Asaid Khateb

Discriminating emotional faces without primary visual cortices involves the right amygdala

Destruction of the brains primary visual areas leads to blindness of cortical origin. Here we report on a subject who, after bilateral destruction of his visual cortices and ensuing cortical blindness, could nevertheless correctly guess the type of emotional facial expression being displayed, but could not guess other types of emotional or non-emotional stimuli. Functional magnetic resonance imaging showed activation of the right amygdala during the unconscious processing of emotionally expressive faces.

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.

Variability of fMRI Activation During a Phonological and Semantic Language Task in Healthy Subjects

Assessing inter‐individual variability of functional activations is of practical importance in the use of functional magnetic resonance imaging (fMRI) in a clinical context. In this fMRI study we addressed this issue in 30 right‐handed, healthy subjects using rhyme detection (phonologic) and semantic categorization tasks. Significant activations, found mainly in the left hemisphere, concerned the inferior frontal gyrus, the superior/middle temporal gyri, the prefrontal cortex, the inferior parietal lobe, the superior parietal lobule/superior occipital gyrus, the pre‐central gyrus, and the supplementary motor area. Intensity/spatial analysis comparing activations in both tasks revealed an increased involvement of frontal regions in the semantic task and of temporo‐parietal regions in the phonologic task. The frequency of activation analyzed in nine regional subdivisions revealed a high inter‐subject variability but showed that the most frequently activated regions were the inferior frontal gyrus and the prefrontal cortex. Laterality indices, strongly lateralizing in both tasks, were slightly higher in the semantic (0.76 ± 0.19) than the phonologic task (0.66 ± 0.27). Frontal dominance indices (a measure of frontal vs. posterior left hemisphere dominance) indicated more robust frontal activations in the semantic than the phonologic task. Our study allowed the characterization of the most frequently involved foci in two language tasks and showed that the combination of these tasks constitutes a suitable tool for determining language lateralization and for mapping major language areas. Hum. Brain Mapping 23:140–155, 2004.

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.

Pharmacological and Immunohistochemical Evidence for Serotonergic Modulation of Cholinergic Nucleus Basalis Neurons

Identified electrophysiologically by low threshold bursts and transient outward rectification, cholinergic nucleus basalis neurons were recorded and labelled intracellularly in guinea‐pig basal forebrain slices. By means of a triple labelling immunofluorescent technique, serotonin‐immunoreactive fibres were visualized in close proximity to the soma and dendrites of the biocytin‐labelled, choline acetyl transferase (ChAT)‐immunoreactive cells. By bath application, 5‐hydroxytryptamine (5‐HT) produced a direct hyperpolarization of the identified cells which was mimicked by 5‐HT1A receptor agonists, suggesting that it may inhibit the tonic firing but also modulate the low threshold bursting of the cholinergic nucleus basalis neurons.

Unraveling the cerebral dynamics of mental imagery

Evidence from functional brain imaging studies suggests that mental imagery processes, like other higher cognitive functions, simultaneously activate different neuronal networks involving multiple cortical areas. The question of whether these different areas are truly simultaneously active or whether they are temporally distinct and might reflect different steps of information processing cannot be answered by these imaging methods. We applied spatiotemporal analysis techniques to multichannel event‐related potential (ERP) recordings in order to elucidate the topography and chronology of brain processes involved in mental rotation. We measured 41‐electrode ERPs in 12 healthy subjects who had to evaluate whether rotated letters were in a normal or mirror‐reflected position. These figures were presented in the left, right, or central visual fields and were randomly rotated by 0°, 50°, 100°, or 150°. Behaviorally, we replicated the observation that reaction time increases with greater angles of rotation. Electrophysiologically, we identified a set of dominant electric potential distributions, each of them stable for a certain time period. Only one of these time segments (appearing between 400–600 msec) increased significantly in duration with greater angles of rotation mirroring reaction time. We suggest that the rotation of mental images is carried out during this time segment. A general linear inverse solution applied to this segment showed occipito‐parietal cerebral activity that was lateralized to the right hemisphere. Hum. Brain Mapping 5:410–421, 1997.

Cholinergic nucleus basalis neurons display the capacity for rhythmic bursting activity mediated by low-threshold calcium spikes

Acetylcholine has long been known to play an important role in the cortical activation that accompanies the states of wakefulness and paradoxical sleep (for review, see Refs 17, 21) when this neurotransmitter is released from the cerebral cortex at the highest rates. The major supply of acetylcholine to the cerebral cortex arises from the cholinergic neurons of Meynerts Basal-ganglion or nucleus basalis of the forebrain. Lying in the substantia innominata within the major ascending pathway from the brain stem reticular formation, magnocellular basalis neurons project upon the cerebral cortex as the important ventral, extrathalamic relay of the ascending reticular activating system. Although the cholinergic basalis nucleus neurons have been shown to be important for cortical activation, the precise manner in which they influence cortical activity has not as yet been elucidated, in part because the cholinergic cells of this nucleus have not been identified in electrophysiological studies. Using intracellular recording in guinea-pig brain slices, we were able to record and fill with biocytin nucleus basalis neurons which were subsequently revealed by immunohistochemical staining to be choline acetyltransferase-positive and thus cholinergic. The cholinergic cells displayed rhythmic bursting activity mediated by a low-threshold calcium spike in vitro, which would endow them with a capacity for phasic (in addition to tonic) firing in vivo. By virtue of these different modes, cholinergic basalis neurons may accordingly deter or facilitate the cortical response to sensory input and may furthermore modulate the major frequencies of cortical activity across the different states of the sleep-waking cycle.

Differential Oscillatory Properties of Cholinergic and Non‐cholinergic Nucleus Basalis Neurons in Guinea Pig Brain Slice

Evidence has suggested that the nucleus basalis magnocellularis has the potential to influence the functional state of the cerebral cortex through topographically organized, widespread projections of the cholinergic cells in that nucleus. It has also been shown that, in addition to the cholinergic neurons, other non‐cholinergic magnocellular basal forebrain neurons, some of which have been identified as gamma‐aminobutyric acid‐ergic, project into the cerebral cortex and thus may also participate in the modulation of its activity. We have performed a comparative study of the intrinsic rhythmic properties of immunohistochemically and morphologically characterized choline acetyltransferase (ChAT)‐positive and ChAT‐negative cells of the nucleus basalis by means of intracellular recordings in guinea pig brain slices. Our results demonstrate that relatively large, multipolar cholinergic and non‐cholinergic neurons each display differential voltage‐dependent properties that allow them to discharge rhythmically in spike bursts and spike clusters, respectively, at low frequencies (<10 Hz). Cholinergic cells display bursts of 2–4 action potentials (at ‐200 Hz) riding on low‐threshold spikes recurring at a low frequency (<5 Hz) when depolarized from a membrane potential more negative than ‐55 mV and display low‐frequency (<10–15 Hz) tonic firing when depolarized from a more positive level. In contrast, non‐cholinergic cells fire in a unique mode, displaying non‐adapting clusters of spikes interspersed with rhythmic subthreshold membrane‐potential oscillations when depolarized from levels less negative than ‐55 mV. The spike clusters repeat rhythmically at relatively low frequencies (2–10 Hz). The intracluster spiking frequency is relatively high and coincides approximately with that of the intervening membrane‐potential oscillations (‐20–70 Hz). The cluster frequency of the non‐cholinergic cells corresponds, in the same manner as the burst frequency of the cholinergic cells, to a delta (1–4 Hz) or theta (4–10 Hz) range of activity, whereas the intra‐cluster and tonic spike frequencies of the non‐cholinergic cells correspond to high beta to gamma ranges of electroencephalographic activity (19–30 Hz and 30–60 Hz, respectively). We propose that the different modes of oscillatory firing by the cholinergic and non‐cholinergic basal forebrain cell populations could collectively contribute to the rhythmic modulation of slow and fast rhythms within the cerebral cortex.

Electrophysiological evidence for early non-conscious processing of fearful facial expressions

Non-conscious processing of emotionally expressive faces has been found in patients with damage to visual brain areas and has been demonstrated experimentally in healthy controls using visual masking procedures. The time at which this subliminal processing occurs is not known. To address this question, a group of healthy participants performed a fearful face detection task in which backward masked fearful and non-fearful faces were presented at durations ranging from 16 to 266 ms. On the basis of the groups behavioural results, high-density event-related potentials were analysed for subliminal, intermediate and supraliminal presentations. Subliminally presented fearful faces were found to produce a stronger posterior negativity at 170 ms (N170) than non-fearful faces. This increase was also observed for intermediate and supraliminal conditions. A later component, the N2 occurring between 260 and 300 ms, was the earliest component related to stimulus detectability, increasing with target duration and differentiating fearful from non-fearful faces at longer durations of presentation. Source localisation performed on the N170 component showed that fear produced a greater activation of extrastriate visual areas, particularly on the right. Whether they are presented subliminally or supraliminally, fearful faces are processed at an early stage in the stream of visual processing, giving rise to enhanced activation of right extrastriate temporal cortex as early as 170 ms post-stimulus onset.

Visual recognition of faces, objects, and words using degraded stimuli: where and when it occurs.

We studied time course and cerebral localisation of word, object, and face recognition using event‐related potentials (ERPs) and source localisation techniques. To compare activation rates of these three categories, we used degraded images that easily pop out without any change in the physical features of the stimuli, once the meaning is revealed. Comparisons before and after identification show additional periods of activation beginning at 100 msec for faces and at around 200 msec for objects and words. For faces, this activation occurs predominantly in right temporal areas, whereas for objects, the specific time period gives rise to bilateral posterior but right dominant foci. Finally, words show a maximum area of activation in the left temporooccipital area at their specific time period. These results provide unequivocal evidence that when effects of low‐level visual features are circumvented, faces, objects, and words are not only distinct in terms of their anatomic routes, but also in terms of their times of processing. Hum. Brain Mapping 22:300–310, 2004.