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Although the cerebellum contributes to higher-order cognitive and emotional functions relevant to posttraumatic stress disorder (PTSD), prior research on cerebellar volume in PTSD is scant, particularly when considering subregions that differentially map on to motor, cognitive, and affective functions. In a sample of 4215 adults (PTSD n = 1642; Control n = 2573) across 40 sites from the ENIGMA-PGC PTSD working group, we employed a new state-of-the-art deep-learning based approach for automatic cerebellar parcellation to obtain volumetric estimates for the total cerebellum and 28 subregions. Linear mixed effects models controlling for age, gender, intracranial volume, and site were used to compare cerebellum volumes in PTSD compared to healthy controls (88% trauma-exposed). PTSD was associated with significant grey and white matter reductions of the cerebellum. Compared to controls, people with PTSD demonstrated smaller total cerebellum volume, as well as reduced volume in subregions primarily within the posterior lobe (lobule VIIB, crus II), vermis (VI, VIII), flocculonodular lobe (lobule X), and corpus medullare (all p-FDR

BACKGROUND: Recent advances in data-driven computational approaches have been helpful in devising tools to objectively diagnose psychiatric disorders. However, current machine learning studies limited to small homogeneous samples, different methodologies, and different imaging collection protocols, limit the ability to directly compare and generalize their results. Here we aimed to classify individuals with PTSD versus controls and assess the generalizability using a large heterogeneous brain datasets from the ENIGMA-PGC PTSD Working group. METHODS: We analyzed brain MRI data from 3,477 structural-MRI; 2,495 resting state-fMRI; and 1,952 diffusion-MRI. First, we identified the brain features that best distinguish individuals with PTSD from controls using traditional machine learning methods. Second, we assessed the utility of the denoising variational autoencoder (DVAE) and evaluated its classification performance. Third, we assessed the generalizability and reproducibility of both models using leave-one-site-out cross-validation procedure for each modality. RESULTS: We found lower performance in classifying PTSD vs. controls with data from over 20 sites (60 % test AUC for s-MRI, 59 % for rs-fMRI and 56 % for d-MRI), as compared to other studies run on single-site data. The performance increased when classifying PTSD from HC without trauma history in each modality (75 % AUC). The classification performance remained intact when applying the DVAE framework, which reduced the number of features. Finally, we found that the DVAE framework achieved better generalization to unseen datasets compared with the traditional machine learning frameworks, albeit performance was slightly above chance. CONCLUSION: These results have the potential to provide a baseline classification performance for PTSD when using large scale neuroimaging datasets. Our findings show that the control group used can heavily affect classification performance. The DVAE framework provided better generalizability for the multi-site data. This may be more significant in clinical practice since the neuroimaging-based diagnostic DVAE classification models are much less site-specific, rendering them more generalizable.

Results of neuroimaging datasets aggregated from multiple sites may be biased by site-specific profiles in participants' demographic and clinical characteristics, as well as MRI acquisition protocols and scanning platforms. We compared the impact of four different harmonization methods on results obtained from analyses of cortical thickness data: (1) linear mixed-effects model (LME) that models site-specific random intercepts (LMEINT), (2) LME that models both site-specific random intercepts and age-related random slopes (LMEINT+SLP), (3) ComBat, and (4) ComBat with a generalized additive model (ComBat-GAM). Our test case for comparing harmonization methods was cortical thickness data aggregated from 29 sites, which included 1,340 cases with posttraumatic stress disorder (PTSD) (6.2-81.8 years old) and 2,057 trauma-exposed controls without PTSD (6.3-85.2 years old). We found that, compared to the other data harmonization methods, data processed with ComBat-GAM was more sensitive to the detection of significant case-control differences (Χ2(3) = 63.704, p < 0.001) as well as case-control differences in age-related cortical thinning (Χ2(3) = 12.082, p = 0.007). Both ComBat and ComBat-GAM outperformed LME methods in detecting sex differences (Χ2(3) = 9.114, p = 0.028) in regional cortical thickness. ComBat-GAM also led to stronger estimates of age-related declines in cortical thickness (corrected p-values < 0.001), stronger estimates of case-related cortical thickness reduction (corrected p-values < 0.001), weaker estimates of age-related declines in cortical thickness in cases than controls (corrected p-values < 0.001), stronger estimates of cortical thickness reduction in females than males (corrected p-values < 0.001), and stronger estimates of cortical thickness reduction in females relative to males in cases than controls (corrected p-values < 0.001). Our results support the use of ComBat-GAM to minimize confounds and increase statistical power when harmonizing data with non-linear effects, and the use of either ComBat or ComBat-GAM for harmonizing data with linear effects.

Studies of posttraumatic stress disorder (PTSD) report volume abnormalities in multiple regions of the cerebral cortex. However, findings for many regions, particularly regions outside commonly studied emotion-related prefrontal, insular, and limbic regions, are inconsistent and tentative. Also, few studies address the possibility that PTSD abnormalities may be confounded by comorbid depression. A mega-analysis investigating all cortical regions in a large sample of PTSD and control subjects can potentially provide new insight into these issues. Given this perspective, our group aggregated regional volumes data of 68 cortical regions across both hemispheres from 1379 PTSD patients to 2192 controls without PTSD after data were processed by 32 international laboratories using ENIGMA standardized procedures. We examined whether regional cortical volumes were different in PTSD vs. controls, were associated with posttraumatic stress symptom (PTSS) severity, or were affected by comorbid depression. Volumes of left and right lateral orbitofrontal gyri (LOFG), left superior temporal gyrus, and right insular, lingual and superior parietal gyri were significantly smaller, on average, in PTSD patients than controls (standardized coefficients = -0.111 to -0.068, FDR corrected P values

Impairments in the detection and perception of resistive loads in healthy aging and chronic obstructive pulmonary disease (COPD) have implications for airway protection and breathlessness. This study investigated load detection and perception in 18 participants with COPD, 17 older adults [i.e., age-matched controls (AMCs)] and 23 young adults [i.e., young controls (YCs)]. Load detection was assessed as the minimal change in airway resistance that could be detected and load perception as the perceived level of effort to breathe through a series of suprathreshold resistive loads, rated on a modified Borg scale. Young and older adults, with and without COPD, could detect similar changes in resistance (∼0.7 cmH2O/L/s) and inspiratory pressure (∼0.5 cmH2O), although this equated to a smaller proportion of predicted maximal inspiratory pressure (MIPpred) for young adults (∼0.5% MIPpred) compared with older adults with and without COPD (∼1.0% MIPpred; P < 0.001). For load perception, the relationship between Borg ratings and resistance was steeper in older adult controls compared with both young adults (P < 0.001) and older adults with COPD (P < 0.01). Borg rating slopes were comparable across all participant groups with changes in inspiratory pressure. There was no correlation between load detection threshold and load perception. In older adults, heightened perception of loaded breaths with large changes in breathing resistance may be due to an increased effort to breathe at these loads. NEW & NOTEWORTHY: We demonstrated that young adults could detect a smaller change in pressure (as a proportion of predicted maximal inspiratory pressure) than older adults. The perceived effort to breathe with increases in the resistance of breathing was heightened in older, compared with young adults. There was no further impairment in chronic obstructive pulmonary disease. Heightened dyspnea perception related to the effort to breathe was not associated with load detection thresholds in older adults. [ABSTRACT FROM AUTHOR]

These guidelines have been developed jointly by the British Gynaecological Cancer Society and British Menopause Society to provide information for all healthcare professionals managing women treated for gynaecological cancer. Menopausal symptoms can have a significant impact on quality of life for women. Cancer therapies, including surgery, pelvic radiotherapy, chemotherapy and endocrine therapy, can all affect ovarian function. The benefits and risks of using hormone replacement therapy are considered by cancer type with guidance on the type of HRT and optimal time of commencement after cancer treatment. Vaginal estrogens can be very effective for improving urogenital symptoms and are safe for the majority of women, including those for whom systemic HRT is contraindicated with rare exceptions. Alternative options to HRT are reviewed including pharmacological and non-pharmacological approaches. [ABSTRACT FROM AUTHOR]

Intramuscular recordings of single motor unit activity from parasternal intercostal muscles show a rostrocaudal gradient in timing and amplitude of inspiratory activity. This study determined the feasibility of surface electromyographic activity (EMG) to measure graded parasternal intercostal activity in young females and males during quiet breathing and breathing with inspiratory resistive loads. Surface EMGs were recorded from the 1st-to-5th parasternal intercostal muscles during 10 min of breathing. EMGs were processed to remove 50 Hz and electrocardiogram artifacts and integrated. Amplitude and onset time of inspiratory activity were measured from waveform averages triggered at the onset of inspiratory flow. Onset times were measured independently by two assessors, blinded to interspace and EMG scale, with excellent agreement (ICC3,k = 0.86). The onset of inspiratory activity in the 1st-to-3rd interspaces was at or within ∼400 ms of the start of inspiratory airflow, but activity in the caudal (4th and 5th) spaces was delayed by up to ∼1,000 ms (P < 0.001). There was no main effect of sex on onset time (P = 0.07), but an interaction with interspace (P < 0.001) revealed that inspiratory activity in the caudal interspaces was delayed by 15% of inspiratory time in female participants compared with 30% of inspiratory time in male participants. Inspiratory loads did not affect EMG onset time (P = 0.31). Thus, surface EMG is feasible to assess the onset time of inspiratory activity as a marker of inspiratory neural drive and pattern of activation across spaces, in both females and males. NEW & NOTEWORTHY: We demonstrated that surface EMG is a valid method to measure graded inspiratory EMG in the parasternal intercostal muscles in healthy young male and female participants during quiet breathing and loaded breathing. Across the 1st-to-5th interspaces, there was more homogenous activation in women and more graded activity in men across parasternal intercostal muscles during breathing. By recording surface EMG from both male and female participants, we have revealed sex differences in inspiratory activity across intercostal muscles. [ABSTRACT FROM AUTHOR]

There is an overlap between the International Classification of Diseases for Mortality and Morbidity Statistics- 11th Revision (ICD-11) diagnoses of complex post-traumatic stress disorder (CPTSD) and personality disorder. When the latter is comorbid with post-traumatic stress disorder (PTSD), this may allow for a false positive CPTSD diagnosis. This fact has both clinical implications and throws into relief theoretical questions about the ontology of trauma and personality disorder-related pathology. These questions are presented as a call for further research. The ICD 11 introduces a new CPTSD diagnosis, and a new conceptualisation of personality disorder. Despite the advances of the ICD 11, the arrangement of these constructs allows for issues which may pose difficulties for clinicians working in this area. There remain a variety of epistemological and ontological questions concerning trauma and the type of difficulties captured by the diagnosis of personality disorder. These will require future research to clarify. [ABSTRACT FROM AUTHOR]