Increase of precuneus metabolism correlates with reduction of PTSD symptoms after EMDR therapy in military veterans: an 18F-FDG PET study during virtual reality exposure to war.

PURPOSE: The prevalence of posttraumatic stress disorder (PTSD) is higher among veterans, and can lead to disastrous consequences such as suicide. Eye movement desensitization and reprocessing (EMDR) is recommended in first-line psychotherapies for PTSD. Virtual reality exposure (VRE) coupled with 18F-FDG PET imaging can highlight the activated brain regions during stress exposure. The objective of this study is to identify, after EMDR therapy, the regions of brain metabolism that evolve during the stress exposure of a war scene with symptomatic remission in a group of military veterans suffering from PTSD, and to secondarily search for predictive metabolic features. METHODS: We recruited 15 military veterans suffering from PTSD who performed an 18F-FDG PET sensitized by the exposure to a virtual war scene, before (T0) and after (T1) EMDR therapy. Statistical parametric mapping was used to compare brain metabolism before and after treatment and to study correlations between metabolism and evolution scores on PTSD clinical scales (PTSD Checklist Scale, PCLS; Clinician-Administered PTSD Scale, CAPS). RESULTS: The metabolic activity of the precuneus was increased after EMDR therapy (p < 0.005 uncorrected, k > 180) and correlated with clinical improvement with the CAPS scale (r = -0.73 and p < 0.001). Moreover, the precuneus metabolic value before therapy predicted the clinical improvement on the PCLS scale (T1-T0) after EMDR (r = -0.667 and p < 0.006). CONCLUSION: The clinical improvement in military patients with PTSD after EMDR is related to increased precuneus metabolism upon VR stress exposure.

Childhood neglect predicts disorganization in schizophrenia through grey matter decrease in dorsolateral prefrontal cortex.

OBJECTIVE: Psychosocial trauma during childhood is associated with schizophrenia vulnerability. The pattern of grey matter decrease is similar to brain alterations seen in schizophrenia. Our objective was to explore the links between childhood trauma, brain morphology and schizophrenia symptoms. METHOD: Twenty-one patients with schizophrenia stabilized with atypical antipsychotic monotherapy and 30 healthy control subjects completed the study. Anatomical MRI images were analysed using optimized voxel-based morphometry (VBM). Childhood trauma was assessed with the Childhood Trauma Questionnaire, and symptoms were rated on the Scale for the Assessment of Negative Symptoms (SANS) and Scale for the Assessment of Positive Symptoms (SAPS) (disorganization, positive and negative symptoms). In the schizophrenia group, we used structural equation modelling in a path analysis. RESULTS: Total grey matter volume was negatively associated with emotional neglect (EN) in patients with schizophrenia. Whole-brain VBM analyses of grey matter in the schizophrenia group revealed a specific inversed association between EN and the right dorsolateral prefrontal cortex (DLPFC). Path analyses identified a well-fitted model in which EN predicted grey matter density in DLPFC, which in turn predicted the disorganization score. CONCLUSION: Our findings suggest that EN during childhood could have an impact on psychopathology in schizophrenia, which would be mediated by developmental effects on brain regions such as the DLPFC.

Sleep parameters improvement in PTSD soldiers after symptoms remission.

Eye movement desensitization and reprocessing (EMDR) is a psychotherapy for the treatment of posttraumatic stress disorder (PTSD). It is still unclear whether symptoms remission through EMDR therapy is associated with a beneficial effect on one of the PTSD symptoms, sleep disturbance. Our objective was therefore to study sleep parameters before and after symptom remission in soldiers with PTSD. The control group consisted of 20 healthy active duty military men who slept in a sleep lab with standard polysomnography (PSG) on two sessions separated by one month. The patient group consisted of 17 active duty military with PTSD who underwent EMDR therapy. PSG-recorded sleep was assessed 1 week before the EMDR therapy began and 1 week after PTSD remission. We found that the increased REMs density after remission was positively correlated with a greater decrease of symptoms. Also, the number of EMDR sessions required to reach remission was correlated with intra-sleep awakenings before treatment. These results confirm the improvement of some sleep parameters in PTSD after symptoms remission in a soldier's population and provide a possible predictor of treatment success. Further experiments will be required to establish whether this effect is specific to the EMDR therapy.

Involvement of the cerebellum in EMDR efficiency: a metabolic connectivity PET study in PTSD.

BACKGROUND: We recently reported an improvement of precuneus PET metabolism after EMDR therapy in military participants suffering from PTSD. OBJECTIVE: The aim of the present study was to investigate the metabolic changes of precuneus connectivity in these participants after such treatment. METHOD: Fifteen participants with PTSD performed a brain 18F-FDG-PET sensitized by virtual reality exposure to war scenes, before and after EMDR treatment. Inter-regional correlation analysis was performed to study metabolic changes of precuneus connectivity through SPMT maps at whole-brain level (p < 0.005 for the voxel, p < 0.05 for the cluster). RESULTS: A decrease of connectivity was observed after EMDR between the precuneus and two significant bilateral clusters of the cerebellum (bilateral Crus I and VI cerebellar lobules, Tmax voxel of 5.8 and 5.3, and cluster size of 343 and 314 voxels, respectively). Moreover, higher cerebellar metabolism before treatment was associated with reduced clinical PTSD scores after EMDR (p = 0.03). CONCLUSIONS: The posterior cerebellum and its metabolic connectivity with the precuneus are involved in the clinical efficiency of EMDR in PTSD.

Antecedentes: Recientemente informamos una mejora del metabolismo de PET precuneus después de la terapia EMDR en participantes militares que padecen TEPT.Objetivo: El objetivo del presente estudio fue investigar los cambios metabólicos en la conectividad precuneus en estos participantes después de dicho tratamiento.Métodos: Quince participantes con trastorno de estrés postraumático se sometieron a 18F-FDG-PET cerebral sensibilizado por la exposición de realidad virtual a escenas de guerra antes y después del tratamiento con EMDR. El análisis de correlación interregional se realizó para estudiar los cambios metabólicos en la conectividad precuneus a través de mapas SPM-T a nivel de todo el cerebro (p <0.005 para el vóxel, p <0.05 para el grupo).Resultados: Se observó una disminución en la conectividad después de la terapia EMDR entre el precúneo y dos grupos bilaterales significativos del cerebelo (vóxeles Tmax de 5.8 y 5.3 y tamaños de racimo de 343 y 314 vóxeles, respectivamente). Además, un metabolismo cerebeloso más alto antes del tratamiento se asoció con puntuaciones clínicas de TEPT reducidas después de EMDR (p = 0.03).Conclusión: el cerebelo y su conectividad metabólica con el precuneus están involucrados en la eficiencia clínica de EMDR en TEPT.

Effect of risperidone versus haloperidol on emotional responding in schizophrenic patients.

RATIONALE: Studies on emotional processing report that schizophrenic patients present a specific pattern of emotional responding that usually includes deficits in emotional expressiveness, increased feelings of unpleasant emotion but decreased feelings of pleasant emotion, and increased physiological reactivity. However, studies have rarely controlled the nature of antipsychotic medication. Yet, the influence of these drugs on emotional response is uncertain and could vary depending on their pharmacological profile. OBJECTIVE: This prospective and randomized study aimed to compare the effects of an atypical antipsychotic, risperidone, to a typical one, haloperidol, on patients' emotional responding during an emotional induction task. MATERIALS AND METHODS: Twenty-five schizophrenic patients underwent two emotional and clinical evaluations: one before treatment initiation and a second 4 weeks after. Emotional states of fear, sadness, anger, joy, and disgust were induced, as well as a neutral baseline state. Video recordings of patients during the induction task allowed for assessment of emotional expressiveness. Self-reports and measures of skin conductance and heart rate were performed to determine both subjective and physiological reactions to emotional experience. RESULTS: Compared to haloperidol, risperidone did not reduce patients' facial expressiveness, decreased physiological reactivity, and decreased experience of unpleasant emotion but maintained experience of pleasant emotion. Emotional expressiveness was negatively correlated to parkisonism. CONCLUSIONS: Our preliminary results suggest that atypical antipsychotics allow for better-adapted patterns of emotional responding than typical ones do. We suggest that this effect is due to reduced striatal D2 blockade, therefore, attenuating akinesia, coupled with increased 5HT and DA levels in prefrontal cortex, which improves emotional regulation.

Undifferentiation of somatic responses to emotions in a case of functional amnesia.

The term functional amnesia (FA) has been proposed for cases of memory impairment presenting with severe retrograde amnesia in the absence of cerebral injury or history of psychiatric disturbance. Emotional flattening has often been reported alongside FA, however the mechanism of such a modification is unknown. This study aimed to explore the emotional processing in a rare case of a patient with FA complaining of severe emotional flattening. We presented ecological dynamic video stimuli conveying strong peaceful and fearful emotions to the patient and 13 controls. We then explored their emotional responses considering both conscious emotional judgements and automatic psychophysiological responses (skin conductance) and facial muscular activity (corrugator supercilii). Both patient P.P. and controls perfectly recognized the emotions conveyed by the films. However, P.P. failed to show an increased skin conductance and corrugator activity as found in controls during fearful film extracts compared with peaceful extracts. Taken together, these finding demonstrate the presence of an emotional deficit, characterized by a failure to generate appropriate somatic responses to positive and negative stimuli. Although this altered somatic processing did not interfere with PP's explicit recognition of emotion, it modified his emotional experience, thereby constituting a possible explanation for his emotional flattening. This study therefore suggests that FA is not limited to a mnemonic impairment, but is a more complex disorder, involving also the processing of emotionally loaded experiences.

Preventing long-lasting fear recovery using bilateral alternating sensory stimulation: A translational study.

Posttraumatic stress disorder (PTSD) is a highly debilitating and prevalent psychological disorder. It is characterized by highly distressing intrusive trauma memories that are partly explained by fear conditioning. Despite efficient therapeutic approaches, a subset of PTSD patients displays spontaneous recurrence of traumatic memories after successful treatment. The development of animal behavioral models mimicking the individual variability in treatment outcome for PTSD patients represent therefore an important challenge as it allows for the identification of predicting factors of resilience or susceptibility to relapse. However, to date, only few animal behavioral models of long-lasting fear recovery have been developed and their predictive validity has not been tested directly. The objectives of this study were twofold. First we aimed to develop a simple animal behavioral model of long-lasting fear recovery based on auditory cued fear conditioning and extinction learning, which recapitulates the heterogeneity of fear responses observed in PTSD patients after successful treatment. Second we aimed at testing the predictive validity of our behavioral model and used to this purpose a translational approach based (i) on the demonstration of the efficiency of Eye Movement Desensitization and Reprocessing (EMDR) therapy to reduce conditioned fear responses in PTSD patients and (ii) on the implementation in our behavioral model of an electrical bilateral alternating stimulation of the eyelid which mimics the core feature of EMDR. Our data indicate that electrical bilateral alternating stimulation of the eyelid during extinction learning alleviates long-lasting fear recovery of conditioned fear responses and dramatically reduces inter-individual variability. These results demonstrate the face and predictive validity of our animal behavioral model and provide an interesting tool to understand the neurobiological underpinnings of long-lasting fear recovery.

Evidence of peripheral auditory activity modulation by the auditory cortex in humans.

At the auditory periphery, the medial olivocochlear system is assumed to be involved in complex sound processing and may be influenced by feedback from higher auditory nuclei. Indeed, the descending auditory pathway includes fibers coming from the auditory cortex that are anatomically well positioned to influence the superior olivary complex, and thus the medial efferent system. The aim of the present study was to verify the hypothesis of an implied influence of the auditory cortex on the peripheral auditory system. In three rare cases of patients presenting with intractable temporal lobe epilepsy, Heschl's gyrus (i.e. the temporal superior gyrus) was surgically removed in the right hemisphere in two patients and in the left hemisphere in a third patient, in order to minimize epilepsy attacks, as preoperative stereoencephalography had shown the epileptic focus or tumor to be situated in those locations. In all three cases, several weeks after the operation the medial olivocochlear system was clearly less functional on both sides, but especially on the side contralateral to the resection. In healthy controls, no such pattern was obtained. In four other epileptic patients, who were operated unilaterally at the anterior temporal pole, amygdala and hippocampus with the temporal gyrus partially spared, efferent suppression grew stronger in the ear ipsilateral to surgery. These results revealed that, in humans, the primary and secondary auditory cortex play a role in modulating auditory periphery activity through direct or indirect efferent fibers. In accordance with previous findings, this descending influence may improve the auditory afferent message by adapting the hearing function according to cortical analysis of the ascending input.

Functional asymmetry of medial olivocochlear system in humans. Towards a peripheral auditory lateralization.

The aim of this study was to investigate the human peripheral auditory system in either ear to allow comparison of right and left medial olivocochlear inhibition during contralateral ear stimulation with a broad band noise. The efferent system showed a statistically significant greater right-side activity among 44 young subjects. This laterality appeared to be related to the presence of spontaneous otoacoustic emission but not to gender. This efferent asymmetry and the parallel spontaneous otoacoustic emission asymmetry could explain the lateralization of auditory sensitivity, temporary threshold shift and tinnitus.

Difference in cochlear efferent activity between musicians and non-musicians.

The present study aimed to confirm and extend the finding, suggested by the results of a previous study, of different auditory neural efferent functioning in musicians compared with non-musicians. The activity of the medial olivocochlear bundle (MOCB), an auditory efferent subsystem, was measured through the contralaterally induced attenuation of the amplitude of evoked otoacoustic emissions (EOAEs) in two groups, one of musicians and one of non-musicians, paired for age and sex. The results indicated a statistically significant difference between the two groups, with the musicians showing greater amplitude reduction upon contralateral noise stimulation than non-musicians (U-test, U = 204, p < 0.025, n = 32). These results indicate greater MOCB activity in musicians than in non-musicians. The possible origins and implications of this finding are discussed.

Stronger bilateral efferent influences on cochlear biomechanical activity in musicians than in non-musicians.

The auditory sensory end organ is under the control of the central nervous system via efferent projections. Contralateral suppression of otoacoustic emissions (acoustic signatures of the cochlear biomechanical activity) provides a non-invasive approach to assess olivocochlear efferent activity in humans. Using this approach, the present study compared professional musicians with musically-inexperienced subjects. The results revealed stronger bilateral cochlear suppression, suggesting larger efferent influences in both ears, in musicians. Furthermore, in indicating no difference in left/right asymmetry of efferent-mediated suppression between the two groups, the present findings suggest that the observed differences in olivocochlear activity reflect bilaterally-enhanced activity of the cortical auditory structures in musicians rather than differences in cerebral hemispheric asymmetry between the two groups.

Peripheral auditory lateralization assessment using TEOAEs.

Previous studies indicate a left-right asymmetry in the function of peripheral auditory system. Contralateral acoustic suppression of TEOAEs (transient evoked otoacoustic emissions) enables assessment of medial olivocochlear efferent system functioning, and has demonstrated that this system is more effective in the right than in the left ear. Moreover, TEOAE amplitudes are lower in the left than in the right ear. The aim of the present experiment was to verify firstly the absence of a relationship between medial efferent system asymmetry and TEOAE amplitude asymmetry, and secondly to study TEOAE input/output function slopes. There was no link between the asymmetries in TEOAE amplitude and in the medial efferent system functioning. Further, as previously shown, the medial olivocochlear system increased the TEOAE input/output function slopes. These TEOAE input/output function slopes seem to be consistent factors in peripheral asymmetry since the slope is lower in the right than in the left ear. Moreover, the lower the TEOAE amplitudes, the greater the TEOAE slopes. The slope asymmetry of the two ears could correspond to earlier saturation or a lower augmentation ability of the TEOAE response in the right ear, where the TEOAE amplitude is higher. This asymmetry in growth slopes reinforces the notion of peripheral auditory lateralization.

Frequency and temporal analysis of contralateral acoustic stimulation on evoked otoacoustic emissions in humans.

Previous studies have shown that the effect of contralateral acoustic stimulation (CAS) on ipsilateral evoked otoacoustic emissions (EOAE) depends somewhat upon the spectrum of the eliciting stimulus. The latency of the EOAE, however, is itself frequency-dependent. Consequently, two general ways of analyzing the effects of CAS may be considered: by frequency band or by temporal segment. In this study, we analyzed the effects of CAS both ways in the same subjects, essentially simultaneously. The frequency analysis of the EOAE derived from the wavelet transform (WT). The WT is known to provide a robust approach to the analysis of non-stationary signals and was anticipated to avoid possible time-frequency confounds of the cochlear mechanical system. For comparison, a more basic analysis - using a temporal moving window - was employed. The results largely support earlier findings and confirm that in humans the greatest suppression of EOAEs by CAS is obtained for lower frequency and/or longer latency EOAE components. Despite expectations for the WT analysis, the more basic, temporal, analysis tended to yield the clearer results.

Evidence of peripheral hearing asymmetry in humans: clinical implications.

Auditory system hemispheric asymmetry in language processing is well-established, and there are many indications of lateralization as of the peripheral auditory system i.e., as of the cochlea. The left ear is more susceptible to noise damage; tinnitus is more predominant there, while spontaneous otoacoustic emissions (SOAEs) are more often found in the right ear. The present study addressed the following two questions: Does this right-ear SOAE prevalence exist as early as preterm birth? Is there any functional asymmetry in the medial olivo-cochlear (MOC) efferent system, known to modulate outer hair cell contractions? The study involved 483 preterm neonates (gestional age: 24-37 weeks) and 70 right-handed adults (age: 18-31 years). In each ear, SOAEs and evoked otoacoustic emissions (EOAEs) were recorded and analysed, and, for the adults, functional MOC system assessment was made. Results showed SOAEs and EOAE amplitude to be right-predominant and in adults a right MOC functional predominance. These results indicate peripheral auditory system lateralisation, and an early origin thereof. The MOC system being thought to play a protective role, its physiological lateralisation may be relevant to the left prevalence of tinnitus and of auditory fatigue.

[Peripheral auditory lateralization]. / Existence d'une latéralisation de l'appareil auditif périphérique.

Neuropsychological studies have demonstrated that language perception is lateralized at the hemispheric level. There is also much evidence for a peripheral lateralization of the auditory system in humans. Spontaneous otoacoustic emissions are more frequent in the right than in the left ear. The medial olivo-cochlear system is also more functional in the right than in the left ear in normal subjects. The study of specific samples shows that this asymmetry is found in professional musicians which have more functional efferent system in both ears. A link is hypothesized between peripheral and central laterality because of a dysfunctional peripheral asymmetry in pathological cases which show hemispheric lateralization disorders. Consequences of those pathological data will be discussed.

[Epidemiology of viral hepatitis in Algeria]. / Epidémiologie des hépatites virales en Algérie.

Viral hepatitis is endemoepidemic in Algeria. Recent serologic and epidemiological surveys have specified the importance of A, B and non A non B viruses respectively and brought out some details. -- Hepatitis A is very common: 96% of individuals have anti-HAV antibodies. Patients come into contact with the virus before the age of 10. No symptoms are found in 95% of cases. Icteric hepatitis occurs in infants. -- Hepatitis B infection includes 40 to 50% of icteric hepatitis in adults. Clinical and biological symptoms are similar to those described in the literature. The prevalence of HBs Ag carriers is within the range of 1,8 to 2,8%, but reach high level in Eastern and Saharian Regions of Algeria. It increases with age and low socio-economic status. In hospital environment, laboratory technicians and room servants is the most frequently contaminated personnel. -- Non A non B hepatitis is so far the least known in Algeria. In 1981, an epidemic of water-borne non A non B hepatitis was reported.

Influence of handedness on peripheral auditory asymmetry.

It is well established that in humans many differences between right- and left-handers, anatomical, physiological and functional, exist. Left- and mixed-handedness is associated with greater bihemispheric representation of cognitive functions than in right-handers. Several studies indicate a left-right asymmetry in the function of hearing pathways between cochlea and auditory cortex, and furthermore, that this asymmetry is associated with handedness. Our investigation focuses on the medial olivo-cochlear system, which has been demonstrated to be more effective in the right than left ear in right-handers. The aim of the study was to investigate this auditory efferent system asymmetry according to handedness, gender, eyedness, footedness and the presence of spontaneous otoacoustic emissions. The medial efferent system has been found to be more effective in the right than left ear in right-handers, while functioning symmetrically in left-handers. Furthermore, the olivo-cochlear system, assumed to be involved in basic language processing, shows an asymmetrical pattern of functioning influenced by handedness as well as by hemispheric language representation. Reverse medial efferent system asymmetry was observed in left-handers compared to that in right-handers, on condition that only left-handed males were considered, or that the left-handers were also left-eyed, or that spontaneous otoacoustic emissions were present in the left ear of the left-handers, or when only left-handers without mixed-handers were considered.

Clinical relevance of medial efferent auditory pathways.

Evoked otoacoustic emissions have been shown to be suppressed by sounds applied in the contralateral ear and this effect can be largely explained by the involvement of medial olivocochlear efferent fibers. Thus, EOAE recording during contralateral stimulation provides a non-invasive means of investigating auditory efferent system functioning in humans. The question remains, however, as to whether this test provides a tool, which could be useful in a variety of clinical applications. This review describes current clinical applications for this test, showing that it may prove useful for improving identification of retrocochlear pathologies. Some new areas are also identified. Methodological topics are discussed and suggestions for maximizing the value of this test are proposed.

Psychometric normalization of a hyperacusis questionnaire.

Clinical hyperacusis consists of a marked intolerance to ordinary environmental sounds, while hearing thresholds are quite often normal. Hyperacusis appears to be a subjective phenomenon, which is not easily defined or quantified by objective measurements. In order to create a tool suitable to quantify and evaluate various hyperacusis symptoms, a questionnaire screening several aspects of auditory symptomatology has been constructed. Two hundred and one subjects (who were either hyperacusic or not), randomly selected from the general population, were tested. A principal component analysis performed on the correlation matrix of the 14 items of the questionnaire isolated three dimensions: attentional, social, and emotional. The three dimensions had satisfactory internal consistency reliability. The mean +/- SD total score was 15 +/- 6.7 out of 42 (maximum of hyperacusis) and a score greater than 28 seems to represent a strong auditory hypersensitivity. This new psychometric tool should further be tested on hyperacusic patients to verify its relevance in pathology and define the involvement of the three dimensions statistically obtained on the hyperacusis symptomatology.

Tones disappear faster in the right ear than in the left.

In order to gain further information on the characteristics and physiological correlates of tone decay in humans, the tone decay test was administered to 58 normal-hearing subjects, successively in the left and right ears and in absence and presence of a contralateral noise. The results revealed that tone decay was greater in the right than in the left ear and was increased by contralateral noise. The contralateral effect of this noise on cochlear biomechanisms was then estimated by measuring contralaterally induced variations in the amplitude of click-evoked otoacoustic emissions in the same subjects. In the right ear, the increase in tone decay and the decrease in otoacoustic emission amplitude--both induced by contralateral noise--were positively correlated (r = .315, p = .016). Furthermore, the contralateral changes in otoacoustic emission amplitude were found to be on average larger in the right than in the left ear, this asymmetry being correlated with that observed for the tone decay. These findings are discussed in relation to previous results on simple and induced loudness adaptation in the vicinity of threshold, on contralateral attenuation of otoacoustic emissions and on the influence of the auditory efferents on cochlear biomechanisms.