Fabrizio Doricchi

Damage to White Matter Pathways in Subacute and Chronic Spatial Neglect: A Group Study and 2 Single-Case Studies with Complete Virtual “In Vivo” Tractography Dissection

The exact anatomical localization of right hemisphere lesions that lead to left spatial neglect is still debated. The effect of confounding factors such as acute diaschisis and hypoperfusion, visual field defects, and lesion size may account for conflicting results that have been reported in the literature. Here, we present a comprehensive anatomical investigation of the gray- and white matter lesion correlates of left spatial neglect, which was run in a sample 58 patients with subacute or chronic vascular strokes in the territory of the right middle cerebral artery. Standard voxel-based correlates confirmed the role played by lesions in the posterior parietal cortex (supramarginal gyrus, angular gyrus, and temporal-parietal junction), in the frontal cortex (frontal eye field, middle and inferior frontal gyrus), and in the underlying parietal-frontal white matter. Using a new diffusion tensor imaging-based atlas of the human brain, we were able to run, for the first time, a detailed analysis of the lesion involvement of subcortical white matter pathways. The results of this analysis revealed that, among the different pathways linking parietal with frontal areas, damage to the second branch of the superior longitudinal fasciculus (SLF II) was the best predictor of left spatial neglect. The group study also revealed a subsample of patients with neglect due to focal lesion in the lateral-dorsal portion of the thalamus, which connects the premotor cortex with the inferior parietal lobule. The relevance of fronto-parietal disconnection was further supported by complete in vivo tractography dissection of white matter pathways in 2 patients, one with and the other without signs of neglect. These 2 patients were studied both in the acute phase and 1 year after stroke and were perfectly matched for age, handedness, stroke onset, lesion size, and for cortical lesion involvement. Taken together, the results of the present study support the hypothesis that anatomical disconnections leading to a functional breakdown of parietal-frontal networks are an important pathophysiological factor leading to chronic left spatial neglect. Here, we propose that different loci of SLF disconnection on the rostro-caudal axis can also be associated with disconnection of short-range white matter pathways within the frontal or parietal areas. Such different local disconnection patterns can play a role in the important clinical variability of the neglect syndrome.

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.

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 Parkinsons 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 Parkinsons disease and controls, using tests sensitive to frontal lobe dysfunction. RESULTS: The multiple system atrophy group, when compared with the Parkinsons 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 Parkinsons disease.

Attention and predictions: control of spatial attention beyond the endogenous-exogenous dichotomy.

The mechanisms of attention control have been extensively studied with a variety of methodologies in animals and in humans. Human studies using non-invasive imaging techniques highlighted a remarkable difference between the pattern of responses in dorsal fronto-parietal regions vs. ventral fronto-parietal (vFP) regions, primarily lateralized to the right hemisphere. Initially, this distinction at the neuro-physiological level has been related to the distinction between cognitive processes associated with strategic/endogenous vs. stimulus-driven/exogenous of attention control. Nonetheless, quite soon it has become evident that, in almost any situation, attention control entails a complex combination of factors related to both the current sensory input and endogenous aspects associated with the experimental context. Here, we review several of these aspects first discussing the joint contribution of endogenous and stimulus-driven factors during spatial orienting in complex environments and, then, turning to the role of expectations and predictions in spatial re-orienting. We emphasize that strategic factors play a pivotal role for the activation of the ventral system during stimulus-driven control, and that the dorsal system makes use of stimulus-driven signals for top-down control. We conclude that both the dorsal and the vFP networks integrate endogenous and exogenous signals during spatial attention control and that future investigations should manipulate both these factors concurrently, so as to reveal to full extent of these interactions.

No inherent left and right side in human ‘mental number line’: evidence from right brain damage

Spatial reasoning has a relevant role in mathematics and helps daily computational activities. It is widely assumed that in cultures with left-to-right reading, numbers are organized along the mental equivalent of a ruler, the mental number line, with small magnitudes located to the left of larger ones. Patients with right brain damage can disregard smaller numbers while mentally setting the midpoint of number intervals. This has been interpreted as a sign of spatial neglect for numbers on the left side of the mental number line and taken as a strong argument for the intrinsic left-to-right organization of the mental number line. Here, we put forward the understanding of this cognitive disability by discovering that patients with right brain damage disregard smaller numbers both when these are mapped on the left side of the mental number line and on the right side of an imagined clock face. This shows that the right hemisphere supports the representation of small numerical magnitudes independently from their mapping on the left or the right side of a spatial-mental layout. In addition, the study of the anatomical correlates through voxel-based lesion-symptom mapping and the mapping of lesion peaks on the diffusion tensor imaging-based reconstruction of white matter pathways showed that the rightward bias in the imagined clock-face was correlated with lesions of high-level middle temporal visual areas that code stimuli in object-centred spatial coordinates, i.e. stimuli that, like a clock face, have an inherent left and right side. In contrast, bias towards higher numbers on the mental number line was linked to white matter damage in the frontal component of the parietal-frontal number network. These anatomical findings show that the human brain does not represent the mental number line as an object with an inherent left and right side. We conclude that the bias towards higher numbers in the mental bisection of number intervals does not depend on left side spatial, imagery or object-centred neglect and that it rather depends on disruption of an abstract non-spatial representation of small numerical magnitudes.

Non-spatial neglect for the mental number line

Several psychophysical investigations, expanding the classical introspective observations by Galton, have suggested that the mental representation of numbers takes the form of a number line along which magnitude is positioned in ascending order according to reading habits, i.e. from left to right in Western cultures. In keeping with the evidence, pathological rightward deviations in the bisection of number intervals due to right brain damage are generally interpreted as originating from a purely spatial-attentional deficit in the processing of the left side of number intervals. However, consistent double dissociations between defective processing of the left side of physical and mental number space have called into question the universality of this interpretation. Recent evidence suggests a link between rightward deviations in number space and defective memory for both spatial and non-spatial sequences of items. Here we describe the case of a left brain-damaged patient exhibiting right-sided neglect for extrapersonal and representational space, and left-sided neglect on the mental number line. Accurate neuropsychological examination revealed that the apparent left-sided neglect in the bisection of number intervals had a purely non-spatial origin and was based on mnemonic difficulties for the initial items of verbal sequences presented visually at an identical spatial position. These findings show that effective position-based verbal working memory might be crucial for numerical tasks that are usually considered to involve purely spatial representation of numerical magnitudes.

Spatial attention and conscious perception: the role of endogenous and exogenous orienting

Attention has often been considered to be a gateway to consciousness (Posner, Proceedings of the National Academy of Sciences of the United States of America, 91(16), 7398–7403, 1994). However, its relationship with conscious perception (CP) remains highly controversial. While theoretical models and experimental data support the role of attention in CP (Chica, Lasaponara, Lupiáñez, Doricchi, & Bartolomeo, NeuroImage, 51, 1205–1212, 2010; Dehaene, Changeux, Naccache, Sackur, & Sergent, Trends in Cognitive Sciences, 10, 204–211, 2006; Mack & Rock, Inattentional blindness,1998), recent studies have claimed that at least some forms of attention—endogenous or top-down spatial attention—are neither sufficient nor necessary for CP (Koch & Tsuchiya, Trends in Cognitive Sciences, 11, 16–22, 2007). In the present experiments, we demonstrate the importance of exogenously triggered attention for the modulation of CP. Weak or null effects were instead observed when attention was triggered endogenously. Our data are discussed in the framework of recent neuropsychological models (Dehaene et al., Trends in Cognitive Sciences, 10, 204–211, 2006), postulating that activity within reverberating frontoparietal networks, as colocalized with spatial--orienting systems, is the brain correlate of consciously processed information.

Effects of Vestibular Rotatory Accelerations on Covert Attentional Orienting in Vision and Touch

Peripheral vestibular organs feed the central nervous system with inputs favoring the correct perception of space during head and body motion. Applying temporal order judgments (TOJs) to pairs of simultaneous or asynchronous stimuli presented in the left and right egocentric space, we evaluated the influence of leftward and rightward vestibular rotatory accelerations given around the vertical head-body axis on covert attentional orienting. In a first experiment, we presented visual stimuli in the left and right hemifield. In a second experiment, tactile stimuli were presented to hands lying on their anatomical side or in a crossed position across the sagittal body midline. In both experiments, stimuli were presented while normal subjects suppressed or did not suppress the vestibulo-ocular response (VOR) evoked by head-body rotation. Independently of VOR suppression, visual and tactile stimuli presented on the side of rotation were judged to precede simultaneous stimuli presented on the side opposite the rotation. When limbs were crossed, attentional facilitatory effects were only observed for stimuli presented to the right hand lying in the left hemispace during leftward rotatory trials with VOR suppression. This result points to spatiotopic rather than somatotopic influences of vestibular inputs, suggesting that cross-modal effects of these inputs on tactile ones operate on a representation of space that is updated following arm crossing. In a third control experiment, we demonstrated that temporal prioritization of stimuli presented on the side of rotation was not determined by response bias linked to spatial compatibility between the directions of rotation and the directional labels used in TOJs (i.e., left or right first). These findings suggest that during passive rotatory head-body accelerations, covert attention is shifted toward the direction of rotation and the direction of the fast phases of the VOR.

Horizontal space misrepresentation in unilateral brain damage. II. Eye-head centered modulation of visual misrepresentation in hemianopia without neglect.

We used a visual distance reproduction task (endpoint task) to evaluate horizontal space representation in two left brain damaged (LBD) and three right brain damaged (RBD) patients with contralateral homonymous hemianopia and no neglect. All patients were examined in the chronic phase of the stroke and were aware of their visual field defect. Along with contralesional deviation in the line bisection task, all patients estimated size (Landmark task) and distances in the contralesional space as being longer than equivalent size and distances located in the ipsilesional space. Misreproduction of distances was abolished or reduced when the task was performed in the ipsilesional head-centred space with the head turned contralesionally. This finding points out that misrepresentation of horizontal space linked to hemianopia can be modulated by combined proprioceptive input from eye and neck muscles. The pattern of misrepresentation found in chronic hemianopic patients is opposite to the one described in chronic neglect patients with concomitant hemianopia. These different patterns of space misrepresentation are the likely consequence of the presence, in hemianopics, and the absence, in neglect patients with hemianopia, of compensatory strategies based on the non-retinotopic and multimodal coding of spatial positions falling in the retinotopically organised blind field.

Spatial orienting biases in the decimal numeral system.

Humans map numbers upon a mental number line (MNL) on which small integers are placed to the left of larger ones [1-9]. Here, we show that human adults systematically shift the subjective midpoints of number intervals away from the borders separating contiguous tens along the MNL. Number intervals are erroneously bisected further to the right the closer they are to the left starting point of the tens and further to the left the closer they are to the right endpoint of the tens. Similarly, right-brain-damaged patients neglecting the left side of the MNL [10-12] show enhanced pathological rightward deviation in the bisection of number intervals located toward the left starting point of the tens and reduced deviation for intervals located toward the right endpoint of the tens. These data disclose the effects that the recursive grouping of symbolic decimal numerals within the tens has brought on the phylogenetically and ontogenetically foregoing spatial representation of magnitudes [13-16].