Clinical neuropsychologist, Division of Neurorehabilitation, University Hospital Geneva and Senior lecturer, Medical school, University of Geneva, Switzerland
Research interests Clinical neuropsychology; Disorders of space perception; Memory disorders; Agnosia; Executive dysfunction and decision-making; Cognitive neurorehabilitation
Abstract: ABSTRACT: BACKGROUND: The role of the inferior parietal lobule (IPL) and superior temporal gyrus (STG) or subcortical pathways as possible anatomical correlates of spatial neglect is currently intensely discussed. Some of the conflicting results might have arisen because patients were examined in the acute stage of disease. METHODS: We examined the anatomical basis of spatial neglect in a sample of patients examined in the post-acute stage following right-hemispheric vascular brain damage. Lesions of 28 patients with chronic spatial neglect were contrasted to lesions of 22 control patients without neglect using lesion subtraction techniques and voxel-wise comparisons. RESULTS: The comparisons identified the temporo-parietal junction (TPJ) with underlying white matter, the supramarginal gyrus, the posterior STG, and the insula as brain regions damaged significantly more often in neglect compared to non-neglect patients. In a subgroup of neglect patients showing particularly large cancellation bias together with small errors on line bisection damage was prevalent deep in the frontal lobe while damage of patients with the reverse pattern was located in the white matter of the TPJ. CONCLUSIONS: Considering our results and the findings of previous studies, spatial neglect appears to be associated with a network of regions involving the TPJ, inferior IPL, posterior STG, the insular cortex, and posterior-frontal projections. Frontal structures or projections may be of particular relevance for spatial exploration, while the IPL may be important for object-based attention as required in line bisection.
Abstract: When we actively explore the visual environment, our gaze preferentially selects regions characterized by high contrast and high density of edges, suggesting that the guidance of eye movements during visual exploration is driven to a significant degree by perceptual characteristics of a scene. Converging findings suggest that the selection of the visual target for the upcoming saccade critically depends on a covert shift of spatial attention. However, it is unclear whether attention selects the location of the next fixation uniquely on the basis of global scene structure or additionally on local perceptual information. To investigate the role of spatial attention in scene processing, we examined eye fixation patterns of patients with spatial neglect during unconstrained exploration of natural images and compared these to healthy and brain-injured control participants. We computed luminance, colour, contrast, and edge information contained in image patches surrounding each fixation and evaluated whether they differed from randomly selected image patches. At the global level, neglect patients showed the characteristic ipsilesional shift of the distribution of their fixations. At the local level, patients with neglect and control participants fixated image regions in ipsilesional space that were closely similar with respect to their local feature content. In contrast, when directing their gaze to contralesional (impaired) space neglect patients fixated regions of significantly higher local luminance and lower edge content than controls. These results suggest that intact spatial attention is necessary for the active sampling of local feature content during scene perception.
Abstract: 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.
Abstract: Patients with spatial neglect show disproportionately slow reactions to a contralesional stimulus presented shortly after an ipsilesional cue. We examined whether this attentional bias reflects purely automatic capture of attention by the cue or whether it is contingent on the similarity between cue and target. Patients with spatial neglect reacted to letters presented in the left or right visual field. These target letters were pre-cued by the same letter (similar cue) or a different letter (dissimilar cue) presented 100 or 1000 ms prior to target onset in the same or the opposite visual field. At the short interval, similar and dissimilar ipsilesional cues captured attention comparably and strongly slowed reactions to contralesional targets. In contrast, while similar ipsilesional cues still captured attention at the long interval dissimilar cues ceased to affect performance. In contrast, the different cueing conditions induced only small and insignificant differences in reaction times to ipsilesional targets. These findings suggest that attention of neglect patients is initially captured by all ipsilesional cues in a reflexive, stimulus-driven fashion, but that prolonged attentional capture may only be observed when cues share a property with the target.
Abstract: Patients with spatial neglect are impaired when detecting contralesional targets presented shortly after an ipsilesional cue. This "disengagement" deficit is believed to reflect reflexive orienting towards ipsilesional stimuli that is independent of behavioural goals. Here, we show that the extent of this spatial bias depends on the behavioural salience of ipsilesional stimuli. Healthy participants, brain-injured patients without neglect and neglect patients reacted to ipsilesional and contralesional visual targets. Prior to target presentation, a visual cue similar or dissimilar to the target was presented at target position or opposite the target. Although participants did not react to the similar cue, it had high behavioural salience since it shared features with the target stimulus. Neglect patients showed dramatically increased reaction times to contralesional targets, but only when these followed behaviourally relevant ipsilesional cues. No decrease of performance was observed with irrelevant cues. This performance pattern was not due to perceptual similarity, since the same effect was found when cue and target were semantically related but differed perceptually. Importantly, semantically related cues ceased to attract attention when they were defined as behaviourally irrelevant. These results show that neglect patients only orient attention reflexively towards ipsilesional stimuli with high behavioural salience.
Abstract: Previous work has reported that in the Iowa gambling task (IGT) advantageous decisions may be taken before the advantageous strategy is known [Bechara, A., Damasio, H., Tranel, D., & Damasio, A. R. (1997). Deciding advantageously before knowing the advantageous strategy. Science, 275, 1293-1295]. In order to test whether explicit memory is essential for the acquisition of a behavioural preference for advantageous choices, we measured behavioural performance and skin conductance responses (SCRs) in five patients with dense amnesia following damage to the basal forebrain and orbitofrontal cortex, six amnesic patients with damage to the medial temporal lobe or the diencephalon, and eight control subjects performing the IGT. Across 100 trials healthy participants acquired a preference for advantageous choices and generated large SCRs to high levels of punishment. In addition, their anticipatory SCRs to disadvantageous choices were larger than to advantageous choices. However, this dissociation occurred much later than the behavioural preference for advantageous alternatives. In contrast, though exhibiting discriminatory autonomic SCRs to different levels of punishment, 9 of 11 amnesic patients performed at chance and did not show differential anticipatory SCRs to advantageous and disadvantageous choices. Further, the magnitude of anticipatory SCRs did not correlate with behavioural performance. These results suggest that the acquisition of a behavioural preference--be it for advantageous or disadvantageous choices--depends on the memory of previous reinforcements encountered in the task, a capacity requiring intact explicit memory.
Abstract: Although impaired visual search is a core deficit of patients with spatial neglect, current evidence is not conclusive about the mechanisms underlying this failure. We present evidence from 14 neglect patients searching for a target defined by two perceptual features that visual search is mediated by mechanisms of attentional competition. Participants were tested in three search conditions with constant target and distracter positions: Distracters did not share any feature with the target; distracters shared one feature with the target; two distracters shared one feature and one distracter shared the other feature with the target (mixed condition). Whereas search performance of healthy participants was comparable across conditions, neglect patients had a significant contralesional slowing in the mixed condition compared with the other two conditions. A detailed lesion analysis revealed that involvement of the parietal lobe did not predict the degree of distractibility in visual search. In contrast, neglect patients with high distractibility had more frequent damage to the inferior temporal lobe, suggesting a preliminary role of this region for competitive attentional processes involved in visual search of spatial neglect patients.
Abstract: One of the most constant findings of studies about selective attention is that detection of visual stimuli is enhanced when a visual cue is presented at the position of the upcoming target. In healthy participants, comparable benefits were reported when the cue was presented in a different modality than the target. The aim of this study was to examine spatial and temporal dynamics of visual attention following auditory cues in patients with spatial neglect. Twelve healthy subjects and five patients with left-sided neglect were asked to react to a small vertical line presented randomly at one of four positions. The target appeared 150 or 1000 ms after an auditory cue that was either static (continuous 380 Hz tone presented to the left or right ear) or dynamic (380 Hz tone moving from the left to the right ear or vice versa). The reaction time pattern of healthy participants was unaffected by the different tones. In contrast, reaction times of neglect patients were significantly faster to left targets following a dynamic tone moving from right to left in comparison to a tone moving from left to right. Interestingly, static unilateral tones modulated visual attention of neglect patients to a lesser degree than dynamic tones. The modulation of visual attention by dynamic auditory cues was of short duration and disappeared after 1000 ms. These results demonstrate a fast automatic shift of spatial attention in the direction of a moving tone, suggesting strong dynamic links between visual and auditory attention in patients with a severe spatial deficit.
Abstract: Balint syndrome after bilateral parietal damage involves a severe disturbance of space representation including impaired oculomotor behaviour, optic ataxia, and simultanagnosia. Binding of object features into a unique spatial representation can also be impaired. We report a patient with bilateral parietal lesions and Balint syndrome, showing severe spatial deficits in several visual tasks predominantly affecting the left hemispace. In particular, we tested whether a loss of spatial representation would affect crossmodal interactions between simultaneous visual and tactile events occurring at the same versus different locations. A tactile discrimination task, where spatially congruent or incongruent visual cues were delivered near the patient's hands, was used. Following stimulation of the left hand in the left side of space, we observed visuo-tactile interactions that were not modulated by spatially congruent conditions. In contrast, performance following stimulation of the right hand in the right side of space was affected in a spatially selective manner--facilitated for congruent stimuli and slowed for incongruent stimuli. To dissociate effects on somatotopic and spatiotopic coordinates, we crossed the patient's hands during unimodal tactile discriminations. Tactile performance of the left hand improved when it was positioned in the right hemispace, whereas placing the right hand in left space produced no significant changes, suggesting that left-sided tactile inputs are coded with respect to a combination of limb- and trunk-centred coordinates. These data converge with recent findings in animals and healthy humans to indicate a critical role of the posterior parietal cortex in multimodal spatial integration, and in the fusion of different coordinates into a unified representation of space.
Abstract: Neurophysiological and functional brain imaging studies suggest the importance of dorsolateral area 9/46 for modality-independent working memory. However, the behavioural manifestations following isolated damage to this area have not been clearly outlined. Here, we describe the dramatic derangement of pragmatic memory after circumscribed lesion of the right area 9/46. A 52 year-old woman had suffered a traumatic brain injury 13 years ago and sought help for what she thought was a severe memory disorder. She regularly missed appointments and had gradually lost all her friends. She had tried different strategies to compensate for her memory problem, such as writing notes on her wrist or using electronic organizers. Intelligence, attention, verbal long-term memory, and executive functions were normal. Furthermore, experimental exploration demonstrated intact time estimation, attribution of memories to ongoing reality, and anticipation of outcomes. However, she failed to rehearse and manipulate information in working memory (n-back task), confirming the findings of functional imaging studies that the mid-dorsolateral prefrontal cortex is involved in mental manipulation of information. This case exemplifies that an isolated lesion of the right area 9/46 may induce severe failure to schedule actions and memory retrieval, a disorder leading to severely disorganised behaviour and disability.
Abstract: Emotional blunting can be found after cerebellar lesions. However, the mechanism of such a modification is not clear. We present a patient with emotional flattening and increased risk taking after left cerebellar infarct who had an impaired autonomic reactivity to negative as compared with positive reinforcement. This impairment was demonstrated by the patient's undifferentiated skin conductance responses to negative and positive reinforcement, whereas controls produced larger skin conductance responses after negative feedback. The cooccurrence of emotional flattening and undifferentiated autonomic reactions to positively and negatively valenced stimuli strengthens the role of the cerebellum in the modulation of the autonomic responses.
Abstract: Visual extinction, the failure of patients with unilateral focal brain damage to report the contralesional of two simultaneously presented stimuli, may be modulated by characteristics of the display such as similarity, collinearity, or connectedness. Since these factors affect the perceptual configuration of stimuli, the modulation of extinction is believed to reflect low-level perceptual grouping. In the present study, patient AG did not show any modulation of contralesional detection when the ipsilesional and contralesional stimulus grouped by colour, by form, or both (Experiment 1). In contrast, identification of the contralesional stimulus was facilitated when the stimuli grouped (Experiment 2), suggesting a modulation of extinction by specific task demands. Experiment 3 used a cueing procedure to demonstrate modulation of extinction by expectation biases. Prior to stimulus presentation, AG was cued to attend to a particular feature (e.g. colour). After stimulus exposure he was prompted to identify the expected feature on valid trials and the unexpected feature on invalid trials. AG showed a significant validity effect for contralesional stimuli i.e. he identified the expected feature (e.g. colour) significantly better than the unexpected feature (e.g. form). These results suggest that competition for selection between visual stimuli may not only be influenced by perceptual characteristics of the display, but also by high-level factors such as the response criterion or expectation biases.
Abstract: A fundamental capacity of the human brain is to learn relations (contingencies) between environmental stimuli and the consequences of their occurrence. Some contingencies are probabilistic; that is, they predict an event in some situations but not in all. Animal studies suggest that damage to limbic structures or the prefrontal cortex may disturb probabilistic learning. The authors studied the learning of probabilistic contingencies in amnesic patients with limbic lesions, patients with prefrontal cortex damage, and healthy controls. Across 120 trials, participants learned contingent relations between spatial sequences and a button press. Amnesic patients had learning comparable to that of control subjects but failed to indicate what they had learned. Across the last 60 trials, amnesic patients and control subjects learned to avoid a noncontingent choice better than frontal patients. These results indicate that probabilistic learning does not depend on the brain structures supporting declarative memory.
Abstract: Previous studies demonstrated that patients producing spontaneous confabulations fail to suppress currently irrelevant memory traces and have anterior limbic lesions, particularly involving the orbitofrontal cortex or the basal forebrain. Here, a woman is described who had sarcoidosis damaging the medial hypothalamus and endocrine dysfunction, and a severe memory failure characterized by spontaneous confabulation, disorientation, and severely impaired free recall with preserved recognition. Isolated hypothalamic damage may produce the same type of memory disorder as orbitofrontal damage.
Abstract: Disorders of tactile object recognition (TOR) may result from primary motor or sensory deficits or higher cognitive impairment of tactile shape representations or semantic memory. Studies with healthy participants suggest the existence of exploratory motor procedures directly linked to the extraction of specific properties of objects. A pure deficit of these procedures without concomitant gnostic disorders has never been described in a brain-damaged patient. Here, we present a patient with a right hemispheric infarction who, in spite of intact sensorimotor functions, had impaired TOR with the left hand. Recognition of 2D shapes and objects was severely deficient under the condition of spontaneous exploration. Tactile exploration of shapes was disorganized and exploratory procedures, such as the contour-following strategy, which is necessary to identify the precise shape of an object, were severely disturbed. However, recognition of 2D shapes under manually or verbally guided exploration and the recognition of shapes traced on the skin were intact, indicating a dissociation in shape recognition between active and passive touch. Functional MRI during sensory stimulation of the left hand showed preserved activation of the spared primary sensory cortex in the right hemisphere. We interpret the deficit of our patient as a pure tactile apraxia without tactile agnosia, i.e. a specific inability to use tactile feedback to generate the exploratory procedures necessary for tactile shape recognition.
Abstract: BACKGROUND: In previous studies, the authors found that patients with spontaneous confabulation differ from those with nonconfabulating amnesia by 1) temporal context confusion (TCC) in memory based on an inability to suppress intrusions of currently irrelevant memory traces into ongoing thinking; and 2) lesions involving the orbitofrontal cortex, basal forebrain, or amygdala and perirhinal cortex. OBJECTIVES: To study the long-term clinical course of spontaneous confabulations, determine whether TCC in memory also parallels the clinical course of spontaneous confabulations, and study the impact of lesion site on clinical course. METHODS: Eight patients with spontaneous confabulation were re-examined 18 months after onset. Tests of memory and executive functioning and measurement of TCC in memory were again applied. MRI according to a standard protocol was performed to determine areas of permanent damage. RESULTS: Seven patients eventually stopped confabulating. TCC, but not common memory or executive tests, precisely paralleled the course of spontaneous confabulations. Patients with isolated, less extensive, orbitofrontal lesions stopped confabulating first and had the best neuropsychological outcome. Patients with basal forebrain lesions continued to confabulate for several months and remained amnesic. One patient with extensive orbitofrontal damage and perirhinal cortex damage continues to confabulate after more than 3 years, continuing to confuse memory traces. CONCLUSIONS: Temporal context confusion in memory is not only the sole feature reliably separating patients with spontaneous confabulation from those with nonconfabulating amnesia in the acute stage, it is also the only feature that precisely parallels the clinical course of spontaneous confabulations. Most patients eventually stop confabulating but duration of confabulations depends on the lesion site.
Abstract: Human actions require integration of past experiences, ongoing percepts and future concepts. To adapt behavior to reality, the brain must identify mental representations of current relevance. Occasional amnesic subjects act according to invented stories ('spontaneous confabulations'), disregarding present reality. We used repeated runs of a continuous recognition task to measure the ability to distinguish currently relevant from previously encountered but currently irrelevant information. Spontaneous confabulators detected target items as accurately as nonconfabulating amnesics, but increasingly failed to suppress false-positive responses, confusing presentation in previous runs with presentation in the current run. Lesions involved the anterior limbic system: medial orbitofrontal cortex, basal forebrain, amygdala and perirhinal cortex or medial hypothalamus. We suggest that the anterior limbic system represents 'now' in human thinking by suppressing currently irrelevant mental associations.
