Fear extinction learning improvement in PTSD after EMDR therapy: an fMRI study.

Objective: Neurobiological models of Posttraumatic Stress Disorder (PTSD) implicate fear processing impairments in the maintenance of the disorder. Eye Movement Desensitization and Reprocessing (EMDR) is one of the most efficient psychotherapies to treat PTSD. We aimed at exploring the brain mechanisms of the fear circuitry involved in PTSD patients' symptom remission after EMDR therapy. Method: Thirty-six PTSD participants were randomly assigned to either EMDR group receiving EMDR therapy or Wait-List (WL) group receiving supportive therapy. Participants underwent a behavioural fear conditioning and extinction paradigm during functional magnetic resonance (fMRI). In the EMDR group, patients were scanned at baseline, before EMDR and one week after remission. In the WL group, patients were scanned at baseline and within the same time interval as the EMDR group. Results: In the EMDR group after treatment, fear responses in the late extinction were significantly lower than before therapy. In parallel, significant functional activity and connectivity changes were found in the EMDR group versus the WL during the late extinction. These changes involve the fear circuit (amygdalae, left hippocampus), the right inferior frontal gyrus, the right frontal eye field and insula (pFWE < .05). Conclusion: These functional modifications underlie a significant improvement of fear extinction learning in PTSD patients after EMDR therapy.

Objetivo: Los modelos neurobiológicos del TEPT implican deficiencias en el procesamiento del miedo en el mantenimiento del trastorno. EMDR es una de las psicoterapias más eficaces para tratar el TEPT. Nuestro objetivo fue explorar los mecanismos cerebrales de los circuitos de miedo implicados en la remisión de los síntomas de los pacientes con el TEPT después de la terapia EMDR.Método: Treinta y seis participantes con el TEPT fueron asignados aleatoriamente a un grupo EMDR que recibió terapia EMDR o un grupo de Lista de Espera (LE) que recibió terapia de apoyo. Los participantes se sometieron a un paradigma de condicionamiento y extinción del miedo conductual durante la resonancia magnética funcional (fMRI). En el grupo EMDR, los pacientes fueron escaneados al inicio del estudio, antes de EMDR y una semana después de la remisión. En el grupo LE, los pacientes fueron escaneados al inicio y en el mismo intervalo de tiempo que el grupo EMDR.Resultados: En el grupo EMDR después del tratamiento, las respuestas de miedo en la extinción tardía fueron significativamente más bajas que antes de la terapia. En paralelo, se encontraron cambios significativos en la actividad funcional y en la conectividad en el grupo EMDR v/s el grupo LE durante la extinción tardía. Estos cambios involucran el circuito de miedo (amígdala, hipocampo izquierdo), el giro frontal inferior derecho, los campos del ojo frontal derecho y la ínsula (pFWE < .05).Conclusión: Estas modificaciones funcionales subyacen a una mejora significativa del aprendizaje de extinción del miedo en pacientes con el TEPT después de la terapia EMDR.

Brain metabolism and related connectivity in patients with acrophobia treated by virtual reality therapy: an 18F-FDG PET pilot study sensitized by virtual exposure.

BACKGROUND: The aim of this pilot study is to investigate the impact of virtual reality exposure therapy (VRET) on brain metabolism and connectivity. Eighteen patients with acrophobia were assessed by an 18F-FDG PET scan sensitized by virtual exposure before treatment, and nine of them were assessed again after eight sessions of VRET. Statistical Parametric Mapping was used to study the correlations between metabolism and pretherapeutic clinical scores and to compare metabolism before and after VRET (p voxel < 0.005, corrected for cluster volume). Metabolic connectivity was evaluated through interregional correlation analysis. RESULTS: Before therapy, a positive correlation was found between scores on the behavioural avoidance test and left occipital metabolism (BA17-18). After VRET, patients presented increased metabolism in the left frontal superior gyri and the left precentral gyrus, which showed increased metabolic connectivity with bilateral occipital areas (BA17-18-19), concomitant with clinical recovery. CONCLUSIONS: This study highlights the exciting opportunity to use brain PET imaging to investigate metabolism during virtual exposure and reports the involvement of the visual-motor control system in the treatment of acrophobia by VRET.

Grey matter density changes of structures involved in Posttraumatic Stress Disorder (PTSD) after recovery following Eye Movement Desensitization and Reprocessing (EMDR) therapy.

Recovery of stress-induced structural alterations in Posttraumatic Stress Disorder (PTSD) remains largely unexplored. This study aimed to determine whether symptoms improvement is associated with grey matter (GM) density changes of brain structures involved in PTSD. Two groups of PTSD patients were involved in this study. The first group was treated with Eye Movement Desensitization and Reprocessing (EMDR) therapy and recovered from their symptoms (recovery group) (n = 11); Patients were scanned prior to therapy (T1), one week (T2) and five months after the end of therapy (T3). The second group included patients which followed a supportive therapy and remained symptomatic (wait-list group) (n = 7). They were scanned at three time-steps mimicking the same inter-scan intervals. Voxel-based morphometry (VBM) was used to characterize GM density evolution. GM density values showed a significant group-by-time interaction effect between T1 and T3 in prefrontal cortex areas. These interaction effects were driven by a GM density increase in the recovery group with respect to the wait-list group. Symptoms removal goes hand-in-hand with GM density enhancement of structures involved in emotional regulation.

Dissociating Bottom-Up and Top-Down Mechanisms in the Cortico-Limbic System during Emotion Processing.

The cortico-limbic system is critically involved in emotional responses and resulting adaptive behaviors. Within this circuit, complementary regions are believed to be involved in either the appraisal or the regulation of affective state. However, the respective contribution of these bottom-up and top-down mechanisms during emotion processing remains to be clarified. We used a new functional magnetic resonance imaging (fMRI) paradigm varying 3 parameters: emotional valence, emotional congruency, and allocation of attention, to distinguish the functional variation in activity and connectivity between amygdala, anterior cingulate cortex (ACC), and dorsolateral prefrontal cortex (DLPFC). Bottom-up appraisal of negative compared with positive stimuli led to a greater amygdala response and stronger functional interaction between amygdala and both dorsal ACC and DLPFC. Top-down resolution of emotional conflict was associated with increased activity within ACC and higher functional connectivity between this structure, and both the amygdala and DLPFC. Finally, increased top-down attentional control caused greater engagement of the DLPFC, accompanied by increased connectivity between DLPFC and dorsal ACC. This novel task provides an efficient tool for exploring bottom-up and top-down processes underlying emotion and may be particularly helpful for investigating the neurofunctional underpinnings of psychiatric disorders.

Effect of trait anxiety on prefrontal control mechanisms during emotional conflict.

Converging evidence points to a link between anxiety proneness and altered emotional functioning, including threat-related biases in selective attention and higher susceptibility to emotionally ambiguous stimuli. However, during these complex emotional situations, it remains unclear how trait anxiety affects the engagement of the prefrontal emotional control system and particularly the anterior cingulate cortex (ACC), a core region at the intersection of the limbic and prefrontal systems. Using an emotional conflict task and functional magnetic resonance imaging (fMRI), we investigated in healthy subjects the relations between trait anxiety and both regional activity and functional connectivity (psychophysiological interaction) of the ACC. Higher levels of anxiety were associated with stronger task-related activation in ACC but with reduced functional connectivity between ACC and lateral prefrontal cortex (LPFC). These results support the hypothesis that when one is faced with emotionally incompatible information, anxiety leads to inefficient high-order control, characterized by insufficient ACC-LPFC functional coupling and increases, possibly compensatory, in activation of ACC. Our findings provide a deeper understanding of the pathophysiology of the neural circuitry underlying anxiety and may offer potential treatment markers for anxiety disorders.

Acute stress disorder modifies cerebral activity of amygdala and prefrontal cortex.

The diagnosis constraint of acute stress disorder (ASD), consisting of testing individuals in the month following trauma exposure, limits research on the very early and initial stage of the disease. In this regard, this work aims to explore the cerebral mechanism of ASD in a population of fire-fighters before and after trauma exposure. Thirty-six healthy non-traumatized male fire-fighters were explored by an fMRI emotional face-matching task to evaluate the cerebral substrate of emotional recognition. During the two years of the follow-up, two subjects were traumatized, and thus retested, as were 10 non-traumatized subjects among the initial non-exposed ones. In comparison to non-exposed subjects, fire-fighters with ASD had enhanced amygdala, orbitofrontal, and dorsolateral prefrontal BOLD responses to fearful and angry faces (p < .05, FDR-corrected). These results shed new light on the cerebral mechanism associated with ASD. We observed for the first time the existence of an altered fear processing pathway in ASD that is mediated by amygdala and prefrontal cortex hyperactivity, which might be at the core of the disorder.

Relationship between emotional experience and resilience: an fMRI study in fire-fighters.

Resilience refers to the capacity to cope effectively in stressful situations or adversity. It may involve the ability to experience emotions matching the demands of environmental circumstances. The brain mechanisms underlying resilience remain unclear. In this study, we aim to investigate the relationship between the neural basis of emotional experience and resilience. Thirty-six fire-fighters were included. They performed an fMRI script-driven paradigm comprising relaxing and trauma-related scripts to evaluate the cerebral substrate of emotional experience (p<0.05, FDR-corrected). Correlations were examined between fMRI activations and the resilience DRS15 scale (p<0.05). Resilience was positively correlated with the right amygdala and left orbitofrontal activations when performing the contrast of trauma vs. relaxing script. The present study provides neural data on the mechanisms underlying resilience and their relationship with emotional reactivity, suggesting that appropriate emotional response in stressful situations is essential for coping with aversive events in daily life.

Responsive hydrogels produced via organic sol-gel chemistry for cell culture applications.

In this study, we report the synthesis of novel environmentally responsive polyurea hydrogel networks prepared via organic sol-gel chemistry and demonstrate that the networks can stabilize pH while releasing glucose both in simple aqueous media and in mammalian cell culture settings. Hydrogel formulations have been developed based on the combination of an aliphatic triisocyanate with pH-insensitive amine functional polyether and pH-sensitive poly(ethyleneimine) segments in a minimally toxic solvent suitable for the sol-gel reaction. The polyether component of the polyurea network is sufficiently hydrophilic to give rise to some level of swelling independent of environmental pH, while the poly(ethyleneimine) component contains tertiary amine groups providing pH sensitivity to the network in the form of enhanced swelling and release under acidic conditions. The reaction of these materials to form a network is rapid and requires no catalyst. The resultant material exhibits the desired pH-responsive swelling behavior and demonstrates its ability to simultaneously neutralize lactic acid and release glucose in both cell-free culture media and mammalian cell culture, with no detectable evidence of cytotoxicity or changes in cell behavior, in the case of either SA-13 human hybridomas or mouse embryonic stem cells. Furthermore, pH is observed to have a clear effect on the rate at which glucose is released from the hydrogel network. Such characteristics promise to maintain a favorable cell culture environment in the absence of human intervention.

Neuroticism modifies psychophysiological responses to fearful films.

BACKGROUND: Neuroticism is a personality component frequently found in anxious and depressive psychiatric disorders. The influence of neuroticism on negative emotions could be due to its action on stimuli related to fear and sadness, but this remains debated. Our goal was thus to better understand the impact of neuroticism through verbal and physiological assessment in response to stimuli inducing fear and sadness as compared to another negative emotion (disgust). METHODS: Fifteen low neurotic and 18 high neurotic subjects were assessed on an emotional attending task by using film excerpts inducing fear, disgust, and sadness. We recorded skin conductance response (SCR) and corrugator muscle activity (frowning) as indices of emotional expression. RESULTS: SCR was larger in high neurotic subjects than in low neurotics for fear relative to sadness and disgust. Moreover, corrugator activity and SCR were larger in high than in low neurotic subjects when fear was induced. CONCLUSION: After decades of evidence that individuals higher in neuroticism experience more intense emotional reactions to even minor stressors, our results indicate that they show greater SCR and expressive reactivity specifically to stimuli evoking fear rather than to those inducing sadness or disgust. Fear processing seems mainly under the influence of neuroticism. This modulation of autonomic activity by neurotics in response to threat/fear may explain their increased vulnerability to anxious psychopathologies such as PTSD (post traumatic stress disorder).

Attentional bias in post-traumatic stress disorder diminishes after symptom amelioration.

BACKGROUND: Avoidance and hypervigilance to reminders of a traumatic event are among the main characteristics of post-traumatic stress disorder (PTSD). Attentional bias toward aversive cues in PTSD has been hypothesized as being part of the dysfunction causing etiology and maintenance of PTSD. The aim of the present study was to investigate the cognitive strategy underlying attentional bias in PTSD and whether normal cognitive processing is restored after a treatment suppressing core PTSD symptoms. METHODS: Nineteen healthy controls were matched for age, sex and education to 19 PTSD patients. We used the emotional stroop and detection of target tasks, before and after an average of 4.1 sessions of eye movement desensitization and reprocessing (EMDR) therapy. RESULTS: We found that on both tasks, patients were slower than controls in responding in the presence of emotionally negative words compared to neutral ones. After symptoms removal, patients no longer had attentional bias, and responded similarly to controls. CONCLUSION: These results support the existence of an attentional bias in PTSD patients due to a disengagement difficulty. There was also preliminary evidence that the disengagement was linked to PTSD symptomatology. It should be further explored whether attentional bias and PTSD involve common brain mechanisms.

Amygdala activity correlates with attentional bias in PTSD.

Post-traumatic stress disorder (PTSD) is an anxiety disorder arising in the aftermath of a traumatic event. The most prevalent hypothesis is that of an increased amygdala activity to threat cues. The amygdala has also shown an implication in orienting attention toward threat. The aim of the study was to explore the correlations between amygdala activity, symptom severity and attentional bias in PTSD. Patients and healthy controls were assayed on an fMRI emotional face matching task and an attentional detection of target (DOT) task. The amygdala showed enhanced activity in PTSD (vs. controls). It positively correlated with anxiety scores and PTSD symptomatology. It also positively correlated with the disengagement index. Mostly, these results provide preliminary support for an implication of the amygdala in attention orientation to threat in PTSD. These results are further discussed in light of recent theories concerned with cortico-limbic functioning.

Pure-tone auditory thresholds are decreased in depressed people with post-traumatic stress disorder.

BACKGROUND: Depression has been related to sensory modulation and notably to auditory modifications such as alterations in auditory event-related potentials, abnormal patterns of auditory habituation, increased activation of primary and secondary auditory cortex, and higher bilateral auditory thresholds. However, few experiments have considered the exploration of the auditory system in depression. The aim of the experiment is to further explore auditory thresholds across a higher number of frequencies than has previously been undertaken in depressed subjects, to determine whether thresholds are modified as compared to controls, and if so, at which frequencies. METHODS: 25 pure-tones covering a large range of frequencies from 125Hz to 8kHz were used to measure both air and bone conduction (AC and BC respectively) hearing thresholds. 13 patients with depression and post-traumatic disorder matched for age, sex and education level with 13 healthy subjects, were tested. RESULTS: Hearing thresholds were found to be significantly poorer in depressed participants than in controls for frequencies from 2.75Hz to 8kHz in BC, and for 0.5, 0.75, 0.875 and 2.0-8.0kHz pure-tone frequencies in AC. LIMITATIONS: Given that the depressed patients also had comorbid post-traumatic disorder, it should be verified whether their modified pure-tone audiometry is only related to depression. CONCLUSIONS: The AC and BC pure-tone auditory threshold measurement may provide new and different insights into the aetiology and evolution of depression.