Journal of integrative neuroscience最新文献

{"title":"Alterations in Endogenous Stem Cell Populations in the Acute Phase of Blast-Induced Spinal Cord Injury.","authors":"David Valenti, Carly Norris, Margaret Yuan, Benita Luke, Rachel Thomas, Josiah Thomas, Susan Murphy, Pamela VandeVord, Kelly C S Roballo","doi":"10.31083/j.jin2310192","DOIUrl":"https://doi.org/10.31083/j.jin2310192","url":null,"abstract":"<p><strong>Background: </strong>Blast-induced spinal cord injury (bSCI) is prevalent among military populations and frequently leads to irreversible spinal cord tissue damage that manifests as sensorimotor and autonomic nervous system dysfunction. Clinical recovery from bSCI has been proven to be multifactorial, as it is heavily dependent on the function of numerous cell populations in the tissue environment, as well as extensive ongoing inflammatory processes. This varied recovery process is thought to be due to irreversible spinal cord damage after 72 hours post-injury. Stem cell therapy for spinal cord injuries has long been investigated due to these cells' proliferative nature, ability to enhance neuro-regeneration, neuroprotection, remyelination of axons, and modulation of the immune and inflammatory responses. Therefore, this study hypothesizes that the impaired function after injury is due to a lack of specific ectoderm and neural stem cell population activity at the injury site.</p><p><strong>Methods: </strong>This study aimed to elucidate changes in endogenous stem cell patterns by evaluating immunohistochemical staining densities of various stem cell markers using a preclinical thoracolumbar bSCI model. Analysis was performed 24-, 48-, and 72 hours following blast exposure. Behavior tests to assess sensory and mechanical functions were also performed.</p><p><strong>Results: </strong>The following Cluster of differentiation (CD) markers CD105, CD45, CD133, and Vimentin, Nanog homebox (NANOG), and sex determining region Y HMG-box 2 (SOX2) positive cell populations were significantly elevated with trending increases in Octamer-binding transcription factor 4 (OCT4) in the thoracolumbar region of spinal cord tissue at 72 hours following bSCI (<i>p</i> < 0.05). Behavior analyses showed significant decreases in paw withdrawal thresholds in the hind limbs and changes in locomotion at 48- and 72 hours post-injury (<i>p</i> < 0.05).</p><p><strong>Conclusions: </strong>The significant increase in mesenchymal, pluripotent, and neural stem cell populations within the thoracolumbar region post-injury suggests that migratory patterns of stem cell populations are likely altered in response to bSCI. Behavioral deficits were consistent with those experienced by military personnel, such as increased pain-like behavior, reduced proprioception and coordination, and increased anxiety-like behavior post-bSCI, which underlines the translational capabilities of this model. While further research is vital to understand better the intrinsic and synergistic chemical and mechanical factors driving the migration of stem cells after traumatic injury, increased endogenous stem cell populations at the injury site indicate that stem cell-based treatments in patients suffering from bSCI could prove beneficial.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"23 10","pages":"192"},"PeriodicalIF":2.5,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"fNIRS Study of Brain Activation during Multiple Motor Control Conditions in Younger and Older Adults.","authors":"Duoduo Yu, Conghui Wei, Zhen Yuan, Jun Luo","doi":"10.31083/j.jin2310189","DOIUrl":"https://doi.org/10.31083/j.jin2310189","url":null,"abstract":"<p><strong>Background: </strong>Evidence suggests that aging contributes to decreased cerebral blood flow and brain oxyhemoglobin (HbO₂) in the association cortices during rest. However, the influence of aging on functional brain activation is still controversial. The objective of this study was to investigate the age-related dependence of HbO₂ across distinct motor control conditions in both primary and association cortices.</p><p><strong>Methods: </strong>Using functional near-infrared spectroscopy (fNIRS), this study assessed HbO₂ level changes within the primary somatosensory cortex (PSC), primary motor cortex (PMC), supplementary motor cortex (SMC), prefrontal cortex (PFC) and dorsolateral prefrontal cortex (DLPFC) under various motor control conditions. Analysis examined changes in the concentration of HbO₂ measured by fNIRS during rest, motor execution (ME), motor passivity (MP) and motor imagery (MI) with elbow flexion in 30 younger (21.5 ± 1.17 years old) and 30 older (60.9 ± 0.79 years old) adults.</p><p><strong>Results: </strong>During motor execution HbO₂ was higher in younger adults than older adults in bilateral PMC, bilateral PFC, left PSC, left SMC and left DLPFC (<i>p</i> < 0.05). During motor passivity, HbO₂ was higher in younger adults than older adults in bilateral PMC, left PSC and left SMC (<i>p</i> < 0.05). During motor imagery, HbO₂ was higher in younger adults than older adults in bilateral PFC and bilateral DLPFC (<i>p</i> < 0.05).</p><p><strong>Conclusion: </strong>This study provided evidence that HbO₂ levels are different in the primary and association cortices during different motor control conditions in young and old adults and that HbO₂ levels in different brain regions under different motor control conditions can be influenced by age.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"23 10","pages":"189"},"PeriodicalIF":2.5,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in Blood Biomarkers and Diagnosis Approaches for Neurodegenerative Dementias and Related Diseases.","authors":"Tomoki Sekimori, Kohji Fukunaga, David I Finkelstein, Ichiro Kawahata","doi":"10.31083/j.jin2310188","DOIUrl":"https://doi.org/10.31083/j.jin2310188","url":null,"abstract":"<p><p>Neurodegenerative dementias and related diseases, such as Alzheimer's disease, dementia with Lewy bodies, and Parkinson's disease have no fundamental cure yet. Degenerative proteins begin to accumulate before the onset of the symptoms of these diseases, and the early detection of these symptoms can lead to early therapeutic intervention. Therefore, early and simpler diagnostic methods are required. This review focuses on blood biomarkers, which are less expensive and easier to use than cerebrospinal fluid biomarkers and diagnostic imaging. A variety of approaches exist for establishing diagnostic methods for neurodegenerative dementias using blood biomarkers, such as disease differentiation using a single molecule, methods that combine multiple biomarkers, studies that search for important markers by comprehensively analyzing many molecules, and methods that combine other data. Finally, we discuss the future prospects for blood biomarker research based on the characteristics of each approach.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"23 10","pages":"188"},"PeriodicalIF":2.5,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association Between Enlarged Perivascular Spaces and Early Acute Ischemic Stroke with Cognitive Impairment: A Cross-Sectional Study.","authors":"Yu Tu, Jiewei Peng, Xuan Gong, Peipei Zhu, Chengtao Zhang, Yuqi Liu, Rong Huang, Baizhu Li, Wenyan Zhuo","doi":"10.31083/j.jin2310187","DOIUrl":"10.31083/j.jin2310187","url":null,"abstract":"<p><strong>Background: </strong>Enlarged perivascular spaces (EPVSs) are commonly detected via magnetic resonance imaging. It is unclear whether EPVSs are associated with cognitive impairment within one month after an acute ischemic stroke (AIS) (i.e., early AIS with cognitive impairment (EAIS-CI)). This study explored the severity and location of EPVSs and their association with EAIS-CI severity and provides clinicians with early warning indicators before the onset of typical clinical symptoms in the Chinese population.</p><p><strong>Methods: </strong>The clinical data of 208 patients (176 AIS patients and 32 controls) were prospectively analyzed using the Montreal Cognitive Assessment Beijing version (MoCA-BJ) score as the primary group criterion and the Mini-Mental State Examination (MMSE) score as a supplementary criterion. When EPVS I as the main EPVS type detected by imaging, the basal ganglia (BG) is the area most severely affected. Statistical analysis was conducted on the relevant clinical data.</p><p><strong>Results: </strong>AIS patients were grouped based on MoCA-BJ scores. Age (<i>p</i> < 0.01), education level (<i>p</i> = 0.02), EPVS I as the main EPVS type (<i>p</i> < 0.01), the number of right-sided BG-EPVSs (<i>p</i> = 0.04), white matter hyperintensities (WMHs) (Fazekas scores: <i>p</i> = 0.02), brain atrophy (global cortical atrophy scores: <i>p</i> < 0.01, Koedam posterior atrophy visual scale scores: <i>p</i> = 0.01, medial temporal lobe atrophy scores: <i>p</i> < 0.01) and AIS lesion volume (<i>p</i> = 0.01) were significantly greater in the EAIS-CI group than in the EAIS without cognitive impairment group. The cognitive domains of attention (<i>p</i> = 0.04) and orientation (<i>p</i> < 0.01) were more closely associated with EPVS I as the main EPVS type. However, multivariate regression analysis did not identify EPVS I as the main EPVS type as the main risk factor for EAIS-CI (<i>p</i> = 0.098). Grouping by MMSE scores revealed that EPVS I as the main EPVS type was linked to low education level (<i>p</i> < 0.01) and was significantly associated with EAIS in individuals with cognitive dementia (<i>p</i> < 0.01).</p><p><strong>Conclusions: </strong>As a result of multiple factors, EAIS-CI is significantly associated with a low education level, BG-EPVS, WMHs, and worsening brain atrophy severity. Imaging markers, such as the severity of BG-EPVS, can assist in the early diagnosis and assessment of EAIS-CI.</p><p><strong>Clinical trial registration: </strong>The study was registered with the China Clinical Trial Registry (https://www.chictr.org.cn/), registration number: ChiCTR2000038819.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"23 10","pages":"187"},"PeriodicalIF":2.5,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Luteolin Mitigates Dopaminergic Neuron Degeneration and Restrains Microglial M1 Polarization by Inhibiting Toll Like Receptor 4.","authors":"Yangzhi Xie, Hao Zhang, Jiacheng Chen, Sicong Xu, Yan Luo","doi":"10.31083/j.jin2310185","DOIUrl":"https://doi.org/10.31083/j.jin2310185","url":null,"abstract":"<p><strong>Background: </strong>Luteolin is a natural flavonoid and its neuroprotective and anti-inflammatory effects have been confirmed to mitigate neurodegeneration. Despite these findings, the underlying mechanisms responsible for these effects remain unclear. Toll-like receptor 4 (TLR4) is widely distributed in microglia and plays a pivotal role in neuroinflammation and neurodegeneration. Here studies are outlined that aimed at determining the mechanisms responsible for the anti-inflammatory and neuroprotective actions of luteolin using a rodent model of Parkinson's disease (PD) and specifically focusing on the role of TLR4 in this process.</p><p><strong>Methods: </strong>The mouse model of PD used in this experiment was established through a single injection of lipopolysaccharide (LPS). Mice were then subsequently randomly allocated to either the luteolin or vehicle-treated group, then motor performance and dopaminergic neuronal injury were evaluated. BV2 microglial cells were treated with luteolin or vehicle saline prior to LPS challenge. MRNA expression of microglial specific marker ionized calcium-binding adapter molecule 1 (<i>IBA-1</i>) and M1/M2 polarization markers, as well as the abundance of indicated pro-inflammatory cytokines in the mesencephalic tissue and BV2 were quantified by real time-polymerase chain reaction (RT-PCR) and Enzyme-linked Immunosorbent Assay (ELISA), respectively. Cell viability and apoptosis of neuron-like PC12 cell line co-cultured with BV2 were detected. TLR4 RNA transcript and protein abundance in mesencephalic tissue and BV2 cells were detected. Nuclear factor kappa-gene binding (NF-κB) p65 subunit phosphorylation both <i>in vitro</i> and <i>in vivo</i> was evaluated by immunoblotting.</p><p><strong>Results: </strong>Luteolin treatment induced functional improvements and alleviated dopaminergic neuronal loss in the PD model. Luteolin inhibited apoptosis and promoted cell survival in PC12 cells. Luteolin treatment shifted microglial M1/M2 polarization towards an anti-inflammatory M2 phenotype both <i>in vitro and in vivo</i>. Finally, it was found that luteolin treatment significantly downregulated both <i>TLR4</i> mRNA and protein expression as well as restraining NF-κB p65 subunit phosphorylation.</p><p><strong>Conclusions: </strong>Luteolin restrained dopaminergic degeneration <i>in vitro</i> and <i>in vivo</i> by blocking TLR4-mediated neuroinflammation.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"23 10","pages":"185"},"PeriodicalIF":2.5,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurodiversity and Autism Spectrum Disorder: An Ostriches' Head in the Sand?","authors":"Gerry Leisman","doi":"10.31083/j.jin2310186","DOIUrl":"https://doi.org/10.31083/j.jin2310186","url":null,"abstract":"","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"23 10","pages":"186"},"PeriodicalIF":2.5,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic Reorganization Patterns of Brain Modules after Stroke Reflecting Motor Function.","authors":"Xin Yu, Kang Wu, Yuanyuan Li, Chen Chen, Tianzhu Chen, Xinyue Shi, Zhongjian Tan, Yihuai Zou","doi":"10.31083/j.jin2310182","DOIUrl":"https://doi.org/10.31083/j.jin2310182","url":null,"abstract":"<p><strong>Objective: </strong>Advancements in neuroimaging technologies have significantly deepened our understanding of the neural physiopathology associated with stroke. Nevertheless, the majority of studies ignored the characteristics of dynamic changes in brain networks. The relationship between dynamic changes in brain networks and the severity of motor dysfunction after stroke needs further investigation. From the perspective of multilayer network module reconstruction, we aimed to explore the dynamic reorganization of the brain and its relationship with motor function in subcortical stroke patients.</p><p><strong>Methods: </strong>We recruited 35 healthy individuals and 50 stroke patients with unilateral limb motor dysfunction (further divided into mild-moderate group and severe group). Using dynamic multilayer network modularity analysis, we investigated changes in the dynamic modular reconfiguration of brain networks. Additionally, we assessed longitudinal clinical scale changes in stroke patients. Correlation and regression analyses were employed to explore the relationship between characteristic dynamic indicators and impairment and recovery of motor function, respectively.</p><p><strong>Results: </strong>We observed increased temporal flexibility in the Default Mode Network (DMN) and decreased recruitment of module reconfiguration in the Attention Network (AN), Sensorimotor Network (SMN), and DMN after stroke. We also observed reduced module loyalty following stroke. Additionally, correlation analysis showed that hyper-flexibility of the DMN was associated with better lower limb motor function performance in stroke patients with mild-to-moderate impairment. Regression analysis indicated that increased flexibility within the DMN and decreased recruitment coefficient within the AN may predict good lower limb function prognosis in patients with mild to moderate motor impairment.</p><p><strong>Conclusions: </strong>Our study revealed more frequent modular reconfiguration and hyperactive interaction of brain networks after stroke. Notably, dynamic modular remodeling was closely related to the impairment and recovery of motor function. Understanding the temporal module reconfiguration patterns in multilayer networks after stroke can provide valuable information for more targeted treatments.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"23 10","pages":"182"},"PeriodicalIF":2.5,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Key Synaptic Pathology in Autism Spectrum Disorder: Genetic Mechanisms and Recent Advances.","authors":"Yuan Zhang, Rui Tang, Zhi-Min Hu, Xi-Hao Wang, Xia Gao, Tao Wang, Ming-Xi Tang","doi":"10.31083/j.jin2310184","DOIUrl":"https://doi.org/10.31083/j.jin2310184","url":null,"abstract":"<p><p>Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interactions and verbal communication, accompanied by symptoms of restricted and repetitive patterns of behavior or interest. Over the past 30 years, the morbidity of ASD has increased in most areas of the world. Although the pathogenesis of ASD is not fully understood, it has been associated with over 1000 genes or genomic loci, indicating the importance and complexity of the genetic mechanisms involved. This review focuses on the synaptic pathology of ASD and particularly on genetic variants involved in synaptic structure and functions. These include <i>SHANK</i>, <i>NLGN</i>, <i>NRXN</i>, <i>FMR1</i>, and <i>MECP2</i> as well as other potentially novel genes such as <i>CHD8</i>, <i>CHD2</i>, and <i>SYNGAP1</i> that could be core elements in ASD pathogenesis. Here, we summarize several pathological pathways supporting the hypothesis that synaptic pathology caused by genetic mutations may be the pathogenic basis for ASD.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"23 10","pages":"184"},"PeriodicalIF":2.5,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimization of the Operant Silent Gap-in-Noise Detection Paradigm in Humans.","authors":"Louis Negri, Patrick Oliver, Rebecca Mitchell, Lavanya Sinha, Jacob Kearney, Dominic Saad, Fernando R Nodal, Victoria M Bajo","doi":"10.31083/j.jin2310183","DOIUrl":"https://doi.org/10.31083/j.jin2310183","url":null,"abstract":"<p><strong>Background: </strong>In the auditory domain, temporal resolution is the ability to respond to rapid changes in the envelope of a sound over time. Silent gap-in-noise detection tests assess temporal resolution. Whether temporal resolution is impaired in tinnitus and whether those tests are useful for identifying the condition is still debated. We have revisited these questions by assessing the silent gap-in-noise detection performance of human participants.</p><p><strong>Methods: </strong>Participants were seventy-one young adults with normal hearing, separated into preliminary, tinnitus and matched-control groups. A preliminary group (n = 18) was used to optimise the silent gap-in-noise detection two-alternative forced-choice paradigm by examining the effect of the position and the salience of the gap. Temporal resolution was tested in case-control observational study of tinnitus (n = 20) and matched-control (n = 33) groups using the previously optimized silent gap-in-noise behavioral paradigm. These two groups were also tested using silent gap prepulse inhibition of the auditory startle reflex (GPIAS) and Auditory Brain Responses (ABRs).</p><p><strong>Results: </strong>In the preliminary group, reducing the predictability and saliency of the silent gap increased detection thresholds and reduced gap detection sensitivity (slope of the psychometric function). In the case-control study, tinnitus participants had higher gap detection thresholds than controls for narrowband noise stimuli centred at 2 and 8 kHz, with no differences in GPIAS or ABRs. In addition, ABR data showed latency differences across the different tinnitus subgroups stratified by subject severity.</p><p><strong>Conclusions: </strong>Operant silent gap-in-noise detection is impaired in tinnitus when the paradigm is optimized to reduce the predictability and saliency of the silent gap and to avoid the ceiling effect. Our behavioral paradigm can distinguish tinnitus and control groups suggesting that temporal resolution is impaired in tinnitus. However, in young adults with normal hearing, the paradigm is unable to objectively identify tinnitus at the individual level. The GPIAS paradigm was unable to differentiate the tinnitus and control groups, suggesting that operant, as opposed to reflexive, silent gap-in-noise detection is a more sensitive measure for objectively identifying tinnitus.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"23 10","pages":"183"},"PeriodicalIF":2.5,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Topography of Cholinergic Nerve Terminal Vulnerability and Balance Self-Efficacy in Parkinson's Disease.","authors":"Jaimie Barr, Robert Vangel, Prabesh Kanel, Stiven Roytman, Chatkaew Pongmala, Roger L Albin, Peter J H Scott, Nicolaas I Bohnen","doi":"10.31083/j.jin2309178","DOIUrl":"https://doi.org/10.31083/j.jin2309178","url":null,"abstract":"<p><strong>Background: </strong>Postural instability and gait disturbances (PIGD) represent a significant cause of disability in Parkinson's disease (PD). Cholinergic system dysfunction has been implicated in falls in PD. The occurrence of falls typically results in fear of falling (FoF) that in turn may lead to poorer balance self-efficacy. Balance self-efficacy refers to one's level of confidence in their ability to balance while completing activities of daily living like getting dressed, bathing, and walking. Lower self-efficacy, or greater FoF during these activities is a function of motor, cognitive, and emotional impairments and may impact quality of life in PD. Unlike known cholinergic reduction, especially in the right lateral geniculate and caudate nuclei, little is known about the role of cholinergic transporters in FoF or mobility self-efficacy in PD.</p><p><strong>Methods: </strong>[¹⁸F]fluoroethoxybenzovesamicol ([¹⁸F]FEOBV) positron emission tomography (PET) studies were conducted to assess vesicular acetylcholine transporter (VAChT) expression in 126 patients with PD (male (m) = 95, female (f) = 31). Participants had a mean age of 67.3 years (standard deviation (SD) = 7.1) and median Hoehn Yahr stage of 2.5. Patients also completed the Short Falls Efficacy Scale (sFES-I) as a survey measure of concerns about falling. [¹⁸F]FEOBV data were processed in Statistical Parametric Mapping (SPM) using a voxel-wise regression model with sFES-I scores as the outcome measure.</p><p><strong>Results: </strong>Reduced [¹⁸F]FEOBV binding in tectum, metathalamic (lateral more than medial geniculate nuclei), thalamus proper, bilateral mesiotemporal (hippocampal, parahippocampal, fusiform gyri and fimbriae), and right cerebellar lobule VI significantly associated with higher sFES-I scores (<i>p</i> < 0.05, family-wise error (FWE) correction after Threshold-Free Cluster Enhancement (TFCE)).</p><p><strong>Conclusions: </strong>Unlike the more limited involvement of the brainstem-thalamic complex and caudate nuclei cholinergic topography associated with falls in PD, cholinergic reductions in the extended connectivity between the thalamic complex and the temporal limbic system via the fimbriae associates with FoF. Additional cholinergic changes were seen in the cerebellum. The temporal limbic system plays a role not only in episodic memory but also in spatial navigation, scene and contextual (<i>e.g.</i>, emotional) processing. Findings may augur novel therapeutic approaches to treat poor mobility self-efficacy in PD.</p><p><strong>Clinical trial registration: </strong>No: NCT02458430. Registered 18 March, 2015, https://www.</p><p><strong>Clinicaltrials: </strong>gov/study/NCT02458430; No: NCT05459753. Registered 01 July, 2022, https://www.</p><p><strong>Clinicaltrials: </strong>gov/study/NCT05459753.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"23 9","pages":"178"},"PeriodicalIF":2.5,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}