High field brain proton magnetic resonance spectroscopy and volumetry in children with chronic, compensated liver disease - A pilot study.

BACKGROUND: There is increasing evidence that children or young adults having acquired liver disease in childhood display neurocognitive impairment which may become more apparent as they grow older. The molecular, cellular and morphological underpinnings of this clinical problem are incompletely understood. AIM: Therefore, we used the advantages of highly-resolved proton magnetic resonance spectroscopy at ultra-high magnetic field to analyze the neurometabolic profile and brain morphometry of children with chronic, compensated liver disease, hypothesizing that with high field spectroscopy we would identify early evidence of rising brain glutamine and decreased myoinositol, such as has been described both in animals and humans with more significant liver disease. METHODS: Patients (n = 5) and age-matched controls (n = 19) underwent 7T MR scans and short echo time 1H MR spectra were acquired using the semi-adiabatic SPECIAL sequence in two voxels located in gray and white matter dominated prefrontal cortex, respectively. A 3D MP2RAGE sequence was also acquired for brain volumetry and T1 mapping. Liver disease had to have developed at least 6 months before entering the study. Subjects underwent routine blood analysis and neurocognitive testing using validated methods within 3 months of MRI and MRS. RESULTS: Five children aged 8-16 years with liver disease acquired in childhood were included. Baseline biological characteristics were similar among patients. There were no statistically significant differences between subjects and controls in brain metabolite levels or brain volumetry. Finally, there were minor neurocognitive fluctuations including attention deficit in one child, but none fell in the statistically significant range. CONCLUSION: Children with chronic, compensated liver disease did not display an abnormal neurometabolic profile, neurocognitive abnormalities, or signal intensity changes in the globus pallidus. Despite the absence of neurometabolic changes, it is an opportunity to emphasize that it is only by developing the use of 1H MRS at high field in the clinical arena that we will understand the significance and generalizability of these findings in children with CLD. Healthy children displayed neurometabolic regional differences as previously reported in adult subjects.

The effects of dual tasks on gait in children with cerebral palsy.

AIM: To assess the gait and cognitive performances of children with cerebral palsy (CP) during dual tasks (DT) in comparison to typically developing (TD) children. METHOD: This prospective, observational, case-control study included 18 children with CP (7 girls, 11 boys; median age 12 [10:13] years and 19 controls (9 girls, 10 boys; median age 12 [10:13y6mo] years). Performances were recorded during a simple walking task, 5 DT (walking + cognitive tasks with increasing cognitive load), and 5 simple cognitive tasks (while sitting). Gait parameters were computed using an optoelectronic system during walking tasks. Six parameters were selected for analysis by a principal component analysis. Cognitive performance was measured for each cognitive task. The dual-task cost (DTC) was calculated for each DT. RESULTS: Gait performance decreased in both groups as DT cognitive load increased (e.g., walking speed normalized by leg length, in simple task: 1.25 [1.15:1.46] s-1 for CP, 1.53 [1.38:1.62] s-1 for TD; DT with highest load: 0.64 [0.53:0.80] s-1 for CP, 0.95 [0.75:1.08] s-1 for TD). The CP group performed significantly worse than TD group in every task (including the simple task), but DTC were similar in both groups. A task effect was found for the majority of the gait parameters. INTERPRETATION: The reduced gait performance induced by DT may generate underestimated difficulties for children with CP in daily-life situations, where DT are common. This should be considered in clinical assessments.

Illusory persistence of touch after right parietal damage: neural correlates of tactile awareness.

We studied a patient who experienced 'palinaesthesia', an illusion of persistent touch following tactile stimulation on the left hand, subsequent to a right parietal meningioma affecting primary somatosensory regions in the postcentral gyrus (SI) and superior parietal gyrus (Brodmann area 7), but preserving the secondary somatosensory cortex (SII) in the upper lateral sulcus. This subjective sensation was accompanied by transient increases in objective measures of tactile threshold. The patient had mild deficits in superficial tactile perception, but showed severe left-sided extinction for offsets of tactile stimuli during bilateral stimulation, but not for onsets of stimuli. Functional MRI revealed increased neural activity during palinaesthesia selectively arising within the ipsilesional-right SI cortex, but no abnormality within left SI and bilateral SII. Right SI responded to the onset of new tactile stimuli on the left hand but not to their offset. By contrast, any tactile events on either hand modulated activity in contralateral SII regions, even undetected left-sided offsets. These data demonstrate that illusory persistence of touch following stimulation on the hand may result from sustained neural activity in a restricted region of the SI cortex outlasting the offset of the actual tactile stimuli. These findings also provide direct evidence for a critical role of SI in mediating conscious somatosensory experience on contralateral parts of the body.

Expectation-based attentional modulation of visual extinction in spatial neglect.

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.

The space of senses: impaired crossmodal interactions in a patient with Balint syndrome after bilateral parietal damage.

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.

Impaired perceptual memory of locations across gaze-shifts in patients with unilateral spatial neglect.

Right hemisphere lesions often lead to severe disorders in spatial awareness and behavior, such as left hemispatial neglect. Neglect involves not only pathological biases in attention and exploration but also deficits in internal representations of space and spatial working memory. Here we designed a new paradigm to test whether one potential component may involve a failure to maintain an updated representation of visual locations across delays when a gaze-shift intervenes. Right hemisphere patients with varying severity of left spatial neglect had to encode a single target location and retain it across an interval of 2 or 3 sec, during which the target was transiently removed, before a subsequent probe appeared for a same/different location judgment. During the delay, gaze could have to shift to either side of the remembered location, or no gaze-shift was required. Patients showed a dramatic loss of memory for target location after shifting gaze to its right (toward their "intact" ipsilesional side), but not after leftward gaze-shifts. Such impairment arose even when the target initially appeared in the right visual field, before being updated leftward due to right gaze, and even when gaze returned to the screen center before the memory probe was presented. These findings indicate that location information may be permanently degraded when the target has to be remapped leftward in gaze-centric representations. Across patients, the location-memory deficit induced by rightward gaze-shifts correlated with left neglect severity on several clinical tests. This paradoxical memory deficit, with worse performance following gaze-shifts to the "intact" side of space, may reflect losses in gaze-centric representations of space that normally remap a remembered location dynamically relative to current gaze. Right gaze-shifts may remap remembered locations leftward, into damaged representations, whereas left gaze-shifts will require remapping rightward, into intact representations. Our findings accord with physiological data on normal remapping mechanisms in the primate brain but demonstrate for the first time their impact on perceptual spatial memory when damaged, while providing new insights into possible components that may contribute to the neglect syndrome.

The inferior temporal lobe mediates distracter-resistant visual search of patients with spatial neglect.

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.

Early cortical distinction between memories that pertain to ongoing reality and memories that don't.

Patients with anterior limbic lesions, in particular of the posterior orbitofrontal cortex, often act on the basis of memories that do not relate to ongoing reality and justify their behavior with invented stories that can mostly be traced back to real events (spontaneous confabulation). Recent studies demonstrated that the patients fail to suppress activated memory traces that do not pertain to ongoing reality. In the present study, we used a similar paradigm and high-resolution event-related potentials to explore when this suppression happens. Healthy subjects made two runs of a continuous recognition task, composed of the same set of pictures, and were requested to indicate picture recurrences only within the ongoing run. Thus, performance in the first run depends on new learning, whereas the second run requires the ability to realize whether a picture is solely familiar from its occurrence in the previous run ('distracter') or whether it has already appeared in the ongoing second run ('target'). We find that correct rejection (suppression) of currently irrelevant pictures (distracters of run 2) is associated with absent negative deflection of a frontal potential and absence of a specific cortical potential map configuration after 220-300 ms. By contrast, learning and recognition of repeatedly presented information is associated with cortical amplitude modulation after 400-480 ms. These findings indicate that by the time the content of a mental association is recognized and consolidated, its cortical representation has already been adjusted according to whether it relates to ongoing reality or not. This sequence may also explain the ability to distinguish between the memory of a true event and the memory of a thought.

Hyperfamiliarity for unknown faces after left lateral temporo-occipital venous infarction: a double dissociation with prosopagnosia.

Right hemisphere dominance in face processing is well established and unilateral right inferior temporo-occipital damage can result in prosopagnosia. Here, we describe a 21-year-old right-handed woman with acute impairment in face recognition that selectively concerned unfamiliar faces, following a focal left lateral temporo-occipital venous infarct. She was severely impaired in discerning that unknown people seen in everyday life were unfamiliar, although she had no difficulty recognizing familiar people. Thus, she had no prosopagnosia, but abnormal 'hyperfamiliarity' for unknown faces. Her difficulty was not accompanied by delusions or deficits in discrimination, identification or memory for faces. Standard neuropsychological testing showed that her recognition of familiar faces was entirely normal. By contrast, her sense of personally knowing faces was severely impaired when unknown faces evoked weak signals of familiarity based on spurious cues, to the extent that she would misattribute fame to faces that were unknown but to which she had been incidentally exposed on a prior occasion. Priming experiments also revealed that, unlike normal subjects, she made familiarity judgements without accessing semantic identity representations. Moreover, in face recognition tests, she generally showed bias in that she relied more on right-hemisphere strategies to identify global traits and less on left-hemisphere processes compared with healthy subjects. This case provides novel evidence for a differential contribution of the two hemispheres to face recognition. Hyperfamiliarity for unknown faces might arise from an imbalance between reciprocal hemispheric functions in face recognition, with relative hypoactivation of left hemisphere processes but hyperactivation of right-hemisphere processes for retrieving stored associations about people, linking seen faces to representations of affective and personal relevance. Hence, abnormal bias in attributing some personal meaning to unknown faces could be evoked by spurious signals of familiarity based on irrelevant affective associations in the right hemisphere.

Tactile awareness and limb position in neglect: functional magnetic resonance imaging.

We studied a patient with right parietal damage for whom tactile stimuli on the right/ipsilesional hand (projecting to the intact left hemisphere) were extinguished from awareness during double simultaneous stimulation, when his right hand was positioned in the left/contralesional space. This demonstrates the role of an egocentric spatial reference frame in attention that can determine awareness of stimuli despite intact sensory pathways. Using functional magnetic resonance imaging to elucidate the neural correlates of such perceptual extinction, we found that limb position modulated neural responses to tactile stimuli at early cortical stages (SI) in the intact hemisphere. Activity in bilateral middle frontal gyri also was modulated by limb position and may contribute to integrate sensory inputs into a supramodal, egocentric representation of space.

[Neuropsychological test in daily practice]. / L'examen neuropsychologique en pratique quotidienne.

Neuropsychology is a scientific discipline, born in the XIX century, and bridges the fields of neurology and psychology. Neuropsychologists apply scientific knowledge about the relationship between brain function and mental performances. The major clinical role of a neuropsychological evaluation is to help to establish medical and functional diagnosis in patients (adults or infants) with different neurological pathologies such as stroke, traumatic brain injury, dementia, epilepsy.... Such analysis necessitates accurate observation of behaviour and administration of tests of mental abilities (e.g. language, memory...). Test results can also help to clarify the nature of cognitive difficulties and to support the formulation of plans for neuropsychological therapy and functional adjustment in every day life.