Oral Delta-9-Tetrahydrocannabinol (THC) Increases Parasympathetic Activity and Supraspinal Conditioned Pain Modulation in Chronic Neuropathic Pain Male Patients: A Crossover, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Disordered autonomic nervous system regulation and supraspinal pain inhibition have been repeatedly described in chronic pain. We aimed to explore the effects of δ-9-tetrahydrocannabinol (THC), an emerging treatment option, on autonomic nervous system and central pain modulation measures in patients with chronic pain. METHODS: Twelve male patients with chronic radicular neuropathic pain participated in a randomized, double-blind, crossover, placebo-controlled, single-administration trial. Low/high frequency (LF/HF) heart rate variability (HRV) ratio and conditioned pain modulation (CPM) response were measured and resting-state functional magnetic resonance imaging (MRI) was performed at baseline and after sublingual administration of either 0.2 mg/kg oral THC or placebo. RESULTS: THC significantly reduced the LF/HF ratio compared with placebo (interaction effect F(1,11) = 20.5; p < 0.005) and significantly improved CPM responses (interaction effect F(1,9) = 5.2; p = 0.048). The THC-induced reduction in LF/HF ratio correlated with increased functional connectivity between the rostral ventrolateral medulla and the dorsolateral prefrontal cortex [T(10) = 6.4, cluster p-FDR < 0.005]. CONCLUSIONS: THC shifts the autonomic balance towards increased parasympathetic tone and improves inhibitory pain mechanisms in chronic pain. The increase in vagal tone correlates with connectivity changes in higher-order regulatory brain regions, suggesting THC exerts top-down effects. These changes may reflect a normalizing effect of THC on multiple domains of supraspinal pain dysregulation. CLINICAL TRIAL REGISTRY NUMBER: NCT02560545.

Integration of limbic self-neuromodulation with psychotherapy for complex post-traumatic stress disorder: treatment rationale and case study.

Treatment Rationale: Exposure to repeated sexual trauma, particularly during childhood, often leads to protracted mental health problems. Childhood adversity is specifically associated with complex posttraumatic stress disorder (PTSD) presentation, which is particularly tenacious and treatment refractory, and features severe emotion dysregulation. Augmentation approaches have been suggested to enhance treatment efficacy in PTSD thus integrating first-line psychotherapy with mechanistically informed self-neuromodulation procedures (i.e. neurofeedback) may pave the way to enhanced clinical outcomes. A central neural mechanism of PTSD and emotion dysregulation involves amygdala hyperactivity that can be volitionally regulated by neurofeedback. We outline a treatment rationale that includes a detailed justification for the potential of combining psychotherapy and NF and delineate mechanisms of change. We illustrate key processes of reciprocal interactions between neurofeedback engagement and therapeutic goals.Case Study: We describe a clinical case of a woman with complex PTSD due to early and repetitive childhood sexual abuse using adjunctive neurofeedback as an augmentation to an ongoing, stable, traditional treatment plan. The woman participated in (a) ten sessions of neurofeedback by the use of an fMRI-inspired EEG model of limbic related activity (Amygdala Electrical-Finger-Print; AmygEFP-NF), (b) traditional weekly individual psychotherapy, (c) skills group. Before and after NF training period patient was blindly assessed for PTSD symptoms, followed by a 1, 3- and 6-months self-report follow-up. We demonstrate mechanisms of change as well as the clinical effectiveness of adjunctive treatment as indicated by reduced PTSD symptoms and improved daily functioning within this single case.Conclusions: We outline an integrative neuropsychological framework for understanding the unique mechanisms of change conferring value to conjoining NF applications with trauma-focused psychotherapy in complex PTSD.

Self-neuromodulation procedures that regulates limbic-related activity in adjunction to therapy show clinical effectivity in complex PTSD.We present an integrative perspective of neurofeedback embedded in psychotherapy, illustrated by a single case report.A single case provides an illustration of the potential utility of multifaced treatment including psychotherapy with adjunctive neurofeedback.

Amygdala-related electroencephalogram neurofeedback as add-on therapy for treatment-resistant childhood sexual abuse posttraumatic stress disorder: feasibility study.

AIM: Childhood sexual abuse (CSA) among women is an alarmingly prevalent traumatic experience that often leads to debilitating and treatment-refractory posttraumatic stress disorder (PTSD), raising the need for novel adjunctive therapies. Neuroimaging investigations systematically report that amygdala hyperactivity is the most consistent and reliable neural abnormality in PTSD and following childhood abuse, raising the potential of implementing volitional neural modulation using neurofeedback (NF) aimed at down-regulating amygdala activity. This study aimed to reliably probe limbic activity but overcome the limited applicability of functional magnetic resonance imaging (fMRI) NF by using a scalable electroencephalogram NF probe of amygdala-related activity, termed amygdala electrical-finger-print (amyg-EFP) in a randomized controlled trial. METHOD: Fifty-five women with CSA-PTSD who were in ongoing intensive trauma-focused psychotherapy for a minimum of 1 year but still met Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) PTSD criteria were randomized to either 10 add-on sessions of amyg-EFP-NF training (test group) or continuing psychotherapy (control group). Participants were blindly assessed for PTSD symptoms before and after the NF training period, followed by self-reported clinical follow-up at 1, 3, and 6 months, as well as one session of amygdala real-time fMRI-NF before and after NF training period. RESULTS: Participants in the test group compared with the control group demonstrated a marginally significant immediate reduction in PTSD symptoms, which progressively improved during the follow-up period. In addition, successful neuromodulation during NF training was demonstrated. CONCLUSION: This feasibility study for patients with treatment-resistant CSA-PTSD indicates that amyg-EFP-NF is a viable and efficient intervention.

Greater Early Posttrauma Activation in the Right Inferior Frontal Gyrus Predicts Recovery From Posttraumatic Stress Disorder Symptoms.

BACKGROUND: Posttraumatic stress disorder (PTSD) has been associated with altered emotion processing and modulation in specific brain regions, i.e., the amygdala, insula, and medial prefrontal and anterior cingulate cortices. Functional alterations in these regions, recorded shortly after trauma exposure, may predict changes in PTSD symptoms. METHODS: Survivors (N = 104) of a traumatic event, predominantly a motor vehicle accident, were included. Functional magnetic resonance imaging was used to assess brain activation 1, 6, and 14 months after trauma exposure (T1, T2, and T3, respectively). Participants performed the Shifted-attention Emotional Appraisal Task, which probes 3 affective processes: implicit emotional processing (of emotional faces), emotion modulation by attention shifting (away from these faces), and emotion modulation by appraisal (of the participants' own emotional response to these faces). We defined regions of interest based on task-related activations, extracted beta weights from these regions of interest, and submitted them to a series of analyses to examine relationships between neural activation and PTSD severity over the 3 time points. RESULTS: At T1, a regression model containing activations in the left dorsolateral prefrontal cortex, bilateral inferior frontal gyrus (IFG), and medial prefrontal cortex during emotion modulation by appraisal significantly predicted change in PTSD symptoms. More specifically, greater right IFG activation at T1 was associated with greater reduction in symptom severity (T1-T3). Exploratory analysis also found that activation of the right IFG increased from T1 to T3. CONCLUSIONS: The results suggest that greater early posttrauma activation during emotion appraisal in the right IFG, a region previously linked to cognitive control in PTSD, predicts recovery from PTSD symptoms.

Pilot Study of Prism EFP NeuroFeedback in Adult ADHD.

OBJECTIVE: A pilot study to preliminarily examine the effects of Prism EFP NeuroFeedback (NF) in adult ADHD. METHOD: Prism EFP NF is a form of NF specifically designed to target emotional dysregulation (ED) through down regulation of amygdala activity. Prism EFP NF has been shown to improve other disorders with significant ED. Nine participants with adult ADHD received an open trial of Prism EFP NF consisting of fifteen sessions over 8 weeks; all completed at least 5 weeks of treatment with seven completing all 8 weeks. Outcomes were assessed by change in ADHD symptoms from baseline to End of Treatment. RESULTS: About two-third reduction was seen in total DSM ADHD symptom scores (primary outcome measure) with improvement observed in all other clinical measures. No significant adverse events were seen. CONCLUSION: This preliminary trial found substantial effects of Prism EFP NF on ADHD/ED symptoms and global impairment.

Amygdala-related electrical fingerprint is modulated with neurofeedback training and correlates with deep-brain activation: proof-of-concept in borderline personality disorder.

BACKGROUND: The modulation of brain circuits of emotion is a promising pathway to treat borderline personality disorder (BPD). Precise and scalable approaches have yet to be established. Two studies investigating the amygdala-related electrical fingerprint (Amyg-EFP) in BPD are presented: one study addressing the deep-brain correlates of Amyg-EFP, and a second study investigating neurofeedback (NF) as a means to improve brain self-regulation. METHODS: Study 1 combined electroencephalography (EEG) and simultaneous functional magnetic resonance imaging to investigate the replicability of Amyg-EFP-related brain activation found in the reference dataset (N = 24 healthy subjects, 8 female; re-analysis of published data) in the replication dataset (N = 16 female individuals with BPD). In the replication dataset, we additionally explored how the Amyg-EFP would map to neural circuits defined by the research domain criteria. Study 2 investigated a 10-session Amyg-EFP NF training in parallel to a 12-weeks residential dialectical behavior therapy (DBT) program. Fifteen patients with BPD completed the training, N = 15 matched patients served as DBT-only controls. RESULTS: Study 1 replicated previous findings and showed significant amygdala blood oxygenation level dependent activation in a whole-brain regression analysis with the Amyg-EFP. Neurocircuitry activation (negative affect, salience, and cognitive control) was correlated with the Amyg-EFP signal. Study 2 showed Amyg-EFP modulation with NF training, but patients received reversed feedback for technical reasons, which limited interpretation of results. CONCLUSIONS: Recorded via scalp EEG, the Amyg-EFP picks up brain activation of high relevance for emotion. Administering Amyg-EFP NF in addition to standardized BPD treatment was shown to be feasible. Clinical utility remains to be investigated.

Dynamic Modelling of Mental Resilience in Young Adults: Protocol for a Longitudinal Observational Study (DynaM-OBS).

BACKGROUND: Stress-related mental disorders are highly prevalent and pose a substantial burden on individuals and society. Improving strategies for the prevention and treatment of mental disorders requires a better understanding of their risk and resilience factors. This multicenter study aims to contribute to this endeavor by investigating psychological resilience in healthy but susceptible young adults over 9 months. Resilience is conceptualized in this study as the maintenance of mental health or quick recovery from mental health perturbations upon exposure to stressors, assessed longitudinally via frequent monitoring of stressors and mental health. OBJECTIVE: This study aims to investigate the factors predicting mental resilience and adaptive processes and mechanisms contributing to mental resilience and to provide a methodological and evidence-based framework for later intervention studies. METHODS: In a multicenter setting, across 5 research sites, a sample with a total target size of 250 young male and female adults was assessed longitudinally over 9 months. Participants were included if they reported at least 3 past stressful life events and an elevated level of (internalizing) mental health problems but were not presently affected by any mental disorder other than mild depression. At baseline, sociodemographic, psychological, neuropsychological, structural, and functional brain imaging; salivary cortisol and α-amylase levels; and cardiovascular data were acquired. In a 6-month longitudinal phase 1, stressor exposure, mental health problems, and perceived positive appraisal were monitored biweekly in a web-based environment, while ecological momentary assessments and ecological physiological assessments took place once per month for 1 week, using mobile phones and wristbands. In a subsequent 3-month longitudinal phase 2, web-based monitoring was reduced to once a month, and psychological resilience and risk factors were assessed again at the end of the 9-month period. In addition, samples for genetic, epigenetic, and microbiome analyses were collected at baseline and at months 3 and 6. As an approximation of resilience, an individual stressor reactivity score will be calculated. Using regularized regression methods, network modeling, ordinary differential equations, landmarking methods, and neural net-based methods for imputation and dimension reduction, we will identify the predictors and mechanisms of stressor reactivity and thus be able to identify resilience factors and mechanisms that facilitate adaptation to stressors. RESULTS: Participant inclusion began in October 2020, and data acquisition was completed in June 2022. A total of 249 participants were assessed at baseline, 209 finished longitudinal phase 1, and 153 finished longitudinal phase 2. CONCLUSIONS: The Dynamic Modelling of Resilience-Observational Study provides a methodological framework and data set to identify predictors and mechanisms of mental resilience, which are intended to serve as an empirical foundation for future intervention studies. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/39817.

Feeling the Beat: Temporal Predictability is Associated with Ongoing Changes in Music-Induced Pleasantness.

Music is a complex phenomenon that elicits a range of emotional responses, influenced by numerous variables, such as rhythm, melody and harmony. One interesting aspect of music is listeners' ability to predict its continuation as it unfolds - an inherent attribute hypothesized to contribute to our emotional response to music. In this study, we investigated this link by examining the relationship between temporal predictability - the ability to predict the timing of the next event - and the ongoing changes in music-induced pleasantness. Temporal predictability was operationalized as the degree to which taps of 20 musically trained participants, who tapped to the beat along three naturalistic and highly contrastive musical pieces, were aligned. We then examined the degree to which this measure could explain the ongoing emotional experience, as reflected in continuous measures of arousal and valence, in a separate group of 40 participants that listened to these pieces. Our findings reveal a positive correlation between fluctuations in reported valence and temporal predictability, even when controlling for a set of other musical features, in four out of five musical sections. The only exception being a lyrical slow section. These findings were further supported by a large online database of annotated musical emotions (n = 1780 songs), where a consistent and robust correlation between valence ratings and an automatically extracted feature of pulse clarity was demonstrated. Overall, our findings shed light on the significance of temporal predictability as a contributing factor to the hedonic experience of music, especially within the tempo range of salient beat perception.

Reduced emotion regulatory selection flexibility in post-traumatic stress disorder: converging performance-based evidence from two PTSD populations.

BACKGROUND: Contemporary views of emotion dysregulation in post-traumatic stress disorder (PTSD) highlight reduced ability to flexibly select regulatory strategies according to differing situational demands. However, empirical evidence of reduced regulatory selection flexibility in PTSD is lacking. Multiple studies show that healthy individuals demonstrate regulatory selection flexibility manifested in selecting attentional disengagement regulatory strategies (e.g. distraction) in high-intensity emotional contexts and selecting engagement meaning change strategies (e.g. reappraisal) in low-intensity contexts. Accordingly, we hypothesized that PTSD populations will show reduced regulatory selection flexibility manifested in diminished increase in distraction (over reappraisal) preference as intensity increases from low to high intensity. METHODS: Study 1 compared student participants with high (N = 22) post-traumatic symptoms (PTS, meeting the clinical cutoff for PTSD) and participants with low (N = 22) post-traumatic symptoms. Study 2 compared PTSD diagnosed women (N = 31) due to childhood sexual abuse and matched non-clinical women (N = 31). In both studies, participants completed a well-established regulatory selection flexibility performance-based paradigm that involves selecting between distraction and reappraisal to regulate negative emotional words of low and high intensity. RESULTS: Beyond demonstrating adequate psychometric properties, Study 1 confirmed that relative to the low PTS group, the high PTS group presented reduced regulatory selection flexibility (p = 0.01, ŋ²â‚š= 0.14). Study 2 critically extended findings of Study 1, in showing similar reduced regulatory selection flexibility in a diagnosed PTSD population, relative to a non-clinical population (p = 0.002, ŋ²â‚š= 0.114). CONCLUSIONS: Two studies provide converging evidence for reduced emotion regulatory selection flexibility in two PTSD populations.

Limbic self-neuromodulation as a novel treatment option for emotional dysregulation in premenstrual dysphoric disorder (PMDD); a proof-of-concept study.

AIM: To assess the efficacy of a novel neurofeedback (NF) method, targeting limbic activity, to treat emotional dysregulation related to premenstrual dysphoric disorder (PMDD). METHODS: We applied a NF probe targeting limbic activity using a functional magnetic resonance imaging-inspired electroencephalogram model (termed Amyg-EFP-NF) in a double-blind randomized controlled trial. A frontal alpha asymmetry probe (AAS-NF), served as active control. Twenty-seven participants diagnosed with PMDD (mean age = 33.57 years, SD = 5.67) were randomly assigned to Amyg-EFP-NF or AAS-NF interventions with a 2:1 ratio, respectively. The treatment protocol consisted of 11 NF sessions through three menstrual cycles, and a follow-up assessment 3 months thereafter. The primary outcome measure was improvement in the Revised Observer Version of the Premenstrual Tension Syndrome Rating Scale (PMTS-OR). RESULTS: A significant group by time effect was observed for the core symptom subscale of the PMTS-OR, with significant improvement observed at follow-up for the Amyg-EFP group compared with the AAS group [F(1, 15)=4.968, P = 0.042]. This finding was specifically robust for reduction in anger [F(1, 15) = 22.254, P < 0.001]. A significant correlation was found between learning scores and overall improvement in core symptoms (r = 0.514, P = 0.042) suggesting an association between mechanism of change and clinical improvement. CONCLUSION: Our preliminary findings suggest that Amyg-EFP-NF may serve as an affordable and accessible non-invasive treatment option for emotional dysregulation in women suffering from PMDD. Our main limitations were the relatively small number of participants and the lack of a sham-NF placebo arm.

Neural evidence for advantaged representation of first items in memory.

Visual areas activated during perception can retain specific information held in memory without the presence of physical stimuli via distributed activity patterns. Neuroimaging studies have shown that the delay-period representation of information in visual areas is modulated by factors such as memory load and task demands, raising the possibility of serial position as another potential modulator. Specifically, enhanced representation of first items during the post-encoding delay period may serve as a mechanism underlying the well-established but not well-understood primacy effect - the mnemonic advantage of first items. To test this hypothesis, 13 males and 16 females performed a human fMRI task, wherein each trial consisted of the sequential encoding of two stimuli (a famous face and landscape, order counterbalanced), followed by a distracting task, a delay period, and then a cued recall of one of the items. Participants exhibited the expected behavioral primacy effect, manifested as faster recall of the first items. In order to elucidate the still debated neural underpinnings of this effect, using multivariate decoding, a classifier was trained on data collected during encoding to differentiate stimulus categories (i.e., faces vs. landscapes) and tested on data collected during the post-encoding period. Greater reactivation of first versus second items was observed in the ventral occipito-temporal cortex during the entire post-encoding period but not during encoding. Moreover, trial-level analyses revealed that the degree of first-item neural advantage during the post-encoding delay predicted the behavioral primacy effect. These findings highlight the role of item reinstatement in ventral occipito-temporal cortex in the primacy effect and are discussed in the context of the uniqueness of the very first item and event boundaries, illuminating putative neural mechanisms underlying the effect.

Neuroscientific account of Guilt- and Shame-Driven PTSD phenotypes.

Background: Guilt and Shame, two core self-related emotions, often emerge following trauma and play an important role in the development and maintenance of post-traumatic stress disorder (PTSD). Importantly, Guilt and Shame exhibit specific focal and non-specific global impacts of trauma on self-perception, respectively.Objective and Methods: Integrating psychological theories with neuroscientific knowledge, we suggest a scheme of two diverging clinical phenotypes of PTSD, associated with distinct self-related processes and differential functionality of relevant neural networks.Proposal: The Guilt-driven phenotype is characterized by preoccupation with negative self-attributes of one's actions in the traumatic event. It involves altered functionality of both the salience network (SN) and the default-mode network (DMN), associated with heightened interoceptive signalling and ruminative introspection which may lead to hyperarousal and intrusive symptoms, respectively. On the contrary, the Shame-driven phenotype is characterized by global, identity-related negative self-attributions. It involves altered functionality of both the SN and the DMN, associated with blunted interoceptive signalling and diminished introspection which may result in withdrawal and anhedonia symptoms together with dissociative experiences, respectively.Conclusion: The proposed PTSD phenotypes may inform neuropsychological therapeutic interventions (e.g. self-focused psychotherapy and neuromodulation) aiming to restore the function of large-scale self-related neural processing.

Guilt and Shame are two self-related emotions that often emerge following traumatic events and may contribute to the clinical profile of post-traumatic stress disorder (PTSD).Our framework suggests Guilt and Sham driven phenotypes of post-traumatic psychopathology, associated with two self-processing deficiencies related to specific action or global identity, respectively.The proposed phenotypes may inform neuropsychological treatments aiming to restore dysfunctional neural networks, later to be evident in alleviating Guilt and Shame and improving clinical outcomes.

Development and validation of an fMRI-informed EEG model of reward-related ventral striatum activation.

Reward processing is essential for our mental-health and well-being. In the current study, we developed and validated a scalable, fMRI-informed EEG model for monitoring reward processing related to activation in the ventral-striatum (VS), a significant node in the brain's reward system. To develop this EEG-based model of VS-related activation, we collected simultaneous EEG/fMRI data from 17 healthy individuals while listening to individually-tailored pleasurable music - a highly rewarding stimulus known to engage the VS. Using these cross-modal data, we constructed a generic regression model for predicting the concurrently acquired Blood-Oxygen-Level-Dependent (BOLD) signal from the VS using spectro-temporal features from the EEG signal (termed hereby VS-related-Electrical Finger Print; VS-EFP). The performance of the extracted model was examined using a series of tests that were applied on the original dataset and, importantly, an external validation dataset collected from a different group of 14 healthy individuals who underwent the same EEG/FMRI procedure. Our results showed that the VS-EFP model, as measured by simultaneous EEG, predicted BOLD activation in the VS and additional functionally relevant regions to a greater extent than an EFP model derived from a different anatomical region. The developed VS-EFP was also modulated by musical pleasure and predictive of the VS-BOLD during a monetary reward task, further indicating its functional relevance. These findings provide compelling evidence for the feasibility of using EEG alone to model neural activation related to the VS, paving the way for future use of this scalable neural probing approach in neural monitoring and self-guided neuromodulation.

Decoding human spontaneous spiking activity in medial temporal lobe from scalp EEG.

Linking scalp electroencephalography (EEG) signals and spontaneous firing activity from deep nuclei in humans is not trivial. To examine this, we analyzed simultaneous recordings of scalp EEG and unit activity in deeply located sites recorded overnight from patients undergoing pre-surgical invasive monitoring. We focused on modeling the within-subject average unit activity of two medial temporal lobe areas: amygdala and hippocampus. Linear regression model correlates the units' average firing activity to spectral features extracted from the EEG during wakefulness or non-REM sleep. We show that changes in mean firing activity in both areas and states can be estimated from EEG (Pearson r > 0.2, p≪0.001). Region specificity was shown with respect to other areas. Both short- and long-term fluctuations in firing rates contributed to the model accuracy. This demonstrates that scalp EEG frequency modulations can predict changes in neuronal firing rates, opening a new horizon for non-invasive neurological and psychiatric interventions.

Brain activation in individuals suffering from bulimia nervosa and control subjects during sweet and sour taste stimuli.

Introduction: Episodes of eating great quantities of extremely sweet and often aversive tasting food are a hallmark of bulimia nervosa. This unique eating pattern led researchers to seek and find differences in taste perception between patients and healthy control subjects. However, it is currently not known if these originate from central or peripheral impairment in the taste perception system. In this cross sectional study, we compare brain response to sweet and sour stimuli in 5 bulimic and 8 healthy women using functional magnetic resonance imaging (fMRI). Materials and methods: Sweet, sour and neutral (colorless and odorless) taste solutions were presented to subjects while undergoing fMRI scanning. Data were analyzed using a block design paradigm. Results: Between-group differences in brain activation in response to both sweet and sour tastes were found in 11 brain regions, including operculum, anterior cingulate cortex, midbrain, and cerebellum. These are all considered central to perception and processing of taste. Conclusion: Our data propose that sweet and sour tastes may have reward or aversion eliciting attributes in patients suffering from bulimia nervosa not found in healthy subjects, suggesting that alteration in taste processing may be a core dysfunction in bulimia nervosa (BN).

Evaluating the Evidence for Brain-Based Biotypes of Psychiatric Vulnerability in the Acute Aftermath of Trauma.

OBJECTIVE: The weak link between subjective symptom-based diagnostic methods for posttraumatic psychopathology and objectively measured neurobiological indices forms a barrier to the development of effective personalized treatments. To overcome this problem, recent studies have aimed to stratify psychiatric disorders by identifying consistent subgroups based on objective neural markers. Along these lines, a promising 2021 study by Stevens et al. identified distinct brain-based biotypes associated with different longitudinal patterns of posttraumatic symptoms. Here, the authors conducted a conceptual nonexact replication of that study using a comparable data set from a multimodal longitudinal study of recent trauma survivors. METHODS: A total of 130 participants (mean age, 33.61 years, SD=11.21; 48% women) admitted to a general hospital emergency department following trauma exposure underwent demographic, clinical, and neuroimaging assessments 1, 6, and 14 months after trauma. All analyses followed the pipeline outlined in the original study and were conducted in collaboration with its authors. RESULTS: Task-based functional MRI conducted 1 month posttrauma was used to identify four clusters of individuals based on profiles of neural activity reflecting threat and reward reactivity. These clusters were not identical to the previously identified brain-based biotypes and were not associated with prospective symptoms of posttraumatic psychopathology. CONCLUSIONS: Overall, these findings suggest that the original brain-based biotypes of trauma resilience and psychopathology may not generalize to other populations. Thus, caution is warranted when attempting to define subtypes of psychiatric vulnerability using neural indices before treatment implications can be fully realized. Additional replication studies are needed to identify more stable and generalizable neuroimaging-based biotypes of posttraumatic psychopathology.

Neural and functional validation of fMRI-informed EEG model of right inferior frontal gyrus activity.

The right inferior frontal gyrus (rIFG) is a region involved in the neural underpinning of cognitive control across several domains such as inhibitory control and attentional allocation process. Therefore, it constitutes a desirable neural target for brain-guided interventions such as neurofeedback (NF). To date, rIFG-NF has shown beneficial ability to rehabilitate or enhance cognitive functions using functional Magnetic Resonance Imaging (fMRI-NF). However, the utilization of fMRI-NF for clinical purposes is severely limited, due to its poor scalability. The present study aimed to overcome the limited applicability of fMRI-NF by developing and validating an EEG model of fMRI-defined rIFG activity (hereby termed "Electrical FingerPrint of rIFG"; rIFG-EFP). To validate the computational model, we employed two experiments in healthy individuals. The first study (n = 14) aimed to test the target engagement of the model by employing rIFG-EFP-NF training while simultaneously acquiring fMRI. The second study (n = 41) aimed to test the functional outcome of two sessions of rIFG-EFP-NF using a risk preference task (known to depict cognitive control processes), employed before and after the training. Results from the first study demonstrated neural target engagement as expected, showing associated rIFG-BOLD signal changing during simultaneous rIFG-EFP-NF training. Target anatomical specificity was verified by showing a more precise prediction of the rIFG-BOLD by the rIFG-EFP model compared to other EFP models. Results of the second study suggested that successful learning to up-regulate the rIFG-EFP signal through NF can reduce one's tendency for risk taking, indicating improved cognitive control after two sessions of rIFG-EFP-NF. Overall, our results confirm the validity of a scalable NF method for targeting rIFG activity by using an EEG probe.

Longitudinal volumetric evaluation of hippocampus and amygdala subregions in recent trauma survivors.

The hippocampus and the amygdala play a central role in post-traumatic stress disorder (PTSD) pathogenesis. While alternations in volumes of both regions have been consistently observed in individuals with PTSD, it remains unknown whether these reflect pre-trauma vulnerability traits or acquired post-trauma consequences of the disorder. Here, we conducted a longitudinal panel study of adult civilian trauma survivors admitted to a general hospital emergency department (ED). One hundred eligible participants (mean age = 32.97 ± 10.97, n = 56 females) completed both clinical interviews and structural MRI scans at 1-, 6-, and 14-months after ED admission (alias T1, T2, and T3). While all participants met PTSD diagnosis at T1, only n = 29 still met PTSD diagnosis at T3 (a "non-Remission" Group), while n = 71 did not (a "Remission" Group). Bayesian multilevel modeling analysis showed robust evidence for smaller right hippocampus volume (P+ of ~0.014) and moderate evidence for larger left amygdala volume (P+ of ~0.870) at T1 in the "non-Remission" group, compared to the "Remission" group. Subregion analysis further demonstrated robust evidence for smaller volume in the subiculum and right CA1 hippocampal subregions (P+ of ~0.021-0.046) in the "non-Remission" group. No time-dependent volumetric changes (T1 to T2 to T3) were observed across all participants or between groups. Results support the "vulnerability trait" hypothesis, suggesting that lower initial volumes of specific hippocampus subregions are associated with non-remitting PTSD. The stable volume of all hippocampal and amygdala subregions does not support the idea of consequential, progressive, stress-related atrophy during the first critical year following trauma exposure.

Lesions to both somatic and affective pain pathways lead to decreased salience network connectivity.

Human pain is a salient stimulus composed of two main components: a sensory/somatic component, carrying peripheral nociceptive sensation via the spinothalamic tract and brainstem nuclei to the thalamus and then to sensory cortical regions, and an affective (suffering) component, where information from central thalamic nuclei is carried to the anterior insula, dorsal anterior cingulate cortex and other regions. While the sensory component processes information about stimulus location and intensity, the affective component processes information regarding pain-related expectations, motivation to reduce pain and pain unpleasantness. Unlike investigations of acute pain that are based on the introduction of real-time stimulus during brain recordings, chronic pain investigations are usually based on longitudinal and case-control studies, which are limited in their ability to infer the functional network topology of chronic pain. In the current study, we utilized the unique opportunity to target the CNS's pain pathways in two different hierarchical locations to establish causality between pain relief and specific connectivity changes seen within the salience and sensorimotor networks. We examined how lesions to the affective and somatic pain pathways affect resting-state network topology in cancer patients suffering from severe intractable pain. Two procedures have been employed: percutaneous cervical cordotomy (n = 15), hypothesized to disrupt the transmission of the sensory component of pain along the spinothalamic tract, or stereotactic cingulotomy (n = 7), which refers to bilateral intracranial ablation of an area in the dorsal anterior cingulate cortex and is known to ameliorate the affective component of pain. Both procedures led to immediate significant alleviation of experienced pain and decreased functional connectivity within the salience network. However, only the sensory procedure (cordotomy) led to decreased connectivity within the sensorimotor network. Thus, our results support the existence of two converging systems relaying experienced pain, showing that pain-related suffering can be either directly influenced by interfering with the affective pathway or indirectly influenced by interfering with the ascending spinothalamic tract.

Self-evaluation of social-rank in socially anxious individuals associates with enhanced striatal reward function.

BACKGROUND: Negative self-views, especially in the domain of power (i.e. social-rank), characterize social anxiety (SA). Neuroimaging studies on self-evaluations in SA have mainly focused on subcortical threat processing systems. Yet, self-evaluation may concurrently invoke diverse affective processing, as motivational systems related to desired self-views may also be activated. To investigate the conflictual nature that may accompany self-evaluation of certain social domains in SA, we examined brain activity related to both threat and reward processing. METHODS: Participants (N = 74) differing in self-reported SA-severity underwent fMRI while completing a self-evaluation task, wherein they judged the self-descriptiveness of high- v. low-intensity traits in the domains of power and affiliation (i.e. social connectedness). Participants also completed two auxiliary fMRI tasks designated to evoke reward- and threat-related activations in the ventral striatum (VS) and amygdala, respectively. We hypothesized that self-evaluations in SA, particularly in the domain of power, involve aberrant brain activity related to both threat and reward processing. RESULTS: SA-severity was more negatively associated with power than with affiliation self-evaluations. During self-evaluative judgment of high-power (e.g. dominant), SA-severity associated with increased activity in the VS and ventromedial prefrontal cortex. Moreover, SA-severity correlated with higher similarity between brain activity patterns activated by high-power traits and patterns activated by incentive salience (i.e. reward anticipation) in the VS during the reward task. CONCLUSIONS: Our findings indicate that self-evaluation of high-power in SA involves excessive striatal reward-related activation, and pinpoint the downregulation of VS-VMPFC activity within such self-evaluative context as a potential neural outcome for therapeutic interventions.