a focal coil over right or left posterior parietal cortex (P5 and P6 sites) and triggered synchronously with visual stimulus. Randomly intermixed sham rTMS trains were employed to control for non-specific effects. Right parietal rTMS induced a significant rightward bias in symmetry judgements as compared with basal and sham rTMS conditions. No differences emerged between other conditions.

Anisometry of space representation in unilateral neglect: empirical test of a former hypothesis.

When left-neglect patients are required to extend horizontal segments to double their original length, relative left overextension is frequently observed. Less frequently, relative left underextension may also be found. It was hypothesized that this contrast could depend on the degree of horizontal anisometry of the medium for the representation of spatial properties. The present paper reports an experiment conducted in order to test that hypothesis, on the basis of which left overextension should be larger with shorter than with longer segments and with segments lying in the right rather than in the left hemispace. Although supportive, the results unveiled unexpected complications: the expected effect of line length was found only in neglect patients with frontal damage, while the expected effect of side of presentation was found only in neglect patients without frontal damage.

Unilateral neglect and disambiguation of the Necker cube.

Three groups of patients (right brain-damaged patients with or without left neglect, and left brain-damaged patients) and a group of healthy subjects, matched for age and educational level to the three groups of patients, were asked to report which of the two frontal surfaces of Necker cubes oriented in four different ways looked, at first sight, nearer to the viewer. The extent to which, and the way in which, disambiguation of the apparent perspective of Necker cubes occurred was found to vary across the four orientations and to be different in left-neglect patients compared with subjects of the other three groups. With normal subjects, the disambiguating factor is suggested to be a disposition to perceive the upper surface, which is nearly orthogonal to the frontal plane, as external to the cube. This would result from a navigation of the observer's spatial attention towards its target along a particular path that is altered in patients suffering from left neglect. It is suggested that comparison of the paths followed by the attentional vectors of normal subjects and left-neglect patients is potentially fruitful for a better understanding of the brain's normal mechanisms of spatial attention and of unresolved issues concerning the perception of the Necker cube.

Two-dimensional distortion of space representation in unilateral neglect: perceptual and response-related factors.

The paper reports the results of an experiment in which left-neglect patients were required to point at the location they judged vertically to correspond (within the frame of the visual stimulus display they were given) with a cue that was variably located along a left-right axis lying proximally or distally with respect to the left-right axis over which they had to give their response. Patients were found to make rightward errors as in a similar, single-case study. The significant positive correlation between those errors and the degree of response bias on a manual-response version of the Milner Landmark Task suggests that rightward pointing errors made by left-neglect patients in conditions such as those set in the present experiment are due to a dysfunction selectively affecting an output-related component of space representation.

Hypermnesia in unilateral neglect.

Thirteen right brain-damaged patients who were found to neglect pictures presented on the left of a display were presented the same stimuli, intermixed with foils, in a yes-no recognition test. Fifty per cent of patients claimed to have already seen one or more of the previously neglected pictures. This demonstrates that visual information that fails to access consciousness in neglect patients does retain the ability to surface as explicit memory at a later stage.

Visual awareness and anisometry of space representation in unilateral neglect: a panoramic investigation by means of a line extension task.

UNLABELLED: Ninety-one right brain-damaged patients with left neglect and 43 right brain-damaged patients without neglect were asked to extend horizontal segments, either left- or rightward, starting from their right or left endpoints, respectively. Earlier experiments based on similar tasks had shown, in left neglect patients, a tendency to overextend segments toward the left side. This seemingly paradoxical phenomenon was held to undermine current explanations of unilateral neglect. The results of the present extensive research demonstrate that contralesional overextension is also evident in most right brain-damaged patients without contralesional neglect. Furthermore, they show that in a minority of left neglect patients, the opposite behavior, i.e., right overextension can be found. The paper also reports the results of correlational analyses comprising the parameters of line-extension, line-bisection, and cancellation tasks, as well as the parameters relative to the Milner Landmark Task, by which a distinction is drawn between perceptual and response biases in unilateral neglect. A working hypothesis is then advanced about the brain dysfunction underlying neglect and an attempt is made at finding an explanation of neglect and the links between the mechanisms of space representation and consciousness through the study of the changes induced by unilateral brain lesions in the characteristics of space-coding neurons. ABBREVIATIONS: C, control group; GN+91, full group of neglect patients; GN+27, group of neglect patients with relative left overextension; GN+14, group of neglect patients with relative right overextension; GN-43, full group of non-neglect patients; GN-9, group of non-neglect patients with relative left overextension; H canc, H cancellation task; LE, left extension; LE/RE, ratio of left-right extension; N+, neglect patients; N-, non-neglect patients; PB Land-M, perceptual bias on Landmark motor task; PB Land-V, perceptual bias on Landmark verbal task; RB Land-M, response bias on Landmark motor task; RB Land-V, response bias on Landmark verbal task; RE, right extension.

Perceptual and response bias in unilateral neglect: two modified versions of the milner landmark task.

Perceptual and response bias in estimating the proportion of the two segments of prebisected lines were disambiguated in a group of 121 patients suffering from left neglect by means of two variants of the Milner Landmark task (Milner et al., 1993). The first variant, LANDMARK-V, required a verbal response; the second variant, LANDMARK-M, required manual pointing. The paper reports and discusses the results obtained on each task and their correlations, as well as the relationships between either kind of bias and the intrahemispheric location of the lesion. It is argued that besides their usefulness as a diagnostic tool the proposed variants of the Milner Landmark task provide results that are worth further investigation in their own right.

Unilateral neglect and space constancy during passive locomotion.

Space constancy was investigated in seven blindfolded left-neglect patients by driving them along routes involving one or two, left or right, 90 degrees turns. At the end of each route patients had to indicate its starting point while still blindfolded. On average, no considerable left/right differences were found in pointing accuracy. The entailments of this finding for the understanding of neglect phenomena are briefly discussed.

Perceptual and premotor components of unilateral auditory neglect.

Recent investigations have distinguished between ophthalmokinetic and melokinetic factors of unilateral neglect. The aim of our study was to investigate the possible dissociation between melokinetic (premotor) and perceptual factors, avoiding any overt oculokinetic components. We asked four blindfolded left neglect patients to set a dichotic sound in central position, by moving a handle controlling the difference of intensity between the sounds delivered to the left and to the right ears. Two conflicting conditions were used. In the congruent condition, the sound moved in the same direction as the hand movement; in the noncongruent condition, it moved in the opposite direction. One patient performed as if suffering from melokinetic neglect, and another as if suffering from perceptual neglect. The behavior of the other two subjects did not lend itself to a clearcut interpretation.

Beyond unilateral neglect.

When required to set the endpoints of an imaginary horizontal line of a given length on the basis of its midpoint printed on a sheet of paper, left neglect patients most frequently misplaced endpoints leftwards. Though giving rise to the very same disproportion usually found with these patients on canonical line bisection tasks, this behaviour cannot be accommodated by current explanations of unilateral neglect. When the task was executed during leftward optokinetic stimulation (OKS), a manoeuvre known temporarily to improve neglect symptoms, the disproportion increased instead of vanishing. We therefore suggest that unilateral neglect is a manifestation of a disorder primarily implying a horizontal anisometry of space representation and that manipulations such as OKS may remove neglect without normalizing the representational medium itself.

Analogical representation and language structure.

Severe impairment of the analogue of mental representation is not compensated for by putative language-based cognitive processes in non-dysphasic brain-damaged patients. This undermines the hypothesis of an independent role for language in the generation of thought. Against this view it may be contended that there seems to be no obvious way in which analogical mental representation can decide between alternative syntactical structures available for the expression of thought. We performed a visual imagery experiment in which we asked 40 subjects to imagine visual scenes representing the meanings of simple utterances presented to them. The subjects then had to indicate the relative position, in each visual image, of two objects mentioned in each utterance. Series of utterances were presented differing syntactically (active or passive phrase) and semantically (specifying in different ways the spatial and temporal relations between the objects mentioned). The results of this mental imagery experiment indirectly support the hypothesis that syntactical structures can be represented in a nonlinguistic analogue medium.

Dissociation of ophthalmokinetic and melokinetic attention in unilateral neglect.

A line cancellation task was performed by 36 right brain-damaged patients with unilateral neglect under four different conditions: normal and mirror-reversed view, with and without cueing. Two types of unilateral neglect were distinguished by directing ophthalmo- and melokinetic components of visuomanual scanning to opposite sides of the stimulus array. In ophthalmokinetic neglect, contralesional visual scanning of the stimulus array was defective, while manual scanning was unimpaired. The converse was true of melokinetic neglect. Ophthalmokinetic neglect was predominantly associated with posterior brain damage, while melokinetic neglect was predominantly associated with frontal or subcortical brain damage. In a few instances, cueing visuomanual scanning toward the neglected side of the stimulus array converted ophthalmokinetic into melokinetic neglect, and vice versa. The results are held to be indicative of two components of space representation and to provide further evidence of response-driven modulation of perceptual awareness.

Vestibular stimulation, spatial hemineglect and dysphasia, selective effects.

The selectivity of the effects of vestibular stimulation was investigated in a left brain-damaged patient suffering from right visuo-spatial hemineglect and severe dysplasia. Vestibular stimulation temporarily improved the former but not the latter disorder. These results support the view that this treatment improves hemineglect by a specific effect, running counter the rightward distortion of egocentric co-ordinates, rather than by a general hemispheric activation.

Spatial hemineglect in back space.

The subjective location of the mid-sagittal plane was assessed by a free-field auditory localization task in the front and in the back half-spaces in 11 right brain-damaged patients with spatial hemineglect, 10 right brain-damaged patients without spatial hemineglect, and 11 normal control subjects. In patients with hemineglect the subjective mid-sagittal plane was found to be displaced rightwards in both half-spaces. Both patients without hemineglect and controls, in contrast, made a minor error, and showed a greater displacement towards the left side in the back half-space. In four right brain-damaged patients the rightward displacement was confined either to the front, or to the back half-space. This pattern of impairment may be explained by a rightward, ipsilesional, pathological translation of an egocentric co-ordinate system, rather than by a rotation around the vertical axis of the body.

Awareness of and memory for arm weakness during intracarotid sodium amytal testing.

The traditional association between anosognosia for hemiplegia and the right hemisphere was investigated in 31 patients with unilateral temporal lobe pathology during intracarotid sodium amytal testing (ISA) before epilepsy surgery. Recall of arm weakness was examined by questioning at the end of the test, when memory for items presented during the hemiplegia was also examined. Significantly more patients were amnesic for left arm weakness than for right. Amnesia for right arm weakness (and speech arrest) was significantly associated with pathology in the temporal lobe on the non-injected side and with impaired recognition of the memory items. Amnesia for left arm weakness was independent of both. Examination of cases where injection was contralateral to a hemisphere without pathology, and which showed normal memory capacity under ISA conditions, revealed that 87% recalled right arm weakness, but only 22% recalled left arm weakness. Awareness of arm weakness during left hemiplegia was examined in nine patients. Five of them were not aware of the weakness. Three of the four others could not subsequently recall it. By inference from the generally unimpaired recall of right arm weakness, following left hemisphere inactivation by amytal, an intact right hemisphere is capable of both recognizing right arm weakness and mediating its subsequent recall. In contrast, the left hemisphere was aware of left arm weakness only in approximately 50% of cases and even when there had been awareness usually could not mediate its subsequent recall. The suggestion is made that the right hemisphere may have a specific mnestic function for arm weakness, and presumably for hemiplegia, additional to the gnostic function.

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.