Pure Global Acalculia Following a Left Subangular Lesion

We describe the case of a right-handed patient who presented a severe acalculia in the context of a pure Gerstmann syndrome following a subangular lesion that spared the left inferior parietal lobule (IPL). The patient showed impairments in Arabic and verbal codes, in number production and comprehension, as well as in numerical facts and problem solving. By using the EC301 calculation battery, semantic and syntactic tasks in Arabic and verbal codes, we tested the different hypotheses raised by the cognitive neuropsychological models of acalculia. The patients’ difficulties, which were not associated with a general intellectual deterioration, and those affecting number processing as a particular semantic class, were indicative of a “ global acalculia ”. This deficit, which exceeded the anarithmetia usually described in Gerstmann syndrome following left IPL lesion, suggested that the isolation of this area may constitute a sufficient condition for producing such a global acalculia. These results are discussed in terms of a disorder in the manipulation of mental images of spatially related objects.     

Is the right amygdala involved in visuospatial memory? Evidence from MRI volumetric measures

Quantitative MRI measurement of hippocampal sclerosis in patients suffering from temporal lobe epilepsy (TLE) have, as yet, failed to evidence any correlation between the right hippocampus and visuospatial memory. In this report, word learning and design learning tasks were carried out as well as MRI volumetric measurements of the hippocampus and amygdala in order to verify possible modality-specific correlations between function and structure. Delayed recall indices in our memory tasks provided significant results. Visuoverbal ratios differed between right and left TLE groups, as did laterality indices of hippocampal and amygdalar volumes. Furthermore, correlations were found between the left hippocampal volume and verbal memory, and between the right amygdala and visuospatial memory. We suggest that the difficulty encountered in establishing a correlation between right temporal structures and visuospatial memory could come both from the type of test employed and the structures considered.     

Cognition-enhancing effects of donepezil in traumatic brain injury

The purpose of this study was to investigate the effects of donepezil, a cholinergic agent, on chronic cognitive impairment due to traumatic brain injury (TBI). Chronic patients underwent two standardized neuropsychological evaluations--one before and the other 3 months following treatment with donepezil. Together with global inventories that appraised behaviour, fatigue, anxiety and depression, these evaluations also assessed executive functioning, memory and attention. Of the 10 patients who followed the therapy, 8 reported subjective improvement in at least one cognitive domain following therapy and most of them reported better functioning in everyday activities. This effect was supported by a slight global improvement when considering the global score of the different affectivo-behavioural scales. At the neuropsychological level, although we could observe a slight improvement in the majority of the considered tests, significant positive changes were mainly found in tests assessing speed of processing, learning and divided attention. These findings suggest that donepezil may lead to better general functioning and improve attentional skills in patients with chronic TBI.     

Visual search for facial expressions of emotion is less affected in simultanagnosia

Evidence in healthy human subjects has suggested that angry faces may be enhanced during spatial processing, perhaps even "popping-out" of a crowd. These contentions have remained controversial, but two recent reports in patients suffering from unilateral spatial neglect have lent some support to these views, suggesting that emotional faces capture attention more efficiently than neutral stimuli in the neglected field. Here, we investigate this phenomenon in a patient suffering from severe Balint's syndrome and consequent simultanagnosia. Using a visual search paradigm, we studied differences in the detection of angry, happy and neutral faces, as well as non-emotional stimuli. Results revealed that emotionally expressive faces, in particular anger, were detected more efficiently than other stimuli. These findings corroborate claims that facial expressions of emotion constitute a specific category of stimuli that attract attention more effectively, and are processed prior to attentional engagement.     

Medial vestibular nucleus in the guinea-pig: NMDA-induced oscillations

Summary We have recently shown in vivo that N-Methyl-D-Aspartate (NMDA) receptors are present in the guinea-pig vestibular complex and demonstrated that they are involved in the regulation of the resting discharge of vestibular neurones. A parallel in vitro study has identified in the guinea-pig medial vestibular nuclei (MVN) two main neuronal cell types, A and B MVNn, differing by their intrinsic membrane properties. One subtype of B MVNn was further characterized by the presence of a low threshold calcium spike (LTS). The present study investigated in vitro the responses of these different cell types to NMDA. Both A and B MVNn were depolarized by NMDA, which also induced a decrease in membrane resistance and an increase in the spontaneous firing rate. These effects could be blocked by D-AP5, a specific antagonist of NMDA receptors. Following a 10–30 mV hyperpolarization, a long-lasting oscillatory behavior could be induced in presence of NMDA. These oscillations were however restricted to the subtype of B MVNn without LTS. The NMDA-induced oscillations were tetrodotoxine-resistant, but could be eliminated by D-AP5 or by replacing sodium with choline. Functional implications of this oscillatory behavior are discussed.     

Noradrenergic Modulation of Cholinergic Nucleus Basalis Neurons Demonstrated by in vitro Pharmacological and Immunohistochemical Evidence in the Guinea-pig Brain

The effects of noradrenalin were tested upon electrophysiologically characterized cholinergic nucleus basalis neurons in guinea-pig brain slices. According to their previously established intrinsic membrane properties, the cholinergic cells were distinguished by the presence of low-threshold Ca²⁺ spikes and transient outward rectification that endowed them with the capacity to fire in low-threshold bursts in addition to a slow tonic discharge. A subset of the electrophysiologically identified cholinergic cells that responded to noradrenalin had been filled with biocytin (or biotinamide) and documented in previously published reports as choline acetyltransferase (ChAT)-immunoreactive. The noradrenalin-responsive, biocytin-filled/ChAT+ cells were mapped in the present study and shown to be distributed within the substantia innominata amongst a large population of ChAT+ cells. Slices from another subset of noradrenalin-responsive, electrophysiologically identified cholinergic cells were stained for dopamine-β-hydroxylase to visualize the innervation of the biocytin-filled neurons by noradrenergic fibres. These biocytin-filled neurons were surrounded by a moderate plexus of varicose noradrenergic fibres and were ostensibly contacted by a small to moderate number of noradrenergic boutons abutting their soma and dendrites. Applied in the bath, noradrenalin produced membrane depolarization and a prolonged tonic spike discharge. This excitatory action was associated with an increase in membrane input resistance, suggesting that it occurred through reduction of a K⁺ conductance. These effects persisted when synaptic transmission was eliminated (by tetrodotoxin or low Ca²⁺/high Mg²⁺) and were therefore clearly postsynaptic. The excitatory effect of noradrenalin was blocked by the α₁-adrenergic receptor antagonist prazosin and not by the α₂-antagonist yohimbine, and it was mimicked by the α₁-agonist L-phenylephrine but not by the α₂-agonists clonidine and UK14.304, indicating mediation by an α₁-adrenergic receptor. There was also evidence for a contribution by a β-adrenergic receptor to the effect, since the β-antagonist propranolol partially attenuated the effect of noradrenalin, and the β-agonist isoproterenol produced, like noradrenalin, alone or when applied in the presence of the α₁-antagonist prazosin, membrane depolarization and an increase in tonic spike discharge. These results indicate that through a predominant action upon α₁-adrenergic receptors, but with the additional participation of β-adrenergic receptors, noradrenalin depolarizes and excites cholinergic neurons. This action would tend to drive the cholinergic cells into a tonic mode of firing and to stimulate or increase the rate of repetitive spike discharge for prolonged periods. The noradrenergic locus coeruleus neurons could thereby recruit the cholinergic basalis neurons to act in tandem with them in facilitating cortical activation during wakefulness.     

Electric source imaging of human brain functions

We review recent methodological advances in electromagnetic source imaging and present EEG data from our laboratory obtained by application of these methods. There are two principal steps in our analysis of multichannel electromagnetic recordings: (i) the determination of functionally relevant time periods in the ongoing electric activity and (ii) the localization of the sources in the brain that generate these activities recorded on the scalp. We propose a temporal segmentation of the time-varying activity, which is based on determination of changes in the topography of the electric fields, as an approach to the first step, and a distributed linear inverse solution based on realistic head models as an approach to the second step. Data from studies of visual motion perception, visuo-motor transfer, mental imagery, semantic decision, and cognitive interference illustrate that this analysis allows us to define the patterns of electric activity that are present at given time periods after stimulus presentation, as well as those time periods where significantly different patterns appear between different stimuli and tasks. The presented data show rapid and parallel activation of different areas within complex neuronal networks, including early activity of brain regions remote from the primary sensory areas. In addition, the data indicate information exchange between homologous areas of the two hemispheres in cases where unilateral stimulus presentation requires interhemispheric transfer.     

Group analysis and the subject factor in functional magnetic resonance imaging: analysis of fifty right-handed healthy subjects in a semantic language task

Before considering a given fMRI paradigm as a valid clinical tool, one should first assess the reliability of functional responses across subjects by establishing a normative database and defining a reference activation map that identifies major brain regions involved in the task at hand. However, the definition of such a reference map can be hindered by inter-individual functional variability. In this study, we analysed functional data obtained from 50 healthy subjects during a semantic language task to assess the influence of the number of subjects on the reference map and to characterise inter-individual functional variability. We first compared different group analysis approaches and showed that the extent of the activated network depends not only on the choice of the analysis approach but also on the statistical threshold used and the number of subjects included. This analysis suggested that, while the RFX analysis is suitable to detect confidently true positive activations, the other group approaches are useful for exploratory investigations in small samples. The application of quantitative measures at the voxel and regional levels suggested that while approximately 15-20 subjects were sufficient to reveal reliable and robust left hemisphere activations, >30 subjects were necessary for revealing more variable and weak right hemisphere ones. Finally, to visualise inter-individual variability, we combined two similarity indices that assess the percentages of true positive and false negative voxels in individual activation patterns relative to the group map. We suggest that these measures can be used for the estimation of the degree of 'normality' of functional responses in brain-damaged patients, where this question is often raised, and recommend the use of different quantifications to appreciate accurately the inter-individual functional variability that can be incorporated in group maps.     

A glimpse into your vision

Invasive recordings of local field potentials (LFPs) have been used to "read the mind" of monkeys in real time. Here we investigated whether noninvasive field potentials estimated from the scalp-recorded electroencephalogram (EEG) using the ELECTRA source localization algorithm could provide real-time decoding of mental states in healthy humans. By means of pattern recognition techniques on 500-ms EEG epochs, we were able to discriminate accurately from single trials which of four categories of visual stimuli the subjects were viewing. Our results show that it is possible to reproduce the decoding accuracy previously obtained in animals with invasive recordings. A comparison between the decoding results and the subjects' behavioral performance indicates that oscillatory activity (OA), elicited in specific brain regions) codes better for the visual stimulus category presented than the subjects' actual response, i.e., is insensitive to voluntary or involuntary errors. The identification of brain regions participating in the decoding process allowed us to construct 3D-functional images of the task-related OA. These images revealed the activation of brain regions known for their involvement in the processing of this type of visual stimuli. Electrical neuroimaging therefore appears to have the potential to establish what the brain is processing while the stimuli are being seen or categorized, i.e., concurrently with sensory-perceptual processes.