Functional connectivity changes in neurodegenerative biomarker-positive athletes with repeated concussions.

Multimodal biomarkers may identify former contact sports athletes with repeated concussions and at risk for dementia. Our study aims to investigate whether biomarker evidence of neurodegeneration in former professional athletes with repetitive concussions (ExPro) is associated with worse cognition and mood/behavior, brain atrophy, and altered functional connectivity. Forty-one contact sports athletes with repeated concussions were divided into neurodegenerative biomarker-positive (n = 16) and biomarker-negative (n = 25) groups based on positivity of serum neurofilament light-chain. Six healthy controls (negative for biomarkers) with no history of concussions were also analyzed. We calculated cognitive and mood/behavior composite scores from neuropsychological assessments. Gray matter volume maps and functional connectivity of the default mode, salience, and frontoparietal networks were compared between groups using ANCOVAs, controlling for age, and total intracranial volume. The association between the connectivity networks and sports characteristics was analyzed by multiple regression analysis in all ExPro. Participants presented normal-range mean performance in executive function, memory, and mood/behavior tests. The ExPro groups did not differ in professional years played, age at first participation in contact sports, and number of concussions. There were no differences in gray matter volume between groups. The neurodegenerative biomarker-positive group had lower connectivity in the default mode network (DMN) compared to the healthy controls and the neurodegenerative biomarker-negative group. DMN disconnection was associated with increased number of concussions in all ExPro. Biomarkers of neurodegeneration may be useful to detect athletes that are still cognitively normal, but with functional connectivity alterations after concussions and at risk of dementia.

Pre-treatment brain white matter integrity associated with neuropathic pain relief and changes in temporal summation of pain following ketamine.

Neuropathic pain (NP) is a prevalent condition often associated with heightened pain responsiveness suggestive of central sensitization. Neuroimaging biomarkers of treatment outcomes may help develop personalised treatment strategies, but white matter (WM) properties have been under-explored for this purpose. Here we assessed whether WM pathways of the default mode network (DMN: medial prefrontal cortex (mPFC), posterior cingulate cortex (PCC), precuneus (PCu)) and descending pain modulation system (periaqueductal gray (PAG)) are associated with ketamine analgesia and attenuated temporal summation of pain (TSP, reflecting central sensitization) in NP. We used a fixel-based analysis (FBA) of diffusion weighted imaging data to evaluate WM microstructure (fiber density, FD) and macrostructure (fiber bundle cross-section) within the DMN and mPFC-PAG pathways in 70 individuals who underwent MRI and TSP testing; 35 with NP who underwent ketamine treatment and 35 age- and sex-matched pain-free individuals. Individuals with NP were assessed before and 1-month after treatment; those with ≥30% pain relief were considered responders (n=18), or otherwise as non-responders (n=17). We found that WM structure within the DMN and mPFC-PAG pathways did not differentiate responders from non-responders. However, pre-treatment FD in the anterior limb of the internal capsule correlated with pain relief (r=0.48). Moreover, pre-treatment FD in the DMN (left mPFC-PCu/PCC; r=0.52) and mPFC-PAG (r=0.42) negatively correlated with changes in TSP. This suggests that WM microstructure in the DMN and mPFC-PAG pathway is associated with the degree to which ketamine reduces central sensitization. Thus, fixel metrics of WM structure may hold promise to predict ketamine NP treatment outcomes. PERSPECTIVE: We used advanced fixel-based analyses of MRI diffusion-weighted imaging data to identify pre-treatment white matter microstructure associated with ketamine outcomes including analgesia and markers of attenuated central sensitization. Exploring associations between brain structure and treatment outcomes could contribute to a personalized approach to treatment for individuals with neuropathic pain.

The Influence of Using Novel Predictive Technologies on Judgments of Stigma, Empathy, and Compassion among Healthcare Professionals.

BACKGROUND: Our objective was to evaluate whether the description of a machine learning (ML) app or brain imaging technology to predict the onset of schizophrenia or alcohol use disorder (AUD) influences healthcare professionals' judgments of stigma, empathy, and compassion. METHODS: We randomized healthcare professionals (N = 310) to one vignette about a person whose clinician seeks to predict schizophrenia or an AUD, using a ML app, brain imaging, or a psychosocial assessment. Participants used scales to measure their judgments of stigma, empathy, and compassion. RESULTS: Participants randomized to the ML vignette endorsed less anger and more fear relative to the psychosocial vignette, and the brain imaging vignette elicited higher pity ratings. The brain imaging and ML vignettes evoked lower personal responsibility judgments compared to the psychosocial vignette. Physicians and nurses reported less empathy than clinical psychologists. CONCLUSIONS: The use of predictive technologies may reinforce essentialist views about mental health and substance use that may increase specific aspects of stigma and reduce others.

Central neuropathic pain.

Central neuropathic pain arises from a lesion or disease of the central somatosensory nervous system such as brain injury, spinal cord injury, stroke, multiple sclerosis or related neuroinflammatory conditions. The incidence of central neuropathic pain differs based on its underlying cause. Individuals with spinal cord injury are at the highest risk; however, central post-stroke pain is the most prevalent form of central neuropathic pain worldwide. The mechanisms that underlie central neuropathic pain are not fully understood, but the pathophysiology likely involves intricate interactions and maladaptive plasticity within spinal circuits and brain circuits associated with nociception and antinociception coupled with neuronal hyperexcitability. Modulation of neuronal activity, neuron-glia and neuro-immune interactions and targeting pain-related alterations in brain connectivity, represent potential therapeutic approaches. Current evidence-based pharmacological treatments include antidepressants and gabapentinoids as first-line options. Non-pharmacological pain management options include self-management strategies, exercise and neuromodulation. A comprehensive pain history and clinical examination form the foundation of central neuropathic pain classification, identification of potential risk factors and stratification of patients for clinical trials. Advanced neurophysiological and neuroimaging techniques hold promise to improve the understanding of mechanisms that underlie central neuropathic pain and as predictive biomarkers of treatment outcome.

Misfolded α-Synuclein in Cerebrospinal Fluid of Contact Sport Athletes.

BACKGROUND: Misfolded α-synuclein in Parkinson's disease (PD) and dementia with Lewy bodies (DLB) can be detected using the real-time quaking-induced conversion (RT-QuIC) technique in cerebrospinal fluid (CSF). OBJECTIVES: The objectives are (1) to examine misfolded CSF α-synuclein incidence, and (2) to compare clinical presentation, sports history, brain volumes, and RT-QuIC α-synuclein positivity in former athletes. METHODS: Thirty former athletes with magnetic resonance imaging, neuropsychological testing, and CSF analyzed for phosphorylated tau 181 (p-tau), total tau (t-tau), amyloid-ß 42 (Aß42), and neurofilament light chain (NfL). CSF α-synuclein was detected using RT-QuIC. RESULTS: Six (20%) former athletes were α-synuclein positive. α-Synuclein positive athletes were similar to α-synuclein negative athletes on demographics, sports history, clinical features, CSF p-tau, t-tau, Aß42, and NfL; however, had lower grey matter volumes in the right inferior orbitofrontal, right anterior insula and right olfactory cortices. CONCLUSIONS: α-Synuclein RT-QuIC analysis of CSF may be useful as a prodromal biofluid marker of PD and DLB. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

International Association for the Study of Pain publications over the 50-year span.

ABSTRACT: The International Association for the Study of Pain (IASP) has a 50-year history of publishing educational and research materials, ranging from traditional print format books, journals, and other informational formats to online and electronic formats. Here we provide a historical overview of IASP publications and reflections from the perspective of 5 former or current Editors-in-Chief.

Resilience is associated with cortical gray matter of the antinociceptive pathway in people with chronic pain.

Resilience is an important personal characteristic that influences health and recovery. Previous studies of chronic pain suggest that highly resilient people may be more effective at modulating their pain. Since brain gray matter in the antinociceptive pathway has also been shown to be abnormal in people with chronic pain, we examined whether resilience is related to gray matter in regions of interest (ROIs) of the antinociceptive pathway (rostral and subgenual anterior cingulate cortex (rACC, sgACC), anterior insula (aINS), dorsolateral prefrontal cortex (dlPFC)) normally and in people who are experiencing chronic pain. We extracted gray matter volume (GMV) and cortical thickness (CT) from 3T MRIs of 88 people with chronic pain (half males/females) and 86 healthy controls (HCs), who completed The Resilience Scale and Brief Pain Inventory. We found that resilience scores were significantly lower in people with chronic pain compared to HCs, whereas ROI GMV and CT were not different between groups. Resilience negatively correlated with average pain scores and positively correlated with GMV in the bilateral rACC, sgACC, and left dlPFC of people with chronic pain. Mediation analyses revealed that GMV in the right rACC and left sgACC partially co-mediated the relationship between resilience and average pain in people with chronic pain. The resilience-pain and some resilience-GMV relationships were sex-dependent. These findings suggest that the antinociceptive pathway may play a role in the impact of resilience on one's ability to modulate chronic pain. A better understanding of the brain-resilience relationship may help advance evidence-based approaches to pain management.

Nursing practice leaders' perspectives on continuing challenges related to the Doctor of Nursing Practice Degree.

In 2020, deans from top-ranked nursing schools authored a Nursing Outlook article titled, "Doctor of Nursing Practice (DNP) Degree in the United States: Reflecting, Readjusting, and Getting Back on Track." In 2022, the American Association of Colleges of Nursing published the report, "State of the Doctor of Nursing Practice Education."- Both have been critical to advancing national discussions on the implementation of a universal DNP practiceentry standard in nursing. This paper, written by Chief Nursing Officers from top-ranked academic medical centers, reports on perspectives from practice settings/employers regarding issues raised by educators and deans in those documents. Barriers to acceptance of the DNP degree in practice include a lack of degree standardization, a need for DNP outcomes data, and a desire for a clearer return on investment for the DNP degree among graduates and employers.

Use of CT and MR imaging in radiation therapy planning of imaging-diagnosed canine intracranial meningioma achieves better tumor coverage than CT alone.

The aim of this retrospective, secondary analysis study was to quantify the dosimetric impact of the lack of interobserver agreement on gross tumor volume (GTV) delineation for canine meningioma. This study used a previously reported population of 13 dogs with GTVs contoured on CT alone and on registered CT-MR by 18 radiation oncologists. The "true" GTV was generated for each dog using a simultaneous truth and performance-level estimation algorithm, and "true" brain was defined as the whole brain minus true GTV. Treatment plans were generated for each dog and observer combination, using criteria applied to the observer's GTV and brain contours. Plans were then categorized as a pass (met all planning criteria for true GTV and true brain) or fail. A mixed-effects linear regression was performed to examine differences in metrics between CT and CT-MR plans and mixed-effects logistic regression was performed to examine differences in percentages of pass/fail between CT and CT-MRI plans. The mean percent coverage of true GTV by prescribed dose was higher for CT-MR plans than for CT plans (mean difference 5.9%; 95% CI, 3.7-8.0; P < 0.001). There was no difference in the mean volume of true brain receiving ≥24 Gy and in maximum true brain dose between CT plans and CT-MR plans (P ≥ 0.198). CT-MR plans were significantly more likely to pass the criteria for true GTV and true brain than CT plans (OR 1.75; 95% CI, 1.02-3.01; P = 0.044). This study demonstrated significant dosimetric impact when GTV contouring was performed on CT alone compared with CT-MR.

Joint European Academy of Neurology-European Pain Federation-Neuropathic Pain Special Interest Group of the International Association for the Study of Pain guidelines on neuropathic pain assessment.

BACKGROUND AND PURPOSE: In these guidelines, we aimed to develop evidence-based recommendations for the use of screening questionnaires and diagnostic tests in patients with neuropathic pain (NeP). METHODS: We systematically reviewed studies providing information on the sensitivity and specificity of screening questionnaires, and quantitative sensory testing, neurophysiology, skin biopsy, and corneal confocal microscopy. We also analysed how functional neuroimaging, peripheral nerve blocks, and genetic testing might provide useful information in diagnosing NeP. RESULTS: Of the screening questionnaires, Douleur Neuropathique en 4 Questions (DN4), I-DN4 (self-administered DN4), and Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) received a strong recommendation, and S-LANSS (self-administered LANSS) and PainDETECT weak recommendations for their use in the diagnostic pathway for patients with possible NeP. We devised a strong recommendation for the use of skin biopsy and a weak recommendation for quantitative sensory testing and nociceptive evoked potentials in the NeP diagnosis. Trigeminal reflex testing received a strong recommendation in diagnosing secondary trigeminal neuralgia. Although many studies support the usefulness of corneal confocal microscopy in diagnosing peripheral neuropathy, no study specifically investigated the diagnostic accuracy of this technique in patients with NeP. Functional neuroimaging and peripheral nerve blocks are helpful in disclosing pathophysiology and/or predicting outcomes, but current literature does not support their use for diagnosing NeP. Genetic testing may be considered at specialist centres, in selected cases. CONCLUSIONS: These recommendations provide evidence-based clinical practice guidelines for NeP diagnosis. Due to the poor-to-moderate quality of evidence identified by this review, future large-scale, well-designed, multicentre studies assessing the accuracy of diagnostic tests for NeP are needed.

A Descriptive Methodology for Studying the Ontogeny of Object Play and Breed Differences in Dogs (Canis lupus familiaris).

Play behavior is a prominent aspect of juvenile behavior for many animals, yet early development, especially play with objects, has received little attention. Our previous study on object play introduced our general methods, focusing on litter differences in the developmental trajectory of object play and toy preferences. Here, we present a detailed ethogram of more than 30 observed object play behaviors. We focus on breed differences in the development of play in the three following breeds: Welsh Terriers, Vizslas, and standard Poodles. Puppies were video recorded from 3 to 7 weeks of age at half-week intervals upon the introduction of a standard set of five toys into their home environments. Ten minutes of video from each session for each puppy were analyzed using the Noldus Observer XT program. Aside from analyzing individual behaviors, they were also grouped into three behavioral categories. These were behaviors that occurred only in a solitary context, only in a social context, or in both contexts. Solitary object play developed first, and social object play developed later across breeds. There was a significant three-way interaction between breed, developmental age, and the context in which play occurred. Pairwise comparisons within each breed, age, and context are discussed, but a prominent result is that the onset of many behaviors occurred later in Welsh Terriers compared to the other breeds.

A preliminary investigation to establish conceptual behavior in gray wolves (Canis lupus).

Conceptual behavior represents a type of complex stimulus control where an organism differentially responds to examples and nonexamples of instances within a stimulus class. Different species have demonstrated conceptual behavior both in their natural environments and through experimental investigations. The current paper investigates preliminary methods to teach conceptual behavior to gray wolves (Canis lupus). The researchers used a match-to-sample arrangement to teach three shapes: a triangle, square, and cross varying in size, color, and positions. Probe trials used a novel set of stimuli to test for the emergence of conceptual behavior. Although the wolves did not show an immediate transfer to novel stimuli following initial match-to-sample training, they did show improvement after explicit discrimination training. We discuss the implications of these results as well as future methods that may enhance experimental procedures investigating concept learning in canids.

Can we characterize A-P/IAP behavioural phenotypes in people with chronic pain?

Two behavioural phenotypes in healthy people have been delineated based on their intrinsic attention to pain (IAP) and whether their reaction times (RT) during a cognitively-demanding task are slower (P-type) or faster (A-type) during experimental pain. These behavioural phenotypes were not previously studied in chronic pain populations to avoid using experimental pain in a chronic pain context. Since pain rumination (PR) may serve as a supplement to IAP without needing noxious stimuli, we attempted to delineate A-P/IAP behavioural phenotypes in people with chronic pain and determined if PR can supplement IAP. Behavioural data acquired in 43 healthy controls (HCs) and 43 age-/sex-matched people with chronic pain associated with ankylosing spondylitis (AS) was retrospectively analyzed. A-P behavioural phenotypes were based on RT differences between pain and no-pain trials of a numeric interference task. IAP was quantified based on scores representing reported attention towards or mind-wandering away from experimental pain. PR was quantified using the pain catastrophizing scale, rumination subscale. The variability in RT was higher during no-pain trials in the AS group than HCs but was not significantly different in pain trials. There were no group differences in task RTs in no-pain and pain trials, IAP or PR scores. IAP and PR scores were marginally significantly positively correlated in the AS group. RT differences and variability were not significantly correlated with IAP or PR scores. Thus, we propose that experimental pain in the A-P/IAP protocols can confound testing in chronic pain populations, but that PR could be a supplement to IAP to quantify attention to pain.