The pathobiology of psychomotor slowing in psychosis: altered cortical excitability and connectivity.

Psychomotor slowing is a frequent symptom of schizophrenia. Short-interval intracortical inhibition assessed by transcranial magnetic stimulation demonstrated inhibitory dysfunction in schizophrenia. The inhibitory deficit results from additional noise during information processing in the motor system in psychosis. Here, we tested whether cortical inhibitory dysfunction was linked to psychomotor slowing and motor network alterations. In this cross-sectional study, we included 60 patients with schizophrenia and psychomotor slowing determined by the Salpêtrière Retardation Rating Scale, 23 patients without slowing and 40 healthy control participants. We acquired single and double-pulse transcranial magnetic stimulation effects from the left primary motor cortex, resting-state functional connectivity and diffusion imaging on the same day. Groups were compared on resting motor threshold, amplitude of the motor evoked potentials, as well as short-interval intracortical inhibition. Regression analyses calculated the association between motor evoked potential amplitudes or cortical inhibition with seed-based resting-state functional connectivity from the left primary motor cortex and fractional anisotropy at whole brain level and within major motor tracts. In patients with schizophrenia and psychomotor slowing, we observed lower amplitudes of motor evoked potentials, while the short-interval intracortical inhibition/motor evoked potentials amplitude ratio was higher than in healthy controls, suggesting lower cortical inhibition in these patients. Patients without slowing also had lower amplitudes of motor evoked potentials. Across the combined patient sample, cortical inhibition deficits were linked to more motor coordination impairments. In patients with schizophrenia and psychomotor slowing, lower amplitudes of motor evoked potentials were associated with lower fractional anisotropy in motor tracts. Moreover, resting-state functional connectivity between the primary motor cortex, the anterior cingulate cortex and the cerebellum increased with stronger cortical inhibition. In contrast, in healthy controls and patients without slowing, stronger cortical inhibition was linked to lower resting-state functional connectivity between the left primary motor cortex and premotor or parietal cortices. Psychomotor slowing in psychosis is linked to less cortical inhibition and aberrant functional connectivity of the primary motor cortex. Higher neural noise in the motor system may drive psychomotor slowing and thus may become a treatment target.

Psychomotor Slowing in Psychosis and Inhibitory Repetitive Transcranial Magnetic Stimulation: A Randomized Clinical Trial.

Importance: Psychomotor slowing is a frequent symptom of psychosis, impairing gross and fine motor behavior. It is associated with poor outcomes and functioning, and no treatment is available. Objective: To investigate whether 15 sessions of inhibitory repetitive transcranial magnetic stimulation (rTMS) may reduce psychomotor slowing. Design, Setting, and Participants: This was a 4-arm, double-blind, randomized, sham-controlled trial at a university hospital in Switzerland. Enrollment took place from March 2019 to August 2022. Adults aged 18 to 60 years with schizophrenia spectrum disorders and severe psychomotor slowing were eligible. All patients continued existing medications, including antipsychotics and benzodiazepines. Those with substance misuse (other than nicotine), conditions associated with impaired or aberrant movement, convulsions, history of hearing problems, other conditions typically excluded from magnetic resonance imaging or TMS, any TMS treatment in the past 3 months, or those who were pregnant or breastfeeding were excluded. Of 615 patients screened for eligibility, 103 were randomized and 88 received at least 1 session of rTMS: 22 were assigned to 1-Hz rTMS, 22 to iTBS, 22 to sham, and 22 to the waiting group. Follow-up was conducted at 6 weeks and 24 weeks following the week 3 assessments including clinical, functional, and motor measures. Interventions: Fifteen sessions of rTMS in 3 weeks over the supplementary motor area: 1-Hz rTMS, iTBS, sham, or no treatment (waiting). After 3 weeks, the waiting group received 15 sessions of 1-Hz rTMS over the supplementary motor area. Main Outcomes and Measures: The main outcome was the proportion of responders at week 3 in the Salpêtrière Retardation Rating Scale (SRRS) defined as a 30% or greater reduction from baseline (last-observation-carried-forward). The SRRS has 15 items and a maximum total score of 60. Results: Of the 88 participants analyzed, 45 were men and 43 were women. The mean (SD) age was 36.3 (12.4) years and the mean (SD) SRRS score was 24.0 (5.9). A total of 69 participants completed the study. At week 3, response rates differed between groups: 15 of 22 (68%) in the 1-Hz rTMS group, 8 of 22 (36%) in the iTBS group, 7 of 22 (32%) in the sham group, and 4 of 22 (18%) in the waiting group (χ23 = 12.1; P = .007). The 1-Hz rTMS group had more responders than sham (odds ratio [OR], 0.13; 95% CI, 0.02-0.65; P = .03), iTBS (OR, 0.12; 95% CI, 0.02-0.61; P = .02), and waiting (OR, 0.04; 95% CI, 0.01-0.22; P = .003). In the waiting group, 10 of 16 participants (63%) responded after receiving 15 sessions of 1-Hz rTMS. No serious adverse events occurred. Conclusions and Relevance: In this study, inhibitory add-on rTMS safely alleviated psychomotor slowing in psychosis compared with iTBS, sham, and no treatment. The treatment was also effective with delayed onset. Future studies need to explore the neural changes associated with supplementary motor area rTMS in psychosis. Trial Registration: ClinicalTrials.gov Identifier: NCT03921450.

The neural signature of psychomotor disturbance in depression.

Up to 70% of patients with major depressive disorder present with psychomotor disturbance (PmD), but at the present time understanding of its pathophysiology is limited. In this study, we capitalized on a large sample of patients to examine the neural correlates of PmD in depression. This study included 820 healthy participants and 699 patients with remitted (n = 402) or current (n = 297) depression. Patients were further categorized as having psychomotor retardation, agitation, or no PmD. We compared resting-state functional connectivity (ROI-to-ROI) between nodes of the cerebral motor network between the groups, including primary motor cortex, supplementary motor area, sensory cortex, superior parietal lobe, caudate, putamen, pallidum, thalamus, and cerebellum. Additionally, we examined network topology of the motor network using graph theory. Among the currently depressed 55% had PmD (15% agitation, 29% retardation, and 11% concurrent agitation and retardation), while 16% of the remitted patients had PmD (8% retardation and 8% agitation). When compared with controls, currently depressed patients with PmD showed higher thalamo-cortical and pallido-cortical connectivity, but no network topology alterations. Currently depressed patients with retardation only had higher thalamo-cortical connectivity, while those with agitation had predominant higher pallido-cortical connectivity. Currently depressed patients without PmD showed higher thalamo-cortical, pallido-cortical, and cortico-cortical connectivity, as well as altered network topology compared to healthy controls. Remitted patients with PmD showed no differences in single connections but altered network topology, while remitted patients without PmD did not differ from healthy controls in any measure. We found evidence for compensatory increased cortico-cortical resting-state functional connectivity that may prevent psychomotor disturbance in current depression, but may perturb network topology. Agitation and retardation show specific connectivity signatures. Motor network topology is slightly altered in remitted patients arguing for persistent changes in depression. These alterations in functional connectivity may be addressed with non-invasive brain stimulation.

Epidemiology and pathogenicity of M. equirhinis in equine respiratory disorders.

Mycoplasmas are pathogens involved in respiratory disorders of various animal hosts. In horses, Mycoplasma (M.) equirhinis is the species most frequently detected in clinical respiratory specimens, with a prevalence of 12-16%, but its clinical implication in equine respiratory disorders remains unclear. Here we screened 1948 clinical specimens for the presence of M. equirhinis. The samples were both tracheal washes (TW) and bronchoalveolar lavages (BAL) collected by veterinarians in France in day-to-day work between 2020 and 2022. The samples were associated with a standardized form that served to collect key general and clinical information, such as horse age, breed, and living environment. M. equirhinis was detected using a combination of culture and post-enrichment PCR. Other diagnostic data included virology and bacteriology as well as neutrophil counts, when available. Prevalence of M. equirhinis was examined as a function of a clinical score based on four significant clinical signs (nasal discharge, cough, dyspnoea, and hyperthermia). Multivariate logistic regression analysis was run to identify risk factors for the presence of M. equirhinis, and comparative prevalence analysis was used to test for association with other bacteria and viruses. TW and BAL were analysed independently, as we found that TW samples were associated with a higher prevalence of M. equirhinis. As prevalence remained steady whatever the clinical score, M. equirhinis cannot be considered a primary pathogen. M. equirhinis was more frequently isolated in thoroughbreds and trotters and in horses living exclusively stabled compared to other horses or other living environments. M. equirhinis was never detected in BAL specimens with a 'normal' neutrophil count, i.e. 5%, suggesting it could be associated with an inflammatory response, similar to that observed in equine asthma. Prevalence of M. equirhinis was shown to increase in the presence of other bacteria such as Streptococcus equi subsp. zooepidemicus (S. zoo) or viruses, and S. zoo load was higher in M. equirhinis-positive samples, suggesting a potential increase of clinical signs in the event of co-infection.

In vivo expansion of gene-targeted hepatocytes through transient inhibition of an essential gene.

Homology Directed Repair (HDR)-based genome editing is an approach that could permanently correct a broad range of genetic diseases. However, its utility is limited by inefficient and imprecise DNA repair mechanisms in terminally differentiated tissues. Here, we tested "Repair Drive", a novel method for improving targeted gene insertion in the liver by selectively expanding correctly repaired hepatocytes in vivo. Our system consists of transient conditioning of the liver by knocking down an essential gene, and delivery of an untargetable version of the essential gene in cis with a therapeutic transgene. We show that Repair Drive dramatically increases the percentage of correctly targeted hepatocytes, up to 25%. This resulted in a five-fold increased expression of a therapeutic transgene. Repair Drive was well-tolerated and did not induce toxicity or tumorigenesis in long term follow up. This approach will broaden the range of liver diseases that can be treated with somatic genome editing.

Neural Correlates of Formal Thought Disorder Dimensions in Psychosis.

BACKGROUND AND HYPOTHESIS: Formal thought disorder (FTD) is a core symptom of psychosis, but its neural correlates remain poorly understood. This study tested whether four FTD dimensions differ in their association with brain perfusion and brain structure. STUDY DESIGN: This cross-sectional study investigated 110 patients with schizophrenia spectrum disorders using 3T magnetic resonance imaging (MRI). The Thought and Language Disorder scale (TALD) was utilized, which comprises four subscales: Objective Positive (OP), Objective Negative (ON), Subjective Positive (SP), and Subjective Negative (SN). Resting-state cerebral blood flow (rsCBF), cortical thickness (CortTh), gray matter volume (GMV), and diffusion MRI tractography were tested for associations with TALD subscales controlling for age, medication, total intracranial volume, and for variance of the 3 other TALD subscales. STUDY RESULTS: Following Bonferroni correction, the FTD dimensions presented distinct neural correlates. OP scores were associated with increased rsCBF and increased GMV in the right cerebellum lingual gyrus. Higher SP scores were linked to increased GMV in bilateral prefrontal cortex. In contrast, ON was associated with increased GMV in the right premotor cortex. At more liberal statistical thresholds, higher SP was associated with increased CortTh in the right inferior frontal gyrus, whereas SN scores were linked to decreased GMV in the right prefrontal lobe, the left inferior temporal gyrus, and the left supplementary motor area. Unadjusted analyses mostly corroborated these findings. CONCLUSION: These findings stress the heterogeneity in FTD, suggesting distinct neural patterns for specific FTD experiences. In sum, FTD in psychosis may require distinct treatment strategies and further mechanistic investigations on single-item levels.

The Behavioral Mapping of Psychomotor Slowing in Psychosis Demonstrates Heterogeneity Among Patients Suggesting Distinct Pathobiology.

OBJECTIVES: Psychomotor slowing (PS) occurs in up to half of schizophrenia patients and is linked to poorer outcomes. As standard treatment fails to improve PS, novel approaches are needed. Here, we applied the RDoC framework using 3 units of analysis, ie, behavior, self-report, and physiology to test, whether patients with PS are different from patients without PS and controls. METHODS: Motor behavior was compared between 71 schizophrenia patients with PS, 25 without PS, and 42 healthy controls (HC) using 5 different measures: (1) for behavior, an expert rating scale: Motor score of the Salpêtrière Retardation Rating Scale, (2) for self-report, the International Physical Activity Questionnaire; and for physiology, (3) Actigraphy, which accounts for gross motor behavior, (4) Gait velocity, and (5) coin rotation task to assess manual dexterity. RESULTS: The ANCOVAs comparing the 3 groups revealed differences between patients with PS and HC in expert ratings, self-report, and instrumental measures (all P ≤ .001). Patients with PS also scored higher in expert ratings and had lower instrumental activity levels compared to patients without PS (all P ≤ .045). Instrumental activity levels correlated with an expert rating of PS (rho = -0.51, P-fdr corrected <.001) and classified similarly at 72% accuracy. CONCLUSIONS: PS is characterized by slower gait, lower activity levels, and slower finger movements compared to HC. However, only actigraphy and observer ratings enable to clearly disentangle PS from non-PS patients. Actigraphy may become the standard assessment of PS in neuroimaging studies and clinical trials.

Test-retest reliability of a finger-tapping fMRI task in a healthy population.

Measuring brain activity during functional MRI (fMRI) tasks is one of the main tools to identify brain biomarkers of disease or neural substrates associated with specific symptoms. However, identifying correct biomarkers relies on reliable measures. Recently, poor reliability was reported for task-based fMRI measures. The present study aimed to demonstrate the reliability of a finger-tapping fMRI task across two sessions in healthy participants. Thirty-one right-handed healthy participants aged 18-60 years took part in two MRI sessions 3 weeks apart during which we acquired finger-tapping task-fMRI. We examined the overlap of activations between sessions using Dice similarity coefficients, assessing their location and extent. Then, we compared amplitudes calculating intraclass correlation coefficients (ICCs) in three sets of regions of interest (ROIs) in the motor network: literature-based ROIs (10-mm-radius spheres centred on peaks of an activation likelihood estimation), anatomical ROIs (regions as defined in an atlas) and ROIs based on conjunction analyses (superthreshold voxels in both sessions). Finger tapping consistently activated expected regions, for example, left primary sensorimotor cortices, premotor area and right cerebellum. We found good-to-excellent overlap of activations for most contrasts (Dice coefficients: .54-.82). Across time, ICCs showed large variability in all ROI sets (.04-.91). However, ICCs in most ROIs indicated fair-to-good reliability (mean = .52). The least specific contrast consistently yielded the best reliability. Overall, the finger-tapping task showed good spatial overlap and fair reliability of amplitudes on group level. Although caution is warranted in interpreting correlations of activations with other variables, identification of activated regions in response to a task and their between-group comparisons are still valid and important modes of analysis in neuroimaging to find population tendencies and differences.

Psychomotor slowing alters gait velocity, cadence, and stride length and indicates negative symptom severity in psychosis.

Schizophrenia is a severe mental disorder, in which 50% of the patients present with motor abnormalities such as psychomotor slowing. Slow spontaneous gait has been reported in schizophrenia. However, comprehensive objective instrumental assessments of multiple gait conditions are missing. Finally, the specific gait patterns of subjects with psychomotor slowing are still unknown. Therefore, this study aimed to objectively assess multiple gait parameters at different walking conditions in patients with schizophrenia with and without psychomotor slowing. Also, we hypothesised gait impairments to correlate with expert ratings of hypokinetic movement disorders and negative symptoms. We collected gait data (GAITRite®) in 70 patients with psychomotor slowing (SRRS (Salpetriere retardation rating scale) ≥15), 22 non-psychomotor slowed patients (SRRS < 15), and 42 healthy controls. Participants performed four walking conditions (self-selected speed, maximum speed, head reclined, and eyes closed) and six gait parameters were extracted (velocity, cadence, stride length, functional ambulation profile (FAP), and variance of stride length and time). Patients with psychomotor slowing presented slower velocity, lower cadence, and shorter stride length in all walking conditions compared to healthy controls, with the non-slowed patients in an intermediate position (all F > 16.18, all p < 0.001). Secondly, slower velocity was associated with more severe hypokinetic movement disorders and negative symptoms. In conclusion, gait impairments exist in a spectrum with healthy controls on one end and patients with psychomotor slowing on the other end. Patients with psychomotor slowing are specifically impaired when an adaptation of gait patterns is required, contributing to the deleterious effects of sedentary behaviours.

ANGPTL7, a therapeutic target for increased intraocular pressure and glaucoma.

Glaucoma is a leading cause of blindness. Current glaucoma medications work by lowering intraocular pressure (IOP), a risk factor for glaucoma, but most treatments do not directly target the pathological changes leading to increased IOP, which can manifest as medication resistance as disease progresses. To identify physiological modulators of IOP, we performed genome- and exome-wide association analysis in >129,000 individuals with IOP measurements and extended these findings to an analysis of glaucoma risk. We report the identification and functional characterization of rare coding variants (including loss-of-function variants) in ANGPTL7 associated with reduction in IOP and glaucoma protection. We validated the human genetics findings in mice by establishing that Angptl7 knockout mice have lower (~2 mmHg) basal IOP compared to wild-type, with a trend towards lower IOP also in heterozygotes. Conversely, increasing murine Angptl7 levels via injection into mouse eyes increases the IOP. We also show that acute Angptl7 silencing in adult mice lowers the IOP (~2-4 mmHg), reproducing the observations in knockout mice. Collectively, our data suggest that ANGPTL7 is important for IOP homeostasis and is amenable to therapeutic modulation to help maintain a healthy IOP that can prevent onset or slow the progression of glaucoma.

Structural alterations of the motor cortex and higher order cortical areas suggest early neurodevelopmental origin of catatonia in schizophrenia.

The neurobiology of catatonia is still poorly understood. Particularly structural MRI studies yielded conflicting results. Heterogeneity of findings was suggested to stem from specifics of different rating scales. This study sought to test grey matter differences between patients with catatonia, patients without catatonia, and healthy controls using the two main instruments of catatonia rating. We included 98 patients with schizophrenia spectrum disorders and 42 healthy controls. Catatonia was measured using the Bush Francis Catatonia Rating Scale and the Northoff Catatonia Rating Scale. According to these scales, patients were classified into those with and those without catatonia. We tested whole brain grey matter volume, cortical thickness, and local gyrification across groups. Both catatonia rating scales correlated at tau = 0.65 but failed to classify identical subjects as catatonia patients. However, group differences in grey matter parameters were broadly similar with either rating scale to identify catatonia cases. Catatonia patients had reduced grey matter volume compared to controls in a large network including orbitofrontal cortex, cingulate, thalamus, and amygdala. While there was no group difference in cortical thickness, catatonia patients had increased local gyrification in premotor, motor, and parietal cortices compared to controls. Hypergyrification of the motor cortex and higher order cortical areas was found in catatonia patients compared to patients without catatonia. Both catatonia rating scales find similar symptom severity and group differences in grey matter indices. Catatonia is linked to reduced grey matter volume and increased local gyrification, suggesting some impact of early neurodevelopmental insults.

Measuring catatonia motor behavior with objective instrumentation.

Objective: Catatonia is a neuropsychiatric syndrome, with important psychomotor features, associated with schizophrenia and other psychiatric disorders. The syndrome comprises multiple symptoms including abnormal motor control, behaviors, volition, and autonomic regulation. Catatonia assessment relies on clinical rating scales and clinicians familiar with the catatonia exam. However, objective instrumentation may aid the detection of catatonia. We aimed to investigate the relationship between movement parameters derived from actigraphy and expert ratings of catatonia symptoms measured by the Bush Francis Catatonia Rating Scale (BFCRS) and the Northoff Catatonia scale (NCS). Methods: Eighty-six acutely ill inpatients with schizophrenia spectrum disorders were assessed with the BFCRS, the NCS, and 24 h continuous actigraphy. Non-wear and sleep periods were removed from the actigraphy data prior to analysis. Associations between total catatonia scores, derived from both BFCRS and NCS, and actigraphy parameters as well as between single BFCRS items and actigraphy parameters were calculated using Spearman's rank correlation and non-parametric ANCOVAs (Quade's ANCOVAs), respectively. Results: Both higher BFCRS total scores (r = 0.369, p = 0.006) and NCS total scores (r = 0.384, p = 0.004) were associated with lower activity levels (AL). Higher scores on single BFCRS items such as immobility/stupor or staring were linked to lower AL (immobility/stupor: F = 17.388, p < 0.001, η2 = 0.175; staring: F = 7.849, p = 0.001, η2 = 0.162) and lower metabolic equivalents of task (MET). Conclusion: Specific catatonia symptoms such as immobility/stupor and staring can be measured with actigraphy. This may aid the detection, staging, and monitoring of catatonia in clinical settings.

Perceptions and Experiences of Nutrition Interventions in Individuals with Amyotrophic Lateral Sclerosis (ALS) and their Caregivers.

Nutrition concerns are prevalent in individuals with Amyotrophic Lateral Sclerosis (ALS). Despite the prevalence of nutrition concerns, few data are available on perceptions and experiences of nutrition interventions in individuals with ALS and their caregivers; this study aimed to collect this information. An online survey was developed and hosted on Survey Monkey®. Individuals with ALS and their caregivers from Saskatchewan, Canada, were invited to complete the survey through email to attendees of the ALS Clinic (Saskatoon, Canada), and via the ALS Society of Saskatchewan Facebook page in February-March, 2021. Quantitative data were analyzed using descriptive statistics. Twelve eligible respondents completed the survey (n = 10 individuals with ALS; n = 2 caregivers). The present study found nutrition was important to respondents and there was interest in trying diets and supplements for ALS management; of note, many respondents were interested in exploring the ketogenic diet. Six (50%) respondents had weight loss concerns. All respondents would recommend consulting with a dietitian upon being diagnosed with ALS. Many respondents reported a predefined negative perception of tube feeding. The results of this study suggest that increasing the accessibility of dietitians could positively impact ALS-related care. The findings also provide guidance for dietitians to enhance nutrition care for individuals with ALS.

Motor abnormalities are associated with poor social and functional outcomes in schizophrenia.

BACKGROUND: Up to 50% of patients with schizophrenia are suffering from motor abnormalities, which may contribute to decreased quality of life, impaired work capacity, and a reduced life expectancy by 10-20 years. However, the effect of motor abnormalities on social and global functioning, as well as, functional capacity is not clear. We hypothesized, that the presence of motor abnormalities is associated with poorer functional outcomes in patients with schizophrenia. METHODS: We collected data on 5 different motor abnormalities in 156 patients suffering from schizophrenia spectrum disorders: parkinsonism, catatonia, dyskinesia, neurological soft signs and psychomotor slowing (PS). Additionally, we used three different scales to evaluate the functional outcomes in these patients: the Global Assessment of Functioning (GAF) and the Social and Occupational Functioning Assessment Scale (SOFAS) which use clinicians' judgment; and one using a performance-based measure of functional capacity, the brief version of the UCSD Performance-based Skills Assessment (UPSA-B). RESULTS: Our analysis demonstrated that patients with catatonia (all F > 4.5; p < 0.035) and parkinsonism (all F > 4.9; p < 0.027) scored lower on GAF and SOFAS compared to patients without catatonia and parkinsonism. In contrast, no significant difference on functional outcomes between patients with dyskinesia versus without dyskinesia exist in our study. Furthermore, there are statistically significant negative correlations for parkinsonism and PS with GAF, SOFAS and UPSA-B (all tau are at least -0.152, p-value <0.036). We also found significant negative correlations between catatonia and both GAF & SOFAS (all tau are at least -0.203, p-value<0.001) and between NES and SOFAS (tau = -0.137, p-value = 0.033). CONCLUSION: Here, we showed that four of the most common motor abnormalities observed in schizophrenia were associated with at least one of the patients' functional outcomes. The stronger the motor impairment was the worse the global and social functioning. Future studies need to test, whether amelioration of motor abnormalities is linked to improved community functioning.

A checklist for assessing the methodological quality of concurrent tES-fMRI studies (ContES checklist): a consensus study and statement.

Low-intensity transcranial electrical stimulation (tES), including alternating or direct current stimulation, applies weak electrical stimulation to modulate the activity of brain circuits. Integration of tES with concurrent functional MRI (fMRI) allows for the mapping of neural activity during neuromodulation, supporting causal studies of both brain function and tES effects. Methodological aspects of tES-fMRI studies underpin the results, and reporting them in appropriate detail is required for reproducibility and interpretability. Despite the growing number of published reports, there are no consensus-based checklists for disclosing methodological details of concurrent tES-fMRI studies. The objective of this work was to develop a consensus-based checklist of reporting standards for concurrent tES-fMRI studies to support methodological rigor, transparency and reproducibility (ContES checklist). A two-phase Delphi consensus process was conducted by a steering committee (SC) of 13 members and 49 expert panelists through the International Network of the tES-fMRI Consortium. The process began with a circulation of a preliminary checklist of essential items and additional recommendations, developed by the SC on the basis of a systematic review of 57 concurrent tES-fMRI studies. Contributors were then invited to suggest revisions or additions to the initial checklist. After the revision phase, contributors rated the importance of the 17 essential items and 42 additional recommendations in the final checklist. The state of methodological transparency within the 57 reviewed concurrent tES-fMRI studies was then assessed by using the checklist. Experts refined the checklist through the revision and rating phases, leading to a checklist with three categories of essential items and additional recommendations: (i) technological factors, (ii) safety and noise tests and (iii) methodological factors. The level of reporting of checklist items varied among the 57 concurrent tES-fMRI papers, ranging from 24% to 76%. On average, 53% of checklist items were reported in a given article. In conclusion, use of the ContES checklist is expected to enhance the methodological reporting quality of future concurrent tES-fMRI studies and increase methodological transparency and reproducibility.

Limbic links to paranoia: increased resting-state functional connectivity between amygdala, hippocampus and orbitofrontal cortex in schizophrenia patients with paranoia.

Paranoia is a frequent and highly distressing experience in psychosis. Models of paranoia suggest limbic circuit pathology. Here, we tested whether resting-state functional connectivity (rs-fc) in the limbic circuit was altered in schizophrenia patients with current paranoia. We collected MRI scans in 165 subjects including 89 patients with schizophrenia spectrum disorders (schizophrenia, schizoaffective disorder, brief psychotic disorder, schizophreniform disorder) and 76 healthy controls. Paranoia was assessed using a Positive And Negative Syndrome Scale composite score. We tested rs-fc between bilateral nucleus accumbens, hippocampus, amygdala and orbitofrontal cortex between groups and as a function of paranoia severity. Patients with paranoia had increased connectivity between hippocampus and amygdala compared to patients without paranoia. Likewise, paranoia severity was linked to increased connectivity between hippocampus and amygdala. Furthermore, paranoia was associated with increased connectivity between orbitofrontal and medial prefrontal cortex. In addition, patients with paranoia had increased functional connectivity within the frontal hubs of the default mode network compared to healthy controls. These results demonstrate that current paranoia is linked to aberrant connectivity within the core limbic circuit and prefrontal cortex reflecting amplified threat processing and impaired emotion regulation. Future studies will need to explore the association between limbic hyperactivity, paranoid ideation and perceived stress.

Tobacco-induced sleep disturbances: A systematic review and meta-analysis.

Even though tobacco-induced sleep disturbances (TISDs) have been reported in previous studies, the present article is the first meta-analysis quantitatively assessing the impact of tobacco on sleep parameters. We conducted a systematic review and meta-analysis of the studies comparing objective (i.e. polysomnography and actigraphy) and/or subjective sleep parameters in chronic tobacco smokers without comorbidities versus healthy controls. Studies were retrieved using PubMed, PsycINFO, and Web of Science. Differences are expressed as standardized mean deviations (SMD) and their 95% confidence intervals (95%CI). Fourteen studies were finally included into the review, among which ten were suitable for meta-analysis. Compared to healthy controls, chronic tobacco users displayed increased N1 percentage (SMD = 0.65, 95%CI: 0.22 to 1.07), N2 percentage (SMD = 1.45, 95%CI: 0.26 to 2.63), wake time after sleep onset (SMD = 6.37, 95%CI: 2.48 to 10.26), and decreased slow-wave sleep (SMD = -2.00, 95%CI: -3.30 to -0.70). Objective TISDs preferentially occurred during the first part of the night. Regarding subjective parameters, only the Pittsburgh Sleep Quality Index (PSQI) total score could be analyzed, with no significant between-groups difference (SMD = 0.53, 95%CI: -0.18 to 1.23). Smoking status should be carefully assessed in sleep medicine, while TISDs should be regularly explored in chronic tobacco users.

Reperfusion Therapy for Acute Stroke in Pregnant and Post-Partum Women: A Canadian Survey.

BACKGROUND/OBJECTIVE: A Canadian Stroke Best Practices consensus statement on Acute Stroke Management during pregnancy was published in 2018. The state of individual practice, however, is unknown. METHODS: A survey on treatment of acute stroke in pregnant and post-partum women was distributed via the Canadian Stroke Consortium email list. Descriptive statistics (frequencies and proportions) were calculated for demographic and response variables and free-text responses were coded for thematic content. RESULTS: Thirty-five participants completed the survey; 12 had experience with intravenous tissue plasminogen activator (IV-tPA), endovascular therapy (EVT), or both in pregnant patients. None had treatment-related complications. The majority (92%) of those who had not yet encountered the issue in practice expressed some reservation about giving IV-tPA to an otherwise eligible pregnant woman. In a theoretical scenario where an otherwise eligible pregnant woman was a candidate for both IV-tPA and EVT, 58% of respondents would have opted for EVT alone. Amongst this cohort comprised mainly of stroke sub-specialists, more than a third had treated pregnant patients with reperfusion therapy. CONCLUSIONS: The reported safety experience with both IV-tPA and EVT was reassuring. Overall, there was a hesitancy towards use of IV-tPA in pregnancy that is discordant with the recent consensus statement. Possible barriers to uptake identified through thematic analysis were concerns regarding risks of bleeding in the pregnant patient, presence of EVT as a perceived alternative, and the need for express consent from the patient and family.

Chest Expansion and Lung Function for Healthy Subjects and Individuals With Pulmonary Disease.

BACKGROUND: The purposes of this study were to verify the correlation between chest expansion and lung function within a larger sample of subjects composed of both healthy subjects and subjects affected by pulmonary disease, and to verify the influence of age, body mass index, and gender on chest expansion. METHODS: Adults were recruited prospectively when they visited the lung function lab. Chest expansion was measured with a measuring tape at 2 different levels of the rib cage by 1 blinded examiner. Spirometry was performed for each subject. RESULTS: Data from 251 subjects between 18 and 88 y old were collected and analyzed. Among the analyzed subjects, mean upper and lower chest expansion were 4.82 ± 1.84 cm and 3.99 ± 2.15 cm, respectively. A significant but poor correlation was found between both chest expansion and all lung function parameters (total lung capacity, FVC, and FEV1) (P = .01). Negative significant correlations were found between chest expansion and age as well as body mass index. The difference in upper chest expansion between obese and nonobese subjects was not statistically significant, but the difference in lower chest expansion was significant for these 2 groups. Finally, upper and lower chest expansion were not different between males and females. CONCLUSIONS: Based on these results, one cannot validate the use of chest expansion measurement to define lung function. In centers that have easy access to more precise and complete methods to measure lung function, the measurement of chest expansion for diagnostic purposes seems to be archaic. Additionally, age and body mass index are 2 parameters that can influence chest expansion.