The adolescent brain, with ongoing prefrontal maturation, may be more vulnerable to drug use-related neurotoxic changes as compared to the adult brain. We investigated whether the use of methamphetamine (MA), a highly addictive psychostimulant, during adolescence affect metabolic and cognitive functions of the anterior cingulate cortex (ACC). In adolescent MA users (n = 44) and healthy adolescents (n = 53), the levels of N-acetyl aspartate (NAA), a neuronal marker, were examined in the ACC using proton magnetic resonance spectroscopy. The Stroop color-word task was used to assess Stroop interference, which may reflect cognitive functions of behavior monitoring and response selection that are mediated by the ACC. Adolescent MA users had lower NAA levels in the ACC (t = -2.88, P = 0.005) and relatively higher interference scores (t = 2.03, P = 0.045) than healthy adolescents. Moreover, there were significant relationships between lower NAA levels in the ACC and worse interference scores in adolescent MA users (r = -0.61, P < 0.001). Interestingly, early onset of MA use, as compared to late onset, was related to both lower NAA levels in the ACC (t = -2.24, P = 0.03) as well as lower performance on interference measure of the Stroop color-word task (t = 2.25, P = 0.03). The current findings suggest that metabolic dysfunction in the ACC and its related cognitive impairment may play an important role in adolescent-onset addiction, particularly during early adolescence.

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Background: Low back pain is a very common disease. Many patients with chronic low back pain (CLBP) have been treated by complementary and alternative medicine such as acupuncture (AT) treatment. A type of AT, thread embedding acupuncture (TEA), consists of a thread that can continually stimulate at the AT points and has mechanical and chemical effects. Although TEA was widely used in clinical practice, there was little evidence of its efficacy and safety for CLBP. Methods: This clinical trial was randomized, controlled, assessor-blinded, two-armed, parallel, and conducted in multiple centers. Four Korean medical institutions recruited 38 outpatients with CLBP. The participants were randomly allocated to a treatment group (TEA combined with AT) or a control group (only AT) in a 1:1 ratio. All participants received conventional AT twice a week for 8 weeks (16 sessions) at 15 AT points (GV3 and bilateral BL23, BL24, BL25, BL26, BL40, BL60, and EX-B5) and the treatment group participants additionally received TEA once a week for 8 weeks (8 sessions) on 10 AT points in the multifidus, spinal erector, and lumbar quadrate muscles. The primary outcome measure of this study was the change of visual analog scale (VAS) from baseline (0 week) to the end of intervention (8 weeks). Secondary outcome measures included clinically relevant improvement (minimal clinically important difference) and 3% to 50% decrease on VAS, disability level (Korean version of Roland and Morris disability questionnaire), quality of life (Korean version of European quality of life 5dimension), global assessment (patient global impression of change), economic analysis, credibility test, and safety assessment. Results: The treatment group showed a significant reduction in VAS scores when compared with the control group (–33.7 ± 25.1 vs –15.6 ± 17.0, P = .013). As for the secondary outcome measures, the treatment group showed significant difference in 50% decrease on VAS and patient global impression of change. There was no serious adverse event associated with TEA and AT. Conclusion: This clinical trial documents the efficacy and safety of TEA combined with AT for the management of CLBP.

The neural mechanisms underlying the development and maintenance of posttraumatic stress disorder (PTSD) have long been studied. However, little is known about the neural correlates of the recovery process from PTSD. A 5-year longitudinal study was conducted to investigate the trajectory of structural connectivities of the amygdala in disaster survivors with PTSD. Thirty disaster survivors, who were diagnosed with PTSD, and 29 healthy individuals, who were not exposed to trauma, underwent three waves of assessments including neuroimaging scanning over a 5-year period from the time of the disaster at approximately 1.3-year intervals. All disaster survivors showed significant improvements in PTSD symptoms over time. Using diffusion tensor imaging analysis, a 5-year trajectory of amygdalar structural connectivities with key brain regions was assessed. The amygdala-insula connection was initially strengthened and then normalized during recovery, while the amygdala-prefrontal cortex (PFC) connection was at first unaffected, then strengthened, and eventually normalized. The lower tract strength of the amygdala-thalamus connection normalized during recovery, while that of amygdala-hippocampus connection remained low. The greater amygdala-PFC connectivity was associated with less PTSD symptom severity. The present longitudinal study revealed that recovery from PTSD parallels dynamic and sequential shifts in amygdalar connectivities with multiple brain regions, suggesting the expanded view of fear circuitry including the insula and thalamus, beyond the traditional model which primarily involves the amygdala, PFC, and hippocampus.

Prolonged symptoms after the clearance of acute coronavirus disease 2019 (COVID-19) infection, termed long COVID, are an emerging threat to the post-COVID-19 era. Complementary and alternative medicine (CAM) interventions may play a significant role in the management of long COVID. The present study aimed to identify published studies on the use of CAM interventions for long COVID and provide an overview of the research status using bibliometric analysis. The present scoping review searched MEDLINE, Embase, and Cochrane Library from inception until November 2021 and identified published studies on CAM interventions for long COVID. A narrative analysis of the study types and effectiveness and safety of the CAM interventions are presented and a bibliometric analysis of citation information and references of the included publications were analyzed using the Bibliometrix package for R. An electronic database search identified 16 publications (2 clinical studies and 14 study protocols of systematic reviews or clinical studies) that were included in the present study. Dyspnea or pulmonary dysfunction, quality of life, olfactory dysfunction, and psychological symptoms after COVID-19 infection were assessed in the included publications. The two clinical studies suggested that Chinese herbal medications were effective in relieving symptoms of pulmonary dysfunction. Bibliometric analysis revealed the current trend of research publication in this area was driven by study protocols written by Chinese, Korean, and Indian authors. Thus, the present scoping review and bibliometric analysis revealed that there are few studies published about the use of CAM for long COVID and long-term management for COVID-19 survivors. Original studies on CAM interventions, including randomized controlled trials and systematic reviews, are required to actively support evidence for their use in the management of long COVID. PROSPERO registration: this trial is registered with CRD42021281526.

BackgroundTraditional, Complementary and Integrative Medicine (TCIM) has been reported to use for symptom management of coronavirus disease 2019 (COVID-19). The objective of this review was to identify the overall usage prevalence of TCIM interventions for COVID-19.MethodsSurveys on the general population and observational studies on the COVID-19 patient chart review were located in the search of PubMed, EMBASE and Cochrane Central Register of Controlled Trials databases in September 2021. Observational studies, such as cross-sectional studies, surveys, cohort studies and hospital-based patient case reviews, published in any language, reporting the usage of TCIM in the patients with COVID-19 or the general population during the COVID-19 pandemic were included in this review. Data screening and extraction were performed independently by two reviewers. The reporting quality of the included studies was assessed with the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) statement. To conduct a meta-analysis of the usage prevalence of various TCIM interventions, the effect size of the proportion for each intervention was calculated with the inverse variance method. The main outcome was usage prevalence of TCIM interventions among patients with COVID-19 or the general population during the COVID-19 pandemic.ResultsA total of 62 studies were included in this review. The overall TCIM usage prevalence was estimated to be 0.64 (95% CI 0.54–0.73). The overall prevalence did not differ between the population-based survey (0.65, 95% CI 0.48–0.81) and the hospital-based patient case review (0.63, 95% CI 0.52–0.73). Statistical heterogeneity and comparatively low quality in reporting were observed, which should be cautiously considered when interpreting the results.ConclusionVarious TCIM interventions were reported to be used with comparatively high frequency. Future international collaborative research might overcome the main limitation of this study, i.e., the heterogeneity of the included data.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=278452, identifier: CRD42021278452.

In animal models of Parkinson's disease (PD), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is one of the most widely used agents that damages the nigrostriatal dopaminergic pathway. However, brain structural changes in response to MPTP remain unclear. This study aimed to investigate in vivo longitudinal changes in gray matter (GM) volume and white matter (WM) microstructure in primate models administered with MPTP. In six cynomolgus monkeys, high-resolution magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) scans were acquired 7 times over 32 weeks, and assessments of motor symptoms were conducted over 15 months, before and after the MPTP injection. Changes in GM volume and WM microstructure were estimated on a voxel-by-voxel basis. Mixed-effects regression models were used to examine the trajectories of these structural changes. GM volume initially increased after the MPTP injection and gradually decreased in the striatum, midbrain, and other dopaminergic areas. The cerebellar volume temporarily decreased and returned to its baseline level. The rate of midbrain volume increase was positively correlated with the increase rate of motor symptom severity (Spearman rho = 0.93, p = 0.008). Mean, axial, and radial diffusivity in the striatum and frontal areas demonstrated initial increases and subsequent decreases. The current multi-modal imaging study of MPTP-administered monkeys revealed widespread and dynamic structural changes not only in the nigrostriatal pathway but also in other cortical, subcortical, and cerebellar areas. Our findings may suggest the need to further investigate the roles of inflammatory reactions and glial activation as potential underlying mechanisms of these structural changes.

BackgroundThe amygdala has been known to play a pivotal role in mediating fear-related responses including panic attacks. Given the functionally distinct role of the amygdalar subregions, morphometric measurements of the amygdala may point to the pathophysiological mechanisms underlying panic disorder. The current study aimed to determine the global and local morphometric alterations of the amygdala related to panic disorder.MethodsVolumetric and surface-based morphometric approach to high-resolution three-dimensional T1-weighted images was used to examine the structural variations of the amygdala, with respect to extent and location, in 23 patients with panic disorder and 31 matched healthy individuals.ResultsThere were no significant differences in bilateral amygdalar volumes between patients with panic disorder and healthy individuals despite a trend-level right amygdalar volume reduction related to panic disorder (right, β = -0.23, p = 0.09, Cohen's d = 0.51; left, β = -0.18, p = 0.19, Cohen's d = 0.45). Amygdalar subregions were localized into three groups including the superficial, centromedial, and laterobasal groups based on the cytoarchitectonically defined probability map. Surface-based morphometric analysis revealed shape alterations in the laterobasal and centromedial groups of the right amygdala in patients with panic disorder (false discovery rate corrected p < 0.05).ConclusionsThe current findings suggest that subregion-specific shape alterations in the right amygdala may be involved in the development and maintenance of panic disorder, which may be attributed to the cause or effects of amygdalar hyperactivation.