NeuroSci最新文献

Background: Amputation poses significant physical, psychological, and emotional challenges, with chronic pain being one of the most debilitating outcomes. Pain Pressure Threshold (PPT), a measure of nociceptive sensitivity, is a valuable tool for assessing changes in pain perception. Understanding PPT modulation in amputees is crucial for uncovering the mechanisms underlying pain and developing targeted interventions for pain management.

Objective: This study aimed to evaluate PPT in amputees and identify factors associated with PPT variation in this population.

Methods: This cross-sectional study analyzed neurophysiological, clinical, and demographic data from 86 amputee patients. PPT was assessed as the primary outcome, and its associations with demographic and clinical predictors were examined using both linear and quadratic regression models.

Results: Multivariate analysis identified a significant association between PPT and biological sex, with females exhibiting lower PPT values than males. Quadratic regression analyses revealed inverted U-shaped associations between PPT and age, BMI, and duration since amputation. PPT increased with age, peaking at 45.8 years, followed by a decline. Similar patterns were observed for BMI, peaking at 27.0 kg/m², and for amputation duration, peaking at 26.6 months.

Conclusions: Our findings indicate that sex, age, BMI, and time since amputation are significant factors influencing PPT in amputees, with nonlinear relationships observed for age, BMI, and amputation duration. These results suggest that physiological and disease-related factors (such as age, BMI, and duration of injury) have specific peaks for optimal PPT, highlighting their role in the brain's compensatory system and potential implications for targeted pain management strategies.

Background: Alzheimer's disease (AD) is the fifth leading cause of death for Americans older than 65. Though fluctuations have been noticed over the past two decades, the mortality of Alzheimer's patients increased considerably during the COVID-19 pandemic. This study aims to explore the temporal trends in AD-associated mortality (ADAM) and disparities in these trends, and we aim to discern changes to these trends during the COVID-19 pandemic. Methods: The CDC WONDER Multiple Cause-of-Death Public Use Records from 1999 to 2022 were used to extract population data on deaths related to AD and stratify them based on age, biological sex, race, ethnicity, place of death, census region, and state. ICD-10 codes G30.0, G30.1, G30.8, and G30.9 were used to identify AD-related mortality. Statistical analysis was performed using the Joinpoint Regression Program version 5.0.2. Results: We confirmed an increase in mortality rate in all races, sexes, places of death, age groups above 65, and states/census regions. Interestingly, the age-adjusted mortality rate (AAMR) of AD was consistently higher in females compared to males. Non-Hispanic whites had the highest AD mortality by race and ethnicity. At the intersection of race and biological sex, White females had the highest AAMR with AD. Lastly, we noted an increase in AD mortality at hospice facilities as compared to other places of death. Conclusions: Our findings demonstrate that the number of deaths due to AD was exacerbated by the recent pandemic and that White females were disproportionately affected. The disparities relating to ADAM uncovered in this study may assist healthcare administrators and policymakers in their decisions. Additionally, the findings might help initiate larger studies focusing on these disparities to explore novel risk/prognostic factors for AD.

Background: Fibromyalgia syndrome (FMS), a chronic pain syndrome affecting 0.2-6.6% of the general population, is known for its challenging diagnosis and treatment. The known dysregulation in the Endogenous Pain Modulatory System (EPMS) characteristic of the pathology contributes to enhanced pain sensitivity. Fibromyalgia patients, who are often overmedicated, may experience, in addition to the drug-related known adverse effects, effects on fibromyalgia sensory-related outcomes. Therefore, the focus of this analysis is to explore the bidirectional drug-sensory outcome interactions, indexed by the conditioned pain modulation (CPM), an important assessment element in regard to an EPMS's efficacy.

Methods: Baseline data from a randomized, double-blind, single-center (Boston-based tertiary hospital) clinical trial (NCT03371225) were analyzed. Participants aged 18-65 with an FMS diagnosis and resistance to common analgesics were included. Demographic, clinical, and sensory variables, including CPM, temporal summation, and Pain-60 outcomes, were collected alongside a pain medication diary. Multivariable regression models adjusted for confounders were applied to explore associations between medication classes and quantitative sensory outcomes.

Results: Out of 101 recruited FMS patients, we categorized the use of the following medications: antidepressants with 50% use (n = 50), muscle relaxants with 26% use (n = 26), and gabapentin with 25% use (n = 25). The results showed that antidepressant use correlated with worsened CPM, Odds Ratio = 0.39 (95% CI = 0.17-0.91), while muscle relaxants were linked to increased TSPS, β coefficient = 0.72 (95% CI = 0.0021-1.4431). On the other hand, gabapentin use was associated with elevated Pain-60, OR = 2.68 (95% CI = 0.98-7.31). Interestingly, the use of low doses of opioids was not associated with altered sensory measures.

Conclusion: This cross-sectional analysis suggests that common pain medications may affect quantitative sensory outcomes in FMS patients. We provided important insights into bidirectional drug-sensory outcome interactions and their influence on pain medicine.

Objective: As outlined in our previous study, this study aims to investigate the role of body mass index (BMI) as an effect modifier in the relationship between conditioned pain modulation (CPM) and clinical outcomes, including depression, quality of life, and pain in individuals with knee osteoarthritis (KOA).

Methods: This cross-sectional analysis is part of the DEFINE Study in Rehabilitation. A total of 113 participants with KOA, admitted to the Instituto de Medicina Física e Reabilitação (IMREA) rehabilitation program, were included. Clinical and neurophysiological assessments were conducted, focusing on CPM, the Hamilton Depression Rating Scale (HDRS), and the SF-36 health survey. BMI was stratified into two categories based on the mean BMI of 31.99 kg/m², and linear regression models were used to evaluate BMI as an effect modifier in the relationship between CPM and clinical outcomes. p-values below 0.10 for interaction terms (CPM × BMI) indicated effect modification.

Results: In participants with BMI < 31.99 kg/m², increased CPM was significantly associated with improved depression scores (lower HDRS) and enhanced physical functioning, emotional well-being, and reduced limitations due to emotional problems (SF-36). In contrast, no significant associations between CPM and these outcomes were found in participants with BMI ≥ 31.99 kg/m². The results suggest that a higher BMI disrupts the salutogenic effects of endogenous pain control, diminishing the beneficial associations between CPM and both physical and psychological outcomes, as previously observed in fibromyalgia patients.

Conclusions: BMI acts as an effect modifier in the relationship between CPM and clinical outcomes in individuals with KOA. Obesity appears to hinder the beneficial relationships between clinical symptoms and CPM, leading to a less favorable link between physical and emotional functioning and CPM. These findings highlight the importance of considering BMI in treatment strategies for KOA, particularly when addressing the impact of lifestyle and other modifiable factors that influence pain modulation.

Pattern separation is considered a crucial process that allows us to distinguish among the highly similar and overlapping experiences that constitute our episodic memory. Not only do different episodes share common features, but it is often the case that they share the context in which they occurred. While there have been a great number of studies investigating pattern separation and its behavioral counterpart, a process known as mnemonic discrimination, surprisingly, research exploring the influence of context on pattern separation or mnemonic discrimination has been less common. The available evidence shows that similar items with similar contexts led to a failure in pattern separation due to high similarity that triggers overlap between events. On the other hand, others have shown that pattern separation can take place even under these conditions, allowing humans to distinguish between events with similar items and contexts, as different hippocampal subfields would play complementary roles in enabling both pattern separation and pattern completion. In the present study, we were interested in testing how stability in context influenced pattern separation. Despite the fact that pattern separation is by definition an encoding computation, the existing literature has focused on the retrieval phase. Here, we used a subsequent memory paradigm in which we manipulated the similarity of context during the encoding of visual objects selected from diverse categories. Thus, we manipulated the encoded context of each object category (four items within a category), so that some categories had the same context and others had a different context. This approach allowed us to test not only the items presented but also to include the conditions that entail the greatest demand on pattern separation. After a 20 min period, participants performed a visual mnemonic discrimination task in which they had to differentiate between old, similar, and new items by providing one of the three options for each tested item. Similarly to previous studies, we found no interaction between judgments and contexts, and participants were able to discriminate between old and lure items at the behavioral level in both conditions. Moreover, when averaging the ERPs of all the items presented within a category, a significant SME emerged between hits and new misses, but not between hits and old false alarms or similar false alarms. These results suggest that item recognition emerges from the interaction with subsequently encoded information, and not just between item memory strength and retrieval processes.

Introduction: The current literature suggests hyperglycemia can predict poor outcomes in patients with primary intracerebral hemorrhage (ICH). Chronic hyperglycemia is seen in patients with pre-existing diabetes (DM); however, acute hyperglycemia in non-diabetic patients is defined as stress-induced hyperglycemia (SIH). This study explored the influence of hyperglycemia on outcomes of primary ICH patients both in the presence and absence of pre-existing DM.

Methods: Data regarding admission glucose, pre-existing DM, inpatient mortality, and modified Rankin Scale (mRS) scores at discharge were available for 636 patients admitted to Stony Brook Hospital from January 2011 to December 2022 with a primary diagnosis of ICH. Regression models were used to compare outcomes between patients with admission hyperglycemia and/or pre-existing DM to a control group of normoglycemic and non-diabetic ICH patients.

Results: Patients with SIH had higher inpatient mortality rates and worse mRS scores at discharge (p < 0.001). An association with higher mortality and worse mRS scores at discharge was also seen in patients with hyperglycemia secondary to DM, although the strength of this association was weaker when compared to patients with SIH.

Conclusions: Our findings suggest that SIH may play a greater role in predicting poor outcomes at discharge rather than a history of poorly controlled DM with chronic hyperglycemia. To develop a more thorough understanding of this topic, prospective studies evaluating the effect of changes in serum glucose during hospital stay on short and long-term outcomes is needed.

Alzheimer's disease is the most common form of dementia. Benzodiazepines are the most widely used pharmacological class in the treatment of insomnia and other sleep disorders. Some literature suggests that the chronic use of benzodiazepines is associated with the development of cognitive decline. This review aims to evaluate the use of benzodiazepines and its association with the development of Alzheimer's disease. A systematic review of the literature was carried out using the MEDLINE and Embase databases. Protocols followed the PRISMA-P 2020 methodology, and, after the analysis of the included studies, a narrative synthesis of the results was carried out. Only two cohort studies were identified that met defined eligibility criteria. In the retrospective study, a significant risk of developing Alzheimer's disease after treatment with benzodiazepines was found. In the prospective study, the prevalence of Alzheimer's disease was not associated with treatment with benzodiazepines. Results suggest that only the largest study presented a significant risk of developing Alzheimer's disease. Given the scarce scientific evidence found, it is concluded that further research on this topic is necessary.

This study investigates employment rates and their determinants among individuals with spinal cord injury (SCI) in Romania using data from the Romanian National Spinal Cord Injury Survey (RO-InSCI), part of the International Spinal Cord Injury (InSCI) Community Survey. The cross-sectional study included 215 adults with traumatic or non-traumatic SCI living in the community. Participants were recruited through rehabilitation hospitals and patient organizations. Employment status, demographic characteristics, and injury-related factors were assessed. The observed employment rate was 25.35%, with a 39.45% employment gap compared to the general population. Barriers to employment included health status, disability, inadequate transport, and insufficient access to infrastructure, particularly for those with traumatic SCI. Vocational rehabilitation participation was low (18.7%), despite a strong desire to return to work (82% for traumatic SCI, 61.1% for non-traumatic SCI). Before injury, participants were primarily employed in elementary occupations, with higher rates among those with paraplegia. The findings highlight the need for targeted interventions, inclusive labor market policies, and improved accessibility to vocational rehabilitation to support workforce reintegration and address the specific needs of individuals with SCI in Romania.

Hypoxia due to stroke is a major cause of neuronal damage, leading to loss of cognition and other brain functions. Sevoflurane preconditioning improves recovery after hypoxia. Hypoxia interferes with protein expression at the translational level; however, its effect on mRNA levels for neuronal protein kinase and anti-apoptotic genes is unclear. To investigate the link between sevoflurane preconditioning and gene expression, hippocampal slices were treated with 4% sevoflurane for 15 min, a 5 min washout, 10 min of hypoxia, and 60 min of recovery. We used quantitative PCR to measure mRNA levels in the CA1 region of rat hippocampi. The mRNA levels for specific critical proteins were examined, as follows: Protein kinases, PKCγ (0.22), PKCε (0.38), and PKMζ (0.55) mRNAs, and anti-apoptotic, bcl-2 (0.44) and bcl-xl (0.41), were reduced 60 min after hypoxia relative to their expression in tissue not subjected to hypoxia (set to 1.0). Sevoflurane preconditioning prevented the reduction in PKMζ (0.88 vs. 1.0) mRNA levels after hypoxia. Pro-apoptotic BAD mRNA was not significantly changed after hypoxia, even with sevoflurane preconditioning (hypoxia 0.81, sevo hypoxia 0.84 vs. normoxia 1.0). However, BAD mRNA was increased by sevoflurane in non-hypoxic conditions (1.48 vs. 1.0), which may partially explain the deleterious effects of volatile anesthetics under certain conditions. The DNA repair enzyme poly ADP-ribose polymerase 1 (PARP-1) was increased by sevoflurane in tissue not subjected to hypoxia (1.23). PARP-1 mRNA was reduced in untreated tissue after hypoxia (0.21 vs. 1.0); sevoflurane did not improve PARP-1 after hypoxia (0.27). Interestingly, the mRNA level of the cognitive kinase PKMζ, a kinase essential for learning and memory, was the only one protected against hypoxic downregulation by sevoflurane preconditioning. These findings correlate with previous studies that found that sevoflurane-induced improvement of neuronal survival after hypoxia was dependent on PKMζ. Maintaining mRNA levels for critical proteins may provide an important mechanism for preserving neuronal function after stroke.

Mild Cognitive Impairment (MCI) is a transitional stage between normal aging and Alzheimer's disease. Differentiating early MCI (EMCI) from late MCI (LMCI) is crucial for early diagnosis and intervention. This study used free-water diffusion tensor imaging (fw-DTI) to investigate white matter differences and voxel-based correlations with Mini-Mental State Examination (MMSE) scores. Data from the Alzheimer's Disease Neuroimaging Initiative included 476 healthy controls (CN), 137 EMCI participants, and 62 LMCI participants. Significant MMSE differences were found between the CN and MCI groups, but not between EMCI and LMCI. However, distinct white matter changes were observed: LMCI showed a higher f-index and lower fw-fractional anisotropy (fw-FA) compared to EMCI in several white matter regions. These findings indicate specific white matter tracts involved in MCI progression. Voxel-based correlations between fw-DTI metrics and MMSE scores further supported these results. In conclusion, this study provides crucial insights into white matter changes associated with EMCI and LMCI, offering significant implications for future research and clinical practice.