On the correlation between perceptual inundation caused by realistic immersive environmental auditory scenes and the sensory gating inventory in schizophrenia.

BACKGROUND: In schizophrenia, perceptual inundation related to sensory gating deficit can be evaluated "off-line" with the sensory gating inventory (SGI) and "on-line" during listening tests. However, no study investigated the relation between "off-line evaluation" and "on-line evaluation". The present study investigates this relationship. METHODS: A sound corpus of 36 realistic environmental auditory scenes was obtained from a 3D immersive synthesizer. Twenty schizophrenic patients and twenty healthy subjects completed the SGI and evaluated the feeling of "inundation" from 1 ("null") to 5 ("maximum") for each auditory scene. Sensory gating deficit was evaluated in half of each population group with P50 suppression electrophysiological measure. RESULTS: Evaluation of inundation during sound listening was significantly higher in schizophrenia (3.25) compared to the control group (2.40, P<.001). The evaluation of inundation during the listening test correlated significantly with the perceptual modulation (n=20, rho=.52, P=.029) and the over-inclusion dimensions (n=20, rho=.59, P=.01) of the SGI in schizophrenic patients and with the P50 suppression for the entire group of controls and patients who performed ERP recordings (n=20, rho=-.49, P=.027). CONCLUSION: An evaluation of the external validity of the SGI was obtained through listening tests. The ability to control acoustic parameters of each of the realistic immersive environmental auditory scenes might in future research make it possible to identify acoustic triggers related to perceptual inundation in schizophrenia.

"All that glitters is not alone". Congruity effects in highly and less predictable sentence contexts.

CONTEXT: Using natural connected speech, the aim of the present study was to examine the semantic congruity effect (i.e. the difference between semantically incongruous and congruous words) in sentence contexts that generate high or moderate final word expectancies. METHODS: We used sentences with two levels of word expectancy in the auditory modality: familiar proverbs (that generate high final word expectancy), and unfamiliar sentences (that generate only moderate final word expectancy). RESULTS: Results revealed an early congruity effect (0-200 ms) that developed across all scalp sites for familiar proverbs but not for unfamiliar sentences. By contrast, typical centro-parietal N400 and Late Positivity Component congruity effects developed later (200-500 ms and 600-900 ms ranges) for both familiar proverbs and unfamiliar sentences. DISCUSSION: We argue that the early congruity effect for proverbs comprises both a Phonological Mismatch Negativity, reflecting the processing of the acoustic/phonological mismatch between the expected (congruous) and unexpected (incongruous) sentence completions and a typical N400 semantic congruity effect with an unusual short latency because final words can be predicted from the unusually high contextual constraints of familiar proverbs. These results are considered in the light of current views of anticipation and prediction processes in sentence contexts.

[Biofeedback and drug-resistant epilepsy: back to an earlier treatment?]. / Biofeedback et épilepsie pharmacorésistante : le retour d'une thérapeutique ancienne ?

Biofeedback is a complementary non-pharmacological and non-surgical therapeutic developed over the last thirty years in the management of drug-resistant epilepsy. Biofeedback allows learning cognitive and behavioral strategies via a psychophysiological feedback loop. Firstly, this paper describes the different types of biofeedback protocols used for the treatment of drug-refractory epilepsy and their physiological justifications. Secondly, this paper analyzes the evidence of effectiveness, from a medical point of view, on reducing the numbers of seizures, and from a neurophysiological point of view, on the changing brain activity. Electroencephalography (EEG) biofeedback (neurofeedback) protocol on sensorimotor rhythms (SMR) has been investigated in many studies, the main limitation being small sample sizes and lack of control groups. The newer neurofeedback protocol on slow cortical potential (SCP) and galvanic skin response (GSR) biofeedback protocols have been used in a smaller number of studies. But, these studies are more rigorous with larger sized samples, matched control groups, and attempts to control the placebo effect. These protocols also open the way for innovative neurophysiological researches and may predict a renewal of biofeedback techniques. Biofeedback would have legitimacy in the field of clinical drug-resistant epilepsy at the interface between therapeutic and clinical neurophysiology.

[Mixed depressions: clinical and neurophysiological biomarkers]. / Épisodes dépressifs mixtes : clinique et biomarqueurs neurophysiologiques.

Epidemiological studies of major depressive episodes (MDE) highlighted the frequent association of symptoms or signs of mania or hypomania with depressive syndrome. Beyond the strict definition of DSM-IV, epidemiological recognition of a subset of MDE characterized by the presence of symptoms or signs of the opposite polarity is clinically important because it is associated with pejorative prognosis and therapeutic response compared to the subgroup of "typical MDE". The development of DSM-5 took into account the epidemiological data. DSM-5 opted for a more dimensional perspective in implementing the concept of "mixed features" from an "episode" to a "specification" of mood disorder. As outlined in the DSM-5: "Mixed features associated with a major depressive episode have been found to be a significant risk factor for the development of bipolar I and II disorder. As a result, it is clinically useful to note the presence of this specifier for treatment planning and monitoring of response to therapeutic". However, the mixed features are sometimes difficult to identify, and neurophysiological biomarkers would be useful to make a more specific diagnosis. Two neurophysiological models make it possible to better understand MDE with mixed features : i) the emotional regulation model that highlights a tendency to hyper-reactive and unstable emotion response, and ii) the vigilance regulation model that highlights, through EEG recording, a tendency to unstable vigilance. Further research is required to better understand relationships between these two models. These models provide the opportunity of a neurophysiological framework to better understand the mixed features associated with MDE and to identify potential neurophysiological biomarkers to guide therapeutic strategies.

[Interactive rTMS protocols in psychiatry]. / Protocoles de rTMS interactives en psychiatrie.

BACKGROUND: The efficiency of repetitive transcranial magnetic stimulation (rTMS) in the treatment of psychiatric disorders is robust for major depressive episode (MDE) while results are encouraging for schizophrenia. However, rTMS protocols need to be optimized. Basic researches in TMS led to the concept of "state dependency TMS". This concept suggests that the neural circuits' activation states, before and during the stimulation, influence the pulse effect. Indeed, TMS effect must be seen, not simply as a stimulus, but also as the result of an interaction between a stimulus and a level of brain activity. Those data suggest that rTMS efficiency could be increased in psychiatric disorders by triggering patients' neurocognitive activities during stimulation. Thus "interactive rTMS protocols" have been submitted. OBJECTIVES: This article provides a review and a classification of different interactive protocols implemented in the treatment of MDE and schizophrenia. Protocols' interactions with cognitive activities and brain electrical activities will be discussed. LITERATURE FINDINGS: Interactive rTMS protocols that manipulate cognitive activities have been developed for MDE treatments. They aim at regulating emotional states of depressed patients during the stimulation. The patients perform emotional tasks in order to activate cortical networks involving the left dorsolateral prefrontal cortex (DLPFC) into a state that may be more sensitive to the rTMS pulse effect. Simultaneous cognitive behavioral therapy ("CBT rTMS") and cognitive-emotional reactivation ("affective rTMS") have thus been tested during left DLPFC rTMS in MDE. Interactive rTMS protocols that manipulate brain electrical activities have been developed for MDE and schizophrenia treatments. Two categories of protocols should be identified. In the first set, personalized brain activity has been analyzed to determine the parameters of stimulation (i.e. frequency of stimulation) matching the patient ("personalized rTMS"). Personalized rTMS protocols can be made "online" or "offline" depending on whether the EEG activity is measured during or prior to rTMS. Online protocol is called "contingent rTMS": it consists in stimulating the brain only when a specific EEG pattern involving the intensity of alpha rhythm is recorded and recognized. Offline protocol is called "alpha rTMS", and relies on ascertaining frequency of stimulation in accordance with personalized alpha peak frequency prior to rTMS. In the second set, electrical brain activity is modulated before or during rTMS in order to stimulate the DLPFC in optimal conditions. Brain activity modulation may be obtained by transcranial direct current stimulation ("tDCS rTMS") or EEG-biofeedack ("EEG-biofeedback rTMS"). CONCLUSION: Interactive rTMS studies have various limitations, notably their exploratory character on a small sample of patients. Furthermore, their theoretical neurocognitive framework justification remains unclear. Nonetheless, interactive rTMS protocols allow us to consider a new field of rTMS, where cognitive and cerebral activities would no longer be considered as simple neural noise, leading to a kind of "first person rTMS", and certainly to innovative therapy in psychiatry.

[Electrophysiology and schizophrenic vulnerability: the N400 component as endophenotype candidate?]. / Électrophysiologie et vulnérabilité schizophrénique: la composante N400 comme endophénotype candidat?

Research on early stages of schizophrenia aims to provide early, objective, and stable markers of vulnerability. In this review, we first briefly describe the notion of such markers, or endophenotypes, notably in terms of stability, specificity and heritability. Among other empirical approaches, event-related potentials (ERPs) have been recently considered as putative endophenotypes. The N400 component is an event-related brain potential classically elicited during semantic processing, as suggested by a growing body of empirical studies with a large variety of paradigms. We provide here a short account of its typical descriptions and the interpretations of its functional significance. Then we describe the main current results about schizophrenic alterations of the N400 component. Two levels of semantic processing (automatic spreading and controlled mechanisms) are disturbed in schizophrenia, even if the underlying mechanisms remain unclear or discussed. Several controversial issues may also need further research, such as the influence of symptomatology and evolution of schizophrenia. Another crucial topic concerns the putative schizophrenic specificity, and only little is known about possible alterations of N400 in affective disorders. We discuss the notion of heritability, mainly explored in current literature among people with schizotypal personality. Finally, even if N400 studies contribute to a better understanding of linguistic disturbances in schizophrenia, it appears difficult to consider the N400 component as a relevant schizophrenic endophenotype, given the current paucity of results on its stability, its heritability (clinical and genetic vulnerability) and its schizophrenic specificity.

[Towards a new approach of neurophysiology in clinical psychiatry: functional magnetic resonance imaging neurofeedback applied to emotional dysfunctions]. / Vers une nouvelle déclinaison de la neurophysiologie clinique en psychiatrie: le neurofeedback par imagerie par résonance magnétique fonctionnelle appliqué aux dysfonctions des processus émotionnels.

Emotions color in a singular way our everyday life and constitute important determinants of human cognition and behavior. Emotional regulation is an essential process involved in neuropathophysiology and therapeutic efficacy in many psychiatric disorders. Yet, traditional psychiatric therapeutic has focused on symptomatic rather than neurophysiological criteria. Therefore, it was proposed to teach patients to modify their own brain activity directly, in order to obtain a therapeutic effect. These techniques, which are named neurofeedback, were originally developed using electroencephalography. Recent technical advances in fMRI enable real-time acquisition, and open opportunities to its utilization in neurofeedback. This seems particularly interesting in emotion regulation, which, at a neurofunctional level, lies on cortico-limbic pathways that, in great parts, were previously identified by traditional fMRI paradigms. This emotion regulation plays a central role in the etiopathogeny psychiatric, especially depressive and anxious, disorders. It is possible to devise new therapeutic strategies and research approach for addressing directly the neurophysiological processes of emotion regulation by integrating the neurofunctional activities of a subject. These prospects seem to be in line with the neurophenomenology project, which proposes to establish a link between subjective experiences and objective neurophysiological measures.

[The measurement of electrodermal activity]. / La mesure de la réaction électrodermale.

INTRODUCTION: Electrodermal activity (EDA) is an early physiological index and the subject of constant interest, in spite of the bad reputation attached to "lie detectors". This interest is expected to increase in the future, following the development of research related to the neurobiological aspect of emotions of which it is an index. Recent data provided by functional cerebral imaging has added to the significance of this index and should result in further interest. AIM: The authors thus re-examined the various notions related to measuring EDA, and its practical aspect as well as its mechanisms. EDA should be useful both for authors wishing to use this variable and for readers wishing to form their own critical point of view. LITERATURE FINDINGS: The article first defines the various terms used to qualify EDA. Then, it analyses the mechanisms occurring at the sweat glands' level, showing that a distinct innervation of the sweat glands causes sweat to be released in the excretory channels, thereby allowing the recording of a negative surface potential in parallel to the lowering of skin conductance. Arguments are then pointed out to illustrate that the potential's positive phase following this first answer occurs in the case of high intensity stimulations. The study of the central command of sudation demonstrates that, several areas are involved and that different functions such as thermal regulation and motricity may interfere with emotive reactions. Difficulties regarding the mode of measurement of these answers as to their number and amplitude are also brought to light. DISCUSSION: A particular interest of measuring EDA is its ability to highlight individual characteristic and unconscious emotional reactivity. Subjects who constitutionally present many spontaneous and therefore habitual EDA can indeed be opposed to subjects whose EDA reflexes are very few and hardly habitual. A theory suggests that for the first category, whose subjects are named labiles, emotional control may be at the origin of EDA. This characteristic brings to mind the case of antisocial subjects whose rate of EDA is also reduced, although for the latter a primitive drop in behavioral inhibition is involved. The production of EDA in response to non-conscious emotive stimulations can be objectified in the rare cases of prosopagnosia. These subjects who are unable to recognize familiar faces can produce EDA when presented faces with an emotional load. These cases contrast with the delusional denial of the Capgras syndrome where subjects do not present EDA, suggesting that the dysfunction of visual analysis occurs at a different level. There are other rare cases represented by cortical blindness where EDA shows that an unconscious emotional analysis is preserved. These subjects are known however to be capable of unconscious visual discriminations, which are possibly accompanied by EDA. This possibility of a "blind vision" is experimentally studied via subliminal vision testing (backward masking tests). These demonstrate that a rudimentary visual analysis is carried out in the subcortical circuits while taking into account the affective aspect of stimulations. CONCLUSION: Present or future data should allow a greater comprehension of electrodermal signals, making it possible to overcome the difficulties related to their interpretation and facilitate their applications.

[Neurophysiological endophenotypes and schizophrenic disorder: emergence and evolution of a clinical concept]. / Endophénotypes neurophysiologiques et trouble schizophrénique : naissance et évolution d'un concept clinique.

It is proposed an historical approach to concepts leading to the development of operational paradigms for measuring objectives neurophysiological endophenotypes. It is hypothesized that psychiatric interest for paradigms measuring Event-Related Potential (ERP) come from Bleuler (1911) and McGhie and Chapman (1961) phenomenological and clinical descriptions. They noted, first that patients with schizophrenia generally feel as if they are being flooded by an overwhelming mass of sensory input combined with a heightened sensory perception, second that they were distractible to irrelevant sensory stimuli. These subjective abnormalities may be related, first to inability to filter incongruent information measured in a double click paradigm by a deficit in P50 amplitude gating, and second to an inability to select a stimulus of interest measured in the oddball paradigm by a deficit in P300 amplitude. The analysis of these P50 and P300 ERP in cohorts of patients with schizophrenia found most of Gottesman endophenotype criteria. P50 and P300 ERP are therefore relevant neurophysiological endophenotypes. However, from a clinical point of view, these endophenotypes lack specificity. The hypothesis of this article leads us to formulate ways of research. It is shown the value of combining objective neurophysiological measures with subjective measures using self-administered questionnaires ("offline") or psychophysiological tests ("online") to develop rigorous neurophysiological experimental paradigms especially as clinical observations of their origins are not forgotten.

[Electrophysiology and schizophrenic vulnerability: the P300 component as endophenotype candidate?]. / Électrophysiologie et vulnérabilité schizophrénique : la composante P300 comme endophénotype candidat?

INTRODUCTION: Studies on early stages of schizophrenia imply the observation of stable markers of vulnerability. Among other research fields, these early and objective markers, or potential endophenotypes, can be described in event-related potential (ERP) paradigms. LITERATURE FINDINGS: The P300 component, elicited during the allocation of attentional resources, is the most studied ERP among people with schizophrenia. In this review, we first develop the notion of endophenotypes in schizophrenia, notably in terms of stability, heritability and specificity. We also give a short account of the P300 component, its typical description, the classical paradigms which elicit it, and several interpretations of its significance. DISCUSSION: After reviewing the main features of the schizophrenic alterations of P300 (their topography, amplitude and latency), we discuss the relevance of P300 when described as a potential schizophrenic endophenotype. In spite of an important number of studies, results remain controversial and incomplete. First, P300 in schizophrenia shows complex patterns of temporal evolution, and thus can be described as either a stable trait or a state marker. Second, its heritability is still discussed among high-risk participants with genetic, schizotypal or clinical vulnerability. Third, the issue of its specificity is the less studied criteria. In line with the debate of its specificity, only little is known about specific alterations of P300 among unipolar or bipolar disorders. In the discussion, we describe a few possible origins of such controversial results in both empirical and conceptual perspectives, and we provide several experimental propositions in order to develop a more systematic exploration of P300 alterations.

[Single-voxel proton spectroscopy using a press sequence with a 135 ms echotime: normal values]. / Valeurs controles obtenues avec une sequence press 135 ms en neurospectroscopie monovoxel du proton.

The clinical value of MR spectroscopy is now well established and this technique has been added to the current French classification of medical acts (CCAM). This paper presents a set of normal control values for 3 metabolite ratios obtained using a PRESS sequence with a TE of 135 ms at 1.5T: NAA/Cho, NAA/Cr and Cho/CR. Spectroscopy data acquisition were obtained from the following 12 anatomical regions: parieto-occipital white matter, centrum semiovale, frontal white matter, thalamus, basal ganglia, cerebellum (hemisphere, including dentate nucleus), brain stem (including pons, medulla and midbrain), anterior and posterior temporal lobe, parietal, occipital and pre-frontal cortices. The presented data allow radiologists equipped with a similar MR system to implement a clinical spectroscopy program without undergoing research protocols in order to obtain control values.

Proton magnetic resonance neurospectroscopy and EEG cartography in corticobasal degeneration: correlations with neuropsychological signs.

OBJECTIVE: To document the asymmetrical functional brain lesions in corticobasal degeneration (CBD) using proton magnetic resonance neurospectroscopy (MRS) and EEG cartography (EEGq). METHODS: Eight patients with probable CBD were included in the study after full neurological examination and extensive neuropsychological testing, single photon emission computed tomography, anatomical x ray tomodensitometry (TDM), magnetic resonance imaging, and MRS examination. RESULTS: MR spectra were abnormal in all seven patients in whom the examination could be completed. The EEG was also always modified in the CBD patients, and the abnormalities were enhanced by activation procedures. There was a good correlation between MRS anomalies and clinical presentation, between EEG modifications and neuropsychological patterns, and between metabolic (MRS) impairment and electrophysiological (EEG) slowing. CONCLUSIONS: These results confirm the asymmetrical features of CBD. Combined EEGq/MRS examinations at disease onset and during its subsequent course could provide strong diagnostic evidence of CBD.

[Proton magnetic resonance spectrometry for the non-invasive exploration of human brain metabolism: current and future clinical applications]. / La spectrométrie de résonance magnétique du proton dans l'exploration non invasive du métabolisme cérébral humain: applications cliniques actuelles et futures.

Magnetic resonance spectrometry (MRS) is now a routine investigation method in neurology. In some situations, its diagnostic sensitivity is better than MRI. In this review, we propose a critical analysis of the large body of literature on brain MRS concerning a wide range of pathologies and many different protocols. The diagnostic value of MRS is not fully determined in all neurological diseases, but the specific properties of MRS (detection of neuron-specific and glial-specific metabolites, quantitative data, reversibility of metabolic lesions) make it a high-performance tool for quantifying neuron, glial and membrane abnormalities. After reviewing the methodological advances in MRS and discussing restrictions on interpretation of spectral data, we describe variations in metabolic patterns detected by MRS in different groups of diseases. The currently reasonable indications for MRS exploration are presented as well as new avenues for research. Based on MRS data, we propose a metabolic definition of encephalopathy which could be useful in better understanding the role of MRS in modern neurology.

In vivo brain proton MR spectroscopy in a case of molybdenum cofactor deficiency.

A 20-day-old infant with molybdenum cofactor deficiency, a rare encephalopathy, was investigated using cerebral MRI and proton MR spectroscopy. Images demonstrated extensive white-matter destruction with large cavities. The short-echo-time MR spectrum acquired in the parieto-occipital area was characterised by global loss of signal and accumulation of lactate. No additional signal in relation to the pathophysiology of the disease was detected. The brain metabolic abnormalities observed in this patient may reflect destruction of white matter and the presence of large cavities.

Brain metabolic impairment in non-cerebral and cerebral forms of X-linked adrenoleukodystrophy by proton MRS: identification of metabolic patterns by discriminant analysis.

Cerebral metabolism in six children with X-linked adrenoleukodystrophy (X-ALD) was studied using 1H magnetic resonance spectroscopy (MRS), and the status of the patients was monitored for evaluating disease progression. Spectra were abnormal even in patients with no cerebral impairment. Four different metabolic patterns were identified, and a metabolic classification of the disease was proposed, from grade 0 to grade III. The evolution of the disease toward grade II appears to be systematic, but many patients did not evolve from this grade to grade III, which is the metabolic mark of severe progressive forms. Metabolic data of X-ALD were processed using discriminant analysis, which provides a classification accuracy of 95.2%. Proton cerebral MRS together with discriminant analysis may be useful during the follow-up in X-ALD for monitoring the evolution of the disease and the effects of therapy.