Abstract The insula and amygdala are implicated in the pathophysiology of posttraumatic stress disorder (PTSD), where both have been shown to be hyper/hypoactive in non-dissociative (PTSD-DS) and ...dissociative subtype (PTSD+DS) PTSD patients, respectively, during symptom provocation. However, the functional connectivity between individual insula subregions and the amygdala has not been investigated in persons with PTSD, with or without the dissociative subtype. We examined insula subregion (anterior, mid, and posterior) functional connectivity with the bilateral amygdala using a region-of-interest seed-based approach via PickAtlas and SPM8. Resting-state fMRI was conducted with ( n =61) PTSD patients ( n =44 PTSD-DS; n =17 PTSD+DS), and ( n =40) age-matched healthy controls. When compared to controls, the PTSD-DS group displayed increased insula connectivity (bilateral anterior, bilateral mid, and left posterior) to basolateral amygdala clusters in both hemispheres, and the PTSD+DS group displayed increased insula connectivity (bilateral anterior, left mid, and left posterior) to the left basolateral amygdala complex. Moreover, as compared to PTSD-DS, increased insula subregion connectivity (bilateral anterior, left mid, and right posterior) to the left basolateral amygdala was found in PTSD+DS. Depersonalization/derealization symptoms and PTSD symptom severity correlated with insula subregion connectivity to the basolateral amygdala within PTSD patients. This study is an important first step in elucidating patterns of neural connectivity associated with unique symptoms of arousal/interoception, emotional processing, and awareness of bodily states, in PTSD and its dissociative subtype.
•Hyperconnectivity of Sensorimotor and posterior Default Mode Networks during Moral Injury Retrieval in PTSD.•Enhanced and expanded functional connectivity of Sensorimotor Network during Moral Injury ...Retrieval in PTSD.•Higher subjective re-experiencing intensity reported in PTSD during Moral Injury retrieval.•Supramarginal gyrus may be a hub for re-experiencing/re-enactment processes in MI-related traumatic memory.
Neural representations of sensory percepts and motor responses constitute key elements of autobiographical memory. However, these representations may remain as unintegrated sensory and motor fragments in traumatic memory, thus contributing toward re-experiencing and reliving symptoms in trauma-related conditions such as post-traumatic stress disorder (PTSD). Here, we investigated the sensorimotor network (SMN) and posterior default mode network (pDMN) using a group independent component analysis (ICA) by examining their functional connectivity during a script-driven memory retrieval paradigm of (potentially) morally injurious events in individuals with PTSD and healthy controls. Moral injury (MI), where an individual acts or fails to act in a morally aligned manner, is examined given its inherent ties to disrupted motor planning and thus sensorimotor mechanisms. Our findings revealed significant differences in functional network connectivity across the SMN and pDMN during MI retrieval in participants with PTSD (n = 65) as compared to healthy controls (n = 25). No such significant group-wise differences emerged during retrieval of a neutral memory. PTSD-related alterations included hyperconnectivity between the SMN and pDMN, enhanced within-network connectivity of the SMN with premotor areas, and increased recruitment of the supramarginal gyrus into both the SMN and the pDMN during MI retrieval. In parallel with these neuroimaging findings, a positive correlation was found between PTSD severity and subjective re-experiencing intensity ratings after MI retrieval. These results suggest a neural basis for traumatic re-experiencing, where reliving and/or re-enacting a past morally injurious event in the form of sensory and motor fragments occurs in place of retrieving a complete, past-contextualized narrative as put forth by Brewin and colleagues (1996) and Conway and Pleydell-Pearce (2000). These findings have implications for bottom-up treatments targeting directly the sensory and motoric elements of traumatic experiences.
The 'default mode network' is a set of brain regions showing correlated, low-frequency activity during rest. It includes the posterior cingulate/precuneus, medial prefrontal cortex, and bilateral ...inferior parietal cortex. Earlier studies have characterized this network using either region of interest-based correlation analyses or data-driven techniques; however, there is some disagreement over which method is superior. We conducted both types of analysis on a large (N=40) data set and also investigated age and sex differences in the network. Both region of interest-based analyses and independent component analysis identified the default mode network. Age and sex differences were small and there was less agreement between analytic techniques regarding age and sex effects than regarding default mode network structure.
Electroencephalogram (EEG) neurofeedback aimed at reducing the amplitude of the alpha-rhythm has been shown to alter neural networks associated with posttraumatic stress disorder (PTSD), leading to ...symptom alleviation. Critically, the amygdala is thought to be one of the central brain regions mediating PTSD symptoms. In the current study, we compare directly patterns of amygdala complex connectivity using fMRI, before and after EEG neurofeedback, in order to observe subcortical mechanisms associated with behavioural and alpha oscillatory changes among patients.
We examined basolateral (BLA), centromedial (CMA), and superficial (SFA) amygdala complex resting-state functional connectivity using a seed-based approach via SPM Anatomy Toolbox. Amygdala complex connectivity was measured in twenty-one individuals with PTSD, before and after a 30-minute session of EEG neurofeedback targeting alpha desynchronization.
EEG neurofeedback was associated with a shift in amygdala complex connectivity from areas implicated in defensive, emotional, and fear processing/memory retrieval (left BLA and left SFA to the periaqueductal gray, and left SFA to the left hippocampus) to prefrontal areas implicated in emotion regulation/modulation (right CMA to the medial prefrontal cortex). This shift in amygdala complex connectivity was associated with reduced arousal, greater resting alpha synchronization, and was negatively correlated to PTSD symptom severity.
These findings have significant implications for developing targeted non-invasive treatment interventions for PTSD patients that utilize alpha oscillatory neurofeedback, showing evidence of neuronal reconfiguration between areas highly implicated in the disorder, in addition to acute symptom alleviation.
•EEG microstates reveal significant temporal differences in PTSD.•Microstate E (with centro-posterior maximum) is temporally underrepresented in PTSD.•In PTSD, microstate E has a reduced occurrence ...and a shorter mean duration.•Spectral decomposition of EEG microstates improves microstate-based classification.•Alpha band SVM features yield the highest classification accuracy of PTSD (76%).
Microstates offer a promising framework to study fast-scale brain dynamics in the resting-state electroencephalogram (EEG). However, microstate dynamics have yet to be investigated in post-traumatic stress disorder (PTSD), despite research demonstrating resting-state alterations in PTSD. We performed microstate-based segmentation of resting-state EEG in a clinical population of participants with PTSD (N = 61) and a non-traumatized, healthy control group (N = 61). Microstate-based measures (i.e., occurrence, mean duration, time coverage) were compared group-wise using broadband (1–30 Hz) and frequency-specific (i.e., delta, theta, alpha, beta bands) decompositions. In the broadband comparisons, the centro-posterior maximum microstate (map E) occurred significantly less frequently (d = -0.64, pFWE = 0.03) and had a significantly shorter mean duration in participants with PTSD as compared to controls (d = -0.71, pFWE < 0.01). These differences were reflected in the narrow frequency bands as well, with lower frequency bands like delta (d = -0.78, pFWE < 0.01), theta (d = -0.74, pFWE = 0.01), and alpha (d = -0.65, pFWE = 0.02) repeating these group-level trends, only with larger effect sizes. Interestingly, a support vector machine classification analysis comparing broadband and frequency-specific measures revealed that models containing only alpha band features significantly out-perform broadband models. When classifying PTSD, the classification accuracy was 76 % and 65 % for the alpha band and the broadband model, respectively (p = 0.03). Taken together, we provide original evidence supporting the clinical utility of microstates as diagnostic markers of PTSD and demonstrate that filtering EEG into distinct frequency bands significantly improves microstate-based classification of a psychiatric disorder.
Spontaneous low-frequency fluctuations in the blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (MRI) signal have been shown to reflect neural synchrony between brain regions. ...A "default network" of spontaneous low-frequency fluctuations has been described in healthy volunteers during stimulus-independent thought. Negatively correlated with this network are regions activated during attention-demanding tasks. Both these networks involve brain regions and functions that have been linked with schizophrenia in previous research. The present study examined spontaneous slow fluctuations in the BOLD signal at rest, as measured by correlation with low-frequency oscillations in the posterior cingulate, in 17 schizophrenic patients, and 17 comparable healthy volunteers. Healthy volunteers demonstrated correlation between spontaneous low-frequency fluctuations of the BOLD signal in the posterior cingulate and fluctuations in the lateral parietal, medial prefrontal, and cerebellar regions, similar to previous reports. Schizophrenic patients had significantly less correlation between spontaneous slow activity in the posterior cingulate and that in the lateral parietal, medial prefrontal, and cerebellar regions. Connectivity of the posterior cingulate was found to vary with both positive and negative symptoms in schizophrenic patients. Because these data suggest significant abnormalities in resting-state neural networks in schizophrenia, further investigations of spontaneous slow fluctuations of the BOLD signal seem warranted in this population.
Posttraumatic stress disorder (PTSD) has been associated with a disturbance in neural intrinsic connectivity networks (ICN), including the central executive network (CEN), default mode network (DMN), ...and salience network (SN). Here, we conducted a preliminary investigation examining potential changes in ICN recruitment as a function of real‐time fMRI neurofeedback (rt‐fMRI‐NFB) during symptom provocation where we targeted the downregulation of neural response within the amygdala—a key region‐of‐interest in PTSD neuropathophysiology. Patients with PTSD (n = 14) completed three sessions of rt‐fMRI‐NFB with the following conditions: (a) regulate: decrease activation in the amygdala while processing personalized trauma words; (b) view: process trauma words while not attempting to regulate the amygdala; and (c) neutral: process neutral words. We found that recruitment of the left CEN increased over neurofeedback runs during the regulate condition, a finding supported by increased dlPFC activation during the regulate as compared to the view condition. In contrast, DMN task‐negative recruitment was stable during neurofeedback runs, albeit was the highest during view conditions and increased (normalized) during rest periods. Critically, SN recruitment was high for both the regulate and the view conditions, a finding potentially indicative of CEN modality switching, adaptive learning, and increasing threat/defense processing in PTSD. In conclusion, this study provides provocative, preliminary evidence that downregulation of the amygdala using rt‐fMRI‐NFB in PTSD is associated with dynamic changes in ICN, an effect similar to those observed using EEG modalities of neurofeedback.
Background
Posttraumatic stress disorder (PTSD) is associated with hyperarousal and active fight or flight defensive responses. By contrast, the dissociative subtype of PTSD, characterized by ...depersonalization and derealization symptoms, is frequently accompanied by additional passive or submissive defensive responses associated with autonomic blunting. Here, the periaqueductal gray (PAG) plays a central role in defensive responses, where the dorsolateral (DL‐PAG) and ventrolateral PAG (VL‐PAG) are thought to mediate active and passive defensive responses, respectively.
Methods
We examined PAG subregion (dorsolateral and ventrolateral) resting‐state functional connectivity in three groups: PTSD patients without the dissociative subtype (n = 60); PTSD patients with the dissociative subtype (n = 37); and healthy controls (n = 40) using a seed‐based approach via PickAtlas and SPM12.
Results
All PTSD patients showed extensive DL‐ and VL‐PAG functional connectivity at rest with areas associated with emotional reactivity and defensive action as compared to controls (n = 40). Although all PTSD patients demonstrated DL‐PAG functional connectivity with areas associated with initiation of active coping strategies and hyperarousal (e.g., dorsal anterior cingulate; anterior insula), only dissociative PTSD patients exhibited greater VL‐PAG functional connectivity with brain regions linked to passive coping strategies and increased levels of depersonalization (e.g., temporoparietal junction; rolandic operculum).
Conclusions
These findings suggest greater defensive posturing in PTSD patients even at rest and demonstrate that those with the dissociative subtype show unique patterns of PAG functional connectivity when compared to those without the subtype. Taken together, these findings represent an important first step toward identifying neural and behavioral targets for therapeutic interventions that address defensive strategies in trauma‐related disorders.
Posttraumatic stress disorder patients exhibited widespread periaqueductal gray functional connectivity during resting state, which may suggest the presence of greater defensive posturing at rest in these patients. Furthermore, those with the dissociative subtype of PTSD demonstrated unique functional connectivity patterns of the periaqueductal gray, with notable differences in connectivity between the dorsolateral and ventrolateral subdivisions.
Background
Intrinsic connectivity networks, including the default mode network (DMN), are frequently disrupted in individuals with posttraumatic stress disorder (PTSD). The posterior cingulate cortex ...(PCC) is the main hub of the posterior DMN, where the therapeutic regulation of this region with real‐time fMRI neurofeedback (NFB) has yet to be explored.
Methods
We investigated PCC downregulation while processing trauma/stressful words over 3 NFB training runs and a transfer run without NFB (total n = 29, PTSD n = 14, healthy controls n = 15). We also examined the predictive accuracy of machine learning models in classifying PTSD versus healthy controls during NFB training.
Results
Both the PTSD and healthy control groups demonstrated reduced reliving symptoms in response to trauma/stressful stimuli, where the PTSD group additionally showed reduced symptoms of distress. We found that both groups were able to downregulate the PCC with similar success over NFB training and in the transfer run, although downregulation was associated with unique within‐group decreases in activation within the bilateral dmPFC, bilateral postcentral gyrus, right amygdala/hippocampus, cingulate cortex, and bilateral temporal pole/gyri. By contrast, downregulation was associated with increased activation in the right dlPFC among healthy controls as compared to PTSD. During PCC downregulation, right dlPFC activation was negatively correlated to PTSD symptom severity scores and difficulties in emotion regulation. Finally, machine learning algorithms were able to classify PTSD versus healthy participants based on brain activation during NFB training with 80% accuracy.
Conclusions
This is the first study to investigate PCC downregulation with real‐time fMRI NFB in both PTSD and healthy controls. Our results reveal acute decreases in symptoms over training and provide converging evidence for EEG‐NFB targeting brain networks linked to the PCC.
This is the first study to investigate PCC downregulation with real‐time fMRI NFB in both PTSD and healthy controls. Our results reveal acute decreases in symptoms over training and provide converging evidence for EEG‐NFB targeting brain networks linked to the PCC.
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