Lateralization of olfactory processing: Differential impact of right and left temporal lobe epilepsies.

Olfactory processes were reported to be lateralized. The purpose of this study was to further explore this phenomenon and investigate the effect of the hemispheric localization of epileptogenic foci on olfactory deficits in patients with temporal lobe epilepsy (TLE). Olfactory functioning was assessed in 61 patients and 60 healthy control (HC) subjects. The patients and HC subjects were asked to rate the intensity, pleasantness, familiarity, and edibility of 12 common odorants and then identify them. Stimulations were delivered monorhinally in the nostril ipsilateral to the epileptogenic focus in TLE and arbitrarily in either the left or the right nostril in the HC subjects. The results demonstrated that regardless of the side of stimulation, patients with TLE had reduced performance in all olfactory tasks compared with the HC subjects. With regard to the side of the epileptogenic focus, patients with left TLE judged odors as less pleasant and had more difficulty with identification than patients with right TLE, underlining a privileged role of the left hemisphere in the emotional and semantic processing of odors. Finally, irrespective of group, a tendency towards a right-nostril advantage for judging odor familiarity was found in agreement with a prominent role of the right hemisphere in odor memory processing.

Emotional attention as a modulatory system of perception

Report for the scientific sojourn carried out at the University Medical Center, Swiss, from 2010 to 2012. Abundant evidence suggests that negative emotional stimuli are prioritized in the perceptual systems, eliciting enhanced neural responses in early sensory regions as compared with neutral information. This facilitated detection is generally paralleled by larger neural responses in early sensory areas, relative to the processing of neutral information. In this sense, the amygdala and other limbic regions, such as the orbitofrontal cortex, may play a critical role by sending modulatory projections onto the sensory cortices via direct or indirect feedback.The present project aimed at investigating two important issues regarding these mechanisms of emotional attention, by means of functional magnetic resonance imaging. In Study I, we examined the modulatory effects of visual emotion signals on the processing of task-irrelevant visual, auditory, and somatosensory input, that is, the intramodal and crossmodal effects of emotional attention. We observed that brain responses to auditory and tactile stimulation were enhanced during the processing of visual emotional stimuli, as compared to neutral, in bilateral primary auditory and somatosensory cortices, respectively. However, brain responses to visual task-irrelevant stimulation were diminished in left primary and secondary visual cortices in the same conditions. The results also suggested the existence of a multimodal network associated with emotional attention, presumably involving mediofrontal, temporal and orbitofrontal regions Finally, Study II examined the different brain responses along the low-level visual pathways and limbic regions, as a function of the number of retinal spikes during visual emotional processing. The experiment used stimuli resulting from an algorithm that simulates how the visual system perceives a visual input after a given number of retinal spikes. The results validated the visual model in human subjects and suggested differential emotional responses in the amygdala and visual regions as a function of spike-levels. A list of publications resulting from work in the host laboratory is included in the report.

Emotional attention as a modulatory system of perception

Report for the scientific sojourn carried out at the University Medical Center, Swiss, from 2010 to 2012. Abundant evidence suggests that negative emotional stimuli are prioritized in the perceptual systems, eliciting enhanced neural responses in early sensory regions as compared with neutral information. This facilitated detection is generally paralleled by larger neural responses in early sensory areas, relative to the processing of neutral information. In this sense, the amygdala and other limbic regions, such as the orbitofrontal cortex, may play a critical role by sending modulatory projections onto the sensory cortices via direct or indirect feedback.The present project aimed at investigating two important issues regarding these mechanisms of emotional attention, by means of functional magnetic resonance imaging. In Study I, we examined the modulatory effects of visual emotion signals on the processing of task-irrelevant visual, auditory, and somatosensory input, that is, the intramodal and crossmodal effects of emotional attention. We observed that brain responses to auditory and tactile stimulation were enhanced during the processing of visual emotional stimuli, as compared to neutral, in bilateral primary auditory and somatosensory cortices, respectively. However, brain responses to visual task-irrelevant stimulation were diminished in left primary and secondary visual cortices in the same conditions. The results also suggested the existence of a multimodal network associated with emotional attention, presumably involving mediofrontal, temporal and orbitofrontal regions Finally, Study II examined the different brain responses along the low-level visual pathways and limbic regions, as a function of the number of retinal spikes during visual emotional processing. The experiment used stimuli resulting from an algorithm that simulates how the visual system perceives a visual input after a given number of retinal spikes. The results validated the visual model in human subjects and suggested differential emotional responses in the amygdala and visual regions as a function of spike-levels. A list of publications resulting from work in the host laboratory is included in the report.

Informed Control Over Inputs and Extent of Industrial Processing, June 2005

Stylized facts regarding the industrial process include emphases on obtaining information about and control over the quality of raw materials. We provide a model that establishes conditions under which informed control involves ensuring uniformity in inputs and increased uniformity encourages more extensive processing. We show when the Boltzmann-Shannon entropy statistic is an appropriate measure of uniformity.

@neurIST infrastructure for advanced disease management through integration of heterogeneous data, computing, and complex processing services

The increasing volume of data describing humandisease processes and the growing complexity of understanding, managing, and sharing such data presents a huge challenge for clinicians and medical researchers. This paper presents the@neurIST system, which provides an infrastructure for biomedical research while aiding clinical care, by bringing together heterogeneous data and complex processing and computing services. Although @neurIST targets the investigation and treatment of cerebral aneurysms, the system’s architecture is generic enough that it could be adapted to the treatment of other diseases.Innovations in @neurIST include confining the patient data pertaining to aneurysms inside a single environment that offers cliniciansthe tools to analyze and interpret patient data and make use of knowledge-based guidance in planning their treatment. Medicalresearchers gain access to a critical mass of aneurysm related data due to the system’s ability to federate distributed informationsources. A semantically mediated grid infrastructure ensures that both clinicians and researchers are able to seamlessly access andwork on data that is distributed across multiple sites in a secure way in addition to providing computing resources on demand forperforming computationally intensive simulations for treatment planning and research.

What is the value of joint processing of pilots and data in block-fading channels?

The spectral efficiency achievable with joint processing of pilot and data symbol observations is compared with that achievable through the conventional (separate) approach of first estimating the channel on the basis of the pilot symbols alone, and subsequently detecting the datasymbols. Studied on the basis of a mutual information lower bound, joint processing is found to provide a non-negligible advantage relative to separate processing, particularly for fast fading. It is shown that, regardless of the fading rate, only a very small number of pilot symbols (at most one per transmit antenna and per channel coherence interval) shouldbe transmitted if joint processing is allowed.

Role of the superior parietal lobules in letter-identity processing within strings: FMRI evidence from skilled and dyslexic readers.

Traditionally, the ventral occipito-temporal (vOT) area, but not the superior parietal lobules (SPLs), is thought as belonging to the neural system of visual word recognition. However, some dyslexic children who exhibit a visual attention span disorder - i.e. poor multi-element parallel processing - further show reduced SPLs activation when engaged in visual multi-element categorization tasks. We investigated whether these parietal regions further contribute to letter-identity processing within strings. Adult skilled readers and dyslexic participants with a visual attention span disorder were administered a letter-string comparison task under fMRI. Dyslexic adults were less accurate than skilled readers to detect letter identity substitutions within strings. In skilled readers, letter identity differs related to enhanced activation of the left vOT. However, specific neural responses were further found in the superior and inferior parietal regions, including the SPLs bilaterally. Two brain regions that are specifically related to substituted letter detection, the left SPL and the left vOT, were less activated in dyslexic participants. These findings suggest that the left SPL, like the left vOT, may contribute to letter string processing.

Allostatic working memory processing in schizophrenia: Human and animal model coherence

The most evident symptoms of schizophrenia are severe impairment of cognitive functions like attention, abstract reasoning and working memory. The latter has been defined as the ability to maintain and manipulate on-line a limited amount of information. Whereas several studies show that working memory processes are impaired in schizophrenia, the specificity of this deficit is still unclear. Results obtained with a new paradigm, involving visuospatial, dynamic and static working memory processing, suggest that schizophrenic patients rely on a specific compensatory strategy. An animal model of schizophrenia with a transient deficit in glutathione during the development reveals similar substitutive processing, masking the impairment in working memory functions in specific test conditions only. Taken together, these results show coherence between working memory deficits in schizophrenic patients and in animal models. More generally, it is possible to consider that the pathological state may be interpreted as a reduced homeostatic reserve. However, this may be balanced in specific situations by efficient allostatic strategies. Thus, the pathological condition would remain latent in several situations, due to such allostatic regulations. However, to maintain a performance based on highly specific strategies requires in turn specific conditions, limitating adaptative resources in humans and in animals. In summary, we suggest that the psychological and physical load to maintain this rigid allostatic state is very high in patients and animal subjects.

Processing of tumor-associated antigen by the proteasomes of dendritic cells controls in vivo T-cell responses.

Dendritic cells are unique in their capacity to process antigens and prime naive CD8(+) T cells. Contrary to most cells, which express the standard proteasomes, dendritic cells express immunoproteasomes constitutively. The melanoma-associated protein Melan-A(MART1) contains an HLA-A2-restricted peptide that is poorly processed by melanoma cells expressing immunoproteasomes in vitro. Here, we show that the expression of Melan-A in dendritic cells fails to elicit T-cell responses in vitro and in vivo because it is not processed by the proteasomes of dendritic cells. In contrast, dendritic cells lacking immunoproteasomes induce strong anti-Melan-A T-cell responses in vitro and in vivo. These results suggest that the inefficient processing of self-antigens, such as Melan-A, by the immunoproteasomes of professional antigen-presenting cells prevents the induction of antitumor T-cell responses in vivo.

Distribution of neuronal and metabolic markers in the human auditory cortex

SUMMARY The human auditory cortex, located on the supratemporal plane of the temporal lobe, is divided in a primary auditory area and several non-primary areas surrounding it. These different areas show anatomical and functional differences. Many studies have focussed on auditory areas in non-human primates, using investigation techniques such as electrophysiological recordings, tracing of neural connections, or immunohistochemical and histochemical staining. Some of these studies have suggested parallel and hierarchical organization of the cortical auditory areas as well as subcortical auditory relays. In humans, only few studies have investigated these regions immunohistochemically, but activation and lesion studies speak in favour of parallel and hierarchical organization, very similar to that of non-human primates. Calcium-binding proteins and metabolic markers were used to investigate possible correlates of hierarchical and parallel organization in man. Calcium-binding proteins, parvalbumin, calretinin and calbindin, modulate the concentration of intracellular free calcium ions and were found in distinct subpopulations of GABAergic neurons in non-human primates species. In our study, their distribution showed several differences between auditory areas: the primary auditory area was darkly stained for both parvalbumin and calbindin, and their expression rapidly decreased while moving away from the primary area. This staining pattern suggests a hierarchical organization of the areas, in which the more darkly stained areas could correspond to an earlier integration level and the areas showing light staining may correspond to higher level integration areas. Parallel organization of primary and non-primary auditory areas was suggested by the complementarity, within a given area, between parvalbumin and calbindin expression across layers. To investigate the possible differences in the energetic metabolism of the cortical auditory areas, several metabolic markers were used: cytochrome oxidase and LDH1 were used as oxidative metabolism markers and LDH5 was used as glycolytic metabolism marker. The results obtained show a difference in the expression of enzymes involved in oxidative metabolism between areas. In the primary auditory area the oxidative metabolism markers were maximally expressed in layer IV. In contrast, higher order areas showed maximal staining in supragranular layers. The expression of LDH5 varied in patches, but did not differ between the different hierarchical auditory areas. The distribution of the two LDH enzymes isoforms also provides information about cellular aspects of metabolic organization, since neurons expressed the LDH1 isoform whereas astrocytes express primarily LDH5, but some astrocytes also contained the LDH1 isoform. This cellular distribution pattern supports the hypothesis of the existence of an astrocyte-neuron lactate shuttle, previously suggested in rodent studies, and in particular of lactate transfer from astrocytes, which produce lactate from the glucose obtained from the circulation, to neurons that use lactate as energy substrate. In conclusion, the hypothesis of parallel and hierarchical organization of the auditory areas can be supported by CaBPs, cytochrome oxidase and LDH1 distribution. Moreover, the two LDHs cellular distribution pattern support the hypothesis of an astrocyte-neuron lactate shuttle in human cortex.

Emotional processing in a ten-session general psychiatric treatment for borderline personality disorder: a case study.

This study examines the effects of a borderline-specific treatment, called general psychiatric management, on emotional change, outcome and therapeutic alliance of an outpatient presenting with borderline personality disorder. Based on the sequential model of emotional processing, emotional states were assessed in a 10-session setting. The case showed an increase in expressions of distress and no change in therapeutic alliance and tended towards general deterioration. Results suggest emotional processing may play a lesser role in general psychiatric management in early phase treatment than previously hypothezised. Copyright © 2015 John Wiley & Sons, Ltd.

Organizing principles across the senses

ABSTRACT This thesis is composed of two main parts. The first addressed the question of whether the auditory and somatosensory systems, like their visual counterpart, comprise parallel functional pathways for processing identity and spatial attributes (so-called `what' and `where' pathways, respectively). The second part examined the independence of control processes mediating task switching across 'what' and `where' pathways in the auditory and visual modalities. Concerning the first part, electrical neuroimaging of event-related potentials identified the spatio-temporal mechanisms subserving auditory (see Appendix, Study n°1) and vibrotactile (see Appendix, Study n°2) processing during two types of blocks of trials. `What' blocks varied stimuli in their frequency independently of their location.. `Where' blocks varied the same stimuli in their location independently of their frequency. Concerning the second part (see Appendix, Study n°3), a psychophysical task-switching paradigm was used to investigate the hypothesis that the efficacy of control processes depends on the extent of overlap between the neural circuitry mediating the different tasks at hand, such that more effective task preparation (and by extension smaller switch costs) is achieved when the anatomical/functional overlap of this circuitry is small. Performance costs associated with switching tasks and/or switching sensory modalities were measured. Tasks required the analysis of either the identity or spatial location of environmental objects (`what' and `where' tasks, respectively) that were presented either visually or acoustically on any given trial. Pretrial cues informed participants of the upcoming task, but not of the sensory modality. - In the audio-visual domain, the results showed that switch costs between tasks were significantly smaller when the sensory modality of the task switched versus when it repeated. In addition, switch costs between the senses were correlated only when the sensory modality of the task repeated across trials and not when it switched. The collective evidence not only supports the independence of control processes mediating task switching and modality switching, but also the hypothesis that switch costs reflect competitive interterence between neural circuits that in turn can be diminished when these neural circuits are distinct. - In the auditory and somatosensory domains, the findings show that a segregation of location vs. recognition information is observed across sensory systems and that these happen around 100ms for both sensory modalities. - Also, our results show that functionally specialized pathways for audition and somatosensation involve largely overlapping brain regions, i.e. posterior superior and middle temporal cortices and inferior parietal areas. Both these properties (synchrony of differential processing and overlapping brain regions) probably optimize the relationships across sensory modalities. - Therefore, these results may be indicative of a computationally advantageous organization for processing spatial anal identity information.

Spontaneous pre-stimulus fluctuations in the activity of right fronto-parietal areas influence inhibitory control performance.

Inhibitory control refers to the ability to suppress planned or ongoing cognitive or motor processes. Electrophysiological indices of inhibitory control failure have been found to manifest even before the presentation of the stimuli triggering the inhibition, suggesting that pre-stimulus brain-states modulate inhibition performance. However, previous electrophysiological investigations on the state-dependency of inhibitory control were based on averaged event-related potentials (ERPs), a method eliminating the variability in the ongoing brain activity not time-locked to the event of interest. These studies thus left unresolved whether spontaneous variations in the brain-state immediately preceding unpredictable inhibition-triggering stimuli also influence inhibitory control performance. To address this question, we applied single-trial EEG topographic analyses on the time interval immediately preceding NoGo stimuli in conditions where the responses to NoGo trials were correctly inhibited [correct rejection (CR)] vs. committed [false alarms (FAs)] during an auditory spatial Go/NoGo task. We found a specific configuration of the EEG voltage field manifesting more frequently before correctly inhibited responses to NoGo stimuli than before FAs. There was no evidence for an EEG topography occurring more frequently before FAs than before CR. The visualization of distributed electrical source estimations of the EEG topography preceding successful response inhibition suggested that it resulted from the activity of a right fronto-parietal brain network. Our results suggest that the fluctuations in the ongoing brain activity immediately preceding stimulus presentation contribute to the behavioral outcomes during an inhibitory control task. Our results further suggest that the state-dependency of sensory-cognitive processing might not only concern perceptual processes, but also high-order, top-down inhibitory control mechanisms.

Automated auditory mismatch negativity paradigm improves coma prognostic accuracy after cardiac arrest and therapeutic hypothermia.

PURPOSE: EEG and somatosensory evoked potential are highly predictive of poor outcome after cardiac arrest; their accuracy for good recovery is however low. We evaluated whether addition of an automated mismatch negativity-based auditory discrimination paradigm (ADP) to EEG and somatosensory evoked potential improves prediction of awakening. METHODS: EEG and ADP were prospectively recorded in 30 adults during therapeutic hypothermia and in normothermia. We studied the progression of auditory discrimination on single-trial multivariate analyses from therapeutic hypothermia to normothermia, and its correlation to outcome at 3 months, assessed with cerebral performance categories. RESULTS: At 3 months, 18 of 30 patients (60%) survived; 5 had severe neurologic impairment (cerebral performance categories = 3) and 13 had good recovery (cerebral performance categories = 1-2). All 10 subjects showing improvements of auditory discrimination from therapeutic hypothermia to normothermia regained consciousness: ADP was 100% predictive for awakening. The addition of ADP significantly improved mortality prediction (area under the curve, 0.77 for standard model including clinical examination, EEG, somatosensory evoked potential, versus 0.86 after adding ADP, P = 0.02). CONCLUSIONS: This automated ADP significantly improves early coma prognostic accuracy after cardiac arrest and therapeutic hypothermia. The progression of auditory discrimination is strongly predictive of favorable recovery and appears complementary to existing prognosticators of poor outcome. Before routine implementation, validation on larger cohorts is warranted.