Smaller total and subregional cerebellar volumes in posttraumatic stress disorder: a mega-analysis by the ENIGMA-PGC PTSD workgroup.

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 < 0.05). Effects of PTSD on volume were consistent, and generally more robust, when examining symptom severity rather than diagnostic status. These findings implicate regionally specific cerebellar volumetric differences in the pathophysiology of PTSD. The cerebellum appears to play an important role in higher-order cognitive and emotional processes, far beyond its historical association with vestibulomotor function. Further examination of the cerebellum in trauma-related psychopathology will help to clarify how cerebellar structure and function may disrupt cognitive and affective processes at the center of translational models for PTSD.

Neuroimaging-based classification of PTSD using data-driven computational approaches: A multisite big data study from the ENIGMA-PGC PTSD consortium.

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.

Questions arising from the application of the ICD-11 diagnoses of complex post traumatic stress disorder and personality disorder.

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.

A comparison of methods to harmonize cortical thickness measurements across scanners and sites.

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.

Cortical volume abnormalities in posttraumatic stress disorder: an ENIGMA-psychiatric genomics consortium PTSD workgroup mega-analysis.

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 < 0.039) and were significantly negatively correlated with PTSS severity. After adjusting for depression symptoms, the PTSD findings in left and right LOFG remained significant. These findings indicate that cortical volumes in PTSD patients are smaller in prefrontal regulatory regions, as well as in broader emotion and sensory processing cortical regions.

The effect of acute intermittent hypoxia on human limb motoneurone output.

NEW FINDINGS: What is the central question of this study? Does a single session of repeated bouts of acute intermittent hypoxic breathing enhance the motoneuronal output of the limb muscles of healthy able-bodied participants? What is the main finding and its importance? Compared to breathing room air, there were some increases in motoneuronal output following acute intermittent hypoxia, but the increases were variable across participants and in time after the intervention and depended on which neurophysiological measure was checked. ABSTRACT: Acute intermittent hypoxia (AIH) induces persistent increases in output from rat phrenic motoneurones. Studies in people with spinal cord injury (SCI) suggest that AIH improves limb performance, perhaps via postsynaptic changes at cortico-motoneuronal synapses. We assessed whether limb motoneurone output in response to reflex and descending synaptic activation is facilitated after one session of AIH in healthy able-bodied volunteers. Fourteen participants completed two experimental days, with either AIH or a sham intervention (randomised crossover design). We measured H-reflex recruitment curves and homosynaptic post-activation depression (HPAD) of the H-reflex in soleus, and motor evoked potentials (MEPs) evoked by transcranial magnetic stimulation (TMS) and their recruitment curves in first dorsal interosseous. All measurements were performed at rest and occurred at baseline, 0, 20, 40 and 60 min post-intervention. The intervention was 30 min of either normoxia (sham, F i O 2 ${F_{{\rm{i}}{{\rm{O}}_{\rm{2}}}}}$  ≈ 0.21) or AIH (alternate 1-min hypoxia [ F i O 2 ${F_{{\rm{i}}{{\rm{O}}_{\rm{2}}}}}$  ≈ 0.09], 1-min normoxia). After AIH, the H-reflex recruitment curve shifted leftward. Lower stimulation intensities were needed to evoke 5%, 50% and 99% of the maximal H-reflex at 40 and 60 min after AIH (P < 0.04). The maximal H-reflex, recruitment slope and HPAD were unchanged after AIH. MEPs evoked by constant intensity TMS were larger 40 min after AIH (P = 0.027). There was no change in MEP recruitment or the maximal MEP. In conclusion, some measures of the evoked responses from limb motoneurones increased after a single AIH session, but only at discrete time points. It is unclear to what extent these changes alter functional performance.

Emotion, Gender and Gaze Discrimination Tasks do not Differentially Impact the Neural Processing of Angry or Happy Facial Expressions-a Mass Univariate ERP Analysis.

Facial expression processing is a critical component of social cognition yet, whether it is influenced by task demands at the neural level remains controversial. Past ERP studies have found mixed results with classic statistical analyses, known to increase both Type I and Type II errors, which Mass Univariate statistics (MUS) control better. However, MUS open-access toolboxes can use different fundamental statistics, which may lead to inconsistent results. Here, we compared the output of two MUS toolboxes, LIMO and FMUT, on the same data recorded during the processing of angry and happy facial expressions investigated under three tasks in a within-subjects design. Both toolboxes revealed main effects of emotion during the N170 timing and main effects of task during later time points typically associated with the LPP component. Neither toolbox yielded an interaction between the two factors at the group level, nor at the individual level in LIMO, confirming that the neural processing of these two face expressions is largely independent from task demands. Behavioural data revealed main effects of task on reaction time and accuracy, but no influence of expression or an interaction between the two. Expression processing and task demands are discussed in the context of the consistencies and discrepancies between the two toolboxes and existing literature.

Neuroanatomy of transgender persons in a Non-Western population and improving reliability in clinical neuroimaging.

Although the neuroanatomy of transgender persons is slowly being charted, findings are presently discrepant. Moreover, the major body of work has focused on Western populations. One important factor is the issue of power and low signal-to-noise (SNR) ratio in neuroimaging studies of rare study populations including endocrine or neurological patient groups. The present study focused on the structural neuroanatomy of a Non-Western (Iranian) sample of 40 transgender men (TM), 40 transgender women (TW), 30 cisgender men (CM), and 30 cisgender women (CW), while assessing whether the reliability of findings across structural anatomical measures including gray matter volume (GMV), cortical surface area (CSA), and cortical thickness (CTh) could be increased by using two back-to-back within-session structural MRI scans. Overall, findings in transgender persons were more consistent with sex assigned at birth in GMV and CSA, while no group differences emerged for CTh. Repeated measures analysis also indicated that having a second scan increased SNR in all regions of interest, most notably bilateral frontal poles, pre- and postcentral gyri and putamina. The results suggest that a simple time and cost-effective measure to improve SNR in rare clinical populations with low prevalence rates is a second anatomical scan when structural MRI is of interest.

Are you as important as me? Self-other discrimination within trait-adjective processing.

Healthy adults typically display enhanced processing for self- (relative to other-) relevant and positive (relative to negative) information. However, it is unclear whether these two biases interact to form a self-positivity bias, whereby self-positive information receives prioritized processing. It is also unclear how a blocked versus mixed referent design impacts reference and valence processing. We addressed these questions using behavioral and electrophysiological indices across two studies using a Self-Referential Encoding Task, followed by surprise recall and recognition tasks. Early (P1) and late (LPP) event-related potentials were time-locked to a series of trait adjectives, encoded relative to oneself or a fictional character, with referent presented in a blocked (Exp. 1) or mixed (Exp. 2) trial design. Regardless of study design, participants recalled and recognized more self- than other-relevant adjectives, and recognized more positive than negative adjectives. Additionally, participants demonstrated larger LPP amplitudes for self-relevant and positive adjectives. The LPP self-relevance effect emerged earlier and persisted longer in the blocked (400-800 ms) versus mixed design (600-800 ms). The LPP valence effect was not apparent in the blocked design, but appeared late in the mixed design (600-1200 ms). Critically, the interaction between self-relevance and valence appeared only behaviorally in the mixed design, suggesting that overall self-relevance and valence independently impact neural socio-cognitive processing.

Defining the neural correlates of spontaneous theory of mind (ToM): An fMRI multi-study investigation.

There is a major debate in the theory of mind (ToM) field, concerning whether spontaneous and explicit ToM are based on the same or two distinct cognitive systems. While extensive research on the neural correlates of explicit ToM has demonstrated involvement of the temporo-parietal junction (TPJ) and the medial prefrontal cortex (mPFC), few studies investigated spontaneous ToM, leaving some open questions. Here, we implemented a multi-study approach by pooling data from three fMRI studies to obtain a larger sample to increase power and sensitivity to better define the neurocognitive mechanisms underlying spontaneous ToM. Participants watched videos in which an agent acquires a true or false belief about the location of a ball. Thus, the belief of the agent and that of the participant could either match or differ. Importantly, participants were never asked to consider the belief of the agent and were only instructed to press a button when they detected the presence of the ball after an occluder fell at the end of each video. By analysing the blood-oxygen level dependent signal during the belief formation phase for false versus true beliefs, we found a cluster of activation in the right, and to a lesser extent, left posterior parietal cortex spanning the TPJ, but no mPFC activation. Region of interest (ROI) analysis on bilateral TPJ and mPFC confirmed these results and added evidence to the asymmetry in laterality of the TPJ in spontaneous ToM. Interestingly, the whole brain analysis, supported by an overlap with brain maps, revealed maximum activation in areas involved in visuospatial working memory and attention switching functions, such as the supramarginal gyrus, the middle temporal gyrus, and the inferior frontal gyrus. By contrast, evidence for the presence of brain-behaviour correlations was mixed and there was no evidence for functional connectivity between the TPJ and mPFC. Taken together, these findings help clarifying the brain system supporting spontaneous ToM.

ERS statement on respiratory muscle testing at rest and during exercise.

Assessing respiratory mechanics and muscle function is critical for both clinical practice and research purposes. Several methodological developments over the past two decades have enhanced our understanding of respiratory muscle function and responses to interventions across the spectrum of health and disease. They are especially useful in diagnosing, phenotyping and assessing treatment efficacy in patients with respiratory symptoms and neuromuscular diseases. Considerable research has been undertaken over the past 17 years, since the publication of the previous American Thoracic Society (ATS)/European Respiratory Society (ERS) statement on respiratory muscle testing in 2002. Key advances have been made in the field of mechanics of breathing, respiratory muscle neurophysiology (electromyography, electroencephalography and transcranial magnetic stimulation) and on respiratory muscle imaging (ultrasound, optoelectronic plethysmography and structured light plethysmography). Accordingly, this ERS task force reviewed the field of respiratory muscle testing in health and disease, with particular reference to data obtained since the previous ATS/ERS statement. It summarises the most recent scientific and methodological developments regarding respiratory mechanics and respiratory muscle assessment by addressing the validity, precision, reproducibility, prognostic value and responsiveness to interventions of various methods. A particular emphasis is placed on assessment during exercise, which is a useful condition to stress the respiratory system.

A Principle of Neuromechanical Matching for Motor Unit Recruitment in Human Movement.

What determines which motor units are active in a motor task? In the respiratory muscles, motor units are recruited according to their mechanical advantages. We describe a principle of motor unit recruitment by neuromechanical matching due to mechanisms in the spinal cord that sculpt descending drive to motoneurons. This principle may be applicable to movements in nonrespiratory muscles.

Abdominal functional electrical stimulation to assist ventilator weaning in critical illness: a double-blinded, randomised, sham-controlled pilot study.

BACKGROUND: For every day a person is dependent on mechanical ventilation, respiratory and cardiac complications increase, quality of life decreases and costs increase by > $USD 1500. Interventions that improve respiratory muscle function during mechanical ventilation can reduce ventilation duration. The aim of this pilot study was to assess the feasibility of employing an abdominal functional electrical stimulation (abdominal FES) training program with critically ill mechanically ventilated patients. We also investigated the effect of abdominal FES on respiratory muscle atrophy, mechanical ventilation duration and intensive care unit (ICU) length of stay. METHODS: Twenty critically ill mechanically ventilated participants were recruited over a 6-month period from one metropolitan teaching hospital. They were randomly assigned to receive active or sham (control) abdominal FES for 30 min, twice per day, 5 days per week, until ICU discharge. Feasibility was assessed through participant compliance to stimulation sessions. Abdominal and diaphragm muscle thickness were measured using ultrasound 3 times in the first week, and weekly thereafter by a blinded assessor. Respiratory function was recorded when the participant could first breathe independently and at ICU discharge, with ventilation duration and ICU length of stay also recorded at ICU discharge by a blinded assessor. RESULTS: Fourteen of 20 participants survived to ICU discharge (8, intervention; 6, control). One control was transferred before extubation, while one withdrew consent and one was withdrawn for staff safety after extubation. Median compliance to stimulation sessions was 92.1% (IQR 5.77%) in the intervention group, and 97.2% (IQR 7.40%) in the control group (p = 0.384). While this pilot study is not adequately powered to make an accurate statistical conclusion, there appeared to be no between-group thickness changes of the rectus abdominis (p = 0.099 at day 3), diaphragm (p = 0.652 at day 3) or combined lateral abdominal muscles (p = 0.074 at day 3). However, ICU length of stay (p = 0.011) and ventilation duration (p = 0.039) appeared to be shorter in the intervention compared to the control group. CONCLUSIONS: Our compliance rates demonstrate the feasibility of using abdominal FES with critically ill mechanically ventilated patients. While abdominal FES did not lead to differences in abdominal muscle or diaphragm thickness, it may be an effective method to reduce ventilation duration and ICU length of stay in this patient group. A fully powered study into this effect is warranted. TRIAL REGISTRATION: The Australian New Zealand Clinical Trials Registry, ACTRN12617001180303. Registered 9 August 2017.

Inspiratory pre-motor potentials during quiet breathing in ageing and chronic obstructive pulmonary disease.

KEY POINTS: A cortical contribution to breathing, as indicated by a Bereitschaftspotential (BP) in averaged electroencephalographic signals, occurs in healthy individuals when external inspiratory loads are applied. Chronic obstructive pulmonary disease (COPD) is a condition where changes in the lung, chest wall and respiratory muscles produce an internal inspiratory load. These changes also occur in normal ageing, although to a lesser extent. In the present study, we determined whether BPs are present during quiet breathing and breathing with an external inspiratory load in COPD compared to age-matched and young healthy controls. We demonstrated that increased age, rather than COPD, is associated with a cortical contribution to quiet breathing. A cortical contribution to inspiratory loading is associated with more severe dyspnoea (i.e. the sensation of breathlessness). We propose that cortical mechanisms may be engaged to defend ventilation in ageing with dyspnoea as a consequence. ABSTRACT: A cortical contribution to breathing is determined by the presence of a Bereitschaftspotential, a low amplitude negativity in the averaged electroencephalographic (EEG) signal, which begins ∼1 s before inspiration. It occurs in healthy individuals when external inspiratory loads to breathing are applied. In chronic obstructive pulmonary disease (COPD), changes in the lung, chest wall and respiratory muscles produce an internal inspiratory load. We hypothesized that there would be a cortical contribution to quiet breathing in COPD and that a cortical contribution to breathing with an inspiratory load would be linked to dyspnoea, a major symptom of COPD. EEG activity was analysed in 14 participants with COPD (aged 57-84 years), 16 healthy age-matched (57-87 years) and 15 young (18-26 years) controls during quiet breathing and inspiratory loading. The presence of Bereitschaftspotentials, from ensemble averages of EEG epochs at Cz and FCz, were assessed by blinded assessors. Dyspnoea was rated using the Borg scale. The incidence of a cortical contribution to quiet breathing was significantly greater in participants with COPD (6/14) compared to the young (0/15) (P = 0.004) but not the age-matched controls (6/16) (P = 0.765). A cortical contribution to inspiratory loading was associated with higher Borg ratings (P = 0.007), with no effect of group (P = 0.242). The data show that increased age, rather than COPD, is associated with a cortical contribution to quiet breathing. A cortical contribution to inspiratory loading is associated with more severe dyspnoea. We propose that cortical mechanisms may be engaged to defend ventilation with dyspnoea as a consequence.

The Antifungal Properties of Epidermal Fatty Acid Esters: Insights from White-Nose Syndrome (WNS) in Bats.

Numerous free fatty acids (FFAs) are known to have potent antifungal effects. The mammalian epidermis contains both FFAs and multiple classes of fatty acid esters, including 1-monoacylglycerols and wax esters. We thus hypothesized that wax esters and 1-monoacylglycerols composed of antifungal fatty acids would also have antifungal properties. We tested this hypothesis by examining the effects of 1-monoacylglycerols, 1,3-diacylglycerols, and wax esters on the growth of Pseudogymnoascus destructans (Pd), the fungus that causes White-nose Syndrome (WNS) in North American bats by invading their epidermis. Laboratory experiments with Pd cultures demonstrated that: (a) three 1-monoacylglycerols (1-monopalmitolein, 1-monoolein, and 1-monolinolein), as well as, (b) two wax esters, behenyl oleate and behenyl palmitoleate, profoundly inhibit Pd growth. The normal growth cycle of Pd was interrupted by addition of two cholesterol esters to the media as well. A bat species resistant to cutaneous Pd infections has these 1-monoacylglycerols in the epidermis, and another Pd resistant bat species has these wax esters in the sebum, thus cutaneous lipid composition is one factor which enables some bats to avoid WNS. Our experiments also revealed that the fatty acid esters which inhibit Pd growth are not hydrolyzed by the lipases secreted by this fungus, whereas the esters that do not inhibit Pd growth are hydrolyzed.

Task-dependent output of human parasternal intercostal motor units across spinal levels.

KEY POINTS: During breathing, there is differential activity in the human parasternal intercostal muscles and the activity is tightly coupled to the known mechanical advantages for inspiration of the same regions of muscles. It is not known whether differential activity is preserved for the non-respiratory task of ipsilateral trunk rotation. In the present study, we compared single motor units during resting breathing and axial rotation of the trunk during apnoea. We not only confirmed non-uniform recruitment of motor units across parasternal intercostal muscles in breathing, but also demonstrated that the same motor units show an altered pattern of recruitment in the non-respiratory task of trunk rotation. The output of parasternal intercostal motoneurones is modulated differently across spinal levels depending on the task and these results help us understand the mechanisms that may govern task-dependent differences in motoneurone output. ABSTRACT: During inspiration, there is differential activity in the human parasternal intercostal muscles across interspaces. We investigated whether the earlier recruitment of motor units in the rostral interspaces compared to more caudal spaces during inspiration is preserved for the non-respiratory task of ipsilateral trunk rotation. Single motor unit activity (SMU) was recorded from the first, second and fourth parasternal interspaces on the right side in five participants in two tasks: resting breathing and 'isometric' axial rotation of the trunk during apnoea. Recruitment of the same SMUs was compared between tasks (n = 123). During resting breathing, differential activity was indicated by earlier recruitment of SMUs in the first and second interspaces compared to the fourth space in inspiration (P < 0.01). By contrast, during trunk rotation, the same motor units showed an altered pattern of recruitment because SMUs in the first interspace were recruited later and at a higher rotation torque than those in the second and fourth interspaces (P < 0.05). Tested for a subset of SMUs, the reliability of the breathing and rotation tasks, as well as the SMU recruitment measures, was good-excellent [intraclass correlation (2,1): 0.69-0.91]. Thus, the output of parasternal intercostal motoneurones is modulated differently across spinal levels depending on the task. Given that the differential inspiratory output of parasternal intercostal muscles is linked to their relative mechanical effectiveness for inspiration and also that this output is altered in trunk rotation, we speculate that a mechanism matching neural drive to muscle mechanics underlies the task-dependent differences in output of axial motoneurone pools.

Electroencephalographic detection of respiratory-related cortical activity in humans: from event-related approaches to continuous connectivity evaluation.

The presence of a respiratory-related cortical activity during tidal breathing is abnormal and a hallmark of respiratory difficulties, but its detection requires superior discrimination and temporal resolution. The aim of this study was to validate a computational method using EEG covariance (or connectivity) matrices to detect a change in brain activity related to breathing. In 17 healthy subjects, EEG was recorded during resting unloaded breathing (RB), voluntary sniffs, and breathing against an inspiratory threshold load (ITL). EEG were analyzed by the specially developed covariance-based classifier, event-related potentials, and time-frequency (T-F) distributions. Nine subjects repeated the protocol. The classifier could accurately detect ITL and sniffs compared with the reference period of RB. For ITL, EEG-based detection was superior to airflow-based detection (P < 0.05). A coincident improvement in EEG-airflow correlation in ITL compared with RB (P < 0.05) confirmed that EEG detection relates to breathing. Premotor potential incidence was significantly higher before inspiration in sniffs and ITL compared with RB (P < 0.05), but T-F distributions revealed a significant difference between sniffs and RB only (P < 0.05). Intraclass correlation values ranged from poor (-0.2) to excellent (1.0). Thus, as for conventional event-related potential analysis, the covariance-based classifier can accurately predict a change in brain state related to a change in respiratory state, and given its capacity for near "real-time" detection, it is suitable to monitor the respiratory state in respiratory and critically ill patients in the development of a brain-ventilator interface.

Short-latency inhibitory reflex responses to inspiratory loading of the scalene muscles are impaired in spinal cord injury.

NEW FINDINGS: What is the central question of this study? The aim was to determine whether the reflex inhibition in the electromyographic activity of scalene muscles in response to inspiratory muscle loading is present in individuals with cervical spinal cord injury and to examine whether the intercostal muscle afferents are critical for genesis of the reflex. What is the main finding and its importance? The lack of reflex inhibition in response to inspiratory loading in individuals with complete cervical spinal cord injury suggests that the reflex critically requires input from intercostal afferents and/or an intact intersegmental neural network. In healthy individuals, transient loading of inspiratory muscles with a brief inspiratory occlusion produces a short-latency inhibitory response (IR) in the electromyographic activity of scalene muscles at ∼40 ms, followed by an excitatory response (ER). It has been argued that this reflex plays a protective role in neuromuscular control of the inspiratory muscles and that it is co-ordinated by spinal segmental or supraspinal circuits. In this study, the reflex response to airway occlusion was recorded bilaterally from scalene muscles in 14 subjects and from the right costal diaphragm in seven subjects with spinal cord injury [SCI, C4-C6; American Spinal Injury Association (ASIA) Impairment Scale (AIS) A]. The incidence, latency and size of the reflex were compared with previously published data from able-bodied subjects. Only two subjects with SCI showed an IR, and six subjects had an ER. Latencies to the onset and peak of the IR and ER were 5-50 ms longer than in able-bodied subjects. However, when reflexes were identified, their size in individuals with SCI was similar to that of control subjects. We conclude that afferents from the scalene muscles and diaphragm are insufficient in most subjects with SCI to evoke the usual inhibition to airway occlusion and that input from chest wall afferents below the spinal cord lesion may be important for genesis of the short-latency inhibition in the able-bodied subjects.

Graded onset of parasternal intercostal inspiratory activity detected with surface electromyography in healthy young females and males.

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.