White matter lesional predictors of chronic visual neglect: a longitudinal study.

Chronic visual neglect prevents brain-damaged patients from returning to an independent and active life. Detecting predictors of persistent neglect as early as possible after the stroke is therefore crucial to plan the relevant interventions. Neglect signs do not only depend on focal brain lesions, but also on dysfunction of large-scale brain networks connected by white matter bundles. We explored the relationship between markers of axonal degeneration occurring after the stroke and visual neglect chronicity. A group of 45 patients with unilateral strokes in the right hemisphere underwent cognitive testing for neglect twice, first at the subacute phase (<3 months after onset) and then at the chronic phase (>1 year). For each patient, magnetic resonance imaging including diffusion sequences was performed at least 4 months after the stroke. After masking each patient's lesion, we used tract-based spatial statistics to obtain a voxel-wise statistical analysis of the fractional anisotropy data. Twenty-seven patients had signs of visual neglect at initial testing. Only 10 of these patients had recovered from neglect at follow-up. When compared with patients without neglect, the group including all subacute neglect patients had decreased fractional anisotropy in the second (II) and third (III) branches of the right superior longitudinal fasciculus, as well as in the splenium of the corpus callosum. The subgroup of chronic patients showed reduced fractional anisotropy in a portion the splenium, the forceps major, which provides interhemispheric communication between regions of the occipital lobe and of the superior parietal lobules. The severity of neglect correlated with fractional anisotropy values in superior longitudinal fasciculus II/III for subacute patients and in its caudal portion for chronic patients. Our results confirm a key role of fronto-parietal disconnection in the emergence and chronic persistence of neglect, and demonstrate an implication of caudal interhemispheric disconnection in chronic neglect. Splenial disconnection may prevent fronto-parietal networks in the left hemisphere from resolving the activity imbalance with their right hemisphere counterparts, thus leading to persistent neglect.

When brain damage "improves" perception: neglect patients can localize motion-shifted probes better than controls.

When we look at bars flashed against a moving background, we see them displaced in the direction of the upcoming motion (flash-grab illusion). It is still debated whether these motion-induced position shifts are low-level, reflexive consequences of stimulus motion or high-level compensation engaged only when the stimulus is tracked with attention. To investigate whether attention is a causal factor for this striking illusory position shift, we evaluated the flash-grab illusion in six patients with damaged attentional networks in the right hemisphere and signs of left visual neglect and six age-matched controls. With stimuli in the top, right, and bottom visual fields, neglect patients experienced the same amount of illusion as controls. However, patients showed no significant shift when the test was presented in their left hemifield, despite having equally precise judgments. Thus, paradoxically, neglect patients perceived the position of the flash more veridically in their neglected hemifield. These results suggest that impaired attentional processes can reduce the interaction between a moving background and a superimposed stationary flash, and indicate that attention is a critical factor in generating the illusory motion-induced shifts of location.

Long-lasting reduction in postural asymmetry by prism adaptation after right brain lesion without neglect.

BACKGROUND: Right brain damage (RBD) involves postural asymmetry and spatial frame disorders. In acute RBD patients, postural asymmetry is immediately reduced after one single session of prism adaptation (PA), without assessment of effects on spatial frames. AIM: To assess long-term effects of PA on posture and spatial frames in chronic RBD patients, without neglect. METHOD: Six chronic RBD patients without neglect (mean delay 45 months) were included. Each patient sustained 10 PA sessions of 20 min during 2 weeks. Outcome measures were: (1) posturographic analysis (mediolateral position of centre of pressure (X cop), (2) subjective straight ahead (SSA) and perception of longitudinal body axis (LBA). Each parameter was assessed by three pretests and three post-tests (+2 h, day + 3 and day + 7). RESULTS: In pretests, patients showed a shift of the X cop and SSA. In post-tests, results displayed (1) a significant reduction in mediolateral postural asymmetry at D + 7; (2) a significant left deviation of SSA at D + 3 and enduring at D + 7; and (3) no significant modification of LBA. The mean curves of X cop and SSA between pre- and post-tests were similar. CONCLUSIONS: PA involves persistent reduction in postural asymmetry in RBD patients without neglect. These findings were obtained at a chronic stage. This new effect cannot be explained by reduction in spatial attentional shift. Improvement may be explained by a better calibration of extra personal space frames used for posture, without effect on personal space frame. Findings argue in favour of a bottom-up effect of PA on mechanisms underlying spatial cognition.

Effector-dependent neglect and splenial disconnection: a spherical deconvolution tractography study.

We present the case of a patient with left homonymous hemianopia and chronic left neglect consequent to a stroke in the occipito-temporal regions of the right hemisphere. When the patient performed cancellation tasks with her right (dominant) hand, she had severe and persistent left neglect at retest 7 and 8 years after onset. However, her performance on line bisection was invariably within normal limits. Strikingly, performance on cancellation tests reverted to normal when the patient used her left hand. White matter tractography using spherical deconvolution demonstrated damage to the splenium of the corpus callosum, as well as a relative preservation of the right fronto-parietal network. Effector-dependent neglect may occur because splenial disconnection deprives the right fronto-parietal network from visual information processed by the left hemisphere. Consequently, spatial exploration reverts to normal when the patient uses her left hand, thus involving more directly the fronto-parietal attentional networks in the right-hemisphere.

Cognitive reserve involves decision making and is associated with left parietal and hippocampal hypertrophy in neurodegeneration.

Cognitive reserve is the ability to actively cope with brain deterioration and delay cognitive decline in neurodegenerative diseases. It operates by optimizing performance through differential recruitment of brain networks or alternative cognitive strategies. We investigated cognitive reserve using Huntington's disease (HD) as a genetic model of neurodegeneration to compare premanifest HD, manifest HD, and controls. Contrary to manifest HD, premanifest HD behave as controls despite neurodegeneration. By decomposing the cognitive processes underlying decision making, drift diffusion models revealed a response profile that differs progressively from controls to premanifest and manifest HD. Here, we show that cognitive reserve in premanifest HD is supported by an increased rate of evidence accumulation compensating for the abnormal increase in the amount of evidence needed to make a decision. This higher rate is associated with left superior parietal and hippocampal hypertrophy, and exhibits a bell shape over the course of disease progression, characteristic of compensation.

Graph methods to infer spatial disturbances: Application to Huntington's Disease's speech.

OBJECTIVE: Huntington's Disease (HD) is an inherited neurodegenerative disease caused by the mutation of the Htt gene, impacting all aspects of living and functioning. Among cognitive disabilities, spatial capacities are impaired, but their monitoring remains scarce as limited by lengthy experts' assessments. Language offers an alternative medium to evaluate patients' performance in HD. Yet, its capacities to assess HD's spatial abilities are unknown. Here, we aimed to bring proof-of-concept that HD's spatial deficits can be assessed through speech. METHODS: We developed the Spatial Description Model to graphically represent spatial relations described during the Cookie Theft Picture (CTP) task. We increased the sensitivity of our model by using only sentences with spatial terms, unlike previous studies in Alzheimer's disease. 78 carriers of the mutant Htt, including 56 manifest and 22 premanifest individuals, as well as 25 healthy controls were included from the BIOHD & (NCT01412125) & Repair-HD (NCT03119246) cohorts. The convergence and divergence of the model were validated using the SelfCog battery. RESULTS: Our Spatial Description Model was the only one among the four assessed approaches, revealing that individuals with manifest HD expressed fewer spatial relations and engaged in less spatial exploration compared to healthy controls. Their graphs correlated with both visuospatial and language SelfCog performances, but not with motor, executive nor memory functions. CONCLUSIONS: We provide the proof-of-concept using our Spatial Description Model that language can grasp HD patient's spatial disturbances. By adding spatial capabilities to the panel of functions tested by the language, it paves the way for eventual remote clinical application.

Prism adaptation therapy in spatial neglect: The importance of connectional anatomy.

The meta-analysis conducted by Székely et al. described the lack of beneficial effect of prism adaptation in neglect patients. The authors concluded that the results did "not support the routine use of prism adaptation as a therapy for spatial neglect". However, a possible nuance to this conclusion could be that the response (or lack thereof) of neglect patients to prism adaptation may actually depend on the connectional anatomy of their lesion. We develop this idea in our commentary, in order to offer a more balanced perspective on the implications of the findings obtained by Székely et al.

The striatum in time production: The model of Huntington's disease in longitudinal study.

The unified model of time processing suggests that the striatum is a central structure involved in all tasks that require the processing of temporal durations. Patients with Huntington's disease exhibit striatal degeneration and a deficit in time perception in interval timing tasks (i.e. for duration ranging from hundreds of milliseconds to minutes), but whether this deficit extends to time production remains unclear. In this study, we investigated whether symptomatic patients (HD, N = 101) or presymptomatic gene carriers (Pre-HD, N = 31) of Huntington's disease had a deficit in time production for durations between 4 and 10 s compared to healthy controls and whether this deficit developed over a year for patients. We found a clear deficit in temporal production for HD patients, whereas Pre-HD performed similarly to Controls. For HD patients and Pre-HD participants, task performance was correlated with grey matter volume in the amygdala and caudate, bilaterally. These results confirm that the striatum is involved in interval timing not only in perception but also in production, in accordance with the unified model of time processing. Furthermore, exploratory factor analyses on our data indicated that temporal production was associated with clinical assessments of psychomotor and executive functions. Finally, when retested twelve months later, the deficit of HD patients remained stable, although striatal degeneration was more pronounced. Thus, the simple, short and language-independent temporal production task may be a useful clinical tool to detect striatal degeneration in patients in early stages of Huntington's disease. However, its usefulness to detect presymptomatic stages or for monitoring the evolution of HD over a year seems limited.

A new approach to digitized cognitive monitoring: validity of the SelfCog in Huntington's disease.

Cognitive deficits represent a hallmark of neurodegenerative diseases, but evaluating their progression is complex. Most current evaluations involve lengthy paper-and-pencil tasks which are subject to learning effects dependent on the mode of response (motor or verbal), the countries' language or the examiners. To address these limitations, we hypothesized that applying neuroscience principles may offer a fruitful alternative. We thus developed the SelfCog, a digitized battery that tests motor, executive, visuospatial, language and memory functions in 15 min. All cognitive functions are tested according to the same paradigm, and a randomization algorithm provides a new test at each assessment with a constant level of difficulty. Here, we assessed its validity, reliability and sensitivity to detect decline in early-stage Huntington's disease in a prospective and international multilingual study (France, the UK and Germany). Fifty-one out of 85 participants with Huntington's disease and 40 of 52 healthy controls included at baseline were followed up for 1 year. Assessments included a comprehensive clinical assessment battery including currently standard cognitive assessments alongside the SelfCog. We estimated associations between each of the clinical assessments and SelfCog using Spearman's correlation and proneness to retest effects and sensitivity to decline through linear mixed models. Longitudinal effect sizes were estimated for each cognitive score. Voxel-based morphometry and tract-based spatial statistics analyses were conducted to assess the consistency between performance on the SelfCog and MRI 3D-T1 and diffusion-weighted imaging in a subgroup that underwent MRI at baseline and after 12 months. The SelfCog detected the decline of patients with Huntington's disease in a 1-year follow-up period with satisfactory psychometric properties. Huntington's disease patients are correctly differentiated from controls. The SelfCog showed larger effect sizes than the classical cognitive assessments. Its scores were associated with grey and white matter damage at baseline and over 1 year. Given its good performance in longitudinal analyses of the Huntington's disease cohort, it should likely become a very useful tool for measuring cognition in Huntington's disease in the future. It highlights the value of moving the field along the neuroscience principles and eventually applying them to the evaluation of all neurodegenerative diseases.

Predicting clinical scores in Huntington's disease: a lightweight speech test.

OBJECTIVES: Using brief samples of speech recordings, we aimed at predicting, through machine learning, the clinical performance in Huntington's Disease (HD), an inherited Neurodegenerative disease (NDD). METHODS: We collected and analyzed 126 samples of audio recordings of both forward and backward counting from 103 Huntington's disease gene carriers [87 manifest and 16 premanifest; mean age 50.6 (SD 11.2), range (27-88) years] from three multicenter prospective studies in France and Belgium (MIG-HD (ClinicalTrials.gov NCT00190450); BIO-HD (ClinicalTrials.gov NCT00190450) and Repair-HD (ClinicalTrials.gov NCT00190450). We pre-registered all of our methods before running any analyses, in order to avoid inflated results. We automatically extracted 60 speech features from blindly annotated samples. We used machine learning models to combine multiple speech features in order to make predictions at individual levels of the clinical markers. We trained machine learning models on 86% of the samples, the remaining 14% constituted the independent test set. We combined speech features with demographics variables (age, sex, CAG repeats, and burden score) to predict cognitive, motor, and functional scores of the Unified Huntington's disease rating scale. We provided correlation between speech variables and striatal volumes. RESULTS: Speech features combined with demographics allowed the prediction of the individual cognitive, motor, and functional scores with a relative error from 12.7 to 20.0% which is better than predictions using demographics and genetic information. Both mean and standard deviation of pause durations during backward recitation and clinical scores correlated with striatal atrophy (Spearman 0.6 and 0.5-0.6, respectively). INTERPRETATION: Brief and examiner-free speech recording and analysis may become in the future an efficient method for remote evaluation of the individual condition in HD and likely in other NDD.

The specific role of the striatum in interval timing: The Huntington's disease model.

Time processing over intervals of hundreds of milliseconds to minutes, also known as interval timing, is associated with the striatum. Huntington's disease patients (HD) with striatal degeneration have impaired interval timing, but the extent and specificity of these deficits remain unclear. Are they specific to the temporal domain, or do they extend to the spatial domain too? Do they extend to both the perception and production of interval timing? Do they appear before motor symptoms in Huntington's disease (Pre-HD)? We addressed these issues by assessing both temporal abilities (in the seconds range) and spatial abilities (in the cm range) in 20 Pre-HD, 25 HD patients, and 25 healthy Controls, in discrimination, bisection and production paradigms. In addition, all participants completed a questionnaire assessing temporal and spatial disorientation in daily life, and the gene carriers (i.e., HD and Pre-HD participants) underwent structural brain MRI. Overall, HD patients were more impaired in the temporal than in the spatial domain in the behavioral tasks, and expressed a greater disorientation in the temporal domain in the daily life questionnaire. In contrast, Pre-HD participants showed no sign of a specific temporal deficit. Furthermore, MRI analyses indicated that performances in the temporal discrimination task were associated with a larger striatal grey matter volume in the striatum in gene carriers. Altogether, behavioral, brain imaging and questionnaire data support the hypothesis that the striatum is a specific component of interval timing processes. Evaluations of temporal disorientation and interval timing processing could be used as clinical tools for HD patients.

Effects of prismatic adaptation on balance and postural disorders in patients with chronic right stroke: protocol for a multicentre double-blind randomised sham-controlled trial.

INTRODUCTION: Patients with right stroke lesion have postural and balance disorders, including weight-bearing asymmetry, more pronounced than patients with left stroke lesion. Spatial cognition disorders post-stroke, such as misperceptions of subjective straight-ahead and subjective longitudinal body axis, are suspected to be involved in these postural and balance disorders. Prismatic adaptation has showed beneficial effects to reduce visuomotor disorders but also an expansion of effects on cognitive functions, including spatial cognition. Preliminary studies with a low level of evidence have suggested positive effects of prismatic adaptation on weight-bearing asymmetry and balance after stroke. The objective is to investigate the effects of this intervention on balance but also on postural disorders, subjective straight-ahead, longitudinal body axis and autonomy in patients with chronic right stroke lesion. METHODS AND ANALYSIS: In this multicentre randomised double-blind sham-controlled trial, we will include 28 patients aged from 18 to 80 years, with a first right supratentorial stroke lesion at chronic stage (≥12 months) and having a bearing ≥60% of body weight on the right lower limb. Participants will be randomly assigned to the experimental group (performing pointing tasks while wearing glasses shifting optical axis of 10 degrees towards the right side) or to the control group (performing the same procedure while wearing neutral glasses without optical deviation). All participants will receive a 20 min daily session for 2 weeks in addition to conventional rehabilitation. The primary outcome will be the balance measured using the Berg Balance Scale. Secondary outcomes will include weight-bearing asymmetry and parameters of body sway during static posturographic assessments, as well as lateropulsion (measured using the Scale for Contraversive Pushing), subjective straight-ahead, longitudinal body axis and autonomy (measured using the Barthel Index). ETHICS AND DISSEMINATION: The study has been approved by the ethical review board in France. Findings will be submitted to peer-reviewed journals relative to rehabilitation or stroke. TRIAL REGISTRATION NUMBER: NCT03154138.

Cognitive decline in Huntington's disease in the Digitalized Arithmetic Task (DAT).

BACKGROUND: Efficient cognitive tasks sensitive to longitudinal deterioration in small cohorts of Huntington's disease (HD) patients are lacking in HD research. We thus developed and assessed the digitized arithmetic task (DAT), which combines inner language and executive functions in approximately 4 minutes. METHODS: We assessed the psychometric properties of DAT in three languages, across four European sites, in 77 early-stage HD patients (age: 52 ± 11 years; 27 females), and 57 controls (age: 50 ± 10, 31 females). Forty-eight HD patients and 34 controls were followed up to one year with 96 participants who underwent MRI brain imaging (HD patients = 46) at baseline and 50 participants (HD patients = 22) at one year. Linear mixed models and Pearson correlations were used to assess associations with clinical assessment. RESULTS: At baseline, HD patients were less accurate (p = 0.0002) with increased response time (p<0.0001) when compared to DAT in controls. Test-retest reliability in HD patients ranged from good to excellent for response time (range: 0.63-0.79) and from questionable to acceptable for accuracy (range: r = 0.52-0.69). Only DAT, the Mattis Dementia Rating Scale, the Symbol Digit Modalities Test, and Total Functional Capacity scores were able to detect a decline within a one-year follow-up in HD patients (all p< 0.05). In contrast with all the other cognitive tasks, DAT correlated with striatal atrophy over time (p = 0.037) but not with motor impairment. CONCLUSIONS: DAT is fast, reliable, motor-free, applicable in several languages, and able to unmask cognitive decline correlated with striatal atrophy in small cohorts of HD patients. This likely makes it a useful endpoint in future trials for HD and other neurodegenerative diseases.

Regression of left hyperschematia after prism adaptation: A single case study.

Prism adaptation (PA) is a promising treatment in the rehabilitation of post-stroke cognitive disorders such as unilateral spatial neglect or constructional deficits. Right brain damage can bring about another representational spatial disorder, termed «hyperschematia¼, and defined by a left-sided disproportionate expansion of drawings by copy and from memory, and by an overestimation of left lateral extent when a leftward movement is required. This case study aimed at evaluating the effect of PA induced by prismatic lenses creating a shift to the left on hyperschematia signs. A 63-year-old woman with left hyperschematia, consecutive to a right fronto-temporo-parietal hematoma, was exposed to a leftward optical deviation produced by prismatic lenses. An anatomical MRI studied topography of the brain lesion; the patient's lesion was then mapped onto tractography reconstructions of white matter pathways. Results showed that PA significantly reduced the left-sided expansion of drawing by copy and from memory, and the overestimation of left lateral extent, immediately after prism removal and 4 days later, indicating a persistent long lasting cognitive effect. MRI showed a right hemisphere disconnection of the posterior and long segments of the arcuate fasciculus, and of the inferior longitudinal and fronto-occipital fasciculi. Overall, these findings suggest that: i) PA is effective also in hyperschematia by re-orientating spatial attention towards the right side of space, with a relative rightward PA-induced unbalance, and re-setting the spatial representation to the left side of space, contralateral to the side of the lesion; ii) the left misrepresentation of lateral extent may be related to a disconnection between visual coordinates and attentional networks to the frontal lobe.

Anatomical predictors of successful prism adaptation in chronic visual neglect.

Visual neglect is a frequent and disabling consequence of right hemisphere damage. Previous work demonstrated a probable role of posterior callosal dysfunction in the chronic persistence of neglect signs. Prism adaptation is a non-invasive and convenient technique to rehabilitate chronic visual neglect, but it is not effective in all patients. Here we aimed to assess the hypothesis that prism adaptation improves left neglect by facilitating compensation through the contribution of the left, undamaged hemisphere. We assessed the relationship between prism adaptation effects, cortical thickness and white matter integrity in a group of 14 patients with unilateral right-hemisphere strokes and chronic visual neglect. Results showed that patients who benefitted from prism adaptation had thicker cortex in temporo-parietal, prefrontal and cingulate areas of the left, undamaged hemisphere. Additionally, these patients had a higher fractional anisotropy value in the body and genu of the corpus callosum. Results from normal controls show that these callosal regions connect temporo-parietal, sensorimotor and prefrontal areas. Finally, shorter time intervals from the stroke tended to improve patients' response to prism adaptation. We concluded that prism adaptation may improve left visual neglect by promoting the contribution of the left hemisphere to neglect compensation. These results support current hypotheses on the role of the healthy hemisphere in the compensation for stroke-induced, chronic neuropsychological deficits, and suggest that prism adaptation can foster this role by exploiting sensorimotor/prefrontal circuits, especially when applied at early stages post-stroke.

Attention and spatial cognition: Neural and anatomical substrates of visual neglect.

Unilateral spatial neglect (USN) is a neurological disorder often observed following damage to the right cerebral hemisphere. Patients with USN are no longer able to take into account stimuli presented on the left side of space. In this article, we will discuss the neuroanatomical correlates that underlie visuospatial attention and can cause USN, an area of growing research interest in the past 20 years. This syndrome has often been related to cortical damage, notably in the inferior parietal lobule. Other data have also implicated lesions in the inferior frontal gyrus or the superior temporal gyrus. In this article, we will highlight the relevance of viewing USN as a disconnection syndrome of interconnected cerebral areas, as opposed to a focal cortical syndrome. We will review data that provide evidence of intrahemispheric disconnection, in particular within the right hemisphere's frontoparietal networks connected by the superior longitudinal fasciculus. Recent findings suggest that interhemispheric disconnection could also contribute to the manifestations of USN. Most importantly, interhemispheric disconnection might be a predictive factor for the chronicity of this disorder. This hypothesis implies that the left hemisphere by itself is not able to compensate for the patients' deficits. Recovery requires the ability to exchange information between the two hemispheres, particularly in the posterior parietal and occipital regions.

Improvement of Navigation and Representation in Virtual Reality after Prism Adaptation in Neglect Patients.

Prism adaptation (PA) is responsible for an expansion of sensori-motor after-effects to cognitive domains for patients with spatial neglect. One important question is whether the cognitive after-effects induced by PA may also concern higher aspects of spatial cognition, such as navigation and topographic memory, which are critical in everyday life. The aim of this study was to assess whether multiple sessions of right PA can affect navigation and topographic memory. Seven right brain-damaged (RBD) patients with chronic neglect were included. We used a virtual supermarket named VAP-S which is an original paradigm, similar to the "shopping list test" during which patients had to purchase items from a list of eight products. Furthermore, in order to assess generalization of PA effects on constructing a spatial map from virtual information, each participant was then asked to draw the map of the virtual supermarket from memory. Regarding navigation performance, significant results were obtained: session duration reduction, fewer numbers of pauses and omissions, more items purchased on the left side and more items purchased over all. A long-lasting effect was noted, up to one month after PA. The representational task performance was also significantly increased for map drawing, with a reduction of the right shift of the symmetry axis of the map, more items drawn on the left side of maps and over all, and more items correctly located on the map. Some of these effects lasted for at least 7 days. These results suggest an expansion of PA benefit to a virtual environment. Crucially, the cognitive benefits induced by PA were noted for complex spatial cognition tasks required in everyday life such as navigation and topographic memory and this improvement was maintained for up to 1 month.

Inappropriate rightward saccades after right hemisphere damage: Oculomotor analysis and anatomical correlates.

Patients with right hemisphere damage and visual neglect have severe problems to orient attention towards left-sided objects, often associated with the tendency to produce inappropriate rightward saccades. In its most severe form, this tendency can assume the compulsive character of a rightward deviation of gaze as soon as the visual scene deploys (so-called "magnetic attraction of gaze"). However, little is known about the exact nature of inappropriate rightward saccades, their relation with impaired conscious perception of left-sided stimuli, and their lesional correlates. To explore these issues, we studied three groups of patients with right brain damage: patients with signs of left visual neglect associated to left homonymous hemianopia, neglect patients without hemianopia, and patients without neglect or hemianopia. Participants searched for a gap missing within a target, presented among distractors. Manual responses for target detection were required, while participants were encouraged to move their eyes during search. Endogenous attention could be summoned to the target location by a central cue. All the three groups of patients produced inappropriate rightward saccades, which could not be completely overcome by the endogenous orienting of attention induced by the cues. Anatomical analysis indicated a specific implication of damage to the right frontal eye field and to a long-range white matter tract, the fronto-parietal superior longitudinal fasciculus. Fronto-parietal networks in the right hemisphere appear thus to be essential to integrate covert and overt orienting of attention, and to thoroughly explore space in order to become aware of the multiple competing objects around us.