The Vestibulocerebellum and the Shattered Self: a Resting-State Functional Connectivity Study in Posttraumatic Stress Disorder and Its Dissociative Subtype.

The flocculus is a region of the vestibulocerebellum dedicated to the coordination of neck, head, and eye movements for optimal posture, balance, and orienting responses. Despite growing evidence of vestibular and oculomotor impairments in the aftermath of traumatic stress, little is known about the effects of chronic psychological trauma on vestibulocerebellar functioning. Here, we investigated alterations in functional connectivity of the flocculus at rest among individuals with post-traumatic stress disorder (PTSD) and its dissociative subtype (PTSD + DS) as compared to healthy controls. Forty-four healthy controls, 57 PTSD, and 32 PTSD + DS underwent 6-min resting-state MRI scans. Seed-based functional connectivity analyses using the right and left flocculi as seeds were performed. These analyses revealed that, as compared to controls, PTSD and PTSD + DS showed decreased resting-state functional connectivity of the left flocculus with cortical regions involved in bodily self-consciousness, including the temporo-parietal junction, the supramarginal and angular gyri, and the superior parietal lobule. Moreover, as compared to controls, the PTSD + DS group showed decreased functional connectivity of the left flocculus with the medial prefrontal cortex, the precuneus, and the mid/posterior cingulum, key regions of the default mode network. Critically, when comparing PTSD + DS to PTSD, we observed increased functional connectivity of the right flocculus with the right anterior hippocampus, a region affected frequently by early life trauma. Taken together, our findings point toward the crucial role of the flocculus in the neurocircuitry underlying a coherent and embodied self, which can be compromised in PTSD and PTSD + DS.

Comparing Discounting of Potentially Real Rewards and Losses by Means of Functional Magnetic Resonance Imaging.

Aim: Delay discounting (DD) has often been investigated in the context of decision making whereby individuals attribute decreasing value to rewards in the distant future. Less is known about DD in the context of negative consequences. The aim of this pilot study was to identify commonalities and differences between reward and loss discounting on the behavioral as well as the neural level by means of computational modeling and functional Magnetic Resonance Imaging (fMRI). We furthermore compared the neural activation between anticipation of rewards and losses. Method: We conducted a study combining an intertemporal choice task for potentially real rewards and losses (decision-making) with a monetary incentive/loss delay task (reward/loss anticipation). Thirty healthy participants (age 18-35, 14 female) completed the study. In each trial, participants had to choose between a smaller immediate loss/win and a larger loss/win at a fixed delay of two weeks. Task-related brain activation was measured with fMRI. Results: Hyperbolic discounting parameters of loss and reward conditions were correlated (r = 0.56). During decision-making, BOLD activation was observed in the parietal and prefrontal cortex, with no differences between reward and loss conditions. During reward and loss anticipation, dissociable activation was observed in the striatum, the anterior insula and the anterior cingulate cortex. Conclusion: We observed behavior concurrent with DD in both the reward and loss condition, with evidence for similar behavioral and neural patterns in the two conditions. Intertemporal decision-making recruited the fronto-parietal network, whilst reward and loss anticipation were related to activation in the salience network. The interpretation of these findings may be limited to short delays and small monetary outcomes.

A Model Guided Approach to Evoke Homogeneous Behavior During Temporal Reward and Loss Discounting.

Background: The tendency to devaluate future options as a function of time, known as delay discounting, is associated with various factors such as psychiatric illness and personality. Under identical experimental conditions, individuals may therefore strongly differ in the degree to which they discount future options. In delay discounting tasks, this inter-individual variability inevitably results in an unequal number of discounted trials per subject, generating difficulties in linking delay discounting to psychophysiological and neural correlates. Many studies have therefore focused on assessing delay discounting adaptively. Here, we extend these approaches by developing an adaptive paradigm which aims at inducing more comparable and homogeneous discounting frequencies across participants on a dimensional scale. Method: The proposed approach probabilistically links a (common) discounting function to behavior to obtain a probabilistic model, and then exploits the model to obtain a formal condition which defines how to construe experimental trials so as to induce any desired discounting probability. We first infer subject-level models on behavior on a non-adaptive delay discounting task and then use these models to generate adaptive trials designed to evoke graded relative discounting frequencies of 0.3, 0.5, and 0.7 in each participant. We further compare and evaluate common models in the field through out-of-sample prediction error estimates, to iteratively improve the trial-generating model and paradigm. Results: The developed paradigm successfully increases discounting behavior during both reward and loss discounting. Moreover, it evokes graded relative choice frequencies in line with model-based expectations (i.e., 0.3, 0.5, and 0.7) suggesting that we can successfully homogenize behavior. Our model comparison analyses indicate that hyperboloid models are superior in predicting unseen discounting behavior to more conventional hyperbolic and exponential models. We report out-of-sample error estimates as well as commonalities and differences between reward and loss discounting, demonstrating for instance lower discounting rates, as well as differences in delay perception in loss discounting. Conclusion: The present work proposes a model-based framework to evoke graded responses linked to cognitive function at a single subject level. Such a framework may be used in the future to measure cognitive functions on a dimensional rather than dichotomous scale.

Contrasting Associations Between Heart Rate Variability and Brainstem-Limbic Connectivity in Posttraumatic Stress Disorder and Its Dissociative Subtype: A Pilot Study.

Background: Increasing evidence points toward the need to extend the neurobiological conceptualization of posttraumatic stress disorder (PTSD) to include evolutionarily conserved neurocircuitries centered on the brainstem and the midbrain. The reticular activating system (RAS) helps to shape the arousal state of the brain, acting as a bridge between brain and body. To modulate arousal, the RAS is closely tied to the autonomic nervous system (ANS). Individuals with PTSD often reveal altered arousal patterns, ranging from hyper- to blunted arousal states, as well as altered functional connectivity profiles of key arousal-related brain structures that receive direct projections from the RAS. Accordingly, the present study aims to explore resting state functional connectivity of the RAS and its interaction with the ANS in participants with PTSD and its dissociative subtype. Methods: Individuals with PTSD (n = 57), its dissociative subtype (PTSD + DS, n = 32) and healthy controls (n = 40) underwent a 6-min resting functional magnetic resonance imaging and pulse data recording. Resting state functional connectivity (rsFC) of a central node of the RAS - the pedunculopontine nuclei (PPN) - was investigated along with its relation to ANS functioning as indexed by heart rate variability (HRV). HRV is a prominent marker indexing the flexibility of an organism to react adaptively to environmental needs, with higher HRV representing greater effective adaptation. Results: Both PTSD and PTSD + DS demonstrated reduced HRV as compared to controls. HRV measures were then correlated with rsFC of the PPN. Critically, participants with PTSD and participants with PTSD + DS displayed inverse correlations between HRV and rsFC between the PPN and key limbic structures, including the amygdala. Whereas participants with PTSD displayed a positive relationship between HRV and PPN rsFC with the amygdala, participants with PTSD + DS demonstrated a negative relationship between HRV and PPN rsFC with the amygdala. Conclusion: The present exploratory investigation reveals contrasting patterns of arousal-related circuitry among participants with PTSD and PTSD + DS, providing a neurobiological lens to interpret hyper- and more blunted arousal states in PTSD and PTSD + DS, respectively.

Classification of amyotrophic lateral sclerosis by brain volume, connectivity, and network dynamics.

Emerging studies corroborate the importance of neuroimaging biomarkers and machine learning to improve diagnostic classification of amyotrophic lateral sclerosis (ALS). While most studies focus on structural data, recent studies assessing functional connectivity between brain regions by linear methods highlight the role of brain function. These studies have yet to be combined with brain structure and nonlinear functional features. We investigate the role of linear and nonlinear functional brain features, and the benefit of combining brain structure and function for ALS classification. ALS patients (N = 97) and healthy controls (N = 59) underwent structural and functional resting state magnetic resonance imaging. Based on key hubs of resting state networks, we defined three feature sets comprising brain volume, resting state functional connectivity (rsFC), as well as (nonlinear) resting state dynamics assessed via recurrent neural networks. Unimodal and multimodal random forest classifiers were built to classify ALS. Out-of-sample prediction errors were assessed via five-fold cross-validation. Unimodal classifiers achieved a classification accuracy of 56.35-61.66%. Multimodal classifiers outperformed unimodal classifiers achieving accuracies of 62.85-66.82%. Evaluating the ranking of individual features' importance scores across all classifiers revealed that rsFC features were most dominant in classification. While univariate analyses revealed reduced rsFC in ALS patients, functional features more generally indicated deficits in information integration across resting state brain networks in ALS. The present work undermines that combining brain structure and function provides an additional benefit to diagnostic classification, as indicated by multimodal classifiers, while emphasizing the importance of capturing both linear and nonlinear functional brain properties to identify discriminative biomarkers of ALS.

Model-based experimental manipulation of probabilistic behavior in interpretable behavioral latent variable models.

Introduction: Interpretable latent variable models that probabilistically link behavioral observations to an underlying latent process have increasingly been used to draw inferences on cognition from observed behavior. The latent process usually connects experimental variables to cognitive computation. While such models provide important insights into the latent processes generating behavior, one important aspect has often been overlooked. They may also be used to generate precise and falsifiable behavioral predictions as a function of the modeled experimental variables. In doing so, they pinpoint how experimental conditions must be designed to elicit desired behavior and generate adaptive experiments. Methods: These ideas are exemplified on the process of delay discounting (DD). After inferring DD models from behavior on a typical DD task, the models are leveraged to generate a second adaptive DD task. Experimental trials in this task are designed to elicit 9 graded behavioral discounting probabilities across participants. Models are then validated and contrasted to competing models in the field by assessing the ouf-of-sample prediction error. Results: The proposed framework induces discounting probabilities on nine levels. In contrast to several alternative models, the applied model exhibits high validity as indicated by a comparably low prediction error. We also report evidence for inter-individual differences with respect to the most suitable models underlying behavior. Finally, we outline how to adapt the proposed method to the investigation of other cognitive processes including reinforcement learning. Discussion: Inducing graded behavioral frequencies with the proposed framework may help to highly resolve the underlying cognitive construct and associated neuronal substrates.

Mapping alexithymia: Level of emotional awareness differentiates emotion-specific somatosensory maps.

BACKGROUND: Emotions have been associated with culturally universal and distinct bodily sensation "maps". Despite this knowledge, to date few studies have explored emotion-specific topography along clinically relevant dimensions, such as alexithymia. OBJECTIVE: We aimed to investigate emotion-specific topographies among individuals exposed to childhood maltreatment or neglect with absent (n = 51) or with probable (n = 46) alexithymia in adulthood, as defined by scores on the Toronto Alexithymia Scale (TAS-20). PARTICIPANTS AND SETTING: Ninety eight adult participants with exposure to childhood maltreatment or neglect were recruited to complete an online survey. METHODS: Using the well-validated emBODY tool (Nummenmaa et al., 2014), participants reported on their somatic experience of 17 emotions. RESULTS: Random effects analyses revealed topographically distinct bodily sensation t-maps that differentiated participants who endorsed probable alexithymia from those who did not (p-FDR < .05). Consistent with our a priori hypothesis, the probable alexithymia group reported a muted, diffuse and undifferentiated pattern of emotion-specific bodily sensation, whereas the non-alexithymia group reported a more distinct and localized pattern. CONCLUSIONS: These results suggest that difficulty identifying and labeling emotions, as observed in alexithymia, may arise, in part, from an altered perception of somatic activation. It is well-established that childhood maltreatment predicts the development of alexithymia symptoms. The preliminary findings presented here expand our working understanding of the physical markers of childhood trauma, which may be used in practice to aid detection and to monitor treatment outcomes.

Differential Effects of Early Adversity and Posttraumatic Stress Disorder on Amygdala Reactivity: The Role of Developmental Timing.

BACKGROUND: Posttraumatic stress disorder (PTSD) is associated with altered processing of threat-related stimuli. Neurobiological models implicate right amygdala hyperreactivity in these alterations, but this potential biomarker also has been observed in individuals exposed to adverse childhood experiences (ACEs) (i.e., abuse and neglect) without psychopathology. Separation of the differential contributions of PTSD and ACEs to amygdala reactivity might benefit from incorporating the developmental timing of the events. METHODS: We conducted comprehensive retrospective interviews assessing ACEs for each life year between the ages of 1 and 17 years in a sample of 60 women exposed to trauma (including 34 participants with PTSD and 26 healthy participants). Functional magnetic resonance imaging was used to extract amygdala reactivity to threatening versus neutral scenes. Amygdala reactivity was predicted from PTSD diagnosis, total ACE severity, and ACE severity by life year using random forest regression. RESULTS: PTSD and ACEs significantly predicted reactivity in the right amygdala (R2 = 7%) but did not explain variance in the left amygdala. ACEs during both a prepubertal (ages 3 and 4) and a postpubertal (ages 16 and 17) period emerged as particularly predictive, while total ACE severity did not contribute to prediction. Follow-up analyses revealed a positive relationship between amygdala activity and PTSD and a negative relationship between amygdala activity and ACEs during predictive life years. CONCLUSIONS: The opposing effects of PTSD and ACEs caution against simplistic etiological and diagnostic interpretations of amygdala function. The identification of potentially sensitive periods for the effects of ACEs on amygdala reactivity to threat may help to uncover interactions between traumatization and development of PTSD.

Influence of Severity of Type and Timing of Retrospectively Reported Childhood Maltreatment on Female Amygdala and Hippocampal Volume.

Deleterious effects of adverse childhood experiences (ACE) on human brain volume are widely reported. First evidence points to differential effects of ACE on brain volume in terms of timing of ACE. Upcoming studies additionally point towards the impact of different types (i.e., neglect and abuse) of ACE in terms of timing. The current study aimed to investigate the correlation between retrospectively reported severity of type (i.e., the extent to which subjects were exposed to abuse and/or neglect, respectively) and timing of ACE on female brain volume in a sample of prolonged traumatized subjects. A female sample with ACE (N = 68) underwent structural magnetic resonance imaging and a structured interview exploring the severity of ACE from age 3 up to 17 using the "Maltreatment and Abuse Chronology of Exposure" (MACE). Random forest regression with conditional interference trees was applied to assess the impact of ACE severity as well as the severity of ACE type, (i.e. to what extent individuals were exposed to neglect and/or abuse) at certain ages on pre-defined regions of interest such as the amygdala, hippocampus, and anterior cingulate (ACC) volume. Analyses revealed differential type and timing-specific effects of ACE on stress sensitive brain structures: Amygdala and hippocampal volume were affected by ACE severity during a period covering preadolescence and early adolescence. Crucially, this effect was driven by the severity of neglect.

PTSD and its dissociative subtype through the lens of the insula: Anterior and posterior insula resting-state functional connectivity and its predictive validity using machine learning.

Individuals with post-traumatic stress disorder (PTSD) typically experience states of reliving and hypervigilance; however, the dissociative subtype of PTSD (PTSD+DS) presents with additional symptoms of depersonalization and derealization. Although the insula is critical to emotion processing, its association with these contrasting symptom profiles is yet to be fully delineated. Accordingly, we investigated insula subregion resting-state functional connectivity patterns among individuals with PTSD, PTSD+DS, and healthy controls. Using SPM12 and PRONTO software, we implemented a seed-based resting-state functional connectivity approach, along with multiclass Gaussian process classification machine learning, respectively, in order to evaluate unique patterns and the predictive validity of insula subregion connectivity among individuals with PTSD (n = 84), PTSD+DS (n = 49), and age-matched healthy controls (n = 51). As compared to PTSD and PTSD+DS, healthy controls showed increased right anterior and posterior insula connectivity with frontal lobe structures. By contrast, PTSD showed increased bilateral posterior insula connectivity with subcortical structures, including the periaqueductal gray. Strikingly, as compared to PTSD and controls, PTSD+DS showed increased bilateral anterior and posterior insula connectivity with posterior cortices, including the left lingual gyrus and the left precuneus. Moreover, machine learning analyses were able to classify PTSD, PTSD+DS, and controls using insula subregion connectivity patterns with 80.4% balanced accuracy (p < .01). These findings suggest a neurobiological distinction between PTSD and its dissociative subtype with regard to insula subregion functional connectivity patterns. Furthermore, machine learning algorithms were able to utilize insula resting-state connectivity patterns to discriminate between participant groups with high predictive accuracy.

The neural correlates of trauma-related autobiographical memory in posttraumatic stress disorder: A meta-analysis.

BACKGROUND: Autobiographical memory (AM) refers to memories of events that are personally relevant and are remembered from one's own past. The AM network is a distributed brain network comprised largely by prefrontal medial and posteromedial cortical brain regions, which together facilitate AM. Autobiographical memories with high arousal and negatively valenced emotional states are thought to be retrieved more readily and re-experienced more vividly. This is critical in the case of trauma-related AMs, which are related to altered phenomenological experiences as well as aberrations to the underlying neural systems in posttraumatic stress disorder (PTSD). Critically, these alterations to the AM network have not been explored recently and have never been analyzed with consideration to the different processes of AM, them being retrieval and re-experiencing. METHODS: We conducted a series of effect-size signed differential mapping meta-analyses across twenty-eight studies investigating the neural correlates of trauma-related AMs in participants with PTSD as compared with controls. Studies included either trauma-related scripts or trauma-related materials (i.e., sounds, images, pictures) implemented to evoke the recollection of a trauma-related memory. RESULTS: The meta-analyses revealed that control and PTSD participants displayed greater common brain activation of prefrontal medial and posteromedial cortices, respectively. Whereby the prefrontal medial cortices are suggested to facilitate retrieval monitoring, the posteromedial cortices are thought to enable the visual imagery processes of AM. CONCLUSIONS: Taken together, reduced common activation of prefrontal cortices may be interpreted as a bias toward greater re-experiencing, where the more salient elements of the traumatic memory are relived as opposed to retrieved in a controlled manner in PTSD.

Psychometric Properties and Factor Structure of the German Version of the Clinician-Administered PTSD Scale for DSM-5.

The Clinician-Administered PTSD Scale (CAPS) is a widely used diagnostic interview for posttraumatic stress disorder (PTSD). Following fundamental modifications in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), the CAPS had to be revised. This study examined the psychometric properties (internal consistency, interrater reliability, convergent and discriminant validity, and structural validity) of the German version of the CAPS-5 in a trauma-exposed sample (n = 223 with PTSD; n =51 without PTSD). The results demonstrated high internal consistency (αs = .65-.93) and high interrater reliability (ICCs = .81-.89). With regard to convergent and discriminant validity, we found high correlations between the CAPS severity score and both the Posttraumatic Diagnostic Scale sum score (r = .87) and the Beck Depression Inventory total score (r = .72). Regarding the underlying factor structure, the hybrid model demonstrated the best fit, followed by the anhedonia model. However, we encountered some nonpositive estimates for the correlations of the latent variables (factors) for both models. The model with the best fit without methodological problems was the externalizing behaviors model, but the results also supported the DSM-5 model. Overall, the results demonstrate that the German version of the CAPS-5 is a psychometrically sound measure.

A negative bias in decoding positive social cues characterizes emotion processing in patients with symptom-remitted Borderline Personality Disorder.

BACKGROUND: Impairments in the domain of interpersonal functioning such as the feeling of loneliness and fear of abandonment have been associated with a negative bias during processing of social cues in Borderline Personality Disorder (BPD). Since these symptoms show low rates of remission, high rates of recurrence and are relatively resistant to treatment, in the present study we investigated whether a negative bias during social cognitive processing exists in BPD even after symptomatic remission. We focused on facial emotion recognition since it is one of the basal social-cognitive processes required for successful social interactions and building relationships. METHODS: Ninety-eight female participants (46 symptom-remitted BPD [r-BPD]), 52 healthy controls [HC]) rated the intensity of anger and happiness in ambiguous (anger/happiness blends) and unambiguous (emotion/neutral blends) emotional facial expressions. Additionally, participants assessed the confidence they experienced in their own judgments. RESULTS: R-BPD participants assessed ambiguous expressions as less happy and as more angry when the faces displayed predominantly happiness. Confidence in these judgments did not differ between groups, but confidence in judging happiness in predominantly happy faces was lower in BPD patients with a higher level of BPD psychopathology. CONCLUSIONS: Evaluating social cues that signal the willingness to affiliate is characterized by a negative bias that seems to be a trait-like feature of social cognition in BPD. In contrast, confidence in judging positive social signals seems to be a state-like feature of emotion recognition in BPD that improves with attenuation in the level of acute BPD symptoms.

Increased recruitment of cognitive control in the presence of traumatic stimuli in complex PTSD.

A neurocircuitry model of post-traumatic stress disorder (PTSD) suggests increased amygdala responses to emotional stimuli, coupled with hypoactivation of prefrontal regions associated with cognitive control. However, results are heterogenous across different subsamples of PTSD as well as different paradigms. We investigated cognitive control in a classic and emotional Stroop task in 28 female patients with complex PTSD (cPTSD), 28 female trauma-exposed healthy controls (TCs) and 28 female non-trauma-exposed healthy controls (HCs) using functional neuroimaging. Afterwards, we assessed memory function in a spontaneous free recall and recognition task. Patients with cPTSD displayed significantly greater Stroop interference with trauma-related words (as reflected in slower reaction times and increased errors) compared to the other conditions and compared to the TC and HC groups. Moreover, patients with cPTSD showed increased activation in the context of trauma-related words in brain regions associated with cognitive control (dlPFC, vmPFC, dACC) compared to both control groups, and a trend for increased activation in the insula compared to the HC group. Increased recruitment of regions contributing to cognitive control in patients with cPTSD, together with a lack of amygdala response may point to efforts to compensate for emotional distraction caused by the trauma-related words.

The Innate Alarm System and Subliminal Threat Presentation in Posttraumatic Stress Disorder: Neuroimaging of the Midbrain and Cerebellum.

BACKGROUND: The innate alarm system, a network of interconnected midbrain, other brainstem, and thalamic structures, serves to rapidly detect stimuli in the environment prior to the onset of conscious awareness. This system is sensitive to threatening stimuli and has evolved to process these stimuli subliminally for hastened responding. Despite the conscious unawareness, the presentation of subliminal threat stimuli generates increased activation of limbic structures, including the amygdala and insula, as well as emotionally evaluative structures, including the cerebellum and orbitofrontal cortex. Posttraumatic stress disorder (PTSD) is associated with an increased startle response and decreased extinction learning to conditioned threat. The role of the innate alarm system in the clinical presentation of PTSD, however, remains poorly understood. METHODS: Here, we compare midbrain, brainstem, and cerebellar activation in persons with PTSD (n = 26) and matched controls (n = 20) during subliminal threat presentation. Subjects were presented with masked trauma-related and neutral stimuli below conscious threshold. Contrasts of subliminal brain activation for the presentation of neutral stimuli were subtracted from trauma-related brain activation. Group differences in activation, as well as correlations between clinical scores and PTSD activation, were examined. Imaging data were preprocessed utilizing the spatially unbiased infratentorial template toolbox within SPM12. RESULTS: Analyses revealed increased midbrain activation in PTSD as compared to controls in the superior colliculus, periaqueductal gray, and midbrain reticular formation during subliminal threat as compared to neutral stimulus presentation. Controls showed increased activation in the right cerebellar lobule V during subliminal threat presentation as compared to PTSD. Finally, a negative correlation emerged between PTSD patient scores on the Multiscale Dissociation Inventory for the Depersonalization/Derealization subscale and activation in the right lobule V of the cerebellum during the presentation of subliminal threat as compared to neutral stimuli. CONCLUSION: We interpret these findings as evidence of innate alarm system overactivation in PTSD and of the prominent role of the cerebellum in the undermodulation of emotion observed in PTSD.

The Threatful Self: Midbrain Functional Connectivity to Cortical Midline and Parietal Regions During Subliminal Trauma-Related Processing in PTSD.

BACKGROUND: The innate alarm system consists of a subcortical network of interconnected midbrain, lower brainstem, and thalamic nuclei, which together mediate the detection of evolutionarily-relevant stimuli. The periaqueductal gray is a midbrain structure innervated by the innate alarm system that coordinates the expression of defensive states following threat detection. In participants with post-traumatic stress disorder, the periaqueductal gray displays overactivation during the subliminal presentation of trauma-related stimuli as well as altered resting-state functional connectivity. Aberrant functional connectivity is also reported in post-traumatic stress disorder for the default-mode network, a large-scale brain network recruited during self-referential processing and autobiographical memory. Here, research lacks investigation on the extent to which functional interactions are displayed between the midbrain and the large-scale cortical networks in post-traumatic stress disorder. METHODS: Using a subliminal threat presentation paradigm, we investigated psycho-physiological interactions during functional neuroimaging in participants with post-traumatic stress disorder (n = 26) and healthy control subjects (n = 20). Functional connectivity of the periaqueductal gray was investigated across the whole-brain of each participant during subliminal exposure to trauma-related and neutral word stimuli. RESULTS: As compared to controls during subliminal threat presentation, the post-traumatic stress disorder group showed significantly greater periaqueductal gray functional connectivity with regions of the default-mode network (i.e., angular gyrus, precuneus, superior frontal gyrus). Moreover, multiple regression analyses revealed that the functional connectivity between the periaqueductal gray and the regions of the default-mode network correlated positively to symptoms of avoidance and state dissociation in post-traumatic stress disorder. CONCLUSION: Given that the periaqueductal gray engages the expression of defensive states, stronger midbrain functional coupling with the default-mode network may have clinical implications to self-referential and trauma-related processing in participants with post-traumatic stress disorder.

Back to the Basics: Resting State Functional Connectivity of the Reticular Activation System in PTSD and its Dissociative Subtype.

BACKGROUND: Brainstem and midbrain neuronal circuits that control innate, reflexive responses and arousal are increasingly recognized as central to the neurobiological framework of post-traumatic stress disorder (PTSD). The reticular activation system represents a fundamental neuronal circuit that plays a critical role not only in generating arousal but also in coordinating innate, reflexive responding. Accordingly, the present investigation aims to characterize the resting state functional connectivity of the reticular activation system in PTSD and its dissociative subtype. METHODS: We investigated patterns of resting state functional connectivity of a central node of the reticular activation system, namely, the pedunculopontine nuclei, among individuals with PTSD (n = 77), its dissociative subtype (PTSD+DS; n = 48), and healthy controls (n = 51). RESULTS: Participants with PTSD and PTSD+DS were characterized by within-group pedunculopontine nuclei resting state functional connectivity to brain regions involved in innate threat processing and arousal modulation (i.e., midbrain, amygdala, ventromedial prefrontal cortex). Critically, this pattern was most pronounced in individuals with PTSD+DS, as compared to both control and PTSD groups. As compared to participants with PTSD and controls, individuals with PTSD+DS showed enhanced pedunculopontine nuclei resting state functional connectivity to the amygdala and the parahippocampal gyrus as well as to the anterior cingulate and the ventromedial prefrontal cortex. No group differences emerged between PTSD and control groups. In individuals with PTSD+DS, state derealization/depersonalization was associated with reduced resting state functional connectivity between the left pedunculopontine nuclei and the anterior nucleus of the thalamus. Altered connectivity in these regions may restrict the thalamo-cortical transmission necessary to integrate internal and external signals at a cortical level and underlie, in part, experiences of depersonalization and derealization. CONCLUSIONS: The present findings extend the current neurobiological model of PTSD and provide emerging evidence for the need to incorporate brainstem structures, including the reticular activation system, into current conceptualizations of PTSD and its dissociative subtype.

Difficulties with being socially accepted: An experimental study in borderline personality disorder.

Anxious preoccupation with real or imagined abandonment is a key feature of borderline personality disorder (BPD). Recent experimental research suggests that patients with BPD do not simply show emotional overreactivity to rejection. Instead, they experience reduced connectedness with others in situations of social inclusion. Resulting consequences of these features on social behavior are not investigated yet. The aim of the present study was to investigate the differential impact of social acceptance and rejection on social expectations and subsequent social behavior in BPD. To this end, we developed the Mannheim Virtual Group Interaction Paradigm in which participants interacted with a group of computer-controlled avatars. They were led to believe that these represented real human coplayers. During these interactions, participants introduced themselves, evaluated their coplayers, assessed their social expectations and received feedback signaling either acceptance or rejection by the alleged other participants. Subsequently, participants played a modified trust game, which measured cooperative and aggressive behavior. Fifty-six nonmedicated BPD patients and 56 healthy control participants were randomly and double-blindly assigned to either the group-acceptance or group-rejection condition. BPD patients showed lower initial expectations of being socially accepted than healthy controls. After repeated presentation of social feedback, they adjusted their expectations in response to negative, but not to positive feedback. After the experience of social acceptance, BPD patients behaved less cooperatively. These experimental findings point to a clinically relevant issue in BPD: Altered cognitive and behavioral responses to social acceptance may hamper the forming of stable cooperative relationships and negatively affect future interpersonal relationships. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Detecting implicit cues of aggressiveness in male faces in revictimized female PTSD patients and healthy controls.

Victimized women are thought to have impairments in identifying risk and to have dysfunctional reactions to threatening situations, which increase the risk for revictimization. To investigate possible deficits in revictimized women, we used a method examining women's perceptions of an implicit facial cue of aggressiveness - the facial Width-to-Height Ratio (fWHR). We tested whether revictimized women show impairments in detecting aggressiveness in male faces by neglecting cues of fWHR and choosing a smaller preferred distance to men. Fifty-two revictimized PTSD patients and 52 healthy controls provided ratings of aggressiveness and attractiveness for 65 photographed men and chose their preferred distance towards 11 pictured men. Multiple regression analyses indicated that revictimized women do not show impairments in perceiving and reacting to cues of aggression accurately. Hierarchical linear models, however, indicated that revictimized women rated all men as less aggressive. Revictimized women with histories of intimate partner violence (IPV) rated men with larger fWHRs and higher values of actual aggression to be more attractive than did revictimized women without IPV histories. A reduced appraisal of threat signals as threatening and an attraction to wider-faced and more aggressive men might increase the risk for revictimization.

Behavioural mimicry and loneliness in borderline personality disorder.

INTRODUCTION: Interpersonal problems together with feelings of intense loneliness constitute a core symptom domain in borderline personality disorder (BPD). Mimicry is one social behaviour that serves the forming of social affiliation and building a sense of belonging. In the present study, we investigated whether behavioural mimicry is altered in BPD and whether it is linked to the patient's feeling of loneliness. METHODS: Individuals with BPD (N = 26) and healthy participants (HC, N = 25) performed a finger tapping task with a congruent or incongruent finger movement displayed preceding the presentation of the task relevant stimulus. Additional trials showing an immobile hand were used as a control condition. Mimicry strength was estimated as response facilitation after congruent and response interference after incongruent cues. RESULTS: Both HC and BPD patients showed facilitated responses after congruent finger movements. Only BPD patients exhibited interference by incongruent cues. The lonelier the BPD patients felt, the weaker was the interference of the incongruent cues. In contrast, interference increased with the level of loneliness in the HC group. CONCLUSIONS: Behavioural mimicry was increased in BPD. However, this effect was less pronounced in those BPD patients who reported the highest levels of loneliness. Our findings emphasize that mimicry is a complex construct and only some of the involved processes are altered in BPD. Future studies must further disentangle the contribution of cognitive and social cognitive processes, address a potential causality in the link between loneliness and mimicry in BPD, and relate alterations of mimicry to interpersonal dysfunction during every-day life.