Face versus non-face object perception and the 'other-race' effect: a spatio-temporal event-related potential study.

OBJECTIVE: To investigate a modulation of the N170 face-sensitive component related to the perception of other-race (OR) and same-race (SR) faces, as well as differences in face and non-face object processing, by combining different methods of event-related potential (ERP) signal analysis. METHODS: Sixty-two channel ERPs were recorded in 12 Caucasian subjects presented with Caucasian and Asian faces along with non-face objects. Surface data were submitted to classical waveforms and ERP map topography analysis. Underlying brain sources were estimated with two inverse solutions (BESA and LORETA). RESULTS: The N170 face component was identical for both race faces. This component and its topography revealed a face specific pattern regardless of race. However, in this time period OR faces evoked significantly stronger medial occipital activity than SR faces. Moreover, in terms of maps, at around 170 ms face-specific activity significantly preceded non-face object activity by 25 ms. These ERP maps were followed by similar activation patterns across conditions around 190-300 ms, most likely reflecting the activation of visually derived semantic information. CONCLUSIONS: The N170 was not sensitive to the race of the faces. However, a possible pre-attentive process associated to the relatively stronger unfamiliarity for OR faces was found in medial occipital area. Moreover, our data provide further information on the time-course of face and non-face object processing.

Human brain mapping in dystonia reveals both endophenotypic traits and adaptive reorganization.

Dystonia has a wide clinical spectrum from early-onset generalized to late-onset sporadic, task-specific forms. The genetic origin of the former has been clearly established. A critical role of repetitive skilled motor tasks has been put forward for the latter, while underlying vulnerability traits are still being searched for. Using magnetoencephalography, we looked for structural abnormalities reflecting a preexisting dysfunction. We studied finger representations of both hands in the primary sensory cortex, as compared in 23 patients with unilateral task-specific dystonia and 20 control subjects. A dramatic disorganization of the nondystonic hand representation was found in all patients, and its amount paralleled the severity of the dystonic limb motor impairment. Abnormalities were also observed in the cortex coding the dystonic limb representation, but they were important only in the most severely affected patients. The abnormal cortical finger representations from the nondystonic limb appear to be endophenotypic traits of dystonia. That finger representations from the dystonic limb were almost normal for the less severely affected patients may be due to intrinsic beneficial remapping in reaction against the primary disorder.

An ERP study of famous face incongruity detection in middle age.

Age-related changes in famous face incongruity detection were examined in middle-aged (mean = 50.6) and young (mean = 24.8) subjects. Behavioral and ERP responses were recorded while subjects, after a presentation of a "prime face" (a famous person with the eyes masked), had to decide whether the following "test face" was completed with its authentic eyes (congruent) or with other eyes (incongruent). The principal effects of advancing age were (1) behavioral difficulties in discriminating between incongruent and congruent faces; (2) a reduced N400 effect due to N400 enhancement for both congruent and incongruent faces; (3) a latency increase of both N400 and P600 components. ERPs to primes (face encoding) were not affected by aging. These results are interpreted in terms of early signs of aging.

A high-resolution map of human chromosome 12.

Our sequence-tagged site-content map of chromosome 12 is now integrated with the whole-genome fingerprinting effort. It provides accurate and nearly complete bacterial clone coverage of chromosome 12. We propose that this integrated mapping protocol serves as a model for constructing physical maps for entire genomes.

Anticipation of epileptic seizures from standard EEG recordings.

BACKGROUND: New methods derived from non-linear analysis of intracranial recordings permit the anticipation of an epileptic seizure several minutes before the seizure. Nevertheless, anticipation of seizures based on standard scalp electroencephalographical (EEG) signals has not been reported yet. The accessibility to preictal changes from standard EEGs is essential for expanding the clinical applicability of these methods. METHODS: We analysed 26 scalp-EEG/video recordings, from 60 min before a seizure, in 23 patients with temporal-lobe epilepsy. For five patients, simultaneous scalp and intracranial EEG recordings were assessed. Long-term changes before seizure onset were identified by a measure of non-linear similarity, which is very robust in spite of large artifacts and runs in real-time. FINDINGS: In 25 of 26 recordings, measurement of non-linear changes in EEG signals allowed the anticipation of a seizure several minutes before it occurred (mean 7 min). These preictal changes in the scalp EEG correspond well with concurrent changes in depth recordings. INTERPRETATION: Scalp-EEG recordings retain sufficient dynamical information which can be used for the analysis of preictal changes leading to seizures. Seizure anticipation strategies in real-time can now be envisaged for diverse clinical applications, such as devices for patient warning, for efficacy of ictal-single photon emission computed tomography procedures, and eventual treatment interventions for preventing seizures.

Genetic analysis of the APAF1 gene in male germ cell tumors.

Cytogenetic and molecular analyses have shown that the chromosome band 12q22 is recurrently deleted in male germ cell tumors (GCTs), indicating the presence of a candidate tumor suppressor gene (TSG) in this region. To identify the TSG, we mapped the APAF1 gene, a proapoptotic mammalian homologue of ced-4, to chromosomal band 12q22, that suggested that this might be the candidate deleted gene in GCTs. We further localized the gene between the polymorphic markers D12S1671 and D12S1082 at 12q22 to determine the role of APAF1 in the pathogenesis of GCT, and we characterized its normal genomic structure and analyzed its alterations in GCTs. The APAF1 gene comprises 27 exons, with the coding region spanning 26. The region containing APAF1 was found to be deleted in GCT by fluorescence in situ hybridization analysis, but without evidence of coding sequence alterations. RT-PCR and Western blot analysis showed APAF1 gene expression at detectable levels in all GCT cell lines analyzed. An aberrant-sized APAF1 protein was seen in one cell line. This and 2 other cell lines carrying APAF1 deletions also exhibited defects in dATP-mediated caspase-3 activation. Caspase-3 activity was effectively restored by addition of recombinant caspase-9 and APAF1 proteins, and to a lesser extent by caspase-9 alone, but not by APAF1 alone. These data do not support a TSG role for APAF1, but defects in other components of the apoptotic pathway that may be related to 12q22 deletion cannot be ruled out. Genes Chromosomes Cancer 28:258-268, 2000.

ERPs and PET analysis of time perception: spatial and temporal brain mapping during visual discrimination tasks.

ERPs were recorded from 12 subjects performing duration and intensity visual discrimination tasks which have been previously used in a PET study. PET data showed that the same network was activated in both tasks [P. Maquet et al., NeuroImage 3:119-126, 1996]. Different ERP waveforms were observed for the late latency components depending on the dimension of the stimulus to be processed: frontal negativity (CNV) for the duration task and parieto-occipital positivity (P300) for the intensity task. Using BESA software, the sources were first modelled with a "PET dipolar model" (right prefrontal, right parietal, anterior cingulate, left and right fusiforms). To obtain a better fit for ERPs recorded in each task, two sources (cuneus, left prefrontal area) had to be added. Consistently with PET findings, dipole modelling indicates that duration and intensity dimensions of a visual stimulus are processed in the same areas. However, ERPs also reveal prominent differences between the time course of the dipole activations for each task, particularly for sources contributing to the late latency ERP components. In the intensity task, dipoles located in the cuneus, the anterior cingulate, and the left prefrontal area yield largest activity within the P300 interval, then activity diminishes rapidly as the stimulus ends, whereas in the duration task, the cuneus and anterior cingulate are still active several hundred milliseconds following stimulus offset. Moreover, in the duration task, the activity of the right frontal dipole parallels the CNV waveform, whereas in the intensity task, this dipole is largely inactive. We assume that the right frontal area plays a specific role in the formation of temporal judgments.

Effects of serotonin-selective and classical antidepressants on the auditory P300 cognitive potential.

The cognitive potential, P300, is a phenomenon frequently studied in relation to template matching of the brain. To understand the neurochemical mechanisms of its generation, we compared the effects of three antidepressants, fluoxetine, tianeptine and clomipramine after single and repeated application as well as after 1 week of withdrawal on the P300 and N200 waves in an auditory 'odd-ball' paradigm in three parallel groups of 10 healthy volunteers. Following single administration, both fluoxetine and clomipramine reduced (-39 +/- 14%, p < 0.01) the peak amplitude of P300 at the Pz electrode. For fluoxetine and tianeptine, reduced amplitudes of 19 +/- 7% and 24 +/- 11%, respectively, were found following 8 days of treatment, 2 h after administration. However, for clomipramine no additional diminution was found on day 8 with respect to day 1. Topographic distributions tended to be significantly modified at the frontal scalp area 1 h after the tianeptine administration on day 8, whereas the postdosing changes induced by fluoxetine were localised in the midline and right centrotemporal scalp regions. Only minor reductions in peak latencies have been observed. It can be concluded that serotonin selective drugs have a slower onset of P300 amplitude decrease than clomipramine, which has additional effects on monoaminergic and on cholinergic systems. These results suggest that serotonin has a regulatory function in the neurotransmission of cerebral structures which are involved in the evaluation of stimulus relevance.

Automatic attentional shifts induced by a noradrenergic drug in Alzheimer's disease: evidence from evoked potentials.

Prior research showed that attentional deficits are observed in Alzheimer's disease (AD). These deficits can further impair other cognitive processes. The present experiment was designed to study the shifts in attention induced by a noradrenergic drug (S 12024-2) through their electrophysiological correlates in 12 outpatients with mild AD, using an auditory oddball paradigm. The P3a component, known to be related to automatic attentional processing, was increased by the drug, whereas no changes occurred either in PN or in P3b, which are considered to reflect conscious processing. These results point to an involvement of the noradrenergic system in the modulation of automatic attentional processing, and provide evidence for weakening of the orienting reflex in AD, due to a possible noradrenergic deficit in patients with mild AD.

[Interactions between the epileptic network and brain function: an approach by nonlinear analysis of intracranial EEG]. / Interactions entre réseau épileptique et fonctionnement cérébral: approache par analyse non linéaire de l'EEG intracrânien.

Recent advances in the non-linear dynamics analysis have made it possible to identify hidden recurrences in EEG signals that could be missed by more traditional linear techniques such as power spectrum or coherence analysis. This is particularly true for epileptic EEG recordings either in animals or in humans as epileptic phenomena are usually concomitant with the emergence a strong non-linear EEG behavior. Non-linear dynamical analysis techniques quantify the relations between EEG signals. The literature concerning the spatio-temporal characteristics of the epileptic processes during seizures and interictal periods is reviewed. Our attention has been mainly focused on the interdependences between brain structures or on the dynamical changes of one particular brain region during intracranial recordings. These data could explain in part the dysfunctioning of the cerebral cortex induced by epileptic activities and provide an insight into the spatio-temporal organization of the epileptic network. Futhermore, by tracking the time variation of non-linear indices, one can anticipate the occurrence of seizures in temporal lobe epilepsies. All this information could contribute to improve definitions of the epileptogenic zone in partial epilepsy and also open the way to preventive interventions.

Event-related potentials to structural familiar face incongruity processing.

Thirty scalp sites were used to investigate the specific topography of the event-related potentials (ERPs) related to face associative priming when masked eyes of familiar faces were completed with either the proper features or incongruent ones. The enhanced negativity of N210 and N350, due to structural incongruity of faces, have a "category specific" inferotemporal localization on the scalp. Additional analyses support the existence of multiple ERP features within the temporal interval typically associated with N400 (N350 and N380), involving occipitotemporal and centroparietal areas. Seven reliable dipole locations have been evidenced using the brain electrical source analysis algorithm. Some of these localizations (fusiform, parahippocampal) are already known to be involved in face recognition, the other ones being related to general cognitive processes related to the task's demand. Because of their specific topography, the observed effects suggest that the face structural congruency process might involve early specialized neocortical areas in parallel with cortical memory circuits in the integration of perceptual and cognitive face processing.

A 3-Mb high-resolution BAC/PAC contig of 12q22 encompassing the 830-kb consensus minimal deletion in male germ cell tumors.

Cytogenetic and molecular genetic analyses have shown that the 12q22 region is recurrently deleted in male germ cell tumors (GCTs), suggesting that this site may harbor a tumor suppressor gene (TSG). Previous loss of heterozygosity (LOH) analyses identified a consensus minimal deleted region between the markers D12S377 and D12S296, and a YAC clone contig covering the region was generated. Here, we describe a high-resolution sequence-ready physical map of this contig covering a 3-Mb region. The map comprised of 52 cosmids, 49 PACs, and 168 BACs that were anchored to the previous YAC contig; 99 polymorphic, nonpolymorphic, EST, and gene-based markers are now placed on this map in a unique order. Of these, 61 markers were isolated in the present study, including one that was polymorphic. In addition, we have narrowed the minimal deletion to approximately 830 kb between D12S1716 (proximal) and P382A8-AG (distal) by LOH analysis of 108 normal-tumor DNAs from GCT patients using 21 polymorphic STSs. These physical and deletion maps should prove useful for identification of the candidate TSG in GCTs, provide framework to generate complete DNA sequence, and ultimately generate a gene map of this segment of the chromosome 12. [The sequence data described in this paper have been submitted to the Genome Survey Sequence under accession nos. AQ254896-AQ254955 and AQ269251-AQ269266. Online supplementary material is available at http://www.genome.org]

Differential processing of part-to-whole and part-to-part face priming: an ERP study.

We provide electrophysiological evidence supporting the hypothesis that part and whole face processing involve distinct functional mechanisms. We used a congruency judgment task and studied part-to-whole and part-to-part priming effects. Neither part-to-whole nor part-to-part conditions elicited early congruency effects on face-specific ERP components, suggesting that activation of the internal representations should occur later on. However, these components showed differential responsiveness to whole faces and isolated eyes. In addition, although late ERP components were affected when the eye targets were not associated with the prime in both conditions, their temporal and topographical features depended on the latter. These differential effects suggest the existence of distributed neural networks in the inferior temporal cortex where part and whole facial representations may be stored.

Perception's shadow: long-distance synchronization of human brain activity.

Transient periods of synchronization of oscillating neuronal discharges in the frequency range 30-80 Hz (gamma oscillations) have been proposed to act as an integrative mechanism that may bring a widely distributed set of neurons together into a coherent ensemble that underlies a cognitive act. Results of several experiments in animals provide support for this idea. In humans, gamma oscillations have been described both on the scalp (measured by electroencephalography and magnetoencephalography) and in intracortical recordings, but no direct participation of synchrony in a cognitive task has been demonstrated so far. Here we record electrical brain activity from subjects who are viewing ambiguous visual stimuli (perceived either as faces or as meaningless shapes). We show for the first time, to our knowledge, that only face perception induces a long-distance pattern of synchronization, corresponding to the moment of perception itself and to the ensuing motor response. A period of strong desynchronization marks the transition between the moment of perception and the motor response. We suggest that this desynchronization reflects a process of active uncoupling of the underlying neural ensembles that is necessary to proceed from one cognitive state to another.

The effects of apomorphine on attentional processing in Parkinson's disease.

To ascertain whether variations in central dopaminergic transmission can differentially affect motor and cognitive processing, we studied the effects of apomorphine (APO) in 9 patients with Parkinson's disease (PD). The UPDRS motor scores and auditory event-related potentials (ERPs) obtained in the 'odd-ball' (OB) and in the 'covert orientation of attention' (COA) tasks were studied in the 'off' and in the 'on' state after an injection of APO. Although APO injection improved patients' motor status, it induced a significant increase in the latencies of the P2 and P3 ERP components in the OB. In the COA task, right-hand reaction times (RTs) were markedly shortened in the 'on' state while left hand RTs remained unchanged. The contrasting effects of dopaminergic stimulation on the motor performance and on some aspects of cognitive processing suggest the existence of complex interactions within pre- and postsynaptic brain dopamine receptors, and an intervention of segregated basal ganglia-prefrontal cortex loops in motor and cognitive behaviour.