RESUMO
Trauma-related intrusive memories (TR-IMs) possess unique phenomenological properties that contribute to adverse post-traumatic outcomes, positioning them as critical intervention targets. However, transdiagnostic treatments for TR-IMs are scarce, as their underlying mechanisms have been investigated separate from their unique phenomenological properties. Extant models of more general episodic memory highlight dynamic hippocampal-cortical interactions that vary along the anterior-posterior axis of the hippocampus (HPC) to support different cognitive-affective and sensory-perceptual features of memory. Extending this work into the unique properties of TR-IMs, we conducted a study of eighty-four trauma-exposed adults who completed daily ecological momentary assessments of TR-IM properties followed by resting-state functional magnetic resonance imaging (rs-fMRI). Spatiotemporal dynamics of anterior and posterior hippocampal (a/pHPC)-cortical networks were assessed using co-activation pattern analysis to investigate their associations with different properties of TR-IMs. Emotional intensity of TR-IMs was inversely associated with the frequency and persistence of an aHPC-default mode network co-activation pattern. Conversely, sensory features of TR-IMs were associated with more frequent co-activation of the HPC with sensory cortices and the ventral attention network, and the reliving of TR-IMs in the "here-and-now" was associated with more persistent co-activation of the pHPC and the visual cortex. Notably, no associations were found between HPC-cortical network dynamics and conventional symptom measures, including TR-IM frequency or retrospective recall, underscoring the utility of ecological assessments of memory properties in identifying their neural substrates. These findings provide novel insights into the neural correlates of the unique features of TR-IMs that are critical for the development of individualized, transdiagnostic treatments for this pervasive, difficult-to-treat symptom.
RESUMO
The default mode network (DMN) is the most-prominent intrinsic connectivity network, serving as a key architecture of the brain's functional organization. Conversely, dysregulated DMN is characteristic of major neuropsychiatric disorders. However, the field still lacks mechanistic insights into the regulation of the DMN and effective interventions for DMN dysregulation. The current study approached this problem by manipulating neural synchrony, particularly alpha (8 to 12 Hz) oscillations, a dominant intrinsic oscillatory activity that has been increasingly associated with the DMN in both function and physiology. Using high-definition alpha-frequency transcranial alternating current stimulation (α-tACS) to stimulate the cortical source of alpha oscillations, in combination with simultaneous electroencephalography and functional MRI (EEG-fMRI), we demonstrated that α-tACS (versus Sham control) not only augmented EEG alpha oscillations but also strengthened fMRI and (source-level) alpha connectivity within the core of the DMN. Importantly, increase in alpha oscillations mediated the DMN connectivity enhancement. These findings thus identify a mechanistic link between alpha oscillations and DMN functioning. That transcranial alpha modulation can up-regulate the DMN further highlights an effective noninvasive intervention to normalize DMN functioning in various disorders.
Assuntos
Encéfalo/fisiologia , Rede de Modo Padrão , Rede Nervosa/fisiologia , Regulação para Cima , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Eletroencefalografia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Estimulação Transcraniana por Corrente Contínua , Adulto JovemRESUMO
Synthetic Biology Open Language (SBOL) Visual is a graphical standard for genetic engineering. It consists of symbols representing DNA subsequences, including regulatory elements and DNA assembly features. These symbols can be used to draw illustrations for communication and instruction, and as image assets for computer-aided design. SBOL Visual is a community standard, freely available for personal, academic, and commercial use (Creative Commons CC0 license). We provide prototypical symbol images that have been used in scientific publications and software tools. We encourage users to use and modify them freely, and to join the SBOL Visual community: http://www.sbolstandard.org/visual.
Assuntos
Cromatina/química , DNA/química , Engenharia Genética/métodos , Modelos Genéticos , Simbolismo , Animais , Cromatina/metabolismo , Montagem e Desmontagem da Cromatina , Desenho Assistido por Computador , Comportamento Cooperativo , DNA/metabolismo , Bases de Dados de Ácidos Nucleicos , Engenharia Genética/normas , Engenharia Genética/tendências , Humanos , Internet , Motivos de Nucleotídeos , Publicações , Sequências Reguladoras de Ácido Nucleico , SoftwareRESUMO
Post-traumatic stress disorder is characterized by exaggerated threat response, and theoretical accounts to date have focused on impaired threat processing and dysregulated prefrontal-cortex-amygdala circuitry. Nevertheless, evidence is accruing for broad, threat-neutral sensory hyperactivity in post-traumatic stress disorder. As low-level, sensory processing impacts higher-order operations, such sensory anomalies can contribute to widespread dysfunctions, presenting an additional aetiological mechanism for post-traumatic stress disorder. To elucidate a sensory pathology of post-traumatic stress disorder, we examined intrinsic visual cortical activity (based on posterior alpha oscillations) and bottom-up sensory-driven causal connectivity (Granger causality in the alpha band) during a resting state (eyes open) and a passive, serial picture viewing state. Compared to patients with generalized anxiety disorder (n = 24) and healthy control subjects (n = 20), patients with post-traumatic stress disorder (n = 25) demonstrated intrinsic sensory hyperactivity (suppressed posterior alpha power, source-localized to the visual cortex-cuneus and precuneus) and bottom-up inhibition deficits (reduced posteriorâfrontal Granger causality). As sensory input increased from resting to passive picture viewing, patients with post-traumatic stress disorder failed to demonstrate alpha adaptation, highlighting a rigid, set mode of sensory hyperactivity. Interestingly, patients with post-traumatic stress disorder also showed heightened frontal processing (augmented frontal gamma power, source-localized to the superior frontal gyrus and dorsal cingulate cortex), accompanied by attenuated top-down inhibition (reduced frontalâposterior causality). Importantly, not only did suppressed alpha power and bottom-up causality correlate with heightened frontal gamma power, they also correlated with increased severity of sensory and executive dysfunctions (i.e. hypervigilance and impulse control deficits, respectively). Therefore, sensory aberrations help construct a vicious cycle in post-traumatic stress disorder that is in action even at rest, implicating dysregulated triangular sensory-prefrontal-cortex-amygdala circuitry: intrinsic sensory hyperactivity and disinhibition give rise to frontal overload and disrupt executive control, fuelling and perpetuating post-traumatic stress disorder symptoms. Absent in generalized anxiety disorder, these aberrations highlight a unique sensory pathology of post-traumatic stress disorder (ruling out effects merely reflecting anxious hyperarousal), motivating new interventions targeting sensory processing and the sensory brain in these patients.
Assuntos
Inibição Neural/fisiologia , Descanso/fisiologia , Transtornos de Sensação/fisiopatologia , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Córtex Visual/fisiopatologia , Adulto , Ritmo alfa/fisiologia , Transtornos de Ansiedade/fisiopatologia , Estudos de Casos e Controles , Função Executiva/fisiologia , Feminino , Lobo Frontal/fisiopatologia , Ritmo Gama/fisiologia , Giro do Cíngulo/fisiopatologia , Humanos , Masculino , Estimulação Luminosa , Transtornos de Sensação/complicações , Transtornos de Estresse Pós-Traumáticos/complicações , Percepção Visual/fisiologia , Adulto JovemRESUMO
Large genetic engineering projects require more cistrons and consequently more strong and reliable transcriptional terminators. We have measured the strengths of a library of terminators, including 227 that are annotated in Escherichia coli--90 of which we also tested in the reverse orientation--and 265 synthetic terminators. Within this library we found 39 strong terminators, yielding >50-fold reduction in downstream expression, that have sufficient sequence diversity to reduce homologous recombination when used together in a design. We used these data to determine how the terminator sequence contributes to its strength. The dominant parameters were incorporated into a biophysical model that considers the role of the hairpin in the displacement of the U-tract from the DNA. The availability of many terminators of varying strength, as well as an understanding of the sequence dependence of their properties, will extend their usability in the forward design of synthetic cistrons.
Assuntos
DNA Bacteriano/genética , Escherichia coli/genética , Biologia Sintética/métodos , Regiões Terminadoras Genéticas/genética , Sequência de Bases , Dados de Sequência MolecularRESUMO
Genetic circuits perform computational operations based on interactions between freely diffusing molecules within a cell. When transcription factors are combined to build a circuit, unintended interactions can disrupt its function. Here, we apply 'part mining' to build a library of 73 TetR-family repressors gleaned from prokaryotic genomes. The operators of a subset were determined using an in vitro method, and this information was used to build synthetic promoters. The promoters and repressors were screened for cross-reactions. Of these, 16 were identified that both strongly repress their cognate promoter (5- to 207-fold) and exhibit minimal interactions with other promoters. Each repressor-promoter pair was converted to a NOT gate and characterized. Used as a set of 16 NOT/NOR gates, there are >10(54) circuits that could be built by changing the pattern of input and output promoters. This represents a large set of compatible gates that can be used to construct user-defined circuits.
Assuntos
Genômica , Células Procarióticas , Proteínas Repressoras/genética , Bibliotecas de Moléculas Pequenas , Sequência de Bases , Redes Reguladoras de Genes/genética , Genoma Bacteriano/genética , Regiões Operadoras Genéticas , Regiões Promotoras Genéticas/genéticaRESUMO
Cells react to their environment through gene regulatory networks. Network integrity requires minimization of undesired crosstalk between their biomolecules. Similar constraints also limit the use of regulators when building synthetic circuits for engineering applications. Here, we mapped the promoter specificities of extracytoplasmic function (ECF) σs as well as the specificity of their interaction with anti-σs. DNA synthesis was used to build 86 ECF σs (two from every subgroup), their promoters, and 62 anti-σs identified from the genomes of diverse bacteria. A subset of 20 σs and promoters were found to be highly orthogonal to each other. This set can be increased by combining the -35 and -10 binding domains from different subgroups to build chimeras that target sequences unrepresented in any subgroup. The orthogonal σs, anti-σs, and promoters were used to build synthetic genetic switches in Escherichia coli. This represents a genome-scale resource of the properties of ECF σs and a resource for synthetic biology, where this set of well-characterized regulatory parts will enable the construction of sophisticated gene expression programs.
Assuntos
Proteínas de Escherichia coli/genética , Escherichia coli/genética , Regulação Bacteriana da Expressão Gênica , Genes de Troca , Regiões Promotoras Genéticas , Fator sigma/genética , Mineração de Dados , Escherichia coli/metabolismo , Proteínas de Escherichia coli/metabolismo , Engenharia Genética , Modelos Genéticos , Filogenia , Ligação Proteica , Fator sigma/metabolismo , Transcrição GênicaRESUMO
Posttraumatic stress disorder (PTSD) is widely recognized as involving disruption of core neurocircuitry that underlies processing, regulation, and response to threat. In particular, the prefrontal cortex-hippocampal-amygdala circuit is a major contributor to posttraumatic dysfunction. However, the functioning of core threat neurocircuitry is partially dependent on sensorial inputs, and previous research has demonstrated that dense, reciprocal connections exist between threat circuits and the ventral visual stream. Furthermore, emergent evidence suggests that trauma exposure and resultant PTSD symptoms are associated with altered structure and function of the ventral visual stream. In the current review, we discuss evidence that both threat and visual circuitry together are an integral part of PTSD pathogenesis. An overview of the relevance of visual processing to PTSD is discussed in the context of both basic and translational research, highlighting the impact of stress on affective visual circuitry. This review further synthesizes emergent literature to suggest potential timing-dependent effects of traumatic stress on threat and visual circuits that may contribute to PTSD development. We conclude with recommendations for future research to move the field toward a more complete understanding of PTSD neurobiology.
RESUMO
As the global prevalence of trauma rises, there is a growing need for accessible and scalable treatments for trauma-related disorders like posttraumatic stress disorder (PTSD). Trauma-related intrusive memories (TR-IMs) are a central PTSD symptom and a target of exposure-based therapies, gold-standard treatments that are effective but resource-intensive. This study examined whether a brief ecological momentary assessment (EMA) protocol assessing the phenomenology of TR-IMs could reduce intrusion symptoms in trauma-exposed adults. Participants (N=131) experiencing at least 2 TR-IMs per week related to a DSM-5 criterion A trauma completed a 2-week EMA protocol during which they reported on TR-IM properties three times per day, and on posttraumatic stress symptoms at the end of each day. Longitudinal symptom measurements were entered into linear mixed-effects models to test the effect of Time on TR-IMs. Over the 2-week EMA protocol, intrusion symptom severity (cluster B scores) significantly declined (t = -2.78, p = 0.006), while other symptom cluster scores did not significantly change. Follow-up analyses demonstrated that this effect was specific to TR-IMs (t = -4.02, p < 0.001), and was not moderated by survey completion rate, total PTSD symptom severity, or ongoing treatment. Our findings indicate that implementing an EMA protocol assessing intrusive memories could be an effective trauma intervention. Despite study limitations like its quasi-experimental design and absence of a control group, the specificity of findings to intrusive memories argues against a mere regression to the mean. Overall, an EMA approach could provide a cost-effective and scalable treatment option targeting intrusive memory symptoms.
RESUMO
Trauma-related intrusive memories (TR-IMs) are hallmark symptoms of posttraumatic stress disorder (PTSD), but their neural correlates remain partly unknown. Given its role in autobiographical memory, the hippocampus may play a critical role in TR-IM neurophysiology. The anterior and posterior hippocampi are known to have partially distinct functions, including during retrieval of autobiographical memories. This study aimed to investigate the relationship between TR-IM frequency and the anterior and posterior hippocampi morphology in PTSD. Ninety-three trauma-exposed adults completed daily ecological momentary assessments for fourteen days to capture their TR-IM frequency. Participants then underwent anatomical magnetic resonance imaging to obtain measures of anterior and posterior hippocampal volumes. Partial least squares analysis was applied to identify a structural covariance network that differentiated the anterior and posterior hippocampi. Poisson regression models examined the relationship of TR-IM frequency with anterior and posterior hippocampal volumes and the resulting structural covariance network. Results revealed no significant relationship of TR-IM frequency with hippocampal volumes. However, TR-IM frequency was significantly negatively correlated with the expression of a structural covariance pattern specifically associated with the anterior hippocampus volume. This association remained significant after accounting for the severity of PTSD symptoms other than intrusion symptoms. The network included the bilateral inferior temporal gyri, superior frontal gyri, precuneus, and fusiform gyri. These novel findings indicate that higher TR-IM frequency in individuals with PTSD is associated with lower structural covariance between the anterior hippocampus and other brain regions involved in autobiographical memory, shedding light on the neural correlates underlying this core symptom of PTSD.
Assuntos
Transtornos de Estresse Pós-Traumáticos , Adulto , Humanos , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Avaliação Momentânea Ecológica , Encéfalo/patologia , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Córtex Pré-Frontal/patologia , Imageamento por Ressonância Magnética/métodosRESUMO
The brain operates an advanced complex system to support mental activities. Cognition is thought to emerge from dynamic states of the complex brain system, which are organized spatially through large-scale neural networks and temporally via neural synchrony. However, specific mechanisms underlying these processes remain obscure. Applying high-definition alpha-frequency transcranial alternating-current stimulation (HD α-tACS) in a continuous performance task (CPT) during functional resonance imaging (fMRI), we causally elucidate these major organizational architectures in a key cognitive operation-sustained attention. We demonstrated that α-tACS enhanced both electroencephalogram (EEG) alpha power and sustained attention, in a correlated fashion. Akin to temporal fluctuations inherent in sustained attention, our hidden Markov modeling (HMM) of fMRI timeseries uncovered several recurrent, dynamic brain states, which were organized through a few major neural networks and regulated by the alpha oscillation. Specifically, during sustain attention, α-tACS regulated the temporal dynamics of the brain states by suppressing a Task-Negative state (characterized by activation of the default mode network/DMN) and Distraction state (with activation of the ventral attention and visual networks). These findings thus linked dynamic states of major neural networks and alpha oscillations, providing important insights into systems-level mechanisms of attention. They also highlight the efficacy of non-invasive oscillatory neuromodulation in probing the functioning of the complex brain system and encourage future clinical applications to improve neural systems health and cognitive performance.
RESUMO
The pituitary adenylate cyclase-activating polypeptide (PACAP) system is implicated in posttraumatic stress disorder (PTSD) and related amygdala-mediated arousal and threat reactivity. PTSD is characterized by increased amygdala reactivity to threat and, more recently, aberrant intrinsic connectivity of the amygdala with large-scale resting state networks, specifically the default mode network (DMN). While the influence of PACAP on amygdala reactivity has been described, its association with intrinsic amygdala connectivity remains unknown. To fill this gap, we examined functional connectivity of resting-state functional magnetic resonance imaging (fMRI) in eighty-nine trauma-exposed adults (69 female) screened for PTSD symptoms to examine the association between blood-borne (circulating) PACAP levels and amygdala-DMN connectivity. Higher circulating PACAP levels were associated with increased amygdala connectivity with posterior DMN regions, including the posterior cingulate cortex/precuneus (PCC/Precun) and left angular gyrus (lANG). Consistent with prior work, this effect was seen in female, but not male, participants and the centromedial, but not basolateral, subregions of the amygdala. Clinical association analyses linked amygdala-PCC/Precun connectivity to anxious arousal symptoms, specifically exaggerated startle response. Taken together, our findings converge with previously demonstrated effects of PACAP on amygdala activity in PTSD-related processes and offer novel evidence for an association between PACAP and intrinsic amygdala connectivity patterns in PTSD. Moreover, these data provide preliminary evidence to motivate future work ascertaining the sex- and subregion-specificity of these effects. Such findings may enable novel mechanistic insights into neural circuit dysfunction in PTSD and how the PACAP system confers risk through a disruption of intrinsic resting-state network dynamics.
Assuntos
Transtornos de Estresse Pós-Traumáticos , Adulto , Humanos , Feminino , Transtornos de Estresse Pós-Traumáticos/diagnóstico por imagem , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase , Rede de Modo Padrão , Imageamento por Ressonância Magnética/métodos , Tonsila do Cerebelo/diagnóstico por imagem , Encéfalo , Vias Neurais/diagnóstico por imagemRESUMO
Suicide is the second leading cause of death in adolescents; a frequent precursor of suicide is suicidal ideation (SI). Literature indicates that Post-Traumatic Stress Disorder (PTSD) and SI are robust cross-sectional correlates of one another, with PTSD often being conceptualized as a risk factor (i.e., conferring risk) for SI. Indeed, PTSD is a well-established risk factor for SI; however, SI is an understudied risk factor for PTSD. It is possible that, yet unknown if, PTSD and SI promote each other over time in a bidirectional fashion. We investigated the bidirectional longitudinal associations between PTSD and SI in a large, diverse sample, who at baseline were adolescents. Participants were interviewed between 1995 and 1998 and again between 2004 and 2008. We hypothesized that PTSD and SI would be cross-sectionally, longitudinally, and bidirectionally related and that the number of traumas endorsed at baseline would be positively associated with PTSD and SI at baseline and follow-up. Indeed, PTSD and SI were cross-sectionally correlated at baseline, but not follow-up. PTSD predicted SI over nine years; however, SI during adolescence did not predict PTSD in adulthood. Finally, poly-trauma endorsed at baseline was associated with increased risk of SI, but not PTSD, over nine years.
Assuntos
Transtornos de Estresse Pós-Traumáticos , Suicídio , Adolescente , Adulto , Estudos Transversais , Humanos , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Ideação SuicidaRESUMO
The amygdala-prefrontal-cortex circuit has long occupied the center of the threat system,1 but new evidence has rapidly amassed to implicate threat processing outside this canonical circuit.2-4 Through nonhuman research, the sensory cortex has emerged as a critical substrate for long-term threat memory,5-9 underpinned by sensory cortical pattern separation/completion10,11 and tuning shift.12,13 In humans, research has begun to associate the human sensory cortex with long-term threat memory,14,15 but the lack of mechanistic insights obscures a direct linkage. Toward that end, we assessed human olfactory threat conditioning and long-term (9 days) threat memory, combining affective appraisal, olfactory psychophysics, and functional magnetic resonance imaging (fMRI) over a linear odor-morphing continuum (five levels of binary mixtures of the conditioned stimuli/CS+ and CS- odors). Affective ratings and olfactory perceptual discrimination confirmed (explicit) affective and perceptual learning and memory via conditioning. fMRI representational similarity analysis (RSA) and voxel-based tuning analysis further revealed associative plasticity in the human olfactory (piriform) cortex, including immediate and lasting pattern differentiation between CS and neighboring non-CS and a late onset, lasting tuning shift toward the CS. The two plastic processes were especially salient and lasting in anxious individuals, among whom they were further correlated. These findings thus support an evolutionarily conserved sensory cortical system of long-term threat representation, which can underpin threat perception and memory. Importantly, hyperfunctioning of this sensory mnemonic system of threat in anxiety further implicates a hitherto underappreciated sensory mechanism of anxiety.
Assuntos
Condicionamento Clássico , Memória de Longo Prazo , Tonsila do Cerebelo , Humanos , Aprendizagem , Imageamento por Ressonância Magnética , MemóriaRESUMO
Cognitive dysfunction is a core feature of schizophrenia (SCZ), which unfavorably affects SCZ patients' daily functioning and overall clinical outcome. An increasing body of evidence has shown that cognitive deficits are present not only at the beginning of the illness but also several years before the onset of psychosis. Nonetheless, the majority of treatment interventions targeting cognitive dysfunction in SCZ, using both pharmacological and nonpharmacological approaches, have focused on chronic patients rather than individuals at high risk or in the early stages of the disease. In this article, we provide a narrative review of cognitive interventions in SCZ patients, with a particular focus on pre-emptive interventions in at-risk/early course individuals when available. Furthermore, we discuss current challenges for these pre-emptive treatment interventions and provide some suggestions on how future work may ameliorate cognitive dysfunction in these individuals.
Assuntos
Transtornos Cognitivos , Disfunção Cognitiva , Transtornos Psicóticos , Esquizofrenia , Humanos , Esquizofrenia/terapia , Esquizofrenia/tratamento farmacológico , Transtornos Psicóticos/psicologia , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/terapia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/terapia , CogniçãoRESUMO
People who are engineering biological organisms often find it useful to communicate in diagrams, both about the structure of the nucleic acid sequences that they are engineering and about the functional relationships between sequence features and other molecular species. Some typical practices and conventions have begun to emerge for such diagrams. The Synthetic Biology Open Language Visual (SBOL Visual) has been developed as a standard for organizing and systematizing such conventions in order to produce a coherent language for expressing the structure and function of genetic designs. This document details version 2.3 of SBOL Visual, which builds on the prior SBOL Visual 2.2 in several ways. First, the specification now includes higher-level "interactions with interactions," such as an inducer molecule stimulating a repression interaction. Second, binding with a nucleic acid backbone can be shown by overlapping glyphs, as with other molecular complexes. Finally, a new "unspecified interaction" glyph is added for visualizing interactions whose nature is unknown, the "insulator" glyph is deprecated in favor of a new "inert DNA spacer" glyph, and the polypeptide region glyph is recommended for showing 2A sequences.
Assuntos
Linguagens de Programação , Biologia Sintética , Humanos , IdiomaRESUMO
The Syrian conflict has resulted in the most significant refugee crisis since World War II. Current estimates suggest there are over 13.5 million Syrians in need of comprehensive humanitarian assistance as a direct result of the conflict. These humanitarian needs include mental health services to address the elevated rates of psychiatric disorders in this population. Towards this end, the Syrian American Medical Society conducted its inaugural mental health mission trip to Lebanon and Jordan from June to July 2019 to advance the state of mental health care for displaced Syrians. Following two weeks of trainings by international experts in trauma psychology, the mission concluded with a two-day scientific symposium, identifying two key elements for the advancement of humanitarian mental health care: 1) the need for community-based mental health services, and 2) the importance of transitioning from a crisis-response model in humanitarian mental health towards a model of resilience and post-traumatic growth.
RESUMO
Intrusive re-experiencing of traumatic events is a hallmark symptom of posttraumatic stress disorder, characterized by rich and vivid sensory details as reported in "flashbacks". While prevailing models of trauma intrusions focus on dysregulated emotional processes, we hypothesize that a deficiency in intrinsic sensory inhibition could drive overactivation of sensory representations of trauma memories, precipitating sensory-rich intrusions. In a sample of combat veterans, we examined resting-state alpha (8-12 Hz) oscillatory activity (in both power and posteriorâfrontal connectivity), given its role in sensory cortical inhibition, in association with intrusive re-experiencing symptoms. Veterans further participated in an odor task (including both combat and non-combat odors) to assess olfactory trauma memory and emotional response. We observed an association between intrusive re-experiencing symptoms and attenuated resting-state posteriorâfrontal alpha connectivity, which were both correlated with olfactory trauma memory. Importantly, olfactory trauma memory was identified as a mediator of the relationship between alpha connectivity and intrusive re-experiencing, suggesting that deficits in intrinsic sensory inhibition contributed to intrusive re-experiencing of trauma via heightened trauma memory. Therefore, by permitting unfiltered sensory cues to enter information processing and activate sensory representations of trauma, sensory disinhibition can constitute a sensory mechanism of intrusive re-experiencing in trauma-exposed individuals.
Assuntos
Sinais (Psicologia) , Inibição Psicológica , Memória , Sensação , Transtornos de Estresse Pós-Traumáticos/psicologia , Veteranos/psicologia , Adulto , Cognição , Emoções , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Social anxiety is associated with biased social perception, especially of ambiguous cues. While aberrations in high-level processes (e.g., cognitive appraisal and interpretation) have been implicated in such biases, contributions of early, low-level stimulus processing remain unclear. Categorical perception represents an efficient process to resolve signal ambiguity, and categorical emotion perception can swiftly classify sensory input, "tagging" biologically important stimuli at early stages of processing to facilitate ecological response. However, early threat categorization could be disrupted by exaggerated (or disinhibited) threat processing in anxiety, resulting in biased perception of ambiguous signals. We tested this hypothesis among individuals with low and high trait social anxiety (LSA/HSA; defined relative to the current sample), who performed a two-alternative forced-choice (fear or neutral) task on facial expressions parametrically varied along a neutral-fear continuum. The groups diverged in the reaction time (RT) profile along the neutral-fear continuum, which was characteristic of categorical perception in the LSA (vs. HSA) group with drastically increased RT from neutral to intermediate (boundary) fear intensities, contrasting monotonic, nonsignificant RT changes in the HSA group. Neurometric analysis along the continuum identified an early neutral-fear categorization operation (arising in the P1, an early visual ERP at 100 ms), which was nonetheless impaired in the HSA group (due to disinhibited response at the neutral-fear boundary). Absent group differences in higher-level cognitive operations (identified by later ERPs), current findings highlight a dispositional cognitive vulnerability in early visual categorization of social threat, which could precipitate further cognitive aberrations and, eventually, the onset of social anxiety disorder.
Assuntos
Ansiedade/fisiopatologia , Formação de Conceito/fisiologia , Potenciais Evocados/fisiologia , Reconhecimento Facial/fisiologia , Medo/fisiologia , Personalidade/fisiologia , Percepção Social , Adolescente , Adulto , Eletroencefalografia , Expressão Facial , Feminino , Humanos , Masculino , Tempo de Reação , Adulto JovemRESUMO
Anomalies in default mode network (DMN) activity and α (8-12 Hz) oscillations have been independently observed in posttraumatic stress disorder (PTSD). Recent spatiotemporal analyses suggest that α oscillations support DMN functioning via interregional synchronization and sensory cortical inhibition. Therefore, we examined a unifying pathology of α deficits in the visual-cortex-DMN system in PTSD. Human patients with PTSD (N = 25) and two control groups, patients with generalized anxiety disorder (GAD; N = 24) and healthy controls (HCs; N = 20), underwent a standard eyes-open resting state (S-RS) and a modified resting state (M-RS) of passively viewing salient images (known to deactivate the DMN). High-density electroencephalogram (hdEEG) were recorded, from which intracortical α activity (power and connectivity/Granger causality) was extracted using the exact low-resolution electromagnetic tomography (eLORETA). Patients with PTSD (vs GAD/HC) demonstrated attenuated α power in the visual cortex (VC) and key hubs of the DMN [posterior cingulate cortex (PCC) and medial prefrontal cortex (mPFC)] at both states, the severity of which further correlated with hypervigilance symptoms. With increased visual input (at M-RS vs S-RS), patients with PTSD further demonstrated reduced α-frequency directed connectivity within the DMN (PCCâmPFC) and, importantly, from the VC to both DMN hubs (VCâPCC and VCâmPFC), linking α deficits in the two systems. These interrelated α deficits align with DMN hypoactivity/hypoconnectivity, sensory disinhibition, and hypervigilance in PTSD, representing a unifying neural underpinning of these anomalies. The identification of visual-cortex-DMN α dysrhythmia in PTSD further presents a novel therapeutic target, promoting network-based intervention of neural oscillations.