On the instability and constraints of the interaction between number representation and spatial attention in healthy humans: A concise review of the literature and new experimental evidence.

The relationship between number and space representation is still one of the most debated topics in studies of mathematical cognition. Here we offer a concise review of two important behavioral effects that have pointed out the use of a spatially left-to-right oriented mental number line (MNL) in healthy participants: the SNARC effect and the attentional SNARC effect (Att-SNARC). Following a brief summary of seminal investigations on the introspective properties of the MNL, we review recent empirical evidence and theories on the functional origin of the SNARC effect, where upon left/right response choices faster reaction times are found for small numbers with left-side responses and for large numbers with right-side responses. Then we offer a summary of the studies that have investigated whether the mere perception of visual Arabic numbers presented at central fixation can engender spatially congruent lateral shifts of attention, ie, leftward for small numbers and rightward for large ones, ie, the Att-SNARC effect. Finally, we summarize four experiments that tested whether the Att-SNARC depends on an active rather than passive processing of centrally presented digit cues. In line with other recent studies, these experiment do not replicate the original Att-SNARC and show that the mere perception of Arabic numerals does not trigger automatic shifts of attention. These shifts are instead found when the task requires the explicit left/right spatial coding of digit cues, ie, Spatial Att-SNARC (Fattorini et al., 2015b). Nonetheless, the reliability of the Spatial Att-SNARC effect seems not as strong as that of conventional SNARC effects where left/right codes are mapped onto responses rather than directly mapped on digit cues. Comparing the magnitude of digits to a numerical reference, ie, "5," also produced a Magnitude Comparison Att-SNARC that was weaker than the spatial one. However, the reliability of this Magnitude Comparison Att-SNARC should be considered with caution because, like in a study by Zanolie and Pecher (2014), we recently failed to replicate this effect in a separate behavioral-event-related potentials study in preparation (Fattorini et al., 2015a). All together the results from the present series of experiments support the hypothesis that spatial coding is not an intrinsic part of number representation and that number-space interaction is determined by the use of stimulus- or response-related spatial codes in the task at hand.

Causes of cross-over in unilateral neglect: between-group comparisons, within-patient dissociations and eye movements.

Patients with left unilateral neglect bisect long horizontal lines to the right of the true centre. However, when given short lines, many of the same patients mark the midpoint to the left of the true centre, towards the otherwise neglected space. This paradoxical phenomenon has been termed 'cross-over' and is difficult to explain based on current accounts of the neglect syndrome. To explore the causes of cross-over, in a first study we evaluated bisection of 20, 100 and 200 mm horizontal lines in groups of unilateral brain-damaged patients with neglect and hemianopia, with neglect and no hemianopia, with hemianopia and no neglect and without neglect or hemianopia. Cross-over of 20 mm lines was found only in neglect patients with hemianopia. To ascertain further the influence of visual field defects on cross-over, in a second study we compared the performance of two right-brain-damaged patients with contralesional neglect and inferior quadrantanopia with that of a patient with inferior quadrantanopia and no neglect. Patients bisected lines oriented so as to cross or uncross the blind quadrant of the visual field. When short 20 mm lines crossed the blind quadrant, neglect patients showed cross-over; when the same lines crossed the seeing quadrants cross-over was absent. These findings were confirmed by the examination of a neglect patient with sparing of the central 5 degrees of the contralesional left visual hemifield in the right eye and no sparing in the left eye. In monocular viewing, cross-over was present when 20 mm lines were bisected with the left eye and absent when bisected with the right eye. Recording of eye movements showed that at the moment of bisection left eye fixations shifted towards the contralesional line endpoint whereas right eye fixations remained anchored to the centre of the line. With long lines, both eyes deviated ipsilesionally. These results show that in neglect patients ipsilesional deviation in the bisection of long lines turns into apparently paradoxical contralesional bisection of short ones only when these cross a retinotopically blind sector of the neglected space. Cross-over seems to depend on the small spatial effects produced by reflexive contralesional gaze shifts allowing eccentric fixations with the seeing hemifield. During the bisection of long lines, these effects are cancelled out by the strong attentional deviation induced by the marked extension of the ipsilesional line segment. This explanation establishes coherence between cross-over and current accounts of the neglect syndrome.

Retinotopic modulation of space misrepresentation in unilateral neglect: evidence from quadrantanopia.

A patient with right sided brain damage suffered contralesional neglect, inferior quadrantanopia (with 0 degrees sparing in the left eye and 13 degrees sparing in the right), and a visual field restriction (to 15 degrees ) in the upper contralesional quadrant of the left eye. In binocular vision, the patient showed underestimation of the horizontal size of contralesional line segments unless cued to localise their end points. When asked to reproduce, in monocular vision, 10 degrees and 20 degrees distances between two attentionally cued end points lying on the frontal vertical plane, the patient showed relative contralesional overextension and ipselesional underextension along the directions falling within the blind sectors of the neglected space. No asymmetry was present along the directions falling within the seeing sectors of the same space. These findings suggest precise retinotopic modulation of space misrepresentation in unilateral neglect.

Implicit semantic evaluation of object symmetry and contralesional visual denial in a case of left unilateral neglect with damage of the dorsal paraventricular white matter.

It is well documented that right brain damaged patients with left unilateral neglect may show unconscious processing of contralesional stimuli. However, the anatomical correlates of this phenomenon are still not well defined. Here we report the case of a neglect patient with a circumscribed lesion of the dorsal parietal-occipital white matter showing clear implicit processing of the contralesional side of line drawings and object based neglect. The patient was able to perform correct semantic analysis of the symmetry (or asymmetry) of the drawings. Additional testing disclosed denial of the existence of the contralesional side of asymmetrical geometrical shapes with correct perception of symmetrical ones and of shapes without the left side. These findings provide direct evidence supporting a critical role of the dorsal visual system in the activation of conscious representations of visual stimuli.

Misrepresentation of horizontal space in left unilateral neglect: role of hemianopia.

BACKGROUND: Right-brain-damaged patients with left unilateral neglect are reported to misperceive the horizontal extension of contralesional stimuli as being shorter than that of ipsilesional stimuli. OBJECTIVE: To investigate the functional and anatomic correlates of horizontal space misrepresentation. METHODS: Eight right-brain-damaged patients with contralesional neglect and complete hemianopia (N+H+), nine right-brain-damaged patients with contralesional neglect and no visual field defect (N+H-), and five unilateral brain-damaged patients with contralesional complete hemianopia and no neglect (N-H+) reproduced a horizontal distance (10 cm) in the contralesional and ipsilesional hemispace. RESULTS: N+H+ patients overextended the distance contralesionally and underextended the same distance ipsilesionally. N+H- and N-H+ patients reproduced equivalent distances contralesionally and ipsilesionally. Compared with N+H- patients, N+H+ patients had a greater ipsilesional shift when bisecting horizontal lines; however, these two groups of patients had comparable neglect severity on multiple-item cancellation tasks. In the N+H+ group the area of maximal overlapping of the lesion was in the posterior cerebral lobes. CONCLUSION: Complete contralesional hemianopia after posterior brain damage is an important factor in determining misrepresentation of horizontal space in patients with left unilateral neglect.

Seeing only the right half of the forest but cutting down all the trees?

Unilateral neglect following damage to the right hemisphere of the brain can be characterized by failure of the global attentional mechanisms of the right hemisphere to direct the local detail processors of the left hemisphere towards the contralesional left hemispace. This is suggested by patients who recognize the global form of the left side of shapes (the forest) but fail to cancel out its local details (the trees). Here we report the opposite behavioural dissociation in a patient (Q.M.) with damage to the right hemisphere of the brain. Q.M. detected local details (such as the tail of a dog) on the left or right side of visual shapes, regardless of whether these details belonged to predefined target shapes (a dog in this case) or to distractor shapes differing on the opposite side (a dog with a swan's neck and head, for example). Psychological testing showed an abnormal tendency of this patient to respond to local features, but perfect accuracy in interpreting global features when the local features could not interfere in global processing. The results indicate that the left hemisphere can integrate multiple local features simultaneously but loses global awareness as soon as local features individually compete for response selection. However, awareness of the whole is not necessary for the sequential processing of the parts.

Neural control of fast-regular saccades and antisaccades: an investigation using positron emission tomography.

Regional cerebral blood flow changes related to the performance of two oculomotor tasks and a central fixation task were compared in ten healthy human subjects. The tasks were: (a) performance of fast-regular saccades; (b) performance of voluntary antisaccades away from a peripheral cue; (c) passive maintenance of central visual fixation in the presence of irrelevant peripheral stimulation. The saccadic task was associated with a relative increase in activity in a number of occipitotemporal areas. Compared with both the fixation and the saccadic task, the performance of antisaccades activated a set of areas including: the superior and inferior parietal lobules, the precentral and prefrontal cortex, the cingulate cortex, and the supplementary motor area. The results of the present study suggest that: (a) compared with self-determined saccadic responses the performance of fast regular, reflexive saccades produces a limited activation of the frontal eye fields; (b) in the antisaccadic task the inferior parietal lobes subserve operations of sensory-motor integration dealing with attentional disengagement from the initial peripheral cue (appearing at an invalid spatial location) and with the recomputation of the antisaccadic vector on the basis of the wrong (e.g., spatially opposite) information provided by the same cue.

Gravitational inputs modulate visuospatial neglect.

Right brain-damaged patients with left visuospatial neglect were required to bisect a line placed in front of them in two different body positions (upright and supine) and two different light conditions (light and dark). The neglect patients, unlike right brain-damaged patients without neglect, strongly reduced their rightward directional error in the supine compared with the upright position. No systematic changes were produced by the light-dark manipulation. The present result cannot be explained with an attentional interpretation of hemispatial neglect. We suggest that the present data provide further evidence that hemineglect is the consequence of a mismatch between different afferent information integrated into an egocentric space representation. According to this model, the presence of a lateralized brain lesion produces asymmetries in some intermediate spatial representations (eye-head, head-trunk, body-environment) but not in the retinotopic one. Any experimental manipulation that reduces the asymmetry of the intermediate representation such as the reduction of gravitational inputs may improve the dynamic integration of the egocentric coordinates.

Neglect for low luminance contrast stimuli but not for high colour contrast stimuli: a behavioural and electrophysiological case study.

We describe a patient with a right hemisphere lesion involving the frontal lobe, the post-central gyrus and the superior parietal lobule. Behavioural testing demonstrated severe left unilateral neglect to low luminance contrast stimuli, but not to high colour contrast stimuli. Evoked potentials to low contrast luminance gratings presented in the left hemifield were not reliable. However, equiluminant coloured gratings presented in the same hemifield evoked reliable electrophysiological responses, although longer in latency than those evoked in the right hemifield. These findings suggest that the patient has severe damage of the high contrast sensitivity magnocellular pathway in the right hemisphere, with minor involvement of the parvocellular pathway.

Attentional functions in multiple system atrophy and Parkinson's disease.

OBJECTIVE: To assess cognitive performances of patients with striatonigral degeneration type multiple system atrophy compared with those of patients with Parkinson's disease. METHODS: The cognitive performances of a group of patients with multiple system atrophy of the striatonigral type were compared with those of matched patients with Parkinson's disease and controls, using tests sensitive to frontal lobe dysfunction. RESULTS: The multiple system atrophy group, when compared with the Parkinson's disease group, showed significant deficits in attention tasks, particularly in the Stroop test. CONCLUSION: There was a consistently greater impairment in attention resources in patients with multiple system atrophy than in patients with Parkinson's disease.

Asymmetry of rapid eye movements in chronic unilateral neglect does not change with behavioral improvement induced by rehabilitation treatment.

A strong reduction of leftward rapid eye movements (REMs) during REM sleep was recently documented in patients with severe and chronic left unilateral neglect. The aim of the present research was to study the stability of the unilateral suppression of REMs before and after a rehabilitative treatment for neglect disorders. Six right-brain-damaged patients were tested for neglect at the beginning and at the end of a 2 month cognitive rehabilitation treatment. REMs were recorded during 1 night of undisturbed sleep before and after the training. Five out of 6 patients improved considerably their ability to attend the previously neglected left hemispace; in all patients REM asymmetry remained unchanged. The lack of relationship between the improvement of the neglect disorder and the persistence of REM asymmetry suggests that the sensorimotor mechanisms activated by rehabilitation are different from those involved in the production of REMs. It is proposed that: (a) the directional vectors of REMs are computed on the basis of the exclusive or predominant endogenous activation of the central attentional mechanisms related to vestibular input; (b) the presence of rightward and leftward saccades and the positive effects of the rehabilitation treatment are functionally linked to attentional oculomotor mechanisms that are not active in REM sleep.

Gravity and hemineglect.

Spatial cognition requires the integration of visual inputs with proprioceptive and vestibular information about the position of the eye, the head and the body. All these sources are used by the brain to produce multiple higher-order (e.g. egocentric) representations of space, subserving accurate spatial behaviour. Such spatial representations are disrupted by unilateral cerebral damage producing neglect in the contralateral side of space. In eight brain-damaged patients with left unilateral neglect the manipulation of gravitational-otolithic information, obtained by placing patients in a supine position, produced a significant reduction of the rightward directional error in the line bisection task in all cases. This finding suggests that, in patients with neglect, gravitational information is processed in a non-symmetrical fashion, with a rightward bias towards the side of the lesion. This is the first study showing that manipulation of gravitational input affects neuropsychological disorders of visuo-spatial processing.

Amplitude and speed change of the optokinetic response in patients with and without neglect.

The present study quantitatively investigated the slow and quick phases of optokinetic nystagmus (OKN) in four groups of patients: right unilateral brain-damaged patients with neglect, left and right patients without neglect or hemianopia and patients with left or right retrogeniculate lesions and lateral homonymous hemianopia. Our results indicate that only neglect patients show a perturbation of both components of OKN. A comparison among MRI images of different patients shows that a region involving area 37 and adjacent areas 39 and 19, was impaired in all patients with neglect, but not in any other patient with either right or left lesions.

Generation of skeletal and multipart mental visual images in the cerebral hemispheres: a study in normal subjects.

In a series of three experiments the hemispheric lateralization of structures generating the details and the holistic properties of mental images was investigated in three different samples of normal right-handed subjects. In the first experiment the left hemisphere was faster in discriminating at an imagery level whether animals had short or long tails. No hemispheric dominance was found when the imagery task required the discrimination of the holistic features of objects and a decision of whether they were taller than wider, or vice versa. In the second experiment no hemispheric dominance was found when the same tasks had to be performed perceptually. In the third experiment no hemispheric dominance was found in the speed of lexical recognition of the names that in the first experiment elicited the generation of multipart and skeletal mental images, although the left hemisphere was generally more accurate. These findings provide support to the hypothesis advanced by Kosslyn that multipart mental images are generated by the left hemisphere and skeletal images by both hemispheres. Results are discussed both in terms of Kosslyn's computational theory of imagery generation and in terms of theories advanced by other authors.

Disturbances of the rapid eye movements (REMs) of REM sleep in patients with unilateral attentional neglect: clue for the understanding of the functional meaning of REMs.

Horizontal saccades during wakefulness and horizontal rapid eye movements (REMs) during REM sleep were recorded in 6 unilateral brain damaged patients suffering from attentional neglect and 6 unilateral brain damaged control patients. During REM sleep, patients with neglect showed a nearly total suppression of REMs directed away from the side of the lesion; controls had a significantly milder frequency reduction of the same movements. In all patients the frequency reduction of REMs contralateral to the lesion equally affected isolated REMs (i.e., REMs preceded by intervals of oculomotor quiescence longer than 2 sec) and REM bursts (i.e., REMs preceded by intervals shorter than 2 sec). During voluntary inspection in waking, saccades directed ipsilaterally and contralaterally to the lesion were present in both groups of patients, although patients with neglect confined their inspection to the hemispace ipsilateral to the lesion. Results are discussed in terms of their implications for the understanding of the neurophysiological basis of REM sleep oculomotor activity and dream production, as well as for the neurophysiopathological basis of the neglect syndrome. It is proposed that REMs are functionally equivalent to waking reflex orienting saccades generated by a neural network including the relevant modulatory action of the parietal lobes and the superior colliculi.

Patterns of hemispheric lateralization in dream recallers and non-dream recallers.

Eighteen right handed females reporting 6 or more dreams per week on a home dream and sleep diary (Dream Recallers: DR), and 11 reporting 1 or 0 dreams per week (Non Dream Recallers: NDR) drawn from a sample of 233 college students, were individually tested on two tasks assessing the hemispheric lateralization of visuo-constructive and verbal-semantic functions. NDR showed a significant degree of hemispheric asymmetry of both visuo-constructive (right asymmetry of both visuo-constructive (right hemisphere advantage) and semantic (left hemisphere advantage) functions. DR showed no hemispheric advantage on both tasks. The two groups of subjects did not differ in mean daily amount of sleep time. In keeping with previous studies showing that NDR have an imbalance of interhemispheric activation upon REM awakenings, results from the present research suggest that DR and NDR can be characterized by a different pattern of hemispheric lateralization of cognitive skills. This finding may stimulate further research aimed at evaluating both the possible existence of differences in the lateralization of functions not considered in this study and the concomitance of REM sleep dependent differences in balance of hemispheric functioning.

Disappearance of leftward rapid eye movements during sleep in left visual hemi-inattention.

Contrasting hypotheses have been proposed about the functional equivalence between waking saccades and REMs. Patients with left visual hemi-inattention showed dissociation between the direction of waking saccades and that of REMs. REMs directed toward the left were virtually absent, while waking inspective saccades directed in both lateral directions were present, but confined to the right hemispace. It is concluded that: a) the cortical areas regulating attention are relevant in the production of REMs; b) two separate attentional mechanisms have to be considered in relation to the hemi-inattentive syndrome, one is involved in the cognitive control of visual exploration and plays little or no role in the modulation of REMs, the other deals with REMs during sleep and with reflex-like orienting responses to peripheral stimuli during waking.