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Medicine May 2024Parkinson disease (PD), a prevalent neurodegenerative ailment in the elderly, relies mainly on pharmacotherapy, yet deep brain stimulation (DBS) emerges as a vital...
Parkinson disease (PD), a prevalent neurodegenerative ailment in the elderly, relies mainly on pharmacotherapy, yet deep brain stimulation (DBS) emerges as a vital remedy for refractory cases. This study performs a bibliometric analysis on DBS in PD, delving into research trends and study impact to offer comprehensive insights for researchers, clinicians, and policymakers, illuminating the current state and evolutionary trajectory of research in this domain. A systematic search on March 13, 2023, in the Scopus database utilized keywords like "Parkinson disease," "PD," "Parkinsonism," "Deep brain stimulation," and "DBS." The top 1000 highly cited publications on DBS in PD underwent scientometric analysis via VOS Viewer and R Studio's Bibliometrix package, covering publication characteristics, co-authorship, keyword co-occurrence, thematic clustering, and trend topics. The bibliometric analysis spanned 1984 to 2021, involving 1000 cited articles from 202 sources. The average number of citations per document were 140.9, with 31,854 references. "Movement Disorders" led in publications (n = 98), followed by "Brain" (n = 78) and "Neurology" (n = 65). The University of Oxford featured prominently. Thematic keyword clustering identified 9 core research areas, such as neuropsychological function and motor circuit electrophysiology. The shift from historical neurosurgical procedures to contemporary focuses like "beta oscillations" and "neuroethics" was evident. The bibliometric analysis emphasizes UK and US dominance, outlining 9 key research areas pivotal for reshaping Parkinson treatment. A discernible shift from invasive neurosurgery to DBS is observed. The call for personalized DBS, integration with NIBS, and exploration of innovative avenues marks the trajectory for future research.
Topics: Parkinson Disease; Humans; Bibliometrics; Deep Brain Stimulation; Biomedical Research
PubMed: 38758903
DOI: 10.1097/MD.0000000000038152 -
BMJ Surgery, Interventions, & Health... 2024Build the theoretical and evidence-base for a digital platform (map-OR) which delivers intraoperative language tests during awake craniotomy and facilitates...
OBJECTIVES
Build the theoretical and evidence-base for a digital platform (map-OR) which delivers intraoperative language tests during awake craniotomy and facilitates collaborative sharing of brain mapping data.
DESIGN
Mixed methodology study including two scoping reviews, international survey, synthesis of development guiding principles and a risk assessment using failure modes and effects analysis.
SETTING
The two scoping reviews examined the literature published in the English language. International survey was completed by members of awake craniotomy teams from 14 countries.
MAIN OUTCOME MEASURES
Scoping review 1: number of technologies described for language mapping during awake craniotomy. Scoping review 2: barriers and facilitators to adopting novel technology in surgery. International survey: degree of language mapping technology penetration into clinical practice.
RESULTS
A total of 12 research articles describing 6 technologies were included. The technologies required a range of hardware components including portable devices, virtual reality headsets and large integrated multiscreen stacks. The facilitators and barriers of technology adoption in surgery were extracted from 11 studies and mapped onto the 4 Unified Theory of Acceptance and Use of Technology constructs. A total of 37 awake craniotomy teams from 14 countries completed the survey. Of the responses, 20 (54.1%) delivered their language tests digitally, 10 (27.0%) delivered tests using cards and 7 (18.9%) used a combination of both. The most commonly used devices were tablet computers (67.7%; n=21) and the most common software used was Microsoft PowerPoint (60.6%; n=20). Four key risks for the proposed digital platform were identified, the highest risk being a software and internet connectivity failure during surgery.
CONCLUSIONS
This work represents a rigorous and structured approach to the development of a digital platform for standardized intraoperative language testing during awake craniotomy and for collaborative sharing of brain mapping data.
TRIAL REGISTRATION NUMBER
Scoping review protocol registrations in OSF registries (scoping review 1: osf.io/su9xm; scoping review 2: osf.io/x4wsc).
PubMed: 38756704
DOI: 10.1136/bmjsit-2023-000234 -
Scientific Reports May 2024While short-read sequencing currently dominates genetic research and diagnostics, it frequently falls short of capturing certain structural variants (SVs), which are...
While short-read sequencing currently dominates genetic research and diagnostics, it frequently falls short of capturing certain structural variants (SVs), which are often implicated in the etiology of neurodevelopmental disorders (NDDs). Optical genome mapping (OGM) is an innovative technique capable of capturing SVs that are undetectable or challenging-to-detect via short-read methods. This study aimed to investigate NDDs using OGM, specifically focusing on cases that remained unsolved after standard exome sequencing. OGM was performed in 47 families using ultra-high molecular weight DNA. Single-molecule maps were assembled de novo, followed by SV and copy number variant calling. We identified 7 variants of interest, of which 5 (10.6%) were classified as likely pathogenic or pathogenic, located in BCL11A, OPHN1, PHF8, SON, and NFIA. We also identified an inversion disrupting NAALADL2, a gene which previously was found to harbor complex rearrangements in two NDD cases. Variants in known NDD genes or candidate variants of interest missed by exome sequencing mainly consisted of larger insertions (> 1kbp), inversions, and deletions/duplications of a low number of exons (1-4 exons). In conclusion, in addition to improving molecular diagnosis in NDDs, this technique may also reveal novel NDD genes which may harbor complex SVs often missed by standard sequencing techniques.
Topics: Humans; Neurodevelopmental Disorders; Female; Male; DNA Copy Number Variations; Chromosome Mapping; Exome Sequencing; Child; Genomic Structural Variation; Child, Preschool
PubMed: 38755281
DOI: 10.1038/s41598-024-62009-y -
PloS One 2024Multimorbidity has become an important health challenge in the aging population. Accumulated evidence has shown that multimorbidity has complex association patterns, but...
BACKGROUND
Multimorbidity has become an important health challenge in the aging population. Accumulated evidence has shown that multimorbidity has complex association patterns, but the further mechanisms underlying the association patterns are largely unknown.
METHODS
Summary statistics of 14 conditions/diseases were available from the genome-wide association study (GWAS). Linkage disequilibrium score regression analysis (LDSC) was applied to estimate the genetic correlations. Pleiotropic SNPs between two genetically correlated traits were detected using pleiotropic analysis under the composite null hypothesis (PLACO). PLACO-identified SNPs were mapped to genes by Functional Mapping and Annotation of Genome-Wide Association Studies (FUMA), and gene set enrichment analysis and tissue differential expression were performed for the pleiotropic genes. Two-sample Mendelian randomization analyses assessed the bidirectional causality between conditions/diseases.
RESULTS
LDSC analyses revealed the genetic correlations for 20 pairs based on different two-disease combinations of 14 conditions/diseases, and genetic correlations for 10 pairs were significant after Bonferroni adjustment (P<0.05/91 = 5.49E-04). Significant pleiotropic SNPs were detected for 11 pairs of correlated conditions/diseases. The corresponding pleiotropic genes were differentially expressed in the brain, nerves, heart, and blood vessels and enriched in gluconeogenesis and drug metabolism, biotransformation, and neurons. Comprehensive causal analyses showed strong causality between hypertension, stroke, and high cholesterol, which drive the development of multiple diseases.
CONCLUSIONS
This study highlighted the complex mechanisms underlying the association patterns that include the shared genetic components and causal effects among the 14 conditions/diseases. These findings have important implications for guiding the early diagnosis, management, and treatment of comorbidities.
Topics: Humans; Polymorphism, Single Nucleotide; Multimorbidity; Genome-Wide Association Study; Linkage Disequilibrium; Mendelian Randomization Analysis; Genetic Predisposition to Disease; Genetic Pleiotropy
PubMed: 38753827
DOI: 10.1371/journal.pone.0300740 -
PloS One 2024Dynamic functional connectivity investigates how the interactions among brain regions vary over the course of an fMRI experiment. Such transitions between different...
Dynamic functional connectivity investigates how the interactions among brain regions vary over the course of an fMRI experiment. Such transitions between different individual connectivity states can be modulated by changes in underlying physiological mechanisms that drive functional network dynamics, e.g., changes in attention or cognitive effort. In this paper, we develop a multi-subject Bayesian framework where the estimation of dynamic functional networks is informed by time-varying exogenous physiological covariates that are simultaneously recorded in each subject during the fMRI experiment. More specifically, we consider a dynamic Gaussian graphical model approach where a non-homogeneous hidden Markov model is employed to classify the fMRI time series into latent neurological states. We assume the state-transition probabilities to vary over time and across subjects as a function of the underlying covariates, allowing for the estimation of recurrent connectivity patterns and the sharing of networks among the subjects. We further assume sparsity in the network structures via shrinkage priors, and achieve edge selection in the estimated graph structures by introducing a multi-comparison procedure for shrinkage-based inferences with Bayesian false discovery rate control. We evaluate the performances of our method vs alternative approaches on synthetic data. We apply our modeling framework on a resting-state experiment where fMRI data have been collected concurrently with pupillometry measurements, as a proxy of cognitive processing, and assess the heterogeneity of the effects of changes in pupil dilation on the subjects' propensity to change connectivity states. The heterogeneity of state occupancy across subjects provides an understanding of the relationship between increased pupil dilation and transitions toward different cognitive states.
Topics: Humans; Bayes Theorem; Magnetic Resonance Imaging; Brain; Nerve Net; Models, Neurological; Markov Chains; Connectome; Brain Mapping
PubMed: 38753655
DOI: 10.1371/journal.pone.0298651 -
IScience May 2024Depressive symptoms usually precede the cognitive decline in Alzheimer disease (AD) and worsen the clinical outcome. However, the neural circuitry mediating early...
Depressive symptoms usually precede the cognitive decline in Alzheimer disease (AD) and worsen the clinical outcome. However, the neural circuitry mediating early emotional dysfunction, especially depressive symptoms in AD, remains elusive. Anterior cingulate cortex (ACC) is closely related to depression and vulnerable in AD. By quantitative whole-brain mapping and electrophysiological recording, we found that the decreased axonal calcium activity in neurons of ACC and the glutamatergic projection from ACC to the ventral hippocampal CA1 (vCA1) is significantly impaired in 3-month-old 5×FAD mice, which exhibit depressive-like phenotype before cognition defects in early stage. The activation of ACC-vCA1 circuit by chemogenetic manipulation efficiently ameliorated the early depressive-like behaviors in 5×FAD mice. We further identified the upregulated neuregulin-1 (Nrg1) in ACC impaired the excitatory synaptic transmission from the ACC to vCA1 in AD. Our work reveals the role of ACC-vCA1 circuit in regulating AD associated depression symptom in a mouse model of AD.
PubMed: 38746665
DOI: 10.1016/j.isci.2024.109778 -
Journal of Alzheimer's Disease Reports 2024Some pathological changes occur in patients with Alzheimer's disease (AD) prior to the onset of clinical symptoms.
A Comparative Evaluation of Error Processing Performance and its Relationship with Cognitive Function in Patients with Alzheimer's Disease, Individuals with Mild Cognitive Impairment, and Normal Controls Using the Event-Related Potentials.
BACKGROUND
Some pathological changes occur in patients with Alzheimer's disease (AD) prior to the onset of clinical symptoms.
OBJECTIVE
In the present study, we aimed to investigate the potential of event-related potential (ERP) components in error processing performance as a neuromarker of mild cognitive impairment (MCI) and transition to AD and their relation with cognitive functions.
METHODS
We conducted an evaluation of 16 patients diagnosed with AD, 16 patients with MCI, and 15 normal controls using three subtests from the Cambridge Neuropsychological Testing Automated Battery (CANTAB). The ERP components of error processing were extracted and compared among the three groups using a modified version of the Eriksen flanker task. Additionally, we assessed the correlation between the cognitive results and the ERP components.
RESULTS
Significant differences were observed among the three groups in terms of providing correct responses following errors and the amplitude of error-related negativity (ERN). These differences were also significant between all paired groups. Regarding other ERP components of error processing and the peak latency of ERN, no significant differences were observed among the three groups. The findings revealed that the spatial working memory and new learning were correlated with the amplitude of ERN.
CONCLUSIONS
In the context of error processing performance, both the accuracy of responses following an error and the amplitude of ERN can be considered as indicators of MCI and its progression to AD. The present findings do not support the use of other error processing components as differential markers in the three groups.
PubMed: 38746624
DOI: 10.3233/ADR-230104 -
BioRxiv : the Preprint Server For... May 2024Syntactic processing and verbal working memory are both essential components to sentence comprehension. Nonetheless, the separability of these systems in the brain...
Syntactic processing and verbal working memory are both essential components to sentence comprehension. Nonetheless, the separability of these systems in the brain remains unclear. To address this issue, we performed causal-inference analyses based on lesion and connectome network mapping using MRI and behavioral testing in 103 individuals with chronic post-stroke aphasia. We employed a rhyme judgment task with heavy working memory load without articulatory confounds, controlling for the overall ability to match auditory words to pictures and to perform a metalinguistic rhyme judgment, isolating the effect of working memory load. We assessed noncanonical sentence comprehension, isolating syntactic processing by incorporating residual rhyme judgment performance as a covariate for working memory load. Voxel-based lesion analyses and structural connectome-based lesion symptom mapping controlling for total lesion volume were performed, with permutation testing to correct for multiple comparisons (4,000 permutations). We observed that effects of working memory load localized to dorsal stream damage: posterior temporal-parietal lesions and frontal-parietal white matter disconnections. These effects were differentiated from syntactic comprehension deficits, which were primarily associated with ventral stream damage: lesions to temporal lobe and temporal-parietal white matter disconnections, particularly when incorporating the residual measure of working memory load as a covariate. Our results support the conclusion that working memory and syntactic processing are associated with distinct brain networks, largely loading onto dorsal and ventral streams, respectively.
PubMed: 38746328
DOI: 10.1101/2024.05.05.592577 -
MedRxiv : the Preprint Server For... May 2024The prevalence of co-occurring heavy alcohol consumption and obesity is increasing in the United States. Despite neurobiological overlap in the regulation of alcohol...
BACKGROUND
The prevalence of co-occurring heavy alcohol consumption and obesity is increasing in the United States. Despite neurobiological overlap in the regulation of alcohol consumption and eating behavior, alcohol- and body mass index (BMI)-related phenotypes show no or minimal genetic correlation. We hypothesized that the lack of genetic correlation is due to mixed effect directions of variants shared by AUD and BMI.
METHODS
We applied MiXeR, to investigate shared genetic architecture between AUD and BMI in individuals of European ancestry. We used conjunctional false discovery rate (conjFDR) analysis to detect loci associated with both phenotypes and their directional effect, Functional Mapping and Annotation (FUMA) to identify lead single nucleotide polymorphisms (SNPs), Genotype-Tissue Expression (GTEx) samples to examine gene expression enrichment across tissue types, and BrainXcan to evaluate the shared associations of AUD and BMI with brain image-derived phenotypes.
RESULTS
MiXeR analysis indicated polygenic overlap of 80.9% between AUD and BMI, despite a genetic correlation (r ) of -.03. ConjFDR analysis yielded 56 lead SNPs with the same effect direction and 76 with the opposite direction. Of the 132 shared lead SNPs, 53 were novel for both AUD and BMI. GTEx analyses identified significant overexpression in the frontal cortex (BA9), hypothalamus, cortex, anterior cingulate cortex (BA24), hippocampus, and amygdala. Amygdala and caudate nucleus gray matter volumes were significantly associated with both AUD and BMI in BrainXcan analyses.
CONCLUSIONS
More than half of variants significantly associated with AUD and BMI had opposite directions of effect for the traits, supporting our hypothesis that this is the basis for their lack of genetic correlation. Follow-up analyses identified brain regions implicated in executive functioning, reward, homeostasis, and food intake regulation. Together, these findings clarify the extensive polygenic overlap between AUD and BMI and elucidate several overlapping neurobiological mechanisms.
PubMed: 38746260
DOI: 10.1101/2024.05.03.24306773 -
BioRxiv : the Preprint Server For... May 2024Precision mapping techniques coupled with high resolution image acquisition of the mouse brain permit the study of the spatial organization of gene expression and their...
Precision mapping techniques coupled with high resolution image acquisition of the mouse brain permit the study of the spatial organization of gene expression and their mutual interaction for a comprehensive view of salient structural/functional relationships. Such research is facilitated by standardized anatomical coordinate systems, such as the well-known Allen Common Coordinate Framework (AllenCCFv3), and the ability to spatially map to such standardized spaces. The Advanced Normalization Tools Ecosystem is a comprehensive open-source software toolkit for generalized quantitative imaging with applicability to multiple organ systems, modalities, and animal species. Herein, we illustrate the utility of ANTsX for generating precision spatial mappings of the mouse brain and potential subsequent quantitation. We describe ANTsX-based workflows for mapping domain-specific image data to AllenCCFv3 accounting for common artefacts and other confounds. Novel contributions include ANTsX functionality for velocity flow-based mapping spanning the spatiotemporal domain of a longitudinal trajectory which we apply to the Developmental Common Coordinate Framework. Additionally, we present an automated structural morphological pipeline for determining volumetric and cortical thickness measurements analogous to the well-utilized ANTsX pipeline for human neuroanatomical structural morphology which illustrates a general open-source framework for tailored brain parcellations.
PubMed: 38746199
DOI: 10.1101/2024.05.01.592056