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  1. Article: How Processing of Sensory Information From the Internal and External Worlds Shape the Perception and Engagement With the World in the Aftermath of Trauma: Implications for PTSD.

    Harricharan, Sherain / McKinnon, Margaret C / Lanius, Ruth A

    Frontiers in neuroscience

    2021  Volume 15, Page(s) 625490

    Abstract: Post-traumatic stress disorder (PTSD) is triggered by an individual experiencing or witnessing a traumatic event, often precipitating persistent flashbacks and severe anxiety that are associated with a fearful and hypervigilant presentation. ... ...

    Abstract Post-traumatic stress disorder (PTSD) is triggered by an individual experiencing or witnessing a traumatic event, often precipitating persistent flashbacks and severe anxiety that are associated with a fearful and hypervigilant presentation. Approximately 14-30% of traumatized individuals present with the dissociative subtype of PTSD, which is often associated with repeated or childhood trauma. This presentation includes symptoms of depersonalization and derealization, where individuals may feel as if the world or self is "dream-like" and not real and/or describe "out-of-body" experiences. Here, we review putative neural alterations that may underlie how sensations are experienced among traumatized individuals with PTSD and its dissociative subtype, including those from the outside world (e.g., touch, auditory, and visual sensations) and the internal world of the body (e.g., visceral sensations, physical sensations associated with feeling states). We postulate that alterations in the neural pathways important for the processing of sensations originating in the outer and inner worlds may have cascading effects on the performance of higher-order cognitive functions, including emotion regulation, social cognition, and goal-oriented action, thereby shaping the perception of and engagement with the world. Finally, we introduce a theoretical neurobiological framework to account for altered sensory processing among traumatized individuals with and without the dissociative subtype of PTSD.
    Language English
    Publishing date 2021-04-16
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2411902-7
    ISSN 1662-453X ; 1662-4548
    ISSN (online) 1662-453X
    ISSN 1662-4548
    DOI 10.3389/fnins.2021.625490
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Increased top-down control of emotions during symptom provocation working memory tasks following a RCT of alpha-down neurofeedback in PTSD.

    Shaw, Saurabh Bhaskar / Nicholson, Andrew A / Ros, Tomas / Harricharan, Sherain / Terpou, Braeden / Densmore, Maria / Theberge, Jean / Frewen, Paul / Lanius, Ruth A

    NeuroImage. Clinical

    2023  Volume 37, Page(s) 103313

    Abstract: Background: Posttraumatic stress disorder (PTSD) has been found to be associated with emotion under-modulation from the prefrontal cortex and a breakdown of the top-down control of cognition and emotion. Novel adjunct therapies such as neurofeedback ( ... ...

    Abstract Background: Posttraumatic stress disorder (PTSD) has been found to be associated with emotion under-modulation from the prefrontal cortex and a breakdown of the top-down control of cognition and emotion. Novel adjunct therapies such as neurofeedback (NFB) have been shown to normalize aberrant neural circuits that underlie PTSD psychopathology at rest. However, little evidence exists for NFB-linked neural improvements under emotionally relevant cognitive load. The current study sought to address this gap by examining the effects of alpha-down NFB in the context of an emotional n-back task.
    Methods: We conducted a 20-week double-blind randomized, sham-controlled trial of alpha-down NFB and collected neuroimaging data before and after the NFB protocol. Participants performed an emotional 1-back and 2-back working memory task, with interleaved trauma-neutral and trauma-relevant cues in the fMRI scanner. Data from 35 participants with a primary diagnosis of PTSD were analyzed in this study (n = 18 in the experimental group undergoing alpha-down NFB, n = 17 in the sham-control group).
    Results: Firstly, within-group analyses showed clinically significant reductions in PTSD symptom severity scores at the post-intervention timepoint and 3-month follow-up for the experimental group, and not for the sham-control group. The neuroimaging analyses revealed that alpha-down NFB enhanced engagement of top-down cognitive and emotional control centers, such as the dorsolateral prefrontal cortex (dlPFC), and improved integration of the anterior and posterior parts of the default mode network (DMN). Finally, our results also indicate that increased alpha-down NFB performance correlated with increased activity in brain regions involved in top-down control and bodily consciousness/embodied processing of self (TPJ and posterior insula).
    Conclusion: This is the first study to provide mechanistic insights into how NFB may normalize dysfunctional brain activity and connectivity in PTSD under cognitive load with simultaneous symptom provocation, adding to a growing body of evidence supporting the therapeutic neuromodulatory effects of NFB. This preliminary study highlights the benefits of alpha-down NFB training as an adjunctive therapy for PTSD and warrants further investigation into its therapeutic effects on cognitive and emotion control in those with PTSD.
    MeSH term(s) Humans ; Stress Disorders, Post-Traumatic/diagnostic imaging ; Stress Disorders, Post-Traumatic/therapy ; Memory, Short-Term ; Neurofeedback ; Emotions ; Brain ; Magnetic Resonance Imaging/methods
    Language English
    Publishing date 2023-01-03
    Publishing country Netherlands
    Document type Randomized Controlled Trial ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2701571-3
    ISSN 2213-1582 ; 2213-1582
    ISSN (online) 2213-1582
    ISSN 2213-1582
    DOI 10.1016/j.nicl.2023.103313
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  3. Article ; Online: 'I am afraid you will see the stain on my soul': Direct gaze neural processing in individuals with PTSD after moral injury recall.

    Andrews, Krysta / Lloyd, Chantelle S / Densmore, Maria / Kearney, Breanne E / Harricharan, Sherain / McKinnon, Margaret C / Théberge, Jean / Jetly, Rakesh / Lanius, Ruth A

    Social cognitive and affective neuroscience

    2023  Volume 18, Issue 1

    Abstract: Direct eye contact is essential to understanding others' thoughts and feelings in social interactions. However, those with post-traumatic stress disorder (PTSD) and exposure to moral injury (MI) may exhibit altered theory-of-mind (ToM)/mentalizing ... ...

    Abstract Direct eye contact is essential to understanding others' thoughts and feelings in social interactions. However, those with post-traumatic stress disorder (PTSD) and exposure to moral injury (MI) may exhibit altered theory-of-mind (ToM)/mentalizing processes and experience shame which precludes one's capacity for direct eye contact. We investigated blood oxygenation level-dependent (BOLD) responses associated with direct vs averted gaze using a virtual reality paradigm in individuals with PTSD (n = 28) relative to healthy controls (n = 18) following recall of a MI vs a neutral memory. Associations between BOLD responses and clinical symptomatology were also assessed. After MI recall, individuals with PTSD showed greater activation in the right temporoparietal junction as compared to controls (T = 4.83; pFDR < 0.001; k = 237) during direct gaze. No significant activation occurred during direct gaze after neutral memory recall. Further, a significant positive correlation was found between feelings of distress and right medial superior frontal gyrus activation in individuals with PTSD (T = 5.03; pFDR = 0.049; k = 123). These findings suggest that direct gaze after MI recall prompts compensatory ToM/mentalizing processing. Implications for future interventions aimed at mitigating the effects of PTSD on social functioning are discussed.
    MeSH term(s) Humans ; Stress Disorders, Post-Traumatic ; Coloring Agents ; Emotions/physiology ; Mental Recall/physiology ; Myocardial Infarction ; Magnetic Resonance Imaging
    Chemical Substances Coloring Agents
    Language English
    Publishing date 2023-11-20
    Publishing country England
    Document type Journal Article
    ZDB-ID 2236933-8
    ISSN 1749-5024 ; 1749-5016
    ISSN (online) 1749-5024
    ISSN 1749-5016
    DOI 10.1093/scan/nsad053
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  4. Article ; Online: A randomized controlled trial of Deep Brain Reorienting: a neuroscientifically guided treatment for post-traumatic stress disorder.

    Kearney, Breanne E / Corrigan, Frank M / Frewen, Paul A / Nevill, Stephanie / Harricharan, Sherain / Andrews, Krysta / Jetly, Rakesh / McKinnon, Margaret C / Lanius, Ruth A

    European journal of psychotraumatology

    2023  Volume 14, Issue 2, Page(s) 2240691

    Abstract: Background: Advanced neuroscientific insights surrounding post-traumatic stress disorder (PTSD) and its associated symptomatology should beget psychotherapeutic treatments that integrate these insights into practice. Deep Brain Reorienting (DBR) is a ... ...

    Abstract Background: Advanced neuroscientific insights surrounding post-traumatic stress disorder (PTSD) and its associated symptomatology should beget psychotherapeutic treatments that integrate these insights into practice. Deep Brain Reorienting (DBR) is a neuroscientifically-guided psychotherapeutic intervention that targets the brainstem-level neurophysiological sequence that transpired during a traumatic event. Given that contemporary treatments have non-response rates of up to 50% and high drop-out rates of >18%, DBR is investigated as a putative candidate for effective treatment of some individuals with PTSD.
    Objective: To conduct an interim evaluation of the effectiveness of an eight-session clinical trial of videoconference-based DBR versus waitlist (WL) control for individuals with PTSD.
    Method: Fifty-four individuals with PTSD were randomly assigned to DBR (
    Results: Significant between-group differences in CAPS-total and all subscale scores (re-experiencing, avoidance, negative alterations in cognitions/mood, alterations in arousal/reactivity) were found at post-treatment (CAPS-total: Cohen's
    Conclusions: These findings provide emerging evidence for the effectiveness of DBR as a well-tolerated treatment that is based on theoretical advances highlighting alterations to subcortical mechanisms in PTSD and associated symptomatology. Additional research utilizing larger sample sizes, neuroimaging data, and comparisons or adjacencies with other psychotherapeutic approaches is warranted.
    MeSH term(s) Humans ; Stress Disorders, Post-Traumatic/diagnosis ; Treatment Outcome ; Waiting Lists ; Brain
    Language English
    Publishing date 2023-08-15
    Publishing country United States
    Document type Randomized Controlled Trial ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2586642-4
    ISSN 2000-8066 ; 2000-8066
    ISSN (online) 2000-8066
    ISSN 2000-8066
    DOI 10.1080/20008066.2023.2240691
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  5. Article: Overlapping frontoparietal networks in response to oculomotion and traumatic autobiographical memory retrieval: implications for eye movement desensitization and reprocessing.

    Harricharan, Sherain / McKinnon, Margaret C / Tursich, Mischa / Densmore, Maria / Frewen, Paul / Théberge, Jean / van der Kolk, Bessel / Lanius, Ruth A

    European journal of psychotraumatology

    2019  Volume 10, Issue 1, Page(s) 1586265

    Abstract: ... ...

    Abstract Background
    Language English
    Publishing date 2019-03-25
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2586642-4
    ISSN 2000-8066
    ISSN 2000-8066
    DOI 10.1080/20008198.2019.1586265
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  6. Article ; Online: Resting-state functional connectivity of the bed nucleus of the stria terminalis in post-traumatic stress disorder and its dissociative subtype.

    Rabellino, Daniela / Densmore, Maria / Harricharan, Sherain / Jean, Théberge / McKinnon, Margaret C / Lanius, Ruth A

    Human brain mapping

    2017  Volume 39, Issue 3, Page(s) 1367–1379

    Abstract: The bed nucleus of the stria terminals (BNST) is a subcortical structure involved in anticipatory and sustained reactivity to threat and is thus essential to the understanding of anxiety and stress responses. Although chronic stress and anxiety represent ...

    Abstract The bed nucleus of the stria terminals (BNST) is a subcortical structure involved in anticipatory and sustained reactivity to threat and is thus essential to the understanding of anxiety and stress responses. Although chronic stress and anxiety represent a hallmark of post-traumatic stress disorder (PTSD), to date, few studies have examined the functional connectivity of the BNST in PTSD. Here, we used resting state functional Magnetic Resonance Imaging (fMRI) to investigate the functional connectivity of the BNST in PTSD (n = 70), its dissociative subtype (PTSD + DS) (n = 41), and healthy controls (n = 50). In comparison to controls, PTSD showed increased functional connectivity of the BNST with regions of the reward system (ventral and dorsal striatum), possibly underlying stress-induced reward-seeking behaviors in PTSD. By contrast, comparing PTSD + DS to controls, we observed increased functional connectivity of the BNST with the claustrum, a brain region implicated in consciousness and a primary site of kappa-opioid receptors, which are critical to the dynorphin-mediated dysphoric stress response. Moreover, PTSD + DS showed increased functional connectivity of the BNST with brain regions involved in attention and salience detection (anterior insula and caudate nucleus) as compared to PTSD and controls. Finally, BNST functional connectivity positively correlated with default-mode network regions as a function of state identity dissociation, suggesting a role of BNST networks in the disruption of self-relevant processing characterizing the dissociative subtype. These findings represent an important first step in elucidating the role of the BNST in aberrant functional networks underlying PTSD and its dissociative subtype.
    MeSH term(s) Adult ; Brain Mapping ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Neural Pathways/diagnostic imaging ; Neural Pathways/physiopathology ; Rest ; Septal Nuclei/diagnostic imaging ; Septal Nuclei/physiopathology ; Stress Disorders, Post-Traumatic/diagnostic imaging ; Stress Disorders, Post-Traumatic/physiopathology
    Language English
    Publishing date 2017-12-20
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1197207-5
    ISSN 1097-0193 ; 1065-9471
    ISSN (online) 1097-0193
    ISSN 1065-9471
    DOI 10.1002/hbm.23925
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  7. Article ; Online: Superior colliculus resting state networks in post-traumatic stress disorder and its dissociative subtype.

    Olivé, Isadora / Densmore, Maria / Harricharan, Sherain / Théberge, Jean / McKinnon, Margaret C / Lanius, Ruth

    Human brain mapping

    2017  Volume 39, Issue 1, Page(s) 563–574

    Abstract: Objectives: The innate alarm system (IAS) models the neurocircuitry involved in threat processing in posttraumatic stress disorder (PTSD). Here, we investigate a primary subcortical structure of the IAS model, the superior colliculus (SC), where the SC ... ...

    Abstract Objectives: The innate alarm system (IAS) models the neurocircuitry involved in threat processing in posttraumatic stress disorder (PTSD). Here, we investigate a primary subcortical structure of the IAS model, the superior colliculus (SC), where the SC is thought to contribute to the mechanisms underlying threat-detection in PTSD. Critically, the functional connectivity between the SC and other nodes of the IAS remains unexplored.
    Experimental design: We conducted a resting-state fMRI study to investigate the functional architecture of the IAS, focusing on connectivity of the SC in PTSD (n = 67), its dissociative subtype (n = 41), and healthy controls (n = 50) using region-of-interest seed-based analysis.
    Principal observations: We observed group-specific resting state functional connectivity between the SC for both PTSD and its dissociative subtype, indicative of dedicated IAS collicular pathways in each group of patients. When comparing PTSD to its dissociative subtype, we observed increased resting state functional connectivity between the left SC and the right dorsolateral prefrontal cortex (DLPFC) in PTSD. The DLPFC is involved in modulation of emotional processes associated with active defensive responses characterising PTSD. Moreover, when comparing PTSD to its dissociative subtype, increased resting state functional connectivity was observed between the right SC and the right temporoparietal junction in the dissociative subtype. The temporoparietal junction is involved in depersonalization responses associated with passive defensive responses typical of the dissociative subtype.
    Conclusions: Our findings suggest that unique resting state functional connectivity of the SC parallels the unique symptom profile and defensive responses observed in PTSD and its dissociative subtype. Hum Brain Mapp 39:563-574, 2018. © 2017 Wiley Periodicals, Inc.
    MeSH term(s) Adult ; Analysis of Variance ; Brain Mapping ; Dissociative Disorders/diagnostic imaging ; Dissociative Disorders/physiopathology ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Neural Pathways/diagnostic imaging ; Neural Pathways/physiopathology ; Psychiatric Status Rating Scales ; Rest ; Stress Disorders, Post-Traumatic/diagnostic imaging ; Stress Disorders, Post-Traumatic/physiopathology ; Superior Colliculi/diagnostic imaging ; Superior Colliculi/physiopathology
    Language English
    Publishing date 2017-11-13
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1197207-5
    ISSN 1097-0193 ; 1065-9471
    ISSN (online) 1097-0193
    ISSN 1065-9471
    DOI 10.1002/hbm.23865
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  8. Article ; Online: The effects of trauma on brain and body: A unifying role for the midbrain periaqueductal gray.

    Terpou, Braeden A / Harricharan, Sherain / McKinnon, Margaret C / Frewen, Paul / Jetly, Rakesh / Lanius, Ruth A

    Journal of neuroscience research

    2019  Volume 97, Issue 9, Page(s) 1110–1140

    Abstract: Post-traumatic stress disorder (PTSD), a diagnosis that may follow the experience of trauma, has multiple symptomatic phenotypes. Generally, individuals with PTSD display symptoms of hyperarousal and of hyperemotionality in the presence of fearful ... ...

    Abstract Post-traumatic stress disorder (PTSD), a diagnosis that may follow the experience of trauma, has multiple symptomatic phenotypes. Generally, individuals with PTSD display symptoms of hyperarousal and of hyperemotionality in the presence of fearful stimuli. A subset of individuals with PTSD; however, elicit dissociative symptomatology (i.e., depersonalization, derealization) in the wake of a perceived threat. This pattern of response characterizes the dissociative subtype of the disorder, which is often associated with emotional numbing and hypoarousal. Both symptomatic phenotypes exhibit attentional threat biases, where threat stimuli are processed preferentially leading to a hypervigilant state that is thought to promote defensive behaviors during threat processing. Accordingly, PTSD and its dissociative subtype are thought to differ in their proclivity to elicit active (i.e., fight, flight) versus passive (i.e., tonic immobility, emotional shutdown) defensive responses, which are characterized by the increased and the decreased expression of the sympathetic nervous system, respectively. Moreover, active and passive defenses are accompanied by primarily endocannabinoid- and opioid-mediated analgesics, respectively. Through critical review of the literature, we apply the defense cascade model to better understand the pathological presentation of defensive responses in PTSD with a focus on the functioning of lower-level midbrain and extended brainstem systems.
    MeSH term(s) Brain/diagnostic imaging ; Dissociative Disorders ; Emotions ; Fear ; Humans ; Magnetic Resonance Imaging ; Male ; Periaqueductal Gray/physiopathology ; Stress Disorders, Post-Traumatic
    Language English
    Publishing date 2019-06-28
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 195324-2
    ISSN 1097-4547 ; 0360-4012
    ISSN (online) 1097-4547
    ISSN 0360-4012
    DOI 10.1002/jnr.24447
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  9. Article: Altered Sense of Body Ownership and Agency in Posttraumatic Stress Disorder and Its Dissociative Subtype: A Rubber Hand Illusion Study.

    Rabellino, Daniela / Burin, Dalila / Harricharan, Sherain / Lloyd, Chantelle / Frewen, Paul A / McKinnon, Margaret C / Lanius, Ruth A

    Frontiers in human neuroscience

    2018  Volume 12, Page(s) 163

    Abstract: Traumatic experiences have been linked to the development of altered states of consciousness affecting bodily perception, including alterations in body ownership and in sense of agency, the conscious experience of the body as one's own and under ... ...

    Abstract Traumatic experiences have been linked to the development of altered states of consciousness affecting bodily perception, including alterations in body ownership and in sense of agency, the conscious experience of the body as one's own and under voluntary control. Severe psychological trauma and prolonged distress may lead to posttraumatic stress disorder (PTSD). Together, symptoms of derealization and, related specifically to the sense of body ownership and agency, of depersonalization (where parts of the body or the entire body itself is perceived as detached and out of control), constitute the dissociative subtype (PTSD+DS). In this study, we explored the Rubber Hand Illusion, an experimental paradigm utilized to manipulate sense of body ownership in PTSD (
    Language English
    Publishing date 2018-05-01
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2425477-0
    ISSN 1662-5161
    ISSN 1662-5161
    DOI 10.3389/fnhum.2018.00163
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  10. Article ; Online: Classifying heterogeneous presentations of PTSD via the default mode, central executive, and salience networks with machine learning.

    Nicholson, Andrew A / Harricharan, Sherain / Densmore, Maria / Neufeld, Richard W J / Ros, Tomas / McKinnon, Margaret C / Frewen, Paul A / Théberge, Jean / Jetly, Rakesh / Pedlar, David / Lanius, Ruth A

    NeuroImage. Clinical

    2020  Volume 27, Page(s) 102262

    Abstract: Intrinsic connectivity networks (ICNs), including the default mode network (DMN), the central executive network (CEN), and the salience network (SN) have been shown to be aberrant in patients with posttraumatic stress disorder (PTSD). The purpose of the ... ...

    Abstract Intrinsic connectivity networks (ICNs), including the default mode network (DMN), the central executive network (CEN), and the salience network (SN) have been shown to be aberrant in patients with posttraumatic stress disorder (PTSD). The purpose of the current study was to a) compare ICN functional connectivity between PTSD, dissociative subtype PTSD (PTSD+DS) and healthy individuals; and b) to examine the use of multivariate machine learning algorithms in classifying PTSD, PTSD+DS, and healthy individuals based on ICN functional activation. Our neuroimaging dataset consisted of resting-state fMRI scans from 186 participants [PTSD (n = 81); PTSD + DS (n = 49); and healthy controls (n = 56)]. We performed group-level independent component analyses to evaluate functional connectivity differences within each ICN. Multiclass Gaussian Process Classification algorithms within PRoNTo software were then used to predict the diagnosis of PTSD, PTSD+DS, and healthy individuals based on ICN functional activation. When comparing the functional connectivity of ICNs between PTSD, PTSD+DS and healthy controls, we found differential patterns of connectivity to brain regions involved in emotion regulation, in addition to limbic structures and areas involved in self-referential processing, interoception, bodily self-consciousness, and depersonalization/derealization. Machine learning algorithms were able to predict with high accuracy the classification of PTSD, PTSD+DS, and healthy individuals based on ICN functional activation. Our results suggest that alterations within intrinsic connectivity networks may underlie unique psychopathology and symptom presentation among PTSD subtypes. Furthermore, the current findings substantiate the use of machine learning algorithms for classifying subtypes of PTSD illness based on ICNs.
    MeSH term(s) Adult ; Amygdala/physiopathology ; Brain/physiopathology ; Brain Mapping/methods ; Dissociative Disorders/physiopathology ; Emotions/physiology ; Female ; Humans ; Machine Learning ; Male ; Middle Aged ; Nerve Net/physiopathology ; Neural Pathways/physiopathology ; Stress Disorders, Post-Traumatic/physiopathology
    Language English
    Publishing date 2020-04-22
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2701571-3
    ISSN 2213-1582 ; 2213-1582
    ISSN (online) 2213-1582
    ISSN 2213-1582
    DOI 10.1016/j.nicl.2020.102262
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