Physiological synchronization and innovative moments in psychotherapy: A single-case study of micro-process.

OBJECTIVE: Interpersonal synchronization is increasingly studied as a biomarker of empathy, therapeutic alliance, and treatment outcome. However, most studies average data over sessions, leaving associations between synchrony and actual interactions largely unexplored. We aim to showcase a novel approach examining synchronization during specific micro-processes: Innovative Moments (IM) as markers of exceptions to clients' problematic patterns of meaning. METHODS: Electrodermal activity was recorded over 15 sessions of a psychodynamic psychotherapy single case. Moment-to-moment patient-therapist synchrony was calculated using the Adaptive Matching Interpolated Correlations (AMICo) algorithm. The Innovative Moments Coding System was utilized to identify IMs within session transcripts with precise timing. Monte-Carlo permutation tests were conducted to examine the association between physiological synchrony and IM Levels of increasing complexity (Levels 1-3). RESULTS: Higher-than-random synchronization emerged during Level 3 IMs (p = 0.046; d = 0.21) but not in lower Levels. Post-hoc qualitative analyses linked high synchrony to sub-processes of Level 3 IMs, such as positive contrasts and attributions for change. CONCLUSION: Our findings show it is possible to link moment-by-moment physiological co-regulation to theoretically identified meaning-making processes. While generalization of these observations is undue, this work demonstrates a robust and promising application of a multimodal approach to investigating psychotherapy, providing insights into both the clinical case and the theoretical model adopted.

Emotion Regulation in Psychodynamic and Cognitive-Behavioural Therapy: An Integrative Perspective.

Objective: Psychotherapy fragmentation constitutes a significant barrier to progress. In the present article, we argue that emotion regulation processes operate across psychotherapy approaches, serving as an overarching meta-factor of therapeutic change. Method: Two major therapeutic approaches-psychodynamic and cognitive-behavioural-were examined through the lens of emotion regulation theory. In particular, key constructs within each approach were analyzed in terms of relevant emotion regulation processes. Results: Emotion regulation processes are an overarching meta-factor relevant to a wide range of therapeutic constructs (e.g., defence mechanisms, internal working models, coping strategies, ruptures/reparations of alliance). Different clinical traditions emphasize different aspects of emotion regulation, mainly in terms of implicit vs explicit emotion regulation processes. Conclusions: An integrative emotion regulation perspective contributes to our understanding of the core change mechanisms of psychotherapy, with significant implications both for research and clinical practice.

Movement Synchrony in the Psychotherapy of Adolescents With Borderline Personality Pathology - A Dyadic Trait Marker for Resilience?

Movement synchrony describes the coordination of body movements. In psychotherapy, higher movement synchrony between therapist and patient has been associated with higher levels of empathy, therapeutic alliance, better therapy outcome, and fewer drop-outs. The current study investigated movement synchrony during the psychotherapeutic treatment of female adolescents with borderline personality disorder. It was hypothesized that there are higher levels of movement synchrony in the analyzed therapy sessions compared to pseudo-interactions. Further, we tested whether higher levels of movement synchrony correlate with stronger patients' symptom reduction and whether higher movement synchrony predicts higher post-session ratings. A total of 356 sessions from 16 completed psychotherapies of adolescent patients with BPD were analyzed. Movement synchrony was assessed with motion energy analysis and an index of synchrony was calculated by lagged cross-correlation analysis. As hypothesized, the findings support higher levels of movement synchrony in therapy sessions compared to pseudo-interactions (Cohen's d = 0.85). Additionally, a correlation of movement synchrony with better therapy outcome was found (standardized beta = -0.43 indicating stronger personality functioning impairment reduction). The post-session ratings were negatively associated with higher levels of movement synchrony (standardized beta = -0.1). The relevance of movement synchrony and potential implications for clinical practice are discussed.

Targeted dual inhibition of c-Met/VEGFR2 signalling by foretinib improves antitumour effects of nanoparticle paclitaxel in gastric cancer models.

Elevated expression of multiple growth factors and receptors including c-Met and VEGFR has been reported in gastric adenocarcinoma (GAC) and thus provides a potentially useful therapeutic target. The therapeutic efficacy of foretinib, a c-Met/VEGFR2 inhibitor, was determined in combination with nanoparticle paclitaxel (NPT) in GAC. Animal studies were conducted in NOD/SCID mice in subcutaneous and peritoneal dissemination xenografts. The mechanism of action was assessed by Immunohistochemical and Immunoblot analyses. In c-Met overexpressing MKN-45 cell-derived xenografts, NPT and foretinib demonstrated inhibition in tumour growth, while NPT plus foretinib showed additive effects. In c-Met low-expressing SNU-1 or patient-derived xenografts, the foretinib effect was smaller, while NPT had a similar effect compared with MKN-45, as NPT plus foretinib still exhibited an additive response. Median mice survival was markedly improved by NPT (83%), foretinib (100%) and NPT plus foretinib (230%) in peritoneal dissemination xenografts. Subcutaneous tumour analyses exhibited that foretinib increased cancer cell death and decreased cancer cell proliferation and tumour vasculature. NPT and foretinib suppressed the proliferation of GAC cells in vitro and had additive effects in combination. Further, foretinib caused a dramatic decrease in phosphorylated forms of c-Met, ERK, AKT and p38. Foretinib led to a decrease in Bcl-2, and an increase in p27, Bax, Bim, cleaved PARP-1 and cleaved caspase-3. Thus, these findings highlight the antitumour impact of simultaneous suppression of c-Met and VEGFR2 signalling in GAC and its potential to enhance nanoparticle paclitaxel response. This therapeutic approach might lead to a clinically beneficial combination to increase GAC patients' survival.

Empathy-based supportive treatment in amyotrophic lateral sclerosis: A pragmatic study.

Scarce literature has been dedicated to the psychological treatment of amyotrophic lateral sclerosis (ALS). However, there have been some encouraging findings, such as in hypnosis-based studies, which revealed patient improvements in anxiety, depression and quality of life (QoL). We replicated such a design of a pragmatic study on empathy-based supportive counseling treatment in four weekly domiciliary sessions. Twenty-one people with ALS (pALS) consecutively attending the Motor Neuron Disease Center of Padova University were recruited to the study; in total, 21 pALS who did not undergo any kind of psychological treatment served as the control group. In the treatment group, depression, anxiety and QoL (measured respectively with the HADS-D, HADS-A and ALSSQOL-R) were assessed at pre- and post-treatment levels and at 3- and 6-month follow-ups. Statistical mixed-model regression analyses revealed that in the treated group, perceived conditions of anxiety, depression and QoL were significantly stable compared to worsening in the control patients. Interestingly, there were improvements in the QoL domains "Interaction", "Emotion" and "Physical" at the 6-month follow-up. Overall, even if not directly comparable, our current results on support-based counseling, though interesting, seem not to reach the efficacy of a hypnosis-based study in which the observed dimensions were significantly improved with respect to the baseline. The implications of our results from a psychodynamic perspective are highlighted.

Hydrogen Delocalization in an Asymmetric Biomolecule: The Curious Case of Alpha-Fenchol.

Rotational microwave jet spectroscopy studies of the monoterpenol α-fenchol have so far failed to identify its second most stable torsional conformer, despite computational predictions that it is only very slightly higher in energy than the global minimum. Vibrational FTIR and Raman jet spectroscopy investigations reveal unusually complex OH and OD stretching spectra compared to other alcohols. Via modeling of the torsional states, observed spectral splittings are explained by delocalization of the hydroxy hydrogen atom through quantum tunneling between the two non-equivalent but accidentally near-degenerate conformers separated by a low and narrow barrier. The energy differences between the torsional states are determined to be only 16(1) and 7(1) cm-1hc for the protiated and deuterated alcohol, respectively, which further shrink to 9(1) and 3(1) cm-1hc upon OH or OD stretch excitation. Comparisons are made with the more strongly asymmetric monoterpenols borneol and isopinocampheol as well as with the symmetric, rapidly tunneling propargyl alcohol. In addition, the third-in contrast localized-torsional conformer and the most stable dimer are assigned for α-fenchol, as well as the two most stable dimers for propargyl alcohol.

rMEA: An R package to assess nonverbal synchronization in motion energy analysis time-series.

Introduction. Motion Energy Analysis (MEA) is a procedure that allows to automatically assess the amount of persons' movement from video recordings. Recent studies used MEA to investigate nonverbal synchrony, i.e., the occurrence of simultaneous movement, suggesting the existence of an association with relationship quality. In patient-therapist dyads, synchrony predicted therapeutic alliance, empathy, as well as treatment outcome. Package description. The article presents rMEA, an open-source R package that allows to import, filter, and visualize dyadic time-series of nonverbal behaviour generated by other MEA software. The package includes a fast, state-of-the-art, moving window cross-correlation algorithm with lag analysis, which provides a user-friendly interface for the assessment of nonverbal synchrony. Through the analysis of a motivating example (40 psychotherapy intake interviews split between dropouts and good cases) the article provides an in-depth description of the package main functions and a tutorial for a typical analysis in this field, requiring only the most basic knowledge of the R language and environment. The rich visualization capabilities of the software provide powerful tools for the various steps involved in the diagnostics, analysis, interpretation and publication of these data. Conclusions. Overall, the paper aims to empower psychotherapy researchers and other interaction scientists to investigate nonverbal synchrony in their own dyads.

Enhanced Neural Empathic Responses in Patients with Spino-Bulbar Muscular Atrophy: An Electrophysiological Study.

BACKGROUND: Spino-bulbar muscular atrophy is a rare genetic X-linked disease caused by testosterone insensitivity. An inverse correlation has been described between testosterone levels and empathic responses. The present study explored the profile of neural empathic responding in spino-bulbar muscular atrophy patients. METHODS: Eighteen patients with spino-bulbar muscular atrophy and eighteen healthy male controls were enrolled in the study. Their event-related potentials were recorded during an "Empathy Task" designed to distinguish neural responses linked with experience-sharing (early response) and mentalizing (late response) components of empathy. The task involved the presentation of contextual information (painful vs. neutral sentences) and facial expressions (painful vs. neutral). An explicit dispositional empathy-related questionnaire was also administered to all participants, who were screened via neuropsychological battery tests that did not reveal potential cognitive deficits. Due to electrophysiological artefacts, data from 12 patients and 17 controls were finally included in the analyses. RESULTS: Although patients and controls did not differ in terms of dispositional, explicit empathic self-ratings, notably conservative event-related potentials analyses (i.e., spatio-temporal permutation cluster analyses) showed a significantly greater experience-sharing neural response in patients compared to healthy controls in the Empathy-task when both contextual information and facial expressions were painful. CONCLUSION: The present study contributes to the characterization of the psychological profile of patients with spino-bulbar muscular atrophy, highlighting the peculiarities in enhanced neural responses underlying empathic reactions.

Physiological synchronization in the clinical process: A research primer.

Physiological synchronization is the study of how individuals in interaction coregulate their physiology. The topic has sparked increasing interest in counseling and psychotherapy research, where it has been found to be associated with the therapeutic alliance, clinicians' empathy and patients' outcome. Physiological synchronization allows researcher to investigate subtle but fundamental aspects of the clinical process through objective measures. In this article, we aim to offer a guide to researchers and clinicians to explore this growing field of study. We begin by reviewing the existing literature of physiological synchronization in clinical relationships, and then we provide practical guidelines for research. We discuss the various aspects involved in synchronization studies: study design, selection of physiological signals, data analytic approaches, and interpretation of results. To better illustrate how to implement these types of design, we provide a running example describing the data collection and analysis of a single-case study. In the example we discuss both how to conduct a longitudinal nomothetic analysis, as well as a moment-to-moment idiographic exploration of the clinical content. In this latter analysis, in particular, we show how physiological synchronization can be used in combination with 2 transcripts analysis tools, the Patient Attachment Coding System, and the Therapist Attunement Scales to reach a deeper understanding of the ongoing processes. We conclude by arguing that research in counseling and psychotherapy has much to gain from and contribute to the overall development of our understanding of physiological synchronization in human interaction. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Alternative polyadenylation drives oncogenic gene expression in pancreatic ductal adenocarcinoma.

Alternative polyadenylation (APA) is a gene regulatory process that dictates mRNA 3'-UTR length, resulting in changes in mRNA stability and localization. APA is frequently disrupted in cancer and promotes tumorigenesis through altered expression of oncogenes and tumor suppressors. Pan-cancer analyses have revealed common APA events across the tumor landscape; however, little is known about tumor type-specific alterations that may uncover novel events and vulnerabilities. Here, we integrate RNA-sequencing data from the Genotype-Tissue Expression (GTEx) project and The Cancer Genome Atlas (TCGA) to comprehensively analyze APA events in 148 pancreatic ductal adenocarcinomas (PDACs). We report widespread, recurrent, and functionally relevant 3'-UTR alterations associated with gene expression changes of known and newly identified PDAC growth-promoting genes and experimentally validate the effects of these APA events on protein expression. We find enrichment for APA events in genes associated with known PDAC pathways, loss of tumor-suppressive miRNA binding sites, and increased heterogeneity in 3'-UTR forms of metabolic genes. Survival analyses reveal a subset of 3'-UTR alterations that independently characterize a poor prognostic cohort among PDAC patients. Finally, we identify and validate the casein kinase CSNK1A1 (also known as CK1alpha or CK1a) as an APA-regulated therapeutic target in PDAC. Knockdown or pharmacological inhibition of CSNK1A1 attenuates PDAC cell proliferation and clonogenic growth. Our single-cancer analysis reveals APA as an underappreciated driver of protumorigenic gene expression in PDAC via the loss of miRNA regulation.

Empathy In Neurodegenerative Diseases: A Systematic Review.

INTRODUCTION: Empathy, in its affective and cognitive components, is a crucial interpersonal ability. It is broadly studied in the field of psychopathology, whereas its study in the neurodegenerative diseases is relatively recent. Existing literature, though, focused on a reduced subset of considered diseases, which often found a compromise in empathy abilities. Organized knowledge about a more comprehensive set of diseases is lacking. METHOD: The present PRISMA systematic review was aimed at collecting the current available literature concerning empathic alterations in adult patients affected by neurodegenerative diseases. It considered the different empathy components, evaluated existing patterns, the impact on patients' lives, and treatment considerations. RESULTS: Overall, the 32 retrieved studies describe a spread deterioration of empathic abilities in patients, with each disease displaying its own pattern of empathy functioning. Literature in this field is fragmented and of heterogeneous quality, and further studies are warranted to increase evidence of many preliminary results. DISCUSSION: In conclusion, we highlight the crucial importance of acknowledging empathy deficits in these diseases, showing their repercussion on both patients' and caregivers' quality of life, the establishment of a functional doctor-patient relationship, and the development of efficacious psychological intervention. These clinical approaches can be enriched by the knowledge of the spared abilities of patients affected by neurodegenerative diseases.

Stroke aetiological classification reliability and effect on trial sample size: systematic review, meta-analysis and statistical modelling.

BACKGROUND: Inter-observer variability in stroke aetiological classification may have an effect on trial power and estimation of treatment effect. We modelled the effect of misclassification on required sample size in a hypothetical cardioembolic (CE) stroke trial. METHODS: We performed a systematic review to quantify the reliability (inter-observer variability) of various stroke aetiological classification systems. We then modelled the effect of this misclassification in a hypothetical trial of anticoagulant in CE stroke contaminated by patients with non-cardioembolic (non-CE) stroke aetiology. Rates of misclassification were based on the summary reliability estimates from our systematic review. We randomly sampled data from previous acute trials in CE and non-CE participants, using the Virtual International Stroke Trials Archive. We used bootstrapping to model the effect of varying misclassification rates on sample size required to detect a between-group treatment effect across 5000 permutations. We described outcomes in terms of survival and stroke recurrence censored at 90 days. RESULTS: From 4655 titles, we found 14 articles describing three stroke classification systems. The inter-observer reliability of the classification systems varied from 'fair' to 'very good' and suggested misclassification rates of 5% and 20% for our modelling. The hypothetical trial, with 80% power and alpha 0.05, was able to show a difference in survival between anticoagulant and antiplatelet in CE with a sample size of 198 in both trial arms. Contamination of both arms with 5% misclassified participants inflated the required sample size to 237 and with 20% misclassification inflated the required sample size to 352, for equivalent trial power. For an outcome of stroke recurrence using the same data, base-case estimated sample size for 80% power and alpha 0.05 was n = 502 in each arm, increasing to 605 at 5% contamination and 973 at 20% contamination. CONCLUSIONS: Stroke aetiological classification systems suffer from inter-observer variability, and the resulting misclassification may limit trial power. TRIAL REGISTRATION: Protocol available at reviewregistry540 .

Attachment-security prime effect on skin-conductance synchronization in psychotherapists: An empirical study.

Physiological synchronization (PS) is a phenomenon of simultaneous activity between two persons' physiological signals. It has been associated with empathy, shared affectivity, and efficacious therapeutic relationships. The aim of the present study was to explore the possible connections between PS and the attachment system, seeking preliminary evidence of this link by means of an experimental manipulation of the sense of attachment security in psychotherapists according to a protocol by Mikulincer and Shaver (2001), which has been proven to elicit empathetic behavior. We compared the synchronization of skin-conductance signals in brief psychological interviews between 18 psychodynamic therapists and 18 healthy volunteers. A sense of attachment-security priming was administered to half of the therapists, whereas the other half received a positive-affect control prime. Lag analysis was performed to investigate the "leading" or "following" attitudes of the participants in the two conditions. Mixed-model regressions and evidence-ratio model comparisons were used to investigate the effects of the manipulation on PS. Therapist attachment anxiety and avoidance traits were considered covariates. The attachment-security prime showed a significant effect on PS lag dynamics, but not on overall PS amount. Lag analysis showed that the therapists in the attachment-security condition were significantly more prone to assume a leading attitude in the physiological coupling than the therapists in the control condition. Therapist attachment anxiety and avoidance had no apparent effect. Our result paves the way for further exploration of the clinical relationship from a physiological standpoint. (PsycINFO Database Record

State of the Art of Interpersonal Physiology in Psychotherapy: A Systematic Review.

Introduction: The fast expanding field of Interpersonal Physiology (IP) focuses on the study of co-ordination or synchronization dynamics between the physiological activities of two, or more, individuals. IP has been associated with various relational features (e.g., empathy, attachment security, rapport, closeness…) that overlap with desirable characteristics of clinical relationships, suggesting that the relevant studies might provide objective, economical, and theory-free techniques to investigate the clinical process. The goal of the present work is to systematically retrieve and review the literature on IP in the field of psychotherapy and psychological intervention, in order to consolidate the knowledge of this research domain, highlight its critical issues, and delineate possible developments. Method: Following the guidelines by Okoli and Schabram (2010), a systematic literature search was performed in Scopus, Web of Science, PsycINFO, and PubMed databases by means of multiple keyword combinations; the results were integrated with references to the retrieved articles' bibliography as well as to other published reviews on IP. Results: All the retrieved documents reported clinical interactions that are characterized, at least partially, by IP phenomena. They appear to use fragmented and sometimes ambiguous terminology and show a lack of both specific theory-informed hypotheses and sound analytical procedures. Conclusion: Although the psychological nature of IP and its role in the clinical relationship are still mostly unknown, the potential value of a physiology-based measure of implicit exchanges in psychotherapy drives an acceleration in this research field. On the basis of the highlighted critical issues, possible future directions for clinical IP researchers are discussed.

Targeting brain tumors by intra-arterial delivery of cell-penetrating peptides: a novel approach for primary and metastatic brain malignancy.

Computational modeling shows that intra-arterial delivery is most efficient when the delivered drugs rapidly and avidly bind to the target site. The cell-penetrating peptide trans-activator of transcription (TAT) is a candidate carrier molecule that could mediate such specificity for brain tumor chemotherapeutics. To test this hypothesis we first performed in vitro studies testing the uptake of TAT by one primary and three potentially metastatic brain cancer cell lines (9L, 4T-1, LLC, SKOV-3). Then we performed in vivo studies in a rat model where TAT was delivered either intra-arterially (IA) or intravenously (IV) to 9L brain tumors. We observed robust uptake of TAT by all tumor cell lines in vitro. Flow cytometry and confocal microscopy revealed a rapid uptake of fluorescein-labeled TAT within 5 min of exposure to the cancer cells. IA injections done under transient cerebral hypoperfusion (TCH) generated a four-fold greater tumor TAT concentration compared to conventional IV injections. We conclude that it is feasible to selectively target brain tumors with TAT-linked chemotherapy by the IA-TCH method.

Flow arrest intra-arterial delivery of small TAT-decorated and neutral micelles to gliomas.

The cell-penetrating trans-activator of transcription (TAT) is a cationic peptide derived from human immunodeficiency virus-1. It has been used to facilitate macromolecule delivery to various cell types. This cationic peptide is capable of crossing the blood-brain barrier and therefore might be useful for enhancing the delivery of drugs that target brain tumors. Here we test the efficiency with which relatively small (20 nm) micelles can be delivered by an intra-arterial route specifically to gliomas. Utilizing the well-established method of flow-arrest intra-arterial injection we compared the degree of brain tumor deposition of cationic TAT-decorated micelles versus neutral micelles. Our in vivo and post-mortem analyses confirm glioma-specific deposition of both TAT-decorated and neutral micelles. Increased tumor deposition conferred by the positive charge on the TAT-decorated micelles was modest. Computational modeling suggested a decreased relevance of particle charge at the small sizes tested but not for larger particles. We conclude that continued optimization of micelles may represent a viable strategy for targeting brain tumors after intra-arterial injection. Particle size and charge are important to consider during the directed development of nanoparticles for intra-arterial delivery to brain tumors.

Liposome size and charge optimization for intraarterial delivery to gliomas.

Nanoparticles such as liposomes may be used as drug delivery vehicles for brain tumor therapy. Particle geometry and electrostatic properties have been hypothesized to be important determinants of effective tumor targeting after intraarterial injection. In this study, we investigate the combined roles of liposome size and surface charge on the effectiveness of delivery to gliomas after intraarterial injection. Intracarotid injection of liposomes was performed in separate cohorts of both healthy and C6 glioma-bearing Sprague Dawley rats after induction of transient cerebral hypoperfusion. Large (200 nm) and small (60-80 nm) fluorescent dye-loaded liposomes that were either cationic or neutral in surface charge were utilized. Delivery effectiveness was quantitatively measured both with real-time, in vivo and postmortem diffuse reflectance spectroscopy. Semi-quantitative multispectral fluorescence imaging was also utilized to assess the pattern and extent of liposome targeting within tumors. Large cationic liposomes demonstrated the most effective hemispheric and glioma targeting of all the liposomes tested. Selective large cationic liposome retention at the site of glioma growth was observed. The liposome deposition pattern within tumors after intraarterial injection was variable with both core penetration and peripheral deposition observed in specific tumors. This study provides evidence that liposome size and charge are important determinants of effective brain and glioma targeting after intraarterial injection. Our results support the future development of 200-nm cationic liposomal formulations of candidate intraarterial anti-glioma agents for further pre-clinical testing.

Cationizable lipid micelles as vehicles for intraarterial glioma treatment.

The relative abundance of anionic lipids on the surface of endothelia and on glioma cells suggests a workable strategy for selective drug delivery by utilizing cationic nanoparticles. Furthermore, the extracellular pH of gliomas is relatively acidic suggesting that tumor selectivity could be further enhanced if nanoparticles can be designed to cationize in such an environment. With these motivating hypotheses the objective of this study was to determine whether nanoparticulate (20 nm) micelles could be designed to improve their deposition within gliomas in an animal model. To test this, we performed intra-arterial injection of micelles labeled with an optically quantifiable dye. We observed significantly greater deposition (end-tissue concentration) of cationizable micelles as compared to non-ionizable micelles in the ipsilateral hemisphere of normal brains. More importantly, we noted enhanced deposition of cationizable as compared to non-ionizable micelles in glioma tissue as judged by semiquantitative fluorescence analysis. Micelles were generally able to penetrate to the core of the gliomas tested. Thus we conclude that cationizable micelles may be constructed as vehicles for facilitating glioma-selective delivery of compounds after intraarterial injection.

Hypnosis-based psychodynamic treatment in ALS: a longitudinal study on patients and their caregivers.

BACKGROUND: Evidence of psychological treatment efficacy is strongly needed in ALS, particularly regarding long-term effects. METHODS: Fifteen patients participated in a hypnosis treatment and self-hypnosis training protocol after an in-depth psychological and neurological evaluation. Patients' primary caregivers and 15 one-by-one matched control patients were considered in the study. Measurements of anxiety, depression and quality of life (QoL) were collected at the baseline, post-treatment, and after 3 and 6 months from the intervention. Bayesian linear mixed-models were used to evaluate the impact of treatment and defense style on patients' anxiety, depression, QoL, and functional impairment (ALSFRS-r), as well as on caregivers' anxiety and depression. RESULTS: The statistical analyses revealed an improvement in psychological variables' scores immediately after the treatment. Amelioration in patients' and caregivers' anxiety as well as caregivers' depression, were found to persist at 3 and 6 months follow-ups. The observed massive use of primitive defense mechanisms was found to have a reliable and constant buffer effect on psychopathological symptoms in both patients and caregivers. Notably, treated patients decline in ALSFRS-r score was observed to be slower than that of control group's patients. DISCUSSION: Our brief psychodynamic hypnosis-based treatment showed efficacy both at psychological and physical levels in patients with ALS, and was indirectly associated to long-lasting benefits in caregivers. The implications of peculiar psychodynamic factors and mind-body techniques are discussed. Future directions should be oriented toward a convergence of our results and further psychological interventions, in order to delineate clinical best practices for ALS.

"Reality" of near-death-experience memories: evidence from a psychodynamic and electrophysiological integrated study.

The nature of near-death-experiences (NDEs) is largely unknown but recent evidence suggests the intriguing possibility that NDEs may refer to actually "perceived," and stored, experiences (although not necessarily in relation to the external physical world). We adopted an integrated approach involving a hypnosis-based clinical protocol to improve recall and decrease memory inaccuracy together with electroencephalography (EEG) recording in order to investigate the characteristics of NDE memories and their neural markers compared to memories of both real and imagined events. We included 10 participants with NDEs, defined by the Greyson NDE scale, and 10 control subjects without NDE. Memories were assessed using the Memory Characteristics Questionnaire. Our hypnosis-based protocol increased the amount of details in the recall of all kind of memories considered (NDE, real, and imagined events). Findings showed that NDE memories were similar to real memories in terms of detail richness, self-referential, and emotional information. Moreover, NDE memories were significantly different from memories of imagined events. The pattern of EEG results indicated that real memory recall was positively associated with two memory-related frequency bands, i.e., high alpha and gamma. NDE memories were linked with theta band, a well-known marker of episodic memory. The recall of NDE memories was also related to delta band, which indexes processes such as the recollection of the past, as well as trance states, hallucinations, and other related portals to transpersonal experience. It is notable that the EEG pattern of correlations for NDE memory recall differed from the pattern for memories of imagined events. In conclusion, our findings suggest that, at a phenomenological level, NDE memories cannot be considered equivalent to imagined memories, and at a neural level, NDE memories are stored as episodic memories of events experienced in a peculiar state of consciousness.