Gambling against neglect: unconscious spatial biases induced by reward reinforcement in healthy people and brain-damaged patients.

Orienting attention in space recruits fronto-parietal networks whose damage results in unilateral spatial neglect. However, attention orienting may also be governed by emotional and motivational factors; but it remains unknown whether these factors act through a modulation of the fronto-parietal attentional systems or distinct neural pathways. Here we asked whether attentional orienting is affected by learning about the reward value of targets in a visual search task, in a spatially specific manner, and whether these effects are preserved in right-brain damaged patients with left spatial neglect. We found that associating rewards with left-sided (but not right-sided) targets during search led to progressive exploration biases towards left space, in both healthy people and neglect patients. Such spatially specific biases occurred even without any conscious awareness of the asymmetric reward contingencies. These results show that reward-induced modulations of space representation are preserved despite a dysfunction of fronto-parietal networks associated with neglect, and therefore suggest that they may arise through spared subcortical networks directly acting on sensory processing and/or oculomotor circuits. These effects could be usefully exploited for potentiating rehabilitation strategies in neglect patients.

Ocular scanning and perceptual size distortion in hemispatial neglect: effects of prism adaptation and sequential stimulus presentation

When asked to compare two lateralized shapes for horizontal size, neglect patients often indicate the left stimulus to be smaller. Gainotti and Tiacci (1971) hypothesized that this phenomenon might be related to a rightward bias in the patients' gaze. This study aimed to assess the relation between this size underestimation and oculomotor asymmetries. Eye movements were recorded while three neglect patients judged the horizontal extent of two rectangles. Two experimental manipulations were performed to increase the likelihood of symmetrical scanning of the stimulus display. The first manipulation entailed a sequential, rather than simultaneous presentation of the two rectangles. The second required adaptation to rightward displacing prisms, which is known to reduce many manifestations of neglect. All patients consistently underestimated the left rectangle, but the pattern of verbal responses and eye movements suggested different underlying causes. These include a distortion of space perception without ocular asymmetry, a failure to view the full leftward extent of the left stimulus, and a high-level response bias. Sequential presentation of the rectangles and prism adaptation reduced ocular asymmetries without affecting size underestimation. Overall, the results suggest that leftward size underestimation in neglect can arise for a number of different reasons. Incomplete leftward scanning may perhaps be sufficient to induce perceptual size distortion, but it is not a necessary prerequisite.

Visual search in spatial neglect studied with a preview paradigm.

Impaired visual search is a hallmark of spatial neglect. When searching for an unique feature (e.g., color) neglect patients often show only slight visual field asymmetries. In contrast, when the target is defined by a combination of features (e.g., color and form) they exhibit a severe deficit of contralesional search. This finding suggests a selective impairment of the serial deployment of spatial attention. Here, we examined this deficit with a preview paradigm. Neglect patients searched for a target defined by the conjunction of shape and color, presented together with varying numbers of distracters. The presentation time was varied such that on some trials participants previewed the target together with same-shape/different-color distracters, for 300 or 600 ms prior to the appearance of additional different-shape/same-color distracters. On the remaining trials the target and all distracters were shown simultaneously. Healthy participants exhibited a serial search strategy only when all items were presented simultaneously, whereas in both preview conditions a pop-out effect was observed. Neglect patients showed a similar pattern when the target was presented in the right hemifield. In contrast, when searching for a target in the left hemifield they showed serial search in the no-preview condition, as well as with a preview of 300 ms, and partly even at 600 ms. A control experiment suggested that the failure to fully benefit from item preview was probably independent of accurate perception of time. Our results, when viewed in the context of existing literature, lead us to conclude that the visual search deficit in neglect reflects two additive factors: a biased representation of attentional priority in favor of ipsilesional information and exaggerated capture of attention by ipsilesional abrupt onsets.

Spatial Hyperschematia without Spatial Neglect after Insulo-Thalamic Disconnection.

Different spatial representations are not stored as a single multipurpose map in the brain. Right brain-damaged patients can show a distortion, a compression of peripersonal and extrapersonal space. Here we report the case of a patient with a right insulo-thalamic disconnection without spatial neglect. The patient, compared with 10 healthy control subjects, showed a constant and reliable increase of her peripersonal and extrapersonal egocentric space representations - that we named spatial hyperschematia - yet left her allocentric space representations intact. This striking dissociation shows that our interactions with the surrounding world are represented and processed modularly in the human brain, depending on their frame of reference.

Emotionally negative stimuli can overcome attentional deficits in patients with visuo-spatial hemineglect.

Left unilateral spatial neglect resulting from right brain damage is characterized by loss of awareness for stimuli in the contralesional side of space, despite intact visual pathways. We examined using fMRI whether patients with neglect are more likely to consciously detect in the neglected hemifield, emotionally negative complex scenes rather than visually similar neutral pictures and if so, what neural mechanisms mediate this effect. Photographs of emotional and neutral scenes taken from the IAPS were presented in a divided visual field paradigm. As expected, the detection rate for emotional stimuli presented in the neglected field was higher than for neutral ones. Successful detection of emotional scenes as opposed to neutral stimuli in the left visual field (LVF) produced activations in the parahippocampal and anterior cingulate areas in the right hemisphere. Detection of emotional stimuli presented in the intact right visual field (RVF) activated a distributed network of structures in the left hemisphere, including anterior and posterior cingulate cortex, insula, as well as visual striate and extrastriate areas. LVF-RVF contrasts for emotional stimuli revealed activations in right and left attention related prefrontal areas whereas RVF-LVF comparison showed activations in the posterior cingulate and extrastriate visual cortex in the left hemisphere. An additional analysis contrasting detected vs. undetected emotional LVF stimuli showed involvement of left anterior cingulate, right frontal and extrastriate areas. We hypothesize that beneficial role of emotion in overcoming neglect is achieved by activation of frontal and limbic lobe networks, which provide a privileged access of emotional stimuli to attention by top-down modulation of processing in the higher-order extrastriate visual areas. Our results point to the importance of top-down regulatory role of the frontal attentional systems, which might enhance visual activations and lead to greater salience of emotional stimuli for perceptual awareness.

Effects of pro-cholinergic treatment in patients suffering from spatial neglect.

Spatial neglect is a neurological condition characterized by a breakdown of spatial cognition contralateral to hemispheric damage. Deficits in spatial attention toward the contralesional side are considered to be central to this syndrome. Brain lesions typically involve right fronto-parietal cortices mediating attentional functions and subcortical connections in underlying white matter. Convergent findings from neuroimaging and behavioral studies in both animals and humans suggest that the cholinergic system might also be critically implicated in selective attention by modulating cortical function via widespread projections from the basal forebrain. Here we asked whether deficits in spatial attention associated with neglect could partly result from a cholinergic deafferentation of cortical areas subserving attentional functions, and whether such disturbances could be alleviated by pro-cholinergic therapy. We examined the effect of a single-dose transdermal nicotine treatment on spatial neglect in 10 stroke patients in a double-blind placebo-controlled protocol, using a standardized battery of neglect tests. Nicotine-induced systematic improvement on cancellation tasks and facilitated orienting to single visual targets, but had no significant effect on other tests. These results support a global effect of nicotine on attention and arousal, but no effect on other spatial mechanisms impaired in neglect.

Combination treatment in the rehabilitation of visuo-spatial neglect

Resumen tomado de la publicaci??n

Theta burst stimulation reduces disability during the activities of daily living in spatial neglect

Left-sided spatial neglect is a common neurological syndrome following right-hemispheric stroke. The presence of spatial neglect is a powerful predictor of poor rehabilitation outcome. In one influential account of spatial neglect, interhemispheric inhibition is impaired and leads to a pathological hyperactivity in the contralesional hemisphere, resulting in a biased attentional allocation towards the right hemifield. Inhibitory transcranial magnetic stimulation can reduce the hyperactivity of the contralesional, intact hemisphere and thereby improve spatial neglect symptoms. However, it is not known whether this improvement is also relevant to the activities of daily living during spontaneous behaviour. The primary aim of the present study was to investigate whether the repeated application of continuous theta burst stimulation trains could ameliorate spatial neglect on a quantitative measure of the activities of daily living during spontaneous behaviour. We applied the Catherine Bergego Scale, a standardized observation questionnaire that can validly and reliably detect the presence and severity of spatial neglect during the activities of daily living. Eight trains of continuous theta burst stimulation were applied over two consecutive days on the contralesional, left posterior parietal cortex in patients suffering from subacute left spatial neglect, in a randomized, double-blind, sham-controlled design, which also included a control group of neglect patients without stimulation. The results showed a 37% improvement in the spontaneous everyday behaviour of the neglect patients after the repeated application of continuous theta burst stimulation. Remarkably, the improvement persisted for at least 3 weeks after stimulation. The amelioration of spatial neglect symptoms in the activities of daily living was also generally accompanied by significantly better performance in the neuropsychological tests. No significant amelioration in symptoms was observed after sham stimulation or in the control group without stimulation. These results provide Class I evidence that continuous theta burst stimulation is a viable add-on therapy in neglect rehabilitation that facilitates recovery of normal everyday behaviour.

A non-spatial bias favouring fixated stimuli revealed in patients with spatial neglect

The cardinal feature of spatial neglect is severely impaired exploration of the contralesional space, a failure resulting in unawareness of many contralesional stimuli. This deficit is exacerbated by a reflexive attentional bias toward ipsilesional items. Here we show that, in addition to these spatially lateralized failures, neglect patients also exhibit a severe bias favouring stimuli presented at fixation. We tested neglect patients and matched healthy and right-hemisphere damaged patients without neglect in a task requiring saccade execution to targets in the left or right hemifield. Targets were presented alone or simultaneously with a distracter that appeared in the same hemifield, in the opposite hemifield, or at fixation. We found two fundamental biases in saccade initiation of neglect patients: irrelevant distracters presented in the preserved hemifield tended to capture gaze reflexively, resulting in a large number of saccades erroneously directed toward the distracter. Additionally, distracters presented at fixation severely disrupted saccade initiation irrespective of saccade direction, leading to disproportionately increased latencies of left and right saccades. This latency increase was specific to oculomotor responses of neglect patients and was not observed when a manual response was required. These results show that, in addition to their failure to inhibit reflexive glances toward ipsilesional items neglect patients exhibit a strong oculomotor bias favouring fixated stimuli. We conclude that impaired initiation of saccades in any direction contributes to the deficits of spatial exploration that characterize spatial neglect.

Theta burst stimulation improves overt visual search in spatial neglect independently of attentional load

Visual neglect is considerably exacerbated by increases in visual attentional load. These detrimental effects of attentional load are hypothesised to be dependent on an interplay between dysfunctional inter-hemispheric inhibitory dynamics and load-related modulation of activity in cortical areas such as the posterior parietal cortex (PPC). Continuous Theta Burst Stimulation (cTBS) over the contralesional PPC reduces neglect severity. It is unknown, however, whether such positive effects also operate in the presence of the detrimental effects of heightened attentional load. Here, we examined the effects of cTBS on neglect severity in overt visual search (i.e., with eye movements), as a function of high and low visual attentional load conditions. Performance was assessed on the basis of target detection rates and eye movements, in a computerised visual search task and in two paper-pencil tasks. cTBS significantly ameliorated target detection performance, independently of attentional load. These ameliorative effects were significantly larger in the high than the low load condition, thereby equating target detection across both conditions. Eye movement analyses revealed that the improvements were mediated by a redeployment of visual fixations to the contralesional visual field. These findings represent a substantive advance, because cTBS led to an unprecedented amelioration of overt search efficiency that was independent of visual attentional load.

Evaluación y tratamiento basados en realidad virtual de la negligencia espacial unilateral: análisis del estado de la cuestión y demostración de enfoques alternativos

En el siguiente trabajo se presenta en primer lugar de forma detallada la enfermedad denominada negligencia espacial unilateral (síntomas, tipos, causas, evaluación y tratamientos) para proporcionar una mejor comprensión del principal objetivo del estudio, que es el análisis de las soluciones virtuales, existentes en la literatura, aplicadas al tratamiento de esta enfermedad, incluyéndose una amplia descripción de cada estudio encontrado sobre el tema. A continuación, se han realizado tres implementaciones en realidad virtual de tres técnicas clásicas de rehabilitación llevadas a cabo en un entorno virtual, que son la estimulación optocinética, eye patching, y adaptación prismática y se ha desarrollado una aplicación 3D para evaluar el grado y tipo de negligencia sufrida por los pacientes. Que de forma conjunta, constituyen un primer paso hacia un enfoque alternativo para el tratamiento de la enfermedad, más personalizado y eficaz. Por último, en las conclusiones, se analizan las principales ventajas y desventajas encontradas en el uso de estas tecnologías aplicadas a la enfermedad y los trabajos futuros que pueden derivar de este trabajo.---ABSTRACT---The following work starts by presenting in detail a disease called unilateral spatial neglect (symptoms, types, causes, assessment and treatment) to provide the background for this study's main objective, which is the analysis of the virtual solutions existing in the literature for the treatment of this disease. The document includes an extensive description of the previous work found in this topic. Afterwards, three implementations of three classical rehabilitation techniques were performed in virtual reality: optokinetic stimulation, eye patching and prism adaptation, as a proof-of-concept, and a 3D application was implemented to assess the degree and type of negligence suffered by patients. Altogether, they constitute a first step towards an alternative approach for the treatment of disease, more personalized and effective. Finally, the conclusions analyze the main advantages and disadvantages encountered in the use of these technologies when applied to this disease and suggest future work.