bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and validation of the TabCAT-EXAMINER: tablet-based executive functioning factor score for research and clinical trials
Authors: Sanderson-Cimino Mark , Possin Katherine L. , Mungas Dan M. , Paolillo Emily W. , Asken Breton M. , Tsoy Elena , Jarrott Sabrina , Cobigo Yann , Saloner Rowan , Casaletto Kaitlin B. , Considine Ciaran , Fields Julie A. , Molden Joie , Rascovsky Katya , Weintraub Sandra , Wong Bonnie , Heuer Hilary W. , Forsberg Leah K. , Rojas Julio C. , VandeVrede Lawren , Ljubenkov Peter , Rabinovici Gil D. , Gorno-Tempini Maria L. , Seeley William W. , Miller Bruce L. , Boeve Bradley F. , Rosen Howard J. , Boxer Adam L. , Rankin Katherine P. , Kramer Joel H. , Staffaroni Adam M. 
Published: October 2024

AbstractObjectiveThe National Institute of Health (NIH) Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research (EXAMINER) is a validated laptop-based battery of executive functioning tests. A modified tablet version of the EXAMINER was developed on the UCSF Tablet-based Cognitive Assessment Tool (TabCAT-EXAMINER). Here we describe the battery and investigate the reliability and validity of a composite score.MethodsA diagnostically heterogeneous sample of 2135 individuals (mean age=65.58, SD=16.07), including controls and participants with a variety of neurodegenerative syndromes completed the TabCAT-EXAMINER. A composite score was developed using confirmatory factor analysis and item response theory. Validity was evaluated via linear regressions that tested associations with neuropsychological tests, demographics, clinical diagnosis, and disease severity. Replicability of cross-sectional results was tested in a separate sample of participants (n=342) recruited from a Frontotemporal dementia study. As this separate sample also collected longitudinal TabCAT-EXAMINER measures, we additionally assessed test-retest reliability and associations between baseline disease severity and changes in TabCAT-EXAMINER scores.ResultsThe TabCAT-EXAMINER score was normally distributed, demonstrated high test-retest reliability, and was associated in the expected directions with independent tests of executive functioning, demographics, disease severity, and diagnosis. Greater baseline disease severity was associated with faster longitudinal TabCAT-EXAMINER decline.ConclusionsThe TabCAT-EXAMINER is a tablet-based executive functioning battery developed for observational research and clinical trials. Performance can be summarized as a single composite score, and results of this study support its reliability and validity in cognitive aging and neurodegenerative disease cohorts.
Modulation of leg trajectory by transcranial magnetic stimulation during walking
Authors: Bourgeois H. , Guay-Hottin R. , Meftah E.-M. , Martinez M. , Bonizzato M. , Barthélemy D. 
Published: October 2024

AbstractThe primary motor cortex is involved in initiation and adaptive control of locomotion. However, the role of the motor cortex in controlling gait trajectories remains unclear. In animals, cortical neuromodulation allows for precise control of step height. We hypothesized that a similar control framework applies to humans, whereby cortical stimulation would primarily increase foot elevation.Transcranial magnetic stimulation (TMS) was applied over the motor cortex to assess the involvement of the corticospinal tract over the limb trajectory during human walking. Eight healthy adults (aged 20-32 years) participated in treadmill walking at 1.5 km/h. TMS was applied over the left motor cortex at an intensity of 120% of the threshold to elicit a dorsiflexion of the right ankle during the swing phase of gait. Electromyographic (EMG) measurements and three-dimensional (3D) lower limb kinematics were collected.When delivered during the early swing phase, TMS led to a significant increase in the maximum height of the right toe by a mean of 40.7% ± 14.9% (25.6mm ± 9.4 mm, p = 0.0352) and knee height by 57.8%± 16.8%; (32mm ± 9.3 mm; p = 0.008) across participants.These findings indicate that TMS can influence limb trajectory during walking, highlighting its potential as a tool for studying cortical control of locomotion.
SC10X/U: A High-density Electrode System for Non-Invasive Recording of Neural Activity of the Cervical Spinal Cord
Authors: Mehra Prabhav , Metzger Marjorie , Bista Saroj , Plaitano Serena , Giglia Eileen R. , Nash Leah , Domhnaill Éanna Mac , Mitchell Matthew , Bede Peter , Lowery Madeleine , Muthuraman Muthuraman , Hardiman Orla , Nasseroleslami Bahman 
Published: October 2024

AbstractObjectiveTo design and develop a high-density (HD) electrode system that describes the position of surface electrodes for recording electrophysiological signals from the human cervical spinal cord. The system is intended to standardize experimental recordings and facilitate the subsequent analysis of evoked and spontaneous spinal cord neural activity, using high-density electrospinography (HD-ESG).MethodThe proposed system (SC10-X/U) describes the locations of up to 76 channels with a unique nomenclature, where the division of the spinal cord (SC) electrode space was inspired by the EEG 10-10 system. As proof of concept, spinal evoked potentials in response to median nerve stimulation at the wrist were recorded from 10 participants and characterized based on a 64-channel derivation from the SC10-X/U system.ResultsFollowing the design criteria, the SC10-X/U defines 76 electrode positions and its configuration. HD-ESG system was utilized to successfully record evoked spinal responses and significant N13 and P9 potential were observed in response to the stimulation. The spinal N13 potential had a latency of 13.2 +-1.1ms (mean +-SD) after stimulation. A topographic map of the N13 electro-spinal activity using the 64-channel recording system revealed an epicentre at C5-C7 dorsal-vertebral locations (ML4 - ML6 electrodes).ConclusionThe proposed SC10-X/U system will facilitate standardized recording and analysis of high-density ESG signals from the human cervical spinal cord. The system defines electrode locations to promote standardization across different individuals, studies, and clinical and research centres. The HD-ESG evoked potentials recorded using the proposed system were comparable to those observed in previous non-HD studies. The presented topographic maps conform to known neurophysiological and neuroanatomical findings. This served to validate the design and development of the electrode system and patch for future studies.
Lack of neuroprotection after systemic administration of the soluble TNF inhibitor XPro1595 in an rAAV6-α-Syn+PFFs-induced rat model for Parkinson’s disease
Authors: Fredlund Filip , Fryklund Claes , Trujeque-Ramos Olivia , Staley Hannah A. , Pardo Joaquin , Luk Kelvin C. , Tansey Malú G. , Swanberg Maria 
Published: October 2024

AbstractParkinson’s disease (PD) is characterized by dopaminergic neurodegeneration, α-Synuclein (α-Syn) pathology, and inflammation. Microglia in the substantia nigra pars compacta (SNpc) upregulate major histocompatibility complex class II (MHCII), and variants in genes encoding MHCII affect PD risk. Additionally, elevated TNF levels and α-Syn-reactive T cells in circulation suggest a strong link between innate and adaptive immune responses in PD. We have previously reported that reduced levels of the class II transactivator, the master regulator of MHCII expression, increases susceptibility to α-Syn-induced PD-like pathology in rats and are associated with higher serum levels of soluble TNF (sTNF). Here, we demonstrate that inhibiting sTNF with a dominant-negative TNF variant, XPro1595, known to be neuroprotective in endotoxin- and toxin-induced neurodegeneration models, fails to protect against robust α-Syn-induced PD-like pathology in rats. We used a model combining rAAV-mediated α-Syn overexpression in SNpc with striatal injection of α-Syn preformed fibrils two weeks later. Systemic XPro1595 treatment was initiated one-week post-rAAV-α-Syn. We observed up to 70% loss of striatal dopaminergic fibers without treatment, and no protective effects on dopaminergic neurodegeneration after XPro1595 administration. Pathological α-Syn levels as well as microglial and astrocytic activation were not reduced in SNpc or striatum following XPro1595 treatment. An increase in IL-6 and IL-1β levels in CSF was observed in rats treated with XPro1595, possibly explaining a lack of protective effects following treatment. Our results highlight the need to determine the importance of timing of treatment initiation, which is crucial for future applications of sTNF therapies in PD patients.
Neural Correlates of Psychedelic, Sleep, and Sedated States Support Global Theories of Consciousness
Authors: Dai Rui , Jang Hyunwoo , Hudetz Anthony G. , Huang Zirui , Mashour George A. 
Published: October 2024

AbstractUnderstanding neural mechanisms of consciousness remains a challenging question in neuroscience. A central debate in the field concerns whether consciousness arises from global interactions that involve multiple brain regions or focal neural activity, such as in sensory cortex. Additionally, global theories diverge between the Global Neuronal Workspace (GNW) hypothesis, which emphasizes frontal and parietal areas, and the Integrated Information Theory (IIT), which focuses on information integration within posterior cortical regions. To disentangle the global vs. local and frontoparietal vs. posterior dilemmas, we measured global functional connectivity and local neural synchrony with functional magnetic resonance imaging (fMRI) data across a spectrum of conscious states in humans induced by psychedelics, sleep, and deep sedation. We found that psychedelic states are associated with increased global functional connectivity and decreased local neural synchrony. In contrast, non-REM sleep and deep sedation displayed the opposite pattern, suggesting that consciousness arises from global brain network interactions rather than localized activity. This mirror-image pattern between enhanced and diminished states was observed in both anterior-posterior (A-P) and posterior-posterior (P-P) brain regions but not within the anterior part of the brain alone. Moreover, anterior transmodal regions played a key role in A-P connectivity, while both posterior transmodal and posterior unimodal regions were critical for P-P connectivity. Overall, these findings provide empirical evidence supporting global theories of consciousness in relation to varying states of consciousness. They also bridge the gap between two prominent theories, GNW and IIT, by demonstrating how different theories can converge on shared neuronal mechanisms.
RPE-specific MCT2 expression promotes cone survival in models of retinitis pigmentosa
Authors: Chandler Laurel C. , Gardner Apolonia , Cepko Constance L. 
Published: October 2024

AbstractRetinitis pigmentosa (RP) is the most common cause of inherited retinal degeneration worldwide. It is characterized by the sequential death of rod and cone photoreceptors, the cells responsible for night and daylight vision, respectively. Although mutations in RP are mostly rod-specific, there is a secondary degeneration of cones. One possible mechanism behind cone death is metabolic dysregulation. Photoreceptors are highly metabolically active, consuming large quantities of glucose and producing substantial amounts of lactate. The retinal pigment epithelium (RPE) mediates the transport of glucose from the blood to photoreceptors and, in turn, removes lactate, which it can use as its own source of fuel. The model for metabolic dysregulation in RP suggests that, following the death of rods, lactate levels are substantially diminished causing the RPE to withhold glucose, resulting in nutrient deprivation for cones. Here, we present adeno-associated viral vector-mediated delivery of monocarboxylate transporter 2 (MCT2) into RPE cells with the aim of promoting lactate uptake from the blood and encouraging the passage of glucose to cones. We demonstrate prolonged survival and function of cones in rat and mouse RP models, revealing a possible gene agnostic therapy for preserving vision in RP. We also present the use of fluorescence lifetime imaging-based biosensors for lactate and glucose within the eye. Using this technology, we show changes to lactate and glucose levels within MCT2-expressing RPE, suggesting cone survival is impacted by RPE metabolism.
Convergent olfactory circuits for courtship inDrosophilarevealed byds-Tango
Authors: Fisher John D. , Crown Anthony M. , Sorkaç Altar , Martinez-Machado Sasha , Snell Nathaniel J. , Vishwanath Neel , Monje Silas , Vo An , Wu Annie H. , Moșneanu Rareș A. , Okoro Angel M. , Savaş Doruk , Nkera Bahati , Iturralde Pablo , Kumari Aastha , Chou-Freed Cambria , Hartmann Griffin G. , Talay Mustafa , Barnea Gilad 
Published: October 2024

SummaryAnimals exhibit sex-specific behaviors that are governed by sexually dimorphic circuits. One such behavior in maleDrosophila melanogaster, courtship, is regulated by various sensory modalities, including olfaction. Here, we reveal how sexually dimorphic olfactory pathways in male flies converge at the third-order, onto lateral horn output neurons, to regulate courtship. To achieve this, we developedds-Tango, a modified version of the monosynaptic tracing and manipulation tooltrans-Tango. Inds-Tango, two distinct configurations oftrans-Tango are positioned in series, thus providing selective genetic access not only to the monosynaptic partners of starter neurons but also to their disynaptic connections. Usingds-Tango, we identified a node of convergence for three sexually dimorphic olfactory pathways. Silencing this node results in deficits in sex recognition of potential partners. Our results identify lateral horn output neurons required for proper courtship behavior in male flies and establishds-Tango as a tool for disynaptic circuit tracing.
Touchscreen response precision is sensitive to the explore/exploit tradeoff
Authors: Mueller Dana , Giglio Erin , Chen Cathy S. , Holm Aspen , Ebitz R. Becket , Grissom Nicola M. 
Published: October 2024

AbstractThe explore/exploit tradeoff is a fundamental property of choice selection during reward-guided decision making. In perceptual decision making, higher certainty decisions are more motorically precise, even when the decision does not require motor accuracy. However, while we can parametrically control uncertainty in perceptual tasks, we do not know what variables - if any - shape motor precision and reflect subjective certainty during reward-guided decision making. Touchscreens are increasingly used across species to measure choice, but provide no tactile feedback on whether an action is precise or not, and therefore provide a valuable opportunity to determine whether actions differ in precision due to explore/exploit state, reward, or individual variables. We find all three of these factors exert independent drives towards increased precision. During exploit states, successive touches to the same choice are closer together than those made in an explore state, consistent with exploit states reflecting higher certainty and/or motor stereotypy in responding. However, exploit decisions might be expected to be rewarded more frequently than explore decisions. We find that exploit choice precision is increased independently of a separate increase in precision due to immediate past reward, suggesting multiple mechanisms regulating choice precision. Finally, we see evidence that male mice in general are less precise in their interactions with the touchscreen than females, even when exploiting a choice. These results suggest that as exploit behavior emerges in reward-guided decision making, individuals become more motorically precise reflecting increased certainty, even when decision choice does not require additional motor accuracy, but this is influenced by individual differences and prior reward. These data uncover the hidden potential for touchscreen tasks in any species to uncover the latent neural states that unite cognition and movement.
Hippocampal subfield volume in relation to cerebrospinal fluid Amyloid-ß in early Alzheimer’s disease: Diagnostic Utility of 7T MRI
Authors: Adeyemi Oluwatobi F , Gowland Penny , Bowtell Richard , Mougin Olivier , Hosseini Akram A. 
Published: October 2024

ABSTRACTINTRODUCTIONAlzheimer’s disease (AD) is a neurodegenerative condition characterised by amyloid plaque accumulation and neurofibrillary tangles. Early detection is essential for effective intervention, but current diagnostic methods that enable early diagnosis in clinical practice rely on invasive or costly biomarker scanning. This study aimed to explore the utility of 7T MRI in assessing hippocampal subfield volumes and their correlation with cerebrospinal fluid (CSF) biomarkers in prodromal AD. METHODS: Fifty-six participants, including AD patients and healthy controls, underwent 7T MRI scanning. Automated segmentation delineated hippocampal subfield volumes, with subsequent normalization to whole brain volume.RESULTSSignificant differences in hippocampal and subfield volumes were observed in prodromal AD patients, even when they did not exhibit high MTA scores on 3T MRI or show any whole brain volume loss. Additionally, the volume of the entorhinal cortex (ERC) correlated significantly with CSF amyloid-β levels, suggesting ERC’s potential as a proxy CSF amyloid-ß measurement. Conversely, no significant associations were found between CSF 181-phospho-tau or total tau levels and any hippocampal subfield volumes.DISCUSSIONThese findings show the potential use of 7T MRI, particularly in ERC assessment, as a biomarker for early AD identification. Further validation studies are warranted to confirm these results and elucidate the relationship of ERC volume with CSF biomarkers.
Persistence of training-induced visual improvements after occipital stroke
Authors: Willis Hanna E. , Farenthold Berkeley , Millington-Truby Rebecca S. , Willis Rebecca , Starling Lucy , Cavanaugh Matthew , Tamietto Marco , Huxlin Krystel , Bridge Holly 
Published: October 2024

AbstractDamage to the primary visual cortex causes homonymous visual impairments that appear to benefit from visual discrimination training. However, whether improvements persist without continued training remains to be determined and was the focus of the present study. After a baseline assessment visit, 20 participants trained twice daily in their blind-field for a minimum of six months (median=155 sessions), using a motion discrimination and integration task. At the end of training, a return study visit was used to assess recovery. Three months later, 14 of the participants returned for a third study visit to assess persistence of recovery. At each study visit, motion discrimination and integration thresholds, Humphrey visual fields, and structural MRI scans were collected. Immediately after training, all but four participants showed improvements in the trained discrimination task, and shrinkage of the perimetrically-defined visual defect. While these gains were sustained in seven out of eleven participants who improved with training, four participants lost their improvement in motion discrimination thresholds at the follow-up visit. Persistence of recovery was not related to age, time since lesion, number of training sessions performed, proportion of V1 damaged, deficit size, or optic tract degeneration measured from structural MRI scans. The present findings underscore the potential of extended visual training to induce long-term improvements in stroke-induced vision loss. However, they also highlight the need for further investigations to better understand the mechanisms driving recovery, its persistence post-training, and especially heterogeneity among participants.
Trends in smoking prevalence and socioeconomic inequalities across regions in England: a population study, 2006 to 2024
Authors: Jackson Sarah E. , Cox Sharon , Buss Vera , Tattan-Birch Harry , Brown Jamie 
Published: October 2024

AbstractBackgroundIn addition to national policies and interventions, certain regions in England (particularly in the North) coordinate regional tobacco control programmes. This study examined trends in tobacco smoking prevalence and socioeconomic inequalities in smoking across regions.MethodsData were obtained from monthly household surveys of adults (≥16y) in England, conducted between November 2006 and July 2024 (totaln=368,057). We used logistic regression to estimate time trends in current smoking by region, and tested interactions with occupational social grade to explore differences between more and less advantaged groups.ResultsSmoking prevalence declined most in the North (28.8% to 15.8%; -12.9 percentage points [95%CI -14.4; -11.5]), similar to the national average in the Midlands (25.2% to 16.0%; -9.2 [-10.6; -7.9]), and least in the South (22.7% to 17.3%; -5.3 [-6.5; -4.0]), reducing regional disparities such that prevalence was similar across regions in 2024. Socioeconomic inequalities in smoking prevalence between more and less advantaged social grades fell most in Yorkshire and the Humber (from 17.9 percentage points [14.1; 21.8] to 3.7 [0.4; 7.0]) and the West Midlands (from 16.1 [12.8; 19.6] to 3.0 [-0.03; 6.0]). Regions with sustained regional tobacco control activity saw greater declines in smoking prevalence (−18.1 [-21.4; - 14.7]) than regions with none (−12.8 [-13.9; -11.6]).ConclusionsBetween 2006 and 2024, smoking rates in the North of England fell faster than the national average, aligning with other regions. Regional tobacco control programmes appeared to contribute to this progress.
Impulsive adolescents exhibit inefficient processing and a low decision threshold when decoding facial expressions of emotions
Authors: Schreiber Alison M. , Hall Nathan T. , Parr Daniel F. , Hallquist Michael N. 
Published: October 2024

AbstractBackgroundBorderline personality disorder (BPD) is a debilitating psychiatric illness whose symptoms frequently emerge during adolescence. Initial studies in adults suggest that the interpersonal difficulties common in BPD may emerge from disrupted processing of social and emotional stimuli. Less is known about these processes in adolescents with BPD symptoms, despite substantial changes in socioemotional processing during this developmental period.Methods86 adolescents and young adults with and without BPD symptoms completed an emotional interference task involving the identification of a facial emotion expression in the presence of a conflicting or congruent emotion word. We used hierarchical drift diffusion modeling to index speed of processing and decision boundary. Using Bayesian multilevel regression, we characterized age-related differences in facial emotion processing. We then examined whether BPD symptom dimensions were associated with facial emotion processing on this task. To determine the specificity of our effects, we analyzed behavioral data from a corresponding nonemotional interference task.ResultsImpulsivity, but not negative affectivity or interpersonal dysfunction, predicted inefficient processing when presented with conflicting negative emotional stimuli. Across both tasks, impulsivity in adolescents was further associated with a lower decision boundary. Impulsive adolescents were especially likely to make fast, but inaccurate decisions about another person’s emotional state.ConclusionImpulsive adolescents with BPD symptoms are prone to making errors when appraising facial expressions of emotions, which may potentiate or worsen interpersonal conflicts. Our findings highlight the role of lower-level social cognitive processes in interpersonal difficulties among vulnerable youth during a sensitive developmental window.