The Beginning of the AI-Enabled Preventative PAP Therapy Era: A First-in-Human Proof of Concept Interventional Study.

Positive Airway Pressure (PAP) therapy is the most common and efficacious treatment for Obstructive Sleep Apnea (OSA). However, it suffers from poor patient adherence due to discomfort and may not fully alleviate all adverse consequences of OSA. Identifying abnormal respiratory events before they have occurred may allow for improved management of PAP levels, leading to improved adherence and better patient outcomes. Our previous work has resulted in the successful development of a Machine-Learning (ML) algorithm for the prediction of future apneic events using existing airflow and air pressure sensors available internally to PAP devices. Although researchers have studied the use of ML for the prediction of apneas, research to date has focused primarily on using external polysomnography sensors that add to patient discomfort and has not investigated the use of internal-to-PAP sensors such as air pressure and airflow to predict and prevent respiratory events. We hypothesized that by using our predictive software, OSA events could be proactively prevented while maintaining patients' sleep quality. An intervention protocol was developed and applied to all patients to prevent OSA events. Although the protocol's cool-down period limited the number of prevention attempts, analysis of 11 participants revealed that our system improved many sleep parameters, which included a statistically significant 31.6% reduction in Apnea-Hypopnea Index, while maintaining sleep quality. Most importantly, our findings indicate the feasibility of unobtrusive identification and unique prevention of each respiratory event as well as paving the path to future truly personalized PAP therapy by further training of ML models on individual patients.

White matter microstructure predicts measures of clinical symptoms in chronic back pain patients.

Chronic back pain (CBP) has extensive clinical and social implications for its sufferers and is a major source of disability. Chronic pain has previously been shown to have central neural factors underpinning it, including the loss of white matter (WM), however traditional methods of analyzing WM microstructure have produced mixed and unclear results. To better understand these factors, we assessed the WM microstructure of 50 patients and 40 healthy controls (HC) using diffusion-weighted imaging. The data were analyzed using fixel-based analysis (FBA), a higher-order diffusion modelling technique applied to CBP for the first time here. Subjects also answered questionnaires relating to pain, disability, catastrophizing, and mood disorders, to establish the relationship between fixelwise metrics and clinical symptoms. FBA determined that, compared to HC, CBP patients had: 1) lower fibre density (FD) in several tracts, specifically the right anterior and bilateral superior thalamic radiations, right spinothalamic tract, right middle cerebellar peduncle, and the body and splenium of corpus callosum; 2) higher FD in the genu of corpus callosum; and 3) lower FDC - a combined fibre density and cross-section measure - in the bilateral spinothalamic tracts and right anterior thalamic radiation. Exploratory correlations showed strong negative relationships between fixelwise metrics and clinical questionnaire scores, especially pain catastrophizing. These results have important implications for the intake and processing of sensory data in CBP that warrant further investigation.

Resting state functional connectivity in SLE patients and association with cognitive impairment and blood-brain barrier permeability.

OBJECTIVE: Extensive blood-brain barrier (BBB) leakage has been linked to cognitive impairment in SLE. This study aimed to examine the associations of brain functional connectivity (FC) with cognitive impairment and BBB dysfunction among patients with SLE. METHODS: Cognitive function was assessed by neuropsychological testing (n = 77). Resting-state FC (rsFC) between brain regions, measured by functional MRI (n = 78), assessed coordinated neural activation in 131 regions across five canonical brain networks. BBB permeability was measured by dynamic contrast-enhanced MRI (n = 61). Differences in rsFC were compared between SLE patients with cognitive impairment (SLE-CI) and those with normal cognition (SLE-NC), between SLE patients with and without extensive BBB leakage, and with healthy controls. RESULTS: A whole-brain rsFC comparison found significant differences in intra-network and inter-network FC in SLE-CI vs SLE-NC patients. The affected connections showed a reduced negative rsFC in SLE-CI compared with SLE-NC and healthy controls. Similarly, a reduced number of brain-wide connections was found in SLE-CI patients compared with SLE-NC (P = 0.030) and healthy controls (P = 0.006). Specific brain regions had a lower total number of brain-wide connections in association with extensive BBB leakage (P = 0.011). Causal mediation analysis revealed that 64% of the association between BBB leakage and cognitive impairment in SLE patients was mediated by alterations in FC. CONCLUSION: SLE patients with cognitive impairment had abnormalities in brain rsFC which accounted for most of the association between extensive BBB leakage and cognitive impairment.

Top-down threat bias in pain perception is predicted by intrinsic structural and functional connections of the brain.

Top-down processes such as expectations play a key role in pain perception. In specific contexts, inferred threat of impending pain can affect perceived pain more than the noxious intensity. This biasing effect of top-down threats can affect some individuals more strongly than others due to differences in fear of pain. The specific characteristics of intrinsic brain characteristics that mediate the effects of top-down threat bias are mainly unknown. In this study, we examined whether threat bias is associated with structural and functional brain connectivity. The variability in the top-down bias was mapped to the microstructure of white matter in diffusion weighted images (DWI) using MRTrix3. Mean functional connectivity of five canonical resting state networks was tested for association with bias scores and with the identified DWI metrics. We found that the fiber density of the splenium of the corpus callosum was significantly low in individuals with high top-down threat bias (FWE corrected with 5000 permutations, p < 0.05). The mean functional connectivity within the language/memory and between language/memory and default mode networks predicted the bias scores. Functional connectivity within language memory networks predicted the splenium fiber density, higher pain catastrophizing and lower mindful awareness. Probabilistic tractography showed that the identified region in the splenium connected several sensory regions and high-order parietal regions between the two hemispheres, indicating the splenium's role in sensory integration. These findings demonstrate that individuals who show more change in pain with changes in the threat of receiving a stronger noxious stimulus have lower structural connectivity in the pathway necessary for integrating top-down cue information with bottom-up sensory information. Conversely, systems involved in memory recall, semantic and self-referential processing are more strongly connected in people with top-down threat bias.

Symptoms reported by Canadians posted in Havana are linked with reduced white matter fibre density.

Diplomats representing the USA have reported with unusual neurologic symptoms and MRI changes after being posted in Havana, Cuba between late 2016 and 2018. Here, we examined white matter microstructure and network connectivity of individuals stationed in Havana, using diffusion-weighted MRI, fixel-based analysis and structural connectomics as implemented in MRtrix3. MRI data acquisition and clinical assessments were done in a total of 24 diplomats and their family members and 40 healthy controls. The diplomat data were grouped into an exposed cohort (n = 16) and an unexposed cohort (n = 10), and among these, two individuals were assessed before and after potential exposure. Fixel-based analysis revealed a reduction in fibre density in two specific regions: the fornix and the splenium, in exposed individuals, relative to unexposed individuals and healthy controls. Post hoc analyses showed the effect remained present (P < 0.05) in both regions when comparing exposed and unexposed diplomats; and reduced fibre density was correlated with longer time period stationed in Cuba after age correction. Reduction of fibre density was also found to be linked with clinical symptoms of persistent migraine, tinnitus, sound sensitivity and fatigue. Network statistical comparisons revealed decreased structural connectivity in two distinct networks, comprising subcortical and cortical systems in exposed individuals, relative to unexposed and normative data. While the cause for the differences between the groups remains unknown, our results reveal region-specific white matter injury, that is, significantly correlated with clinical symptoms.