Brain dynamics reflecting an intra-network brain state are associated with increased post-traumatic stress symptoms in the early aftermath of trauma

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Experts consensus on management of tooth luxation and avulsion

Traumatic dental injuries (TDIs) of teeth occur frequently in children and adolescents. TDIs that impact the periodontal tissues and alveolar tissue can be classified into concussion, subluxation, extrusive luxation, intrusive luxation, lateral luxation, and avulsion. In these TDIs, management of injured soft tissue, mainly periodontal ligament, and dental pulp, is crucial in maintaining the function and longevity of the injured teeth. Factors that need to be considered for management in laxation injuries include the maturation stage of the traumatic teeth, mobility, direction of displacement, distance of displacement, and whether there are alveolar fractures. In avulsion, the maturation stage of the permanent tooth, the out-socket time, storage media/condition of the avulsed tooth, and management of the PDL should also be considered. Especially, in this review, we have subdivided the immature tooth into the adolescent tooth (Nolla stage 9) and the very young tooth (Nolla stage 8 and below). This consensus paper aimed to discuss the impacts of those factors on the trauma management and prognosis of TDI to provide a streamlined guide for clinicians from clinical evaluation, diagnostic process, management plan decision, follow-up, and orthodontic treatment for tooth luxation and avulsion injuries.

Stress-induced changes in the molecular processes underlying fear memories: implications for PTSD and relevant animal models

Most of the fear literature on humans and animals tests healthy individuals. However, fear memories can differ between healthy individuals and those previously exposed to traumatic stress, such as a car accident, sexual abuse, military combat and personal assault. Traumatic stress can lead to post-traumatic stress disorder (PTSD) which presents alterations in fear memories, such as an impairment of fear extinction and extinction recall. PTSD-like animal models are exposed to a single highly stressful experience in the laboratory, such as stress immobilization or single-prolonged stress. Some days later, animals exposed to a PTSD-like model can be tested in fear procedures that help uncover molecular mechanisms of fear memories. In this review, there are discussed the molecular mechanisms in stress-induced fear memories of patients with PTSD and PTSD-like animal models. The focus is on the effects of estradiol and cortisol/corticosterone hormones and of different genes, such as FKBP prolyl isomerase 5 gene (FKBP5) – FK506 binding protein 51 (FKBP51), pituitary adenylate cyclase-activating peptide (PACAP) – pituitary adenylate cyclase-activating polypeptide type I receptor (PAC1R), endocannabinoid (eCB) system and the tropomyosin receptor kinase B (TrkB) – brain-derived neurotrophic factor (BDNF). The conclusion is that greater emphasis should be placed on investigating the molecular mechanisms of fear memories in PTSD, through direct testing of patients with PTSD or the use of relevant PTSD-like models.

Dopaminergic modulation and dosage effects on brain state dynamics and working memory component processes in Parkinson’s disease

Parkinson’s disease (PD) is primarily diagnosed through its characteristic motor deficits, yet it also encompasses progressive cognitive impairments that profoundly affect quality of life. While dopaminergic medications are routinely prescribed to manage motor symptoms in PD, their influence extends to cognitive functions as well. Here we investigate how dopaminergic medication influences aberrant brain circuit dynamics associated with encoding, maintenance and retrieval working memory (WM) task-phases processes. PD participants, both on and off dopaminergic medication, and healthy controls, performed a Sternberg WM task during fMRI scanning. We employ a Bayesian state-space computational model to delineate brain state dynamics related to different task phases. Importantly, a within-subject design allows us to examine individual differences in the effects of dopaminergic medication on brain circuit dynamics and task performance. We find that dopaminergic medication alters connectivity within prefrontal-basal ganglia-thalamic circuits, with changes correlating with enhanced task performance. Dopaminergic medication also restores engagement of task-phase-specific brain states, enhancing task performance. Critically, we identify an “inverted-U-shaped” relationship between medication dosage, brain state dynamics, and task performance. Our study provides valuable insights into the dynamic neural mechanisms underlying individual differences in dopamine treatment response in PD, paving the way for more personalized therapeutic strategies.

Childhood trauma cortisol and immune cell glucocorticoid transcript levels are associated with increased risk for suicidality in adolescence

Rising adolescent suicide rates present a growing unmet need. Childhood trauma (CT) has been associated with altered cortisol dynamics and immune cell glucocorticoid reactivity, yet their additive longer-term contributions to later suicide outcomes are less clear. The current study compared CT scores, resting salivary free cortisol and mononuclear cell gene expression levels of the nuclear receptor, subfamily 3, member 1 (NR3C1) coding the glucocorticoid receptor, and its co-chaperons FKBP prolyl isomerase 5 (FKBP5) and KIT Ligand (KITLG), between a cohort of adolescents presenting with a suicidal crisis requiring hospital treatment, and matched healthy controls. Childhood trauma scores and glucocorticoid measures were significantly altered among suicidal adolescents, and CT scores correlated with mononuclear cell glucocorticoid transcripts. Both CT scores and glucocorticoid measures explained substantial additive portions of the variance in adolescent suicidality. Long-term perturbations in cortisol dynamics and immune cell glucocorticoid response elements denote dysregulated immune stress reactivity, and may possess value in prediction and point to modifiable-risk factors in prevention of clinically significant suicidality during the brittle period of adolescence, years after childhood trauma exposure.

Person-centered analyses reveal that developmental adversity at moderate levels and neural threat/safety discrimination are associated with lower anxiety in early adulthood

Parsing heterogeneity in the nature of adversity exposure and neurobiological functioning may facilitate better understanding of how adversity shapes individual variation in risk for and resilience against anxiety. One putative mechanism linking adversity exposure with anxiety is disrupted threat and safety learning. Here, we applied a person-centered approach (latent profile analysis) to characterize patterns of adversity exposure at specific developmental stages and threat/safety discrimination in corticolimbic circuitry in 120 young adults. We then compared how the resultant profiles differed in anxiety symptoms. Three latent profiles emerged: (1) a group with lower lifetime adversity, higher neural activation to threat, and lower neural activation to safety; (2) a group with moderate adversity during middle childhood and adolescence, lower neural activation to threat, and higher neural activation to safety; and (3) a group with higher lifetime adversity exposure and minimal neural activation to both threat and safety. Individuals in the second profile had lower anxiety than the other profiles. These findings demonstrate how variability in within-person combinations of adversity exposure and neural threat/safety discrimination can differentially relate to anxiety, and suggest that for some individuals, moderate adversity exposure during middle childhood and adolescence could be associated with processes that foster resilience to future anxiety.

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