NeuroSci, Volume 6, Issue 1 (March 2025) – 26 articles

Background: Photobiomodulation (PBM), also referred to as low-level light therapy (LLLT), is an emerging non-pharmacological approach. This treatment is considered low-risk, cost-effective, and non-invasive, utilizing near-infrared light (NIR). The purpose of this paper is to explore the underlying mechanism of action and conduct a systematic review of pre-clinical and clinical research on the use of PBM for psychiatric disorders. Methods: A search on the PubMed, Cochrane Library, and EMBASE databases was performed on 18 and 26 January 2024. Publications focused on PBM treatment in psychiatric disorders such as major depressive disorder, general anxiety disorder, dementia, Parkinson’s disease, traumatic brain injury, schizophrenia, and sexual disfunctions were included (n = 23). Results: Near-infrared stimulation is presented as an effective method, comparable to psychopharmacological treatment. The primary suggested mechanism for PBM is the stimulation of mitochondrial metabolism following the absorption of NIR energy by cytochrome C oxidase. Because of the method of implementation, which omits the liver metabolism of cytochrome P450, PMB is recognized as safe as it does not interact with other drugs. Limitations: Clinical studies vary in terms of population and treatment parameters, and most do not include a suitable control group. Conclusions: Preliminary results support the potential of NIR stimulation as a novel and innovative treatment for psychiatry. Further studies are needed to estimate the proper protocols of parameters singly for any disease. Full article

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects over 2% of the population worldwide and is characterized by repetitive behaviors, restricted areas of interest, deficits in social communication, and high levels of anxiety. Currently, there are no known effective treatments for the core features of ASD. The previous literature has established erythropoietin (EPO) as a promising antidepressant, working as a potent neurogenic and neurotrophic agent with hematopoietic side effects. Carbamoylated erythropoietin (CEPO), a chemically engineered non-hematopoietic derivative of EPO, appears to retain the neuroprotective factors of EPO without the hematologic properties. Recent evidence shows that CEPO corrects stress-related depressive behaviors in BALB/cJ (BALB) mice, which also have face validity as an ASD mouse model. We investigated whether CEPO can recover deficient social and anxiety-related behavioral deficits compared to C57BL/6J controls. After administering CEPO (40 μg/kg in phosphate-buffered saline) or vehicle over 21 days, we analyzed the mice’s performance in the three-chamber social approach, the open field, the elevated plus maze, and the Porsolt’s forced swim tasks. CEPO appeared to correct sociability in the three-chamber social approach task to C57 levels, increasing the amount of time the mice interacted with novel, social mice overall rather than altering the overall amount of exploratory activity in the maze. Consistent with this finding, there was no concomitant increase in the distance traveled in the open field, nor were there any alterations in the anxiety-related measures in the task. On the other hand, CEPO administration improved exploratory behavior in the elevated plus maze. This study marks the first demonstration of the benefits of a non-erythropoietic EPO derivative for social behavior in a mouse model of autism and merits further investigation into the mechanisms by which this action occurs. Full article

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the selective loss of dopaminergic (DA) neurons in the midbrain. While dopamine precursor levodopa and D2 receptor agonists are commonly used to alleviate PD symptoms, these treatments do not halt or reverse disease progression. Thus, developing effective neuroprotective strategies remains a critical goal. In this study, we explored neuroprotective mechanisms in a Drosophila primary neuronal culture model of PD, created by administering the environmental toxin rotenone. Using the chemogenetic DREADD (designer receptors exclusively activated by designer drugs) system, we selectively activated cAMP signaling in DA neurons within the rotenone-induced model. Our results demonstrate that increasing cAMP signaling via Gs-coupled DREADD (rM3Ds) is protective against DA neurodegeneration. Furthermore, overexpression of the catalytic PKA-C1 subunit fully rescued DA neurons from rotenone-induced degeneration, with this effect restricted to DA neurons where PKA-C1 was specifically overexpressed. These findings reveal that cAMP-PKA signaling activation is neuroprotective in DA neurons against rotenone-induced degeneration, offering promising insights for developing targeted therapeutic strategies to slow or prevent PD pathology progression. Full article

In recent years, in the pathogenesis of multiple sclerosis, emphasis has been placed on mitochondrial processes that influence the onset of the disease. Oxidative stress would be one of the consequences of mitochondrial dysfunction, and its impact on brain tissue is well described. Microglia, as a brain macrophage, have an important function in removing unwanted metabolites, as well as iron, which is an amplifier of oxidative stress. There are novelties in terms of the connection between these processes, which have redirected research more towards the process of neurodegeneration itself, so that the emphasis is no longer on neuroinflammation, which would initiate the pathological process itself and still exist in the vicinity of lesions with reduced intensity. The aim of this review is to summarize the current knowledge from the literature regarding oxidative stress, mitochondrial dysfunction and iron metabolism and how microglia are involved in these processes in multiple sclerosis. Full article

Environmental noise has been repeatedly linked to negative effects on cognitive functioning among children and adolescents. This research sought to systematically assess studies investigating the relationship between noise exposure and cognitive outcomes in young individuals. Through a meta-analysis of eight primary studies published between 2001 and 2023, this study examined the effects of various noise types on cognitive performance across multiple domains in young populations. The findings reveal that noise exposure significantly impairs cognitive performance in children and adolescents, with a standardized mean difference (SMD) of –0.544 (95% CI: [−0.616, −0.472]), z = −14.85, p < 0.0001. These results underscore the profound impact of environmental noise on cognitive functioning in younger populations. Full article

Background: Stroke and traumatic brain injury (TBI) represent two major health concerns worldwide. There is growing evidence suggesting a potential association between TBI and stroke. In this systematic review and meta-analysis, we aim to explore the association between TBI and stroke risk, with a specific focus on overall stroke risk and subgroup variations based on stroke type, severity, and the post-TBI time period. Methods: PubMed, Web of Science (WOS), Scopus, and Cochrane Library were systematically searched for studies exploring the link between stroke and TBI. The pooled hazard ratios (HRs) with a 95% confidence interval (CI) were calculated. The Comprehensive Meta-Analysis (CMA) software was used for the analysis. Subgroup analyses were conducted based on stroke type, TBI severity, and post-TBI phase. The Newcastle–Ottawa Scale (NOS) was utilized for the quality assessment. Results: We included a total of 13 observational studies, with data from 8 studies used for quantitative analysis. A history of TBI was associated with a significantly higher odds of stroke compared to controls (HR = 2.3, 95% CI (1.79 to 2.958), p < 0.001). The risk was greater for hemorrhagic stroke (HR = 4.8, 95% CI (3.336 to 6.942), p < 0.001) than for ischemic stroke (HR = 1.56, 95% CI (1.28 to 1.9), p < 0.001). Both moderate-to-severe TBI (HR = 3.64, 95% CI (2.158 to 6.142), p < 0.001) and mild TBI (HR = 1.81, 95% CI (1.17 to 2.8), p = 0.007) were associated with a significantly higher risk of stroke. The risk was also higher in the early post-TBI phase (1–30 days) (HR = 4.155, 95% CI (2.25 to 7.67), p < 0.001) compared to later phases (HR = 1.68, 95% CI (1.089 to 2.59), p = 0.019) from 30 days to 1 year and (HR = 1.87, 95% CI (1.375 to 2.544), p < 0.001) after 1 year. Conclusions: This systematic review confirms a significant association between TBI and an increased risk of stroke, regardless of TBI severity, type, or timing of stroke. The findings highlight the need for early monitoring and advocating preventive strategies for stroke in patients with a history of TBI. Full article

People with bipolar disorder (BD) present with mood instability resulting from more frequent and intense emotions in response to environmental conditions relative to healthy subjects. The aim of this study was to investigate the time course of emotion regulation strategies, distraction, and reappraisal in euthymic BD patients (i.e., normal mood range) using electroencephalography (EEG). Fourteen BD patients and 13 matched healthy controls took part in an experiment constituting three conditions, i.e., a passive viewing of positive, negative, and neutral pictures, and two regulation conditions, one with a reappraisal strategy and the other with a distraction strategy. Critically, the ERP results indicated that during passive viewing, the Late Positive Potential (LPP) was larger in BD patients compared with healthy controls, but only for neutral pictures. During emotion regulation, LPP amplitude was reduced in distraction conditions compared with viewing ones, especially for negative emotions in both patients and controls. Importantly, LPP was reduced in reappraisal conditions compared with passive viewing in an early time window for negative emotions and in a later time window for positive emotions in controls but not in patients. Our findings showed that the temporal dynamics of emotion regulation by reappraisal are faster for negative than for positive emotions in controls but not in BD patients. Full article

Insufficient sleep and circadian misalignment increase inflammatory agents. This triggers neuroinflammation and can result in health issues including depression, dementia, lifestyle-related diseases, and industrial accidents. Lactoferrin (LF) confers neuroprotective effects, which are derived from its anti-inflammatory, antioxidant, and iron metabolic properties; however, its roles in acute neuroinflammation and circadian rhythm disruption are yet to be elucidated. Therefore, we aimed to test the effects of LF on rat neuroinflammation and sleep and jetlag in humans. Rats received 7 days of an oral liposomal bovine LF (L-bLF) or vehicle followed by polyriboinosinic:polyribocytidylic acid (poly I:C) peritoneal injections (n = 5–6). Compared with the rats given poly I:C only, the rats given L-bLF and poly I:C had lower Il1b, Tnf, Casp1, Nfe212, Gclm, and Sod2 expression in the hippocampus. This open-label pilot study was carried out on tour conductors performing regular international tour responsibilities, and the data were compared between the initial tour without L-bLF intake and the subsequent tour with L-bLF intake. In the tour with L-bLF intake, L-bLF administration started from one week before the trip and was continued during the trip. In both periods, the tour conductors experienced limited sleep; however, both subjective and objective sleep quality was significantly better with the oral L-bLF intake than without. Overall, we found that prophylactic L-bLF supplementation reduced neuroinflammation in rat hippocampi and improved sleep quality and jetlag in tour conductors. Full article

(1) Background: Multiple lumbar spinal stenosis (LSS) is a degenerative disease that is increasingly prevalent with global aging. Multilevel fusion surgery is burdensome to perform in elderly patients, especially with osteoporosis and underlying disease. This study introduces open midline decompression (OMD) with ligament reconstruction as an alternative stabilization technique for elderly patients with multilevel LSS. (2) Methods: A retrospective review included 42 elderly patients aged 70 or older diagnosed with LSS at three or more levels and who underwent OMD with ligament reconstruction. Pre- and postoperative clinical and radiologic data were analyzed. (3) Results: Thirty-three patients underwent three-level surgeries, and twelve patients underwent four-level surgeries. The mean operative time was 240 ± 42.2 min (74.6 ± 14.9 min per level) with a mean blood loss of 282.9 ± 167.1 cc. Clinical outcome (VAS) and quality of life parameters (SF-12) showed significant improvement after surgery. Postoperative MRI showed sufficient decompression. Dynamic X-rays showed improvement in instability after surgery, but it was statistically insignificant. (4) Conclusions: OMD with ligament reconstruction provides effective neural decompression while preserving the posterior arch and offers soft stabilization with artificial ligaments. It is a safe and viable surgical option for elderly patients with multilevel LSS. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

Background: Hypokinetic dysarthria is a speech disorder observed in almost 90% of PD patients that can appear at any stage of the disease, usually worsening as the disease progresses. Today, speech therapy intervention in PD is seen as a possible therapeutic option to alleviate and slow down the progression of symptoms. This study aims to investigate the validity of traditional speech therapy in dysarthria with the aim of improving the quality of life of PD patients, by comparing subjective clinical assessment with objective instrumental measures (IOPI and voice analysis). Methods: This is an observational study of 30 patients with hypokinetic dysarthria due to PD. The patients underwent speech therapy treatment with a frequency of three times per week for 12 consecutive weeks. Patients were evaluated at the time of enrollment (T0), at the start of treatment (T1), and at the end of the same (T2). Six months after the end of treatment (T3), a follow-up was performed based on disability and phonatory evaluation. Results: This study showed significant improvements (<0.001) from the start (T1) to the end of treatment (T2), with increases in the Barthel Index score, Robertson Dysarthria Profile, and IOPI measurements for tongue and lip strength, along with enhanced phonometer scores and tongue endurance. Correlations highlighted that tongue endurance decreased with age, CIRS, and MDS-UPDRS, while showing a positive association with MoCA scores. Conclusions: Significant improvements were observed in tongue and lip strength, phonatory duration, intensity, and vocal quality between pre- (T1) and post-treatment (T2). This study underscores the importance of early and continuous speech therapy treatment for comprehensive speech function enhancement. Full article

Background: Parkinson’s disease (PD) is a progressive neurodegenerative condition characterized by the degradation of dopaminergic pathways in the brain. As the population in the United States continues to age, it is essential to understand the trends in mortality related to PD. This analysis of PD’s mortality characterizes temporal shifts, examines demographic and regional differences, and provides machine-learning predictions. Methods: PD-related deaths in the United States were gathered from CDC WONDER. Age-adjusted mortality rates (AAMR) were collected, and trends were analyzed based on gender, race, region, age, and place of death. Annual percent change and average annual percent change were calculated using Joinpoint Regression program. Forecasts were obtained using the optimal Autoregressive Integrated Moving Average (ARIMA) model. Results: Overall mortality rate due to Parkinson’s increased from 1999 to 2022. Male gender, White race, Southern region, and older ages were associated with higher mortality compared to other groups. Deaths at home decreased and hospice deaths increased during the study period. Conclusions: This study highlights the increasing rate of PD AAMR and how it may become even more prevalent with time, emphasizing the value of increasing knowledge surrounding the disease and its trends to better prepare health systems and individual families for the burden of PD. Full article

Dementia, including Alzheimer’s disease (AD) and frontotemporal dementia (FTD), presents critical challenges for correctional systems, particularly as global populations age. AD, affecting 60–80% of dementia cases, primarily impairs memory and cognition in individuals over 65. In contrast, FTD, rarer than AD but not uncommon in those under 65, affects the frontal and temporal brain regions, leading to deficits in social behavior, language, and impulse control, often resulting in antisocial actions and legal consequences. Behavioral variant FTD is especially associated with socially inappropriate and impulsive behaviors due to frontal lobe degeneration. The prevalence of cognitive impairment in incarcerated populations is high, exacerbated by prison environments that compound distress and limited access to specialized healthcare. Studies indicate that up to 11% of United States state prison inmates over the age of 55 exhibit cognitive impairments, often undiagnosed, resulting in punitive rather than rehabilitative responses to symptoms like disinhibition and aggression. Ethical concerns around criminal responsibility for individuals with dementia are increasingly prominent, particularly regarding their ability to comprehend and engage in legal proceedings. The growing elderly prison population necessitates reform in correctional healthcare to include early cognitive assessment, targeted intervention, and tailored post-release programs. Addressing these needs is essential to ensure appropriate treatments, alleviate healthcare demands, and support reintegration for cognitively impaired inmates. Full article

Multiple sclerosis (MS) is a multifactorial disease, with diet and lifestyle playing an important role in its development. The Mediterranean diet has been considered to be particularly beneficial for MS patients. The aim of the present study was to investigate the relationship between diet and MS, as well as evaluate the effect of the Mediterranean diet on patients’ quality of life and level of disability. The six-month study included 130 patients, divided into a control and intervention group. Data collection instruments were used for the collection of demographic and medical characteristics of the participants, as well as data regarding disability [(Multiple Sclerosis Rating Scale-Revised (MSRS-R) and Multiple Sclerosis Impact Scale-29 (MSIS-29)], nutrition [Mediterranean Diet Score (MedDiet Score) and Mini Nutritional Assessment (MNA)], and quality of life [Multiple Sclerosis Quality of Life-54 (MSQOL-54)]. The results indicated that the demographic characteristics of the groups were similar. The MNA score was positively associated with physical (p = 0.002) and mental health (p = 0.001). The intervention group reported an improvement in adherence to the Mediterranean diet, an increase in the MedDiet Score, and a decrease in the MSRS-R Score, indicating an improvement in functional capacity, nutritional status, and quality of life. In conclusion, the Mediterranean diet can improve the functionality and quality of life of patients with MS. Nutrition education is therefore deemed critical, and further research is required to reinforce these findings. Full article

This review emphasises the importance of the cardiovascular response to facial cooling (FC) and breath holding in both sexes. The trigemino-cardiac reflex, triggered by FC, reduces heart rate (HR) and constricts blood vessels. When combined with breath holding, this effect intensifies, enhancing the cardiodepressive impact. The cardiovascular reaction to this combination, known as the cold-water face immersion or simulated diving test, varies among individuals and depends on their cardiovascular regulatory profiles, which differ between men and women. Despite extensive research on the cardiovascular response to FC and apnoea, most studies did not categorise participants by sex, leading to a limited understanding of how it influences trigeminal nerve stimulation (TGS) and breath-hold diving (BHD). Despite attempts to address this, the existing findings remain inconsistent due to intra- and inter-individual variability. Key factors influencing the diving response include the influence of the parasympathetic system on HR, vascular sympathetic activity affecting total peripheral resistance (TPR), sensitivity to CO₂, lung capacity, training, physical performance, duration of apnoea, and the stimulation of metaboreceptors in working muscles. These factors differ between men and women, potentially contributing to variations in the effectiveness of the response to the FC combined with breath holding. Full article

Human point-light displays consist of luminous dots representing human articulations, thus depicting actions without pictorial information. These stimuli are widely used in action recognition experiments. Because humans excel in decoding human motion, point-light displays (PLDs) are often masked with additional moving dots (noise masks), thereby challenging stimulus recognition. These noise masks are typically found within proprietary programming software, entail file format restrictions, and demand extensive programming skills. To address these limitations, we present the first user-friendly step-by-step guide to develop visual noise to mask PLDs using free, open-source software that offers compatibility with various file formats, features a graphical interface, and facilitates the manipulation of both 2D and 3D videos. Further, to validate our approach, we tested two generated masks in a pilot experiment with 12 subjects and demonstrated that they effectively jeopardised human agent recognition and, therefore, action visibility. In sum, the main advantages of the presented methodology are its cost-effectiveness and ease of use, making it appealing to novices in programming. This advancement holds the potential to stimulate young researchers’ use of PLDs, fostering further exploration and understanding of human motion perception. Full article

Background: Acute disseminated encephalomyelitis (ADEM) is a rare, immune-mediated inflammatory disorder of the central nervous system (CNS), typically characterized by the acute onset of multifocal demyelination. The pathogenesis of ADEM remains unclear, but it is believed to be triggered by an autoimmune response, often following viral infections or vaccinations. Case report: This case report describes a 3-year-old child who developed ADEM after receiving two concurrent influenza vaccines: one for seasonal influenza and one for the 2009 H1N1 pandemic. The patient presented with motor regression, mild pleocytosis in cerebrospinal fluid (CSF), and typical MRI findings of ADEM. Steroid pulse therapy resulted in rapid improvement, and the patient recovered fully without sequelae. Results: Although the influenza vaccine has been linked to ADEM in some studies, it remains uncertain whether the simultaneous administration of both vaccines contributed to the onset of ADEM. While influenza vaccines are considered safe and effective by health organizations such as the CDC, data suggest that the incidence of ADEM and other neurological complications is significantly higher after natural influenza infections compared to vaccination. This highlights the importance of vaccination in preventing severe outcomes. Conclusions: This case underscores the importance of monitoring and reporting adverse events following vaccination to refine our understanding of rare complications like ADEM. While simultaneous vaccine administration warrants further research, the benefits of vaccination in preventing severe complications from natural infections far outweigh the risks. Continued vigilance and improved surveillance systems are essential for maintaining public confidence in vaccination programs. Full article