Brain-wide correspondence of neuronal epigenomics and distant projections.

Single-cell analyses parse the brain's billions of neurons into thousands of 'cell-type' clusters residing in different brain structures1. Many cell types mediate their functions through targeted long-distance projections allowing interactions between specific cell types. Here we used epi-retro-seq2 to link single-cell epigenomes and cell types to long-distance projections for 33,034 neurons dissected from 32 different regions projecting to 24 different targets (225 source-to-target combinations) across the whole mouse brain. We highlight uses of these data for interrogating principles relating projection types to transcriptomics and epigenomics, and for addressing hypotheses about cell types and connections related to genetics. We provide an overall synthesis with 926 statistical comparisons of discriminability of neurons projecting to each target for every source. We integrate this dataset into the larger BRAIN Initiative Cell Census Network atlas, composed of millions of neurons, to link projection cell types to consensus clusters. Integration with spatial transcriptomics further assigns projection-enriched clusters to smaller source regions than the original dissections. We exemplify this by presenting in-depth analyses of projection neurons from the hypothalamus, thalamus, hindbrain, amygdala and midbrain to provide insights into properties of those cell types, including differentially expressed genes, their associated cis-regulatory elements and transcription-factor-binding motifs, and neurotransmitter use.

The Anatomy and Physiology of Claustrum-Cortex Interactions.

The claustrum is one of the most widely connected regions of the forebrain, yet its function has remained obscure, largely due to the experimentally challenging nature of targeting this small, thin, and elongated brain area. However, recent advances in molecular techniques have enabled the anatomy and physiology of the claustrum to be studied with the spatiotemporal and cell type-specific precision required to eventually converge on what this area does. Here we review early anatomical and electrophysiological results from cats and primates, as well as recent work in the rodent, identifying the connectivity, cell types, and physiological circuit mechanisms underlying the communication between the claustrum and the cortex. The emerging picture is one in which the rodent claustrum is closely tied to frontal/limbic regions and plays a role in processes, such as attention, that are associated with these areas.

Epigenomic diversity of cortical projection neurons in the mouse brain.

Neuronal cell types are classically defined by their molecular properties, anatomy and functions. Although recent advances in single-cell genomics have led to high-resolution molecular characterization of cell type diversity in the brain1, neuronal cell types are often studied out of the context of their anatomical properties. To improve our understanding of the relationship between molecular and anatomical features that define cortical neurons, here we combined retrograde labelling with single-nucleus DNA methylation sequencing to link neural epigenomic properties to projections. We examined 11,827 single neocortical neurons from 63 cortico-cortical and cortico-subcortical long-distance projections. Our results showed unique epigenetic signatures of projection neurons that correspond to their laminar and regional location and projection patterns. On the basis of their epigenomes, intra-telencephalic cells that project to different cortical targets could be further distinguished, and some layer 5 neurons that project to extra-telencephalic targets (L5 ET) formed separate clusters that aligned with their axonal projections. Such separation varied between cortical areas, which suggests that there are area-specific differences in L5 ET subtypes, which were further validated by anatomical studies. Notably, a population of cortico-cortical projection neurons clustered with L5 ET rather than intra-telencephalic neurons, which suggests that a population of L5 ET cortical neurons projects to both targets. We verified the existence of these neurons by dual retrograde labelling and anterograde tracing of cortico-cortical projection neurons, which revealed axon terminals in extra-telencephalic targets including the thalamus, superior colliculus and pons. These findings highlight the power of single-cell epigenomic approaches to connect the molecular properties of neurons with their anatomical and projection properties.

Characterization and biodistribution of under-employed gene therapy vector AAV7.

IMPORTANCE: The use of adeno-associated viruses (AAVs) as gene delivery vectors has vast potential for the treatment of many severe human diseases. Over one hundred naturally existing AAV capsid variants have been described and classified into phylogenetic clades based on their sequences. AAV8, AAV9, AAVrh.10, and other intensively studied capsids have been propelled into pre-clinical and clinical use, and more recently, marketed products; however, less-studied capsids may also have desirable properties (e.g., potency differences, tissue tropism, reduced immunogenicity, etc.) that have yet to be thoroughly described. These data will help build a broader structure-function knowledge base in the field, present capsid engineering opportunities, and enable the use of novel capsids with unique properties.

GluK2 Is a Target for Gene Therapy in Drug-Resistant Temporal Lobe Epilepsy.

OBJECTIVE: Temporal lobe epilepsy (TLE) is characterized by recurrent seizures generated in the limbic system, particularly in the hippocampus. In TLE, recurrent mossy fiber sprouting from dentate gyrus granule cells (DGCs) crea an aberrant epileptogenic network between DGCs which operates via ectopically expressed GluK2/GluK5-containing kainate receptors (KARs). TLE patients are often resistant to anti-seizure medications and suffer significant comorbidities; hence, there is an urgent need for novel therapies. Previously, we have shown that GluK2 knockout mice are protected from seizures. This study aims at providing evidence that downregulating KARs in the hippocampus using gene therapy reduces chronic epileptic discharges in TLE. METHODS: We combined molecular biology and electrophysiology in rodent models of TLE and in hippocampal slices surgically resected from patients with drug-resistant TLE. RESULTS: Here, we confirmed the translational potential of KAR suppression using a non-selective KAR antagonist that markedly attenuated interictal-like epileptiform discharges (IEDs) in TLE patient-derived hippocampal slices. An adeno-associated virus (AAV) serotype-9 vector expressing anti-grik2 miRNA was engineered to specifically downregulate GluK2 expression. Direct delivery of AAV9-anti grik2 miRNA into the hippocampus of TLE mice led to a marked reduction in seizure activity. Transduction of TLE patient hippocampal slices reduced levels of GluK2 protein and, most importantly, significantly reduced IEDs. INTERPRETATION: Our gene silencing strategy to knock down aberrant GluK2 expression demonstrates inhibition of chronic seizure in a mouse TLE model and IEDs in cultured slices derived from TLE patients. These results provide proof-of-concept for a gene therapy approach targeting GluK2 KARs for drug-resistant TLE patients. ANN NEUROL 2023;94:745-761.

Adolescent OCD Patient and Caregiver Perspectives on Identity, Authenticity, and Normalcy in Potential Deep Brain Stimulation Treatment.

The ongoing debate within neuroethics concerning the degree to which neuromodulation such as deep brain stimulation (DBS) changes the personality, identity, and agency (PIA) of patients has paid relatively little attention to the perspectives of prospective patients. Even less attention has been given to pediatric populations. To understand patients' views about identity changes due to DBS in obsessive-compulsive disorder (OCD), the authors conducted and analyzed semistructured interviews with adolescent patients with OCD and their parents/caregivers. Patients were asked about projected impacts to PIA generally due to DBS. All patient respondents and half of caregivers reported that DBS would impact patient self-identity in significant ways. For example, many patients expressed how DBS could positively impact identity by allowing them to explore their identities free from OCD. Others voiced concerns that DBS-related resolution of OCD might negatively impact patient agency and authenticity. Half of patients expressed that DBS may positively facilitate social access through relieving symptoms, while half indicated that DBS could increase social stigma. These views give insights into how to approach decision-making and informed consent if DBS for OCD becomes available for adolescents. They also offer insights into adolescent experiences of disability identity and "normalcy" in the context of OCD.

Repeated closed-head mild traumatic brain injury-induced inflammation is associated with nociceptive sensitization.

BACKGROUND: Individuals who have experienced mild traumatic brain injuries (mTBIs) suffer from several comorbidities, including chronic pain. Despite extensive studies investigating the underlying mechanisms of mTBI-associated chronic pain, the role of inflammation in long-term pain after mTBIs is not fully elucidated. Given the shifting dynamics of inflammation, it is important to understand the spatial-longitudinal changes in inflammatory processes following mTBIs and their effects on TBI-related pain. METHODS: We utilized a recently developed transgenic caspase-1 luciferase reporter mouse model to monitor caspase-1 activation through a thinned skull window in the in vivo setting following three closed-head mTBI events. Organotypic coronal brain slice cultures and acutely dissociated dorsal root ganglion (DRG) cells provided tissue-relevant context of inflammation signal. Mechanical allodynia was assessed by mechanical withdrawal threshold to von Frey and thermal hyperalgesia withdrawal latency to radiant heat. Mouse grimace scale (MGS) was used to detect spontaneous or non-evoked pain. In some experiments, mice were prophylactically treated with MCC950, a potent small molecule inhibitor of NLRP3 inflammasome assembly to inhibit injury-induced inflammatory signaling. Bioluminescence spatiotemporal dynamics were quantified in the head and hind paws, and caspase-1 activation was confirmed by immunoblot. Immunofluorescence staining was used to monitor the progression of astrogliosis and microglial activation in ex vivo brain tissue following repetitive closed-head mTBIs. RESULTS: Mice with repetitive closed-head mTBIs exhibited significant increases of the bioluminescence signals within the brain and paws in vivo for at least one week after each injury. Consistently, immunoblotting and immunofluorescence experiments confirmed that mTBIs led to caspase-1 activation, astrogliosis, and microgliosis. Persistent changes in MGS and hind paw withdrawal thresholds, indicative of pain states, were observed post-injury in the same mTBI animals in vivo. We also observed enhanced inflammatory responses in ex vivo brain slice preparations and DRG for at least 3 days following mTBIs. In vivo treatment with MCC950 significantly reduced caspase-1 activation-associated bioluminescent signals in vivo and decreased stimulus-evoked and non-stimulus evoked nociception. CONCLUSIONS: Our findings suggest that the inflammatory states in the brain and peripheral nervous system following repeated mTBIs are coincidental with the development of nociceptive sensitization, and that these events can be significantly reduced by inhibition of NLRP3 inflammasome activation.

Bearded or smooth? Awns improve yield when wheat experiences heat stress during grain fill in the southeastern United States.

The presence or absence of awns-whether wheat heads are 'bearded' or 'smooth' - is the most visible phenotype distinguishing wheat cultivars. Previous studies suggest that awns may improve yields in heat or water-stressed environments, but the exact contribution of awns to yield differences remains unclear. Here we leverage historical phenotypic, genotypic, and climate data for wheat (Triticum aestivum) to estimate the yield effects of awns under different environmental conditions over a 12-year period in the southeastern USA. Lines were classified as awned or awnless based on sequence data, and observed heading dates were used to associate grain fill periods of each line in each environment with climatic data and grain yield. In most environments, awn suppression was associated with higher yields, but awns were associated with better performance in heat-stressed environments more common at southern locations. Wheat breeders in environments where awns are only beneficial in some years may consider selection for awned lines to reduce year-to-year yield variability, and with an eye towards future climates.

Trust criteria for artificial intelligence in health: normative and epistemic considerations.

Rapid advancements in artificial intelligence and machine learning (AI/ML) in healthcare raise pressing questions about how much users should trust AI/ML systems, particularly for high stakes clinical decision-making. Ensuring that user trust is properly calibrated to a tool's computational capacities and limitations has both practical and ethical implications, given that overtrust or undertrust can influence over-reliance or under-reliance on algorithmic tools, with significant implications for patient safety and health outcomes. It is, thus, important to better understand how variability in trust criteria across stakeholders, settings, tools and use cases may influence approaches to using AI/ML tools in real settings. As part of a 5-year, multi-institutional Agency for Health Care Research and Quality-funded study, we identify trust criteria for a survival prediction algorithm intended to support clinical decision-making for left ventricular assist device therapy, using semistructured interviews (n=40) with patients and physicians, analysed via thematic analysis. Findings suggest that physicians and patients share similar empirical considerations for trust, which were primarily epistemic in nature, focused on accuracy and validity of AI/ML estimates. Trust evaluations considered the nature, integrity and relevance of training data rather than the computational nature of algorithms themselves, suggesting a need to distinguish 'source' from 'functional' explainability. To a lesser extent, trust criteria were also relational (endorsement from others) and sometimes based on personal beliefs and experience. We discuss implications for promoting appropriate and responsible trust calibration for clinical decision-making use AI/ML.

Sleep disturbances are associated with pain intensity and pain-related functional interference in patients experiencing orofacial pain.

BACKGROUND: Sleep and pain have a reciprocal relationship, interacting with psychosocial aspects including depression, anxiety, somatization and significant stressful events. OBJECTIVE: The aim of this study was to assess patients with oro-facial pain (OFP) and related sleep disturbances and determine the strongest psychosocial correlates. METHODS: A cross-sectional study of anonymized data of consecutive patients with OFP {January 2019 and February 2020} were analysed. Diagnostic and Axis-II data were integrated to assess the relationship between sleep disturbances, measured using Chronic Pain Sleep Inventory, and demographic factors, clinical comorbidities, recent stressful events, pain severity and pain- and psychological-related function. RESULTS: Five out of six patients with OFP were presented with pain-related sleep disturbances. Sleep problems were enhanced in patients with primary oro-facial headache compared with other OFP conditions. However, once the level of pain intensity and interference was accounted for, primary headache, was not a significant correlate of pain-related sleep disturbances. Multivariate analysis revealed (average) pain severity and pain interference were both significantly associated with sleep problems. There were also significant independent associations of sleep problems with somatization levels and reported experience of recent stressful events. CONCLUSION: Identifying sleep problems as a part of OFP management may be beneficial and could result in better management outcomes.

Salmonella enterica Serovar Typhimurium Isolates from Wild Birds in the United States Represent Distinct Lineages Defined by Bird Type.

Salmonella enterica serovar Typhimurium is typically considered a host generalist; however, certain isolates are associated with specific hosts and show genetic features of host adaptation. Here, we sequenced 131 S. Typhimurium isolates from wild birds collected in 30 U.S. states during 1978-2019. We found that isolates from broad taxonomic host groups including passerine birds, water birds (Aequornithes), and larids (gulls and terns) represented three distinct lineages and certain S. Typhimurium CRISPR types presented in individual lineages. We also showed that lineages formed by wild bird isolates differed from most isolates originating from domestic animal sources, and that genomes from these lineages substantially improved source attribution of Typhimurium genomes to wild birds by a machine learning classifier. Furthermore, virulence gene signatures that differentiated S. Typhimurium from passerines, water birds, and larids were detected. Passerine isolates tended to lack S. Typhimurium-specific virulence plasmids. Isolates from the passerine, water bird, and larid lineages had close genetic relatedness with human clinical isolates, including those from a 2021 U.S. outbreak linked to passerine birds. These observations indicate that S. Typhimurium from wild birds in the United States are likely host-adapted, and the representative genomic data set examined in this study can improve source prediction and facilitate outbreak investigation. IMPORTANCE Within-host evolution of S. Typhimurium may lead to pathovars adapted to specific hosts. Here, we report the emergence of disparate avian S. Typhimurium lineages with distinct virulence gene signatures. The findings highlight the importance of wild birds as a reservoir for S. Typhimurium and contribute to our understanding of the genetic diversity of S. Typhimurium from wild birds. Our study indicates that S. Typhimurium may have undergone adaptive evolution within wild birds in the United States. The representative S. Typhimurium genomes from wild birds, together with the virulence gene signatures identified in these bird isolates, are valuable for S. Typhimurium source attribution and epidemiological surveillance.

A systematic review of treatment for patients with burning mouth syndrome.

BACKGROUND: Burning mouth syndrome is a chronic idiopathic intractable intraoral dysaesthesia that remains a challenge to clinicians due to its poorly understood pathogenesis and inconsistent response to various treatments. AIM: This review aimed to study the short- (≤3 months) and long-term (>3 months) effectiveness and sustainable benefit of different burning mouth syndrome treatment strategies and the associated side effects. MATERIALS AND METHODS: Randomised controlled trials of burning mouth syndrome treatment compared with placebo or other interventions with a minimum follow up of 2 months were searched from the PubMed, Embase and Cochrane database (published to July 2020). RESULTS: Twenty-two studies were selected based on the inclusion and exclusion criteria and analysed. Nine categories of burning mouth syndrome treatment were identified: Anticonvulsant and antidepressant agents, phytomedicine and alpha lipoic acid supplements, low-level laser therapy, saliva substitute, transcranial magnetic stimulation, and cognitive behaviour therapy. Cognitive behaviour therapy, topical capsaicin and clonazepam, and laser therapy demonstrated favourable outcome in both short- and long-term assessment. Phytomedicines reported a short-term benefit in pain score reduction. The pooled effect of alpha lipoic acid (ALA) pain score improvement was low, but its positive effects increased in long term assessment. CONCLUSION: A more significant volume in terms of sample size, multi-centres, and multi-arm comparison of therapeutic agents with placebo and longitudinal follow-up studies is recommended to establish a standardised burning mouth syndrome treatment protocol. Further studies are required to assess the analgesic benefits of topical clonazepam and capsaicin, alternative medicines with neurodegenerative prevention capability and psychology support in treating burning mouth syndrome and reducing systemic adverse drug reactions.Registration International Prospective Register of Systematic Reviews (PROSPERO):Protocol ID - CRD42020160892.

Exploration of adverse patterns of placement of young people in secure care: The unwanted child?

BACKGROUND: Emerging evidence suggests that distant placements and multiple moves may be detrimental to young people in care settings. Less is known about the characteristics of young people in secure care most affected by these processes. AIMS: This study examined distance from home and number of previous placements in English young people detained in secure care and their relationships with organisational and individual characteristics. METHODS: Data were derived from the (2016) cross-sectional National Adolescent Study census of English young people in secure care, which included 1322 young people across secure mental health, welfare and Youth Justice establishments. Associations were described with odds ratios/95% confidence intervals (OR/CI). RESULTS: Overall, 285 young people (26.4%) were in secure placements over 100 miles from their family/local authority while 54 (5.6%) had 10 or more previous placements. These rates were higher in secure welfare than other settings (73.8%; OR (CI) = 9.62 (5.72, 16.18), 12.7%; OR (CI) = 2.76 (1.29, 5.91) respectively), and there was significant overlap between long-distance placement and multiple placements (n = 22; OR (CI) = 2.26 (1.27, 4.04)). Younger age and presence of neurodevelopmental disorder were also associated with long-distance placements while psychiatric diagnosis, previous secure placement, and previous service contact were linked to multiple placements. CONCLUSIONS: Distant and/or multiple placements in young people in secure care appear common, particularly for those who are placed in secure welfare and who are younger and/or present with a psychiatric disorder. Multi-agency evaluations that capture the longitudinal experience of these vulnerable young people are needed to understand how undesirable patterns of placement in secure care occur and prevent future instances.

Young men and young women in secure care: gender differences in the placement of those with mental health needs.

BACKGROUND: The system of secure care for young people in England and Wales comprises youth justice, welfare and mental health facilities. Empirical studies have failed to investigate the system as a whole. The National Adolescent Study in 2016 was the first to provide comprehensive system wide information. This paper, derived from that data set, addresses equity of service provision for young men and women in secure care who have mental health problems. METHODS: The detained census population of English young people in 2016 was 1322 and detailed data were available on 93% of this population, including 983 young men and 290 young women. The descriptive census data were interrogated to identify associations between gender, other sociodemographic and clinical variables, using Chi-square and Fisher's exact tests. RESULTS: Numerically more young men in secure care than young women in secure care warrant a psychiatric diagnosis but young women had a 9 fold increase in the odds of having a diagnosis compared with the young men. The pattern of mental health diagnoses differed significantly by gender as did the legislative framework under which females and males were placed. This different pattern of secure care placement continued to differ by gender when the nature of the mental health diagnosis was taken into account. CONCLUSIONS: No definitive explanation is evident for the significantly different placement patterns of young men and young women with the same mental health diagnoses, but the anticipated consequences for some, young men and some young women are important. Proper explanation demands an examination of process variables outwith the remit of this study. The lack of routine scrutiny and transparent processes across secure settings could be responsible for the development of these differential placement practices; these practices seem at odds with the duty placed on public services by the Equality Act.

An Aerosol Containment and Filtration Tent for Intubation During the COVID-19 Pandemic.

Background. Exposure to infectious droplets confers a high risk for infection transmission by the SARS-CoV-2 coronavirus. Aerosolizing procedures pose particular concern for increasing healthcare workers' (HCWs) risks of infection. Multiple creative personal protective equipment solutions have been utilized to minimize exposure to infectious particles; however, the overall benefit of many of these devices is limited by a number of factors. Methods. We designed an intubation tent consisting of a metal frame and a clear plastic sheet. The flexible walls of our tent offer increased maneuverability & access, although the efficacy in reducing risk of transmission to HCWs remained unclear. Using an atomizer, particle generator, and matchstick smoke, we simulated the generation of infectious respiratory droplets and aerosols and tested whether our device effectively decreased the concentration of these particles to which a provider might be exposed. Finally, we tested whether the addition of a vacuum fan fit with a high efficiency particulate air filter designed to evacuate contaminated air would influence particle concentrations inside and outside the tent. Results. Droplet dispersion tests with the tent in place showed that the simulated droplet distribution was limited to surfaces within the tent. Aerosol testing under a variety of circumstances consistently showed only a minor rise in particle concentration in the air outside the tent despite an initial peak of particle concentration during generation within. All testing demonstrated declining inside concentrations over time. Conclusions. Our simulations suggest our device has the potential to effectively decrease HCWs' exposure to infectious droplets and aerosolized viral particles.

Catastrophising, pain self-efficacy and acceptance in patients with Burning Mouth Syndrome.

BACKGROUND: Little is known about pain catastrophising, pain self-efficacy and chronic pain acceptance in burning mouth syndrome (BMS) and their effect on health-related quality of life (HRQoL) and symptoms of anxiety and depressive disorders. OBJECTIVES: To describe pain catastrophising, pain self-efficacy and pain acceptance in BMS patients and explore associations with affective function and HRQoL. METHODS: A cross-sectional study of 36 BMS patients (31 female) referred to an Orofacial Pain Clinic completed the Pain Catastrophizing Scale, the Pain Self-Efficacy Questionnaire and the Chronic Pain Acceptance Questionnaire-8 in addition to standardised self-reported questionnaires measuring mood and oral and generic HRQoL. RESULTS: Pain catastrophising levels were markedly higher than (non-clinical) population norms, with 32.0% of patients reporting clinically relevant levels. Pain self-efficacy and chronic pain acceptance varied widely; 24.0% evidenced low confidence to cope with pain, and 53.8% reported low activity engagement and/or low pain willingness. Catastrophising showed moderate-to-strong associations with measures of anxiety (r = 0.63), depression (r = 0.80), and oral (r = 0.61) and generic HRQoL (rho=-0.84). Self-efficacy and acceptance were also closely related to levels of depression (r/rho=-0.83 to -0.73) and generic HRQoL (r/rho = 0.74 to 0.75). These associations were stronger than those between pain severity and affective function/HRQoL and persisted after controlling for pain severity. CONCLUSIONS: A substantial proportion of BMS patients evidence maladaptive beliefs about personal effectiveness in managing pain, which is closely related to affective disorders and impaired HRQoL. As such, treatment approaches targeting catastrophising, pain self-efficacy and acceptance may prove beneficial in improving mood and quality of life in BMS patients.

Core and matrix thalamic sub-populations relate to spatio-temporal cortical connectivity gradients.

Recent neuroimaging experiments have defined low-dimensional gradients of functional connectivity in the cerebral cortex that subserve a spectrum of capacities that span from sensation to cognition. Despite well-known anatomical connections to the cortex, the subcortical areas that support cortical functional organization have been relatively overlooked. One such structure is the thalamus, which maintains extensive anatomical and functional connections with the cerebral cortex across the cortical mantle. The thalamus has a heterogeneous cytoarchitecture, with at least two distinct cell classes that send differential projections to the cortex: granular-projecting 'Core' cells and supragranular-projecting 'Matrix' cells. Here we use high-resolution 7T resting-state fMRI data and the relative amount of two calcium-binding proteins, parvalbumin and calbindin, to infer the relative distribution of these two cell-types (Core and Matrix, respectively) in the thalamus. First, we demonstrate that thalamocortical connectivity recapitulates large-scale, low-dimensional connectivity gradients within the cerebral cortex. Next, we show that diffusely-projecting Matrix regions preferentially correlate with cortical regions with longer intrinsic fMRI timescales. We then show that the Core-Matrix architecture of the thalamus is important for understanding network topology in a manner that supports dynamic integration of signals distributed across the brain. Finally, we replicate our main results in a distinct 3T resting-state fMRI dataset. Linking molecular and functional neuroimaging data, our findings highlight the importance of the thalamic organization for understanding low-dimensional gradients of cortical connectivity.

Self-regulation of ventromedial prefrontal cortex activation using real-time fMRI neurofeedback-Influence of default mode network.

The ventromedial prefrontal cortex (vmPFC) is involved in regulation of negative emotion and decision-making, emotional and behavioral control, and active resilient coping. This pilot study examined the feasibility of training healthy subjects (n = 27) to self-regulate the vmPFC activity using a real-time functional magnetic resonance imaging neurofeedback (rtfMRI-nf). Participants in the experimental group (EG, n = 18) were provided with an ongoing vmPFC hemodynamic activity (rtfMRI-nf signal represented as variable-height bar). Individuals were instructed to raise the bar by self-relevant value-based thinking. Participants in the control group (CG, n = 9) performed the same task; however, they were provided with computer-generated sham neurofeedback signal. Results demonstrate that (a) both the CG and the EG show a higher vmPFC fMRI signal at the baseline than during neurofeedback training; (b) no significant positive training effect was seen in the vmPFC across neurofeedback runs; however, the medial prefrontal cortex, middle temporal gyri, inferior frontal gyri, and precuneus showed significant decreasing trends across the training runs only for the EG; (c) the vmPFC rtfMRI-nf signal associated with the fMRI signal across the default mode network (DMN). These findings suggest that it may be difficult to modulate a single DMN region without affecting other DMN regions. Observed decreased vmPFC activity during the neurofeedback task could be due to interference from the fMRI signal within other DMN network regions, as well as interaction with task-positive networks. Even though participants in the EG did not show significant positive increase in the vmPFC activity among neurofeedback runs, they were able to learn to accommodate the demand of self-regulation task to maintain the vmPFC activity with the help of a neurofeedback signal.

The differential impact of neuropathic, musculoskeletal and neurovascular orofacial pain on psychosocial function.

BACKGROUND: While the psychosocial morbidity of orofacial pain (OFP) is widely recognized, the differential impact of musculoskeletal, neuropathic and neurovascular symptoms on pain and psychosocial function in individuals with and without coexisting OFP conditions is unclear. MATERIALS AND METHODS: This was a comparative cross-sectional study of 350 consecutive patients attending an OFP clinic; 244 completed standardized self-report measures of pain experience, mood, and generic and oral health-related quality of life (HRQoL). The impact of musculoskeletal, neuropathic and neurovascular symptoms on measures was assessed using linear and logistic generalized linear models. RESULTS: Two hundred patients were diagnosed with a neuropathic condition: 125 with musculoskeletal pain and 101 with (neurovascular) headache disorders. 23% of patients presented with multiple OFP conditions; this was more common in patients with neurovascular (62%) than neuropathic (21%) and/or musculoskeletal orofacial symptoms (28%). Patients with neurovascular symptoms experienced significantly higher levels of pain, evidenced less pain self-efficacy and had poorer overall health. Neuropathic OFP was significantly associated with greater psychological and social oral health disability. Multiple OFP symptoms were not linked to pain severity or psychosocial function, although health scores were worse for patients with neurovascular pain and neuropathic/musculoskeletal symptoms compared with patients with only neurovascular symptoms. CONCLUSIONS: The profile and degree of psychosocial morbidity in patients with OFP is significantly related to the types of presenting orofacial symptoms. Patients with neurovascular pain present with higher pain levels and have poorer health while those with neuropathic pain have higher oral functional morbidity; both may require more complex multidisciplinary management.

Biographical films as a person-centered approach to reduce neuropsychiatric symptoms of dementia in residential care: A feasibility study.

OBJECTIVE: Neuropsychiatric symptoms are a major component of dementia irrespective of severity or subtype. We aimed to determine the feasibility of biographical films to reduce neuropsychiatric symptoms in people with moderate to severe dementia over a 32-week period. METHOD: A total of 11 people with dementia situated in a residential care home took part in this mixed-method feasibility study. Carers reported neuropsychiatric symptoms of residents at three time-points, and their experience of the study was obtained at a feedback session. RESULTS: There was a significant reduction in neuropsychiatric symptoms in residents with neuropsychiatric impairment from baseline to the end of study (p = .042; d = .98). Thematic analysis identified three major themes: Triggered memories, knowledge gained to support care, and perceived changes in the resident. CONCLUSION: The findings suggest that it is feasible to use biographical films long-term to reduce neuropsychiatric symptoms of dementia, alongside routine care.