Biomedical subjects

A Khateb

Publications and source records attributed to A Khateb.

At least 19 recordsLinked to original sources

PubMed2003

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.

Brain↗

PubMed2002

[Variability of right hemisphere activation during semantic word processing in aphasic patients: an electrophysiologic study in three patients].

After stroke, the interhemispheric reorganisation of the neural network implicated in language is hypothesized to be a function not only of the site of lesion but also of the residual impairment. With a multiple case approach, we tested this hypothesis in three chronic aphasic patients. Two patients, GE (capsulo-lenticular stroke) and JHN (fronto-temporal stroke) showed formal residual semantic difficulties, while the third patient (EG, large sylvian lesion) did not. Brain electric activity was analysed during a categorisation task of tachistoscopically presented words in the left and the right visual field. The temporal analysis of brain activity showed that both patients with semantic residual difficulties activated the right hemisphere (RH) during some steps of word processing. In the third patient, without semantic impairment, the RH was activated only during a short time period. Further more, RH activation was shown to be dependent on the visual field of word presentation. Phonological impairment was not predictive of RH activation. These results suggest that RH activation, particularly anterior regions, can occur during semantic processing of words as a function of semantic residual impairment.

Adult↗

PubMed2001

Language representation in a patient with a dominant right hemisphere: fMRI evidence for an intrahemispheric reorganisation.

Studies have suggested that congenital left hemispheric (LH) frontal arteriovenous malformations (AVMs) are associated with an early transfer of language to right hemisphere (RH) frontal regions. The question remains whether such anatomofunctional reorganisation is due to RH compensatory abilities or to a general principle of lateral shift. In this study, we used fMRI language paradigms to investigate the case of a patient presenting aphasic symptoms following an haemorrhage due to a right frontal AVM. Prior to surgery, fMRI showed that language processing was confined to the RH, suggesting that language had not shifted during childhood from this congenitally dominant RH to the LH. After surgery, the patient presented severe aphasia that recovered to presurgical level within 70 days. At this time, fMRI showed that language tasks were still not associated with activations in the LH. These results suggest that the principles of early cerebral reorganisation after congenital lesions may differ in the RH and the LH. In addition, they support the idea that efficient restoration of language is achieved if a sufficiently large neuronal network is preserved around the lesion.

Adult↗

PubMed2001

So near yet so far: neglect in far or near space depends on tool use.

The study of unilateral spatial neglect has shown that space can be dissociated on a peripersonal versus extrapersonal basis. We report a novel type of dissociation based on tool use in a patient suffering from left neglect. Line bisection was carried out in near and far space, using a stick and a laser pointer. A rightward bias was always found for the former, but not for the latter. Neglect thus appears to be contingent not only on distance, but also on the motor action required by the task.

Aged↗

PubMed2001

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.

Brain Mapping↗

PubMed2001

The time course of semantic category processing in the cerebral hemispheres: an electrophysiological study.

Using visual half-field presentations of words to the right (RVF) and to the left visual field (LVF), this study investigated the time course of the hemispheric involvement in the processing of semantic category information. Multi-channel event related brain potentials (ERPs) were recorded from 15 healthy subjects during a categorisation task of sequentially presented word pairs. Subjects had to judge mentally after the appearance of the second word whether the words of a pair were semantically related (SR) or not (SU). ERPs were computed, from 100 ms before the onset of the second word to 600 ms, for SR and SU conditions in the LVF and in the RVF separately. The temporal segmentation of ERP map series into sequences of quasi-stable map configurations revealed a total of seven segments in each visual field of which only the first five (S1-S5, appearing between 70 and 400 ms) showed different map configurations as a function of visual field but presented a similar temporal sequence in both visual fields. By contrast, of the last two segments (S6 and S7) which appeared between approximately 400 and approximately 600 ms, only S7 differentiated SR and SU conditions in terms of its duration. Source localisation analysis of the segments showed that following the initial activation of posterior brain regions as a function of the visual field of presentation, a common neural network was activated in the left hemisphere (LH) although the dynamics of activation varied as a function of visual field. Concerning the role of the right hemisphere (RH) in lexico-semantic processing, the results presented here appear to be compatible with a 'callosal relay model' and suggest that, in healthy subjects, information is transferred rapidly ( approximately 150 ms) from the RH to the language dominant-LH.

Adult↗

PubMed2000

Visually induced activity in human frontal motor areas during simple visuomotor performance.

Visuomotor tasks elicit neuronal activity in primate motor areas at relatively short latencies. Although this early activity embodies features of visual responses (short latency, stimulus-dependency), its sensory nature has been questioned. We investigated neural correlates of visuomotor performance in human motor areas using scalp and intracranial event-related potential measures. A simple visuomanual reaction-time task evoked early potentials at 133-145 ms post-stimulus which occurred much earlier than the motor potentials of the same region. The amplitude of the early potentials covaried with stimulus location and was independent of parameters of the motor response. Because of their timing, stimulus-dependency and characteristics of our behavioral task, the early potentials are suggested to reflect neuronal responses of sensory nature rather than processing related to pure motor aspects of the task.

Adult↗

PubMed2000

New insights into the Stroop effect: a spatio-temporal analysis of electric brain activity.

Recent clinical and imaging studies suggest the involvement of anterior brain regions in the Stroop effect without providing consensus on the hemisphere being involved. Here, we investigated the dynamics of brain activation during a modified Stroop task using behavioural, event-related potential map series, and source localization analysis. Behavioural analysis showed an increased RT in the interference (IC) as compared to the neutral (NC) and congruence conditions (CC). Map series analysis in these conditions displayed a similar sequence of 10 stable segments. From these, only segment S6, occurring at approximately 300 ms and displaying a dominant right anterior activation, was of increased duration in IC. Furthermore, in IC only, RT was shown to correlate with S6 duration. These results are discussed in terms of increased duration of an attentional process needed to solve the conflict.

Adult↗

PubMed2000

Semantic category and rhyming processing in the left and right cerebral hemisphere.

In this study, the question of hemispheric abilities in processing explicit semantic and phonological information was addressed by measuring response latencies and performances in two judgement tasks. In the semantic task, word pairs were sequentially presented to the left or right visual field and subjects were asked to judge whether these words were categorically related or not. In the phonological task, the same subjects were asked to decide whether pairs of orthographically dissimilar words rhymed or not. Statistical analysis showed that reaction times (RT) were significantly shorter in both tasks when words were presented to the right visual field. Furthermore, in the semantic task, faster responses were observed in both visual fields when the words were related than when they were unrelated. This response facilitation tended to be stronger when words were presented to the left visual field. This result is in accordance with other results obtained by lexical decision studies showing that priming in the right hemisphere is due to controlled processing. By contrast, RT differences between rhyming and non-rhyming word pairs in the phonological task did not reach significance. This supports previous findings showing that phonological facilitation cannot occur when orthographic and phonological indices are in conflict.

Journal Article↗

PubMed2000

Electrophysiological evidence for fast visual processing through the human koniocellular pathway when stimuli move.

There is increasing evidence from cellular recordings in primates and behavioral studies in humans that motion can be processed by other than the magnocellular (M) pathway and the cortical dorsal stream. Little is known about cortical processing of moving stimuli when the information is conveyed by the third retinogeniculocortical pathway - the so-called koniocellular (K) pathway. We addressed this issue in humans by studying the spatio-temporal dynamics of the brain electrical fields evoked by tritan (S-cone isolating) and luminance-defined moving stimuli. Tritan and luminance stimuli are presumably carried by the K and M pathways respectively. We found two time intervals where significant stimulus-specific electric fields were evoked: an early period between 40 and 75 ms after stimulus onset, and a later period between 175 and 240 ms. Some of these fields were identical for tritanand luminance-motion, suggesting that the processing of moving stimuli share common cortical substrates when mediated via K and M pathway input. However, tritan-motion stimuli also evoked unique electric fields that appeared earlier in time than the common motion-specific fields, indicating very fast activation of cortical areas specific to input through the K pathway. A distributed source localization procedure revealed simultaneous activation of striate and extrastriate areas even at the early processing stages, strongly suggesting a very fast activation of the visual cerebral network.

Adult↗

PubMed1999

Spatio-temporal analysis of electric brain activity during semantic and phonological word processing.

There is an ongoing debate in cognitive neuroscience about the time course and the functional independence of the different processes involved in encoding written language material. New data indicate very fast and highly parallel language analysis networks in the brain. Here we demonstrate a methodological approach to study the temporal dynamics of this network by searching for time periods where different task demands emphasize different aspects of the network. Multi-channel event related potentials (ERPs) were recorded during a semantic and a phonological reading task from 14 healthy subjects. Signals were analyzed exclusively on the basis of the spatial configuration of the electric potential distributions (ERP maps), since differences in these spatial patterns directly reflect changes in the configuration of the active sources in the brain. This analysis did not reveal any differences of the evoked brain electric fields between the two tasks up to 280 ms post-stimulus. The ERP maps then differed for a brief period between 280 and 380 ms, before they were similar again. The analysis of the maps using a global linear localization procedure revealed a network of areas, active in both tasks, that mainly involved the left postero-temporal and left antero-temporal regions. The left posterior activation was found already around 100 ms post-stimulus, indicating that language-specific functions appear early in time. We therefore conclude that phonological and semantic processing are essentially performed in both tasks and that only late decision-related processes influence the relative strength of activity of the different modules in the complex language network.

Adult↗

PubMed1998

Pharmacological characterization and differentiation of non-cholinergic nucleus basalis neurons in vitro.

Using intracellular recordings in guinea pig brain slices, the pharmacology of electrophysiologically identified and immunohistochemically confirmed non-cholinergic nucleus basalis neurons was studied to determine their response to the major neurotransmitters of the subcortical afferents to this region. The cells were differentiated into three types: Type A cells (approximately 44%) were depolarized by noradrenaline (NA) and muscarine, Type B cells (approximately 23%) were depolarized by NA but hyperpolarized by muscarine, and Type C cells (approximately 15%) were hyperpolarized by both agonists. These cell types were also differentially responsive to serotonin (hyperpolarizing B, C) and histamine (depolarizing A, B). Accordingly, the non-cholinergic neurons share certain discharge properties but appear nonetheless to comprise distinct types which respond differentially to the major modulatory neurotransmitters and thus play potentially different roles in cortical modulation across the sleep-wake cycle.

Animals↗

PubMed1998

GABAergic input to cholinergic nucleus basalis neurons.

The potential influence of GABAergic input to cholinergic basalis neurons was studied in guinea-pig basal forebrain slices. GABA and its agonists were applied to electrophysiologically-identified cholinergic neurons, of which some were labelled with biocytin and confirmed to be choline acetyltransferase-immunoreactive. Immunohistochemistry for glutamate decarboxylase was also performed in some slices and revealed GABAergic varicosities in the vicinity of the biocytin-filled soma and dendrites of electrophysiologically-identified cholinergic cells. From rest (average - 63 mV), the cholinergic cells were depolarized by GABA. The depolarization was associated with a decrease in membrane resistance and diminution in firing. The effect was mimicked by muscimol, the specific agonist for GABA(A) receptors, and not by baclofen, the specific agonist for GABA(B) receptors, which had no discernible effect. The GABA- and muscimol-evoked depolarization and decrease in resistance were found to be postsynaptic since they persisted in the presence of solutions containing either high Mg2+/low Ca2+ or tetrodotoxin. They were confirmed as being mediated by a GABA(A) receptor, since they were antagonized by bicuculline. The reversal potential for the muscimol effect was estimated to be approximately -45 mV, which was -15 mV above the resting membrane potential. Finally, in some cholinergic cells, spontaneous subthreshold depolarizing synaptic potentials (average 5 mV in amplitude), which were rarely associated with action potentials, were recorded and found to persist in the presence of glutamate receptor antagonists but to be eliminated by bicuculline. These results suggest that GABAergic input may be depolarizing, yet predominantly inhibitory to cholinergic basalis neurons.

2-Amino-5-phosphonovalerate↗

PubMed1997

Modulation of cholinergic nucleus basalis neurons by acetylcholine and N-methyl-D-aspartate.

Known to exert an important modulatory influence on the cerebral cortex, the cholinergic neurons of the basal forebrain are modulated in turn by neurotransmitters which may include acetylcholine released from processes of brainstem or forebrain neurons. In the present study, we examined the effect of carbachol, a non-specific cholinergic agonist, either alone or in the presence of N-methyl-D-aspartate upon electrophysiologically identified cholinergic basalis neurons in guinea-pig basal forebrain slices. Carbachol produced a direct postsynaptic hyperpolarization, accompanied by a decrease in membrane resistance. Muscarine could mimic this hyperpolarizing effect, whereas nicotine produced a direct postsynaptic membrane depolarization. The interaction of carbachol with N-methyl-D-aspartate was subsequently tested since, in a prior study, N-methyl-D-aspartate was shown to induce rhythmic bursting in cholinergic cells when they were hyperpolarized by continuous injection of outward current. Applied simultaneously with N-methyl-D-aspartate in the absence of current injection, carbachol was also found to promote rhythmic bursting in half of the cells tested. Since the bursts under these conditions were markedly longer in duration than those observed in the presence of N-methyl-D-aspartate alone, it was hypothesized that carbachol might have another action, in addition to the membrane hyperpolarization. Using dissociated cells, it was found that brief applications of carbachol could indeed diminish the slow afterhyperpolarizations that follow single spikes, short bursts or long trains of action potentials in cholinergic basalis neurons. These results indicate that, through its dual ability to hyperpolarize cholinergic neurons and to reduce their afterhyperpolarizations, acetylcholine can promote the occurrence of rhythmic bursting in the presence of N-methyl-D-aspartate. Accordingly, whether derived from brainstem or local sources, acetylcholine may facilitate rhythmic discharge in cholinergic basalis neurons which could in turn impose a rhythmic modulation upon cortical activity during particular states across the sleep-waking cycle.

Acetylcholine↗

PubMed1996

Rhythmic firing of medial septum non-cholinergic neurons.

The presence of theta rhythm (5-10 Hz) in the hippocampus has been shown to enable long-term potentiation, a synaptic mechanism which has been proposed to underlie learning and memory. Medial septum cholinergic and GABAergic neurons that project to the hippocampus have been hypothesized to play conjointly a major role in the genesis of this rhythm. Building upon previous studies that have established the electrophysiological criteria for distinguishing cholinergic and non-cholinergic neurons in this area, it is demonstrated here that medial septum non-cholinergic neurons, putatively GABAergic, have the ability to discharge in rhythmic clusters of action potentials occurring at frequencies ranging from 1 to 8 Hz. Within the clusters, the firing frequency of action potentials varied between 13 and 57 Hz in a voltage-dependent manner. In addition, small voltage-dependent subthreshold membrane potential oscillations (16-54 Hz) were observed between clusters. Both subthreshold oscillations and clusters were eliminated by tetrodotoxin at 1 microM. These results indicate that non-cholinergic medial septum neurons could convey to the hippocampus not only theta but also higher frequency rhythmicity in the beta-gamma range (20-60 Hz).

Animals↗

PubMed1996

Differential oscillatory properties of cholinergic and noncholinergic 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 approximately 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 (approximately 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.

Animals↗

PubMed1995

Rhythmical bursts induced by NMDA in guinea-pig cholinergic nucleus basalis neurones in vitro.

1. Intracellular recordings were performed in neurones within the basal forebrain of guinea-pig brain slices. Following injection of biocytin (or biotinamide), a subset of recorded neurones which displayed distinct intrinsic membrane properties were confirmed as being cholinergic by immunohistochemical staining for choline acetyltransferase (ChAT). They were all located within the nucleus basalis magnocellularis. The response of the cholinergic cells to NMDA and to the agonists of the other glutamate receptors was tested by bath application of NMDA, t-ACPD, AMPA and kainate. 2. When depolarized from a hyperpolarized level, cholinergic basalis neurones display the intrinsic ability to discharge in rhythmic bursts that are generated by low-threshold Ca2+ spikes. In control solution, these rhythmic bursts were not sustained for more than 5-6 cycles. However, in the presence of NMDA when the membrane was held at a hyperpolarized level, low-threshold bursting activity was sustained for prolonged periods of time. This activity could be reversibly eliminated by D(-)-2-amino-5-phosphonopentanoic acid (D-AP5), showing that it depended upon specific activation of NMDA receptors. 3. NMDA-induced, voltage-dependent, rhythmic depolarizations persisted in the presence of tetrodotoxin (TTX), indicating that they did not depend upon a TTX-sensitive Na+ current and were generated postsynaptically. The rhythmic depolarizations were, however, eliminated by the partial replacement of Na+ with choline, demonstrating that they did depend upon Na+, the major carrier of the NMDA current. 4. In the presence of TTX, the NMDA-induced rhythmic depolarizations were also eliminated by removal of Ca2+ from or addition of Ni2+ to the bath, indicating that they also depended upon Ca2+, which is carried by both the NMDA current and the low-threshold Ca2+ current. The duration of the rhythmic depolarizations was increased in the presence of apamin, suggesting that the repolarization of the cells depended in part upon a Ca(2+)-activated K+ (SK) conductance, but that other mechanisms were additionally involved in the repolarization phase of the bursting. 5. In both the absence and presence of TTX, the NMDA-induced rhythmic activity persisted when Mg2+ was removed from the medium, indicating that the sustained rhythmic depolarizations did not hinge upon the Mg2+ block of the NMDA channels during hyperpolarization. The voltage dependence of the NMDA-induced rhythmic depolarizations in the absence of Mg2+ appeared to be determined by the properties of the low-threshold Ca2+ spike in the cholinergic basalis neurones.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

PubMed1995

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-beta-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 alpha 1-adrenergic receptor antagonist prazosin and not by the alpha 2-antagonist yohimbine, and it was mimicked by the alpha 1-agonist L-phenylephrine but not by the alpha 2-agonists clonidine and UK14.304, indicating mediation by an alpha 1-adrenergic receptor. There was also evidence for a contribution by a beta-adrenergic receptor to the effect, since the beta-antagonist propranolol partially attenuated the effect of noradrenalin, and the beta-agonist isoproterenol produced, like noradrenalin, alone or when applied in the presence of the alpha 1-antagonist prazosin, membrane depolarization and an increase in tonic spike discharge. These results indicate that through a predominant action upon alpha 1-adrenergic receptors, but with the additional participation of beta-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.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic alpha-Agonists↗