Trauma-related altered states of consciousness: exploring the 4-D model.
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ABSTRACT:
SUBMITTER: Frewen PA
PROVIDER: S-EPMC4440663 | biostudies-other | 2014 July-September
REPOSITORIES: biostudies-other
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Project description:The primary aim of this commentary is to describe trauma-related dissociation and altered states of consciousness in the context of a four-dimensional model that has recently been proposed (Frewen & Lanius, 2015). This model categorizes symptoms of trauma-related psychopathology into (1) those that occur within normal waking consciousness and (2) those that are dissociative and are associated with trauma-related altered states of consciousness (TRASC) along four dimensions: (1) time; (2) thought; (3) body; and (4) emotion. Clinical applications and future research directions relevant to each dimension are discussed. Conceptualizing TRASC across the dimensions of time, thought, body, and emotion has transdiagnostic implications for trauma-related disorders described in both the Diagnostic Statistical Manual and the International Classifications of Diseases. The four-dimensional model provides a framework, guided by existing models of dissociation, for future research examining the phenomenological, neurobiological, and physiological underpinnings of trauma-related dissociation.
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Project description:Background: The four-dimensional ('4-D') model has been proposed as a theoretical framework to understand and delineate trauma-related dissociative experiences, categorizing symptoms into trauma-related altered states of consciousness (TRASC) and normal waking consciousness (NWC), which occur along four dimensions: time, thought, body and emotion. Objective: The main aim of the present study was to evaluate the validity of this model in patients with post-traumatic stress disorder (PTSD), with and without comorbid dissociative disorders. Method: The predictions of the 4-D model were tested in 142 patients with PTSD, with (N = 46) and without (N = 96) comorbid dissociative disorders. Results: As predicted by the 4-D model, experiences of TRASC were less frequent and more specifically related to other measures of dissociation, dissociative disorder comorbidity and a history of childhood sexual abuse compared to experiences of NWC. The predicted lower intercorrelation of TRASC was not supported. Conclusion: The 4-D model represents a promising framework for understanding dissociation across trauma-related disorders.
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Project description:BACKGROUND:Despite its designation as a 'dissociative anaesthetic,' the dissociative and psychoactive effects of ketamine remain incompletely understood. The goal of this study was to characterise the subjective experiences and accompanying EEG changes with subanaesthetic doses of ketamine. METHODS:High-density EEG was recorded in 15 human volunteers before, during, and after subanaesthetic ketamine infusion (0.5 mg kg-1 over 40 min), with self-reported measures of altered states of consciousness obtained after ketamine exposure. Sensor- and source-level EEG changes were analysed with a focus on spectral power and regional changes. RESULTS:Ketamine-induced altered states were characterised predominantly by dissociative experiences such as disembodiment and ego transcendence; sensory disturbances were also common. Ketamine broadly decreased low-frequency power, with mean reductions largest at alpha (8-12 Hz) in parietal (-0.94 dB, P<0.001) and occipital (-1.8 dB, P<0.001) channel clusters. Significant decreases in alpha were identified in the precuneus and temporal-parietal junction. CONCLUSIONS:Ketamine induces altered states of consciousness during periods of reduced alpha power in the precuneus and temporal-parietal junction. Modulation of these temporal-parietal loci are candidate mechanisms of the psychoactive effects of ketamine, given that this region is involved in multisensory integration, body representation, and consciousness.
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Project description:The OAV questionnaire has been developed to integrate research on altered states of consciousness (ASC). It measures three primary and one secondary dimensions of ASC that are hypothesized to be invariant across ASC induction methods. The OAV rating scale has been in use for more than 20 years and applied internationally in a broad range of research fields, yet its factorial structure has never been tested by structural equation modeling techniques and its psychometric properties have never been examined in large samples of experimentally induced ASC.The present study conducted a psychometric evaluation of the OAV in a sample of psilocybin (n = 327), ketamine (n = 162), and MDMA (n = 102) induced ASC that was obtained by pooling data from 43 experimental studies. The factorial structure was examined by confirmatory factor analysis, exploratory structural equation modeling, hierarchical item clustering (ICLUST), and multiple indicators multiple causes (MIMIC) modeling. The originally proposed model did not fit the data well even if zero-constraints on non-target factor loadings and residual correlations were relaxed. Furthermore, ICLUST suggested that the "oceanic boundlessness" and "visionary restructuralization" factors could be combined on a high level of the construct hierarchy. However, because these factors were multidimensional, we extracted and examined 11 new lower order factors. MIMIC modeling indicated that these factors were highly measurement invariant across drugs, settings, questionnaire versions, and sexes. The new factors were also demonstrated to have improved homogeneities, satisfactory reliabilities, discriminant and convergent validities, and to differentiate well among the three drug groups.The original scales of the OAV were shown to be multidimensional constructs. Eleven new lower order scales were constructed and demonstrated to have desirable psychometric properties. The new lower order scales are most likely better suited to assess drug induced ASC.
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Project description:Psychedelics exert unique effects on human consciousness. The thalamic filter model suggests that core effects of psychedelics may result from gating deficits, based on a disintegration of information processing within cortico-striato-thalamo-cortical (CSTC) feedback loops. To test this hypothesis, we characterized changes in directed (effective) connectivity between selected CTSC regions after acute administration of lysergic acid diethylamide (LSD), and after pretreatment with Ketanserin (a selective serotonin 2A receptor antagonist) plus LSD in a double-blind, randomized, placebo-controlled, cross-over study in 25 healthy participants. We used spectral dynamic causal modeling (DCM) for resting-state fMRI data. Fully connected DCM models were specified for each treatment condition to investigate the connectivity between the following areas: thalamus, ventral striatum, posterior cingulate cortex, and temporal cortex. Our results confirm major predictions proposed in the CSTC model and provide evidence that LSD alters effective connectivity within CSTC pathways that have been implicated in the gating of sensory and sensorimotor information to the cortex. In particular, LSD increased effective connectivity from the thalamus to the posterior cingulate cortex in a way that depended on serotonin 2A receptor activation, and decreased effective connectivity from the ventral striatum to the thalamus independently of serotonin 2A receptor activation. Together, these results advance our mechanistic understanding of the action of psychedelics in health and disease. This is important for the development of new pharmacological therapeutics and also increases our understanding of the mechanisms underlying the potential clinical efficacy of psychedelics.
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Project description:Ketamine commonly and rapidly induces dissociative and other altered states of consciousness (ASCs) in humans. However, the neural mechanisms that contribute to these experiences remain unknown. We used functional neuroimaging to engage key regions of the brain's affective circuits during acute ketamine-induced ASCs within a randomized, multi-modal, placebo-controlled design examining placebo, 0.05 mg/kg ketamine, and 0.5 mg/kg ketamine in nonclinical adult participants (NCT03475277). Licensed clinicians monitored infusions for safety. Linear mixed effects models, analysis of variance, t-tests, and mediation models were used for statistical analyses. Our design enabled us to test our pre-specified primary and secondary endpoints, which were met: effects of ketamine across dose conditions on (1) emotional task-evoked brain activity, and (2) sub-components of dissociation and other ASCs. With this design, we also could disentangle which ketamine-induced affective brain states are dependent upon specific aspects of ASCs. Differently valenced ketamine-induced ASCs mediated opposing effects on right anterior insula activity. Participants experiencing relatively higher depersonalization induced by 0.5 mg/kg of ketamine showed relief from negative brain states (reduced task-evoked right anterior insula activity, 0.39 SD). In contrast, participants experiencing dissociative amnesia showed an exacerbation of insula activity (0.32 SD). These results in nonclinical participants may shed light on the mechanisms by which specific dissociative states predict response to ketamine in depressed individuals.
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Project description:Near-death experiences (NDEs) including out-of-body experiences (OBEs) have been fascinating phenomena of perception both for affected persons and for communities in science and medicine. Modern progress in the recording of changing brain functions during the time between clinical death and brain death opened the perspective to address and understand the generation of NDEs in brain states of altered consciousness. Changes of consciousness can experimentally be induced in well-controlled clinical or laboratory settings. Reports of the persons having experienced the changes can inform about the similarity of the experiences with those from original NDEs. Thus, we collected neuro-functional models of NDEs including OBEs with experimental backgrounds of drug consumption, epilepsy, brain stimulation, and ischemic stress, and included so far largely unappreciated data from fighter pilot tests under gravitational stress generating cephalic nervous system ischemia. Since we found a large overlap of NDE themes or topics from original NDE reports with those from neuro-functional NDE models, we can state that, collectively, the models offer scientifically appropriate causal explanations for the occurrence of NDEs. The generation of OBEs, one of the NDE themes, can be localized in the temporo-parietal junction (TPJ) of the brain, a multimodal association area. The evaluated literature suggests that NDEs may emerge as hallucination-like phenomena from a brain in altered states of consciousness (ASCs).
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Project description:ImportanceGun violence represents a substantial public health issue, and firearm-related injuries rank second among the causes of injury-related deaths in children aged 0 to 17 years in the United States. Ocular trauma from firearm-related injuries can lead to devastating vision loss, but little is known to date about the specific demographics and characteristics of such injuries in children.ObjectiveTo evaluate the epidemiologic pattern of pediatric firearm-related ocular injuries.Design, setting, and participantsThis retrospective analysis used deidentified data from the National Trauma Data Bank, the largest national registry of hospitalized trauma cases in the United States. The firearm-related ocular injuries (n = 1972) of pediatric patients (defined as those younger than 21 years) hospitalized between January 1, 2008, and December 31, 2014, were analyzed. Statistical analyses were conducted from July 15, 2017, to June 15, 2019.ExposureFirearm-related ocular trauma.Main outcomes and measuresPediatric patients with firearm-related ocular injuries were identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes and external causes of injury codes. Patient demographics (age, sex, and race/ethnicity), type of ocular injury, injury intent, geographic location, length of hospital admission, health insurance status, disposition at discharge, Injury Severity Score (ISS), and Glasgow Coma Scale (GCS) score were collected.ResultsA total of 8715 firearm-related ocular injuries were identified. Of these injuries, 1972 (22.6%) occurred in pediatric patients, most of whom were male (1678 [85.1%]) and adolescents (1037 [52.6%]), with a mean (SD) age of 15.2 (5) years. Common locations of injury were home (761 [38.6%]) and street (490 [24.8%]). Mean (SD) hospital length of stay was 7.6 (12) days, ISS was 16 (13.1), and GCS score was 11 (5.1). The most common types of firearm-related ocular injuries were open wound of the eyeball (820 [41.6%]) and ocular adnexa (502 [25.5%]), orbital injuries or fractures (591 [30.0%]), and contusion of the eye or adnexa (417 [21.1%]). Patients aged 0 to 3 years had greater odds of unintentional injuries (odds ratio [OR], 4.41; 95% CI, 2.51-7.75; P < .001) and injuries occurring at home (OR, 5.39; 95% CI, 2.81-10.38; P < .001), and those aged 19 to 21 years had greater odds of assault injuries (OR, 2.17; 95% CI, 1.77-2.66; P < .001) and injuries occurring on the street (OR, 1.61; 95% CI, 1.3-1.98; P < .001). Black patients had the greatest odds of having injuries with assault intention (OR, 4.53; 95% CI, 3.68-5.59; P < .001), and white patients had the greatest likelihood for self-inflicted injury (OR, 7.1; 95% CI, 5.92-9.51; P < .001). Traumatic brain injury resulted mostly from self-inflicted trauma (OR, 5.99; 95% CI, 4.16-8.63; P < .001), as did visual pathway injuries (OR, 2.86; 95% CI, 1.95-4.20; P < .001). The inpatient mortality rate was 12.2%.Conclusions and relevanceThis study found that pediatric firearm-related ocular injuries from 2008 through 2014 were predominantly sight-threatening and associated with traumatic brain injury. If the possible risk factors, including sex, age, race/ethnicity, and injury intention, can be confirmed for 2015 through 2019, these findings may be useful in developing strategies to prevent pediatric firearm-related ocular injuries.
| S-EPMC6802038 | biostudies-literature
Project description:BackgroundLysergic acid diethylamide (LSD) has agonist activity at various serotonin (5-HT) and dopamine receptors. Despite the therapeutic and scientific interest in LSD, specific receptor contributions to its neurobiological effects remain unknown.MethodsWe therefore conducted a double-blind, randomized, counterbalanced, cross-over studyduring which 24 healthy human participants received either (i) placebo+placebo, (ii) placebo+LSD (100 µg po), or (iii) Ketanserin, a selective 5-HT2A receptor antagonist,+LSD. We quantified resting-state functional connectivity via a data-driven global brain connectivity method and compared it to cortical gene expression maps.ResultsLSD reduced associative, but concurrently increased sensory-somatomotor brain-wide and thalamic connectivity. Ketanserin fully blocked the subjective and neural LSD effects. Whole-brain spatial patterns of LSD effects matched 5-HT2A receptor cortical gene expression in humans.ConclusionsTogether, these results strongly implicate the 5-HT2A receptor in LSD’s neuropharmacology. This study therefore pinpoints the critical role of 5-HT2A in LSD’s mechanism, which informs its neurobiology and guides rational development of psychedelic-based therapeutics.FundingFunded by the Swiss National Science Foundation, the Swiss Neuromatrix Foundation, the Usona Institute, the NIH, the NIAA, the NARSAD Independent Investigator Grant, the Yale CTSA grant, and the Slovenian Research Agency.Clinical trial numberNCT02451072
| S-EPMC6202055 | biostudies-literature
Project description:BackgroundRegionalized trauma care improves outcomes; however, access to care is not uniform across the United States. The objective was to evaluate whether geographic distribution of trauma centers correlates with injury mortality across state trauma systems.MethodsLevel I or II trauma centers in the contiguous United States were mapped. State-level age-adjusted injury fatality rates per 100,000 people were obtained and evaluated for spatial autocorrelation. Nearest neighbor ratios (NNRs) were generated for each state. A NNR less than 1 indicates clustering, while a NNR greater than 1 indicates dispersion. NNRs were tested for difference from random geographic distribution. Fatality rates and NNRs were examined for correlation. Fatality rates were compared between states with trauma center clustering versus dispersion. Trauma center distribution and population density were evaluated. Spatial-lag regression determined the association between fatality rate and NNR, controlling for state-level demographics, population density, injury severity, trauma system resources, and socioeconomic factors.ResultsFatality rates were spatially autocorrelated (Moran's I = 0.35, p < 0.01). Nine states had a clustered pattern (median NNR, 0.55; interquartile range [IQR], 0.48-0.60), 22 had a dispersed pattern (median NNR, 2.00; IQR, 1.68-3.99), and 10 had a random pattern (median NNR, 0.90; IQR, 0.85-1.00) of trauma center distribution. Fatality rate and NNR were correlated (ρ = 0.34, p = 0.03). Clustered states had a lower median injury fatality rate compared with dispersed states (56.9 [IQR, 46.5-58.9] vs. 64.9 [IQR, 52.5-77.1]; p = 0.04). Dispersed compared with clustered states had more counties without a trauma center that had higher population density than counties with a trauma center (5.7% vs. 1.2%, p < 0.01). Spatial-lag regression demonstrated that fatality rates increased by 0.02 per 100,000 persons for each unit increase in NNR (p < 0.01).ConclusionGeographic distribution of trauma centers correlates with injury mortality, with more clustered state trauma centers associated with lower fatality rates. This may be a result of access relative to population density. These results may have implications for trauma system planning and require further study to investigate underlying mechanisms.Level of evidenceTherapeutic/care management study, level IV.
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