Journal of Neural Transmission最新文献

This study aimed to analyze the transferability of non-invasive brain stimulation (NIBS) interventions in individuals with major depressive disorder (MDD) based on the FIELD model (Function, Implementation, Ecology, Level, and Duration), encompassing function, implement, ecology, level, and duration. A systematic search of electronic databases yielded a total of 21 eligible studies, comprising 12 transcranial direct current stimulation (tDCS) and 9 transcranial magnetic stimulation (TMS) trials, involving 1029 individuals with MDD. The meta-analysis of effect sizes revealed positive transfer effects across all domains of the FIELD model, suggesting that NIBS interventions have potential efficacy in improving various facets of MDD. The subgroup analysis highlighted that bilateral dlPFC stimulation exhibited the highest effect size for transferability, indicating greater transferability for rTMS, a higher dose of stimulation, and the integration of additional interventions. Additionally, the study discusses the implications of bilateral dorsolateral prefrontal cortex (dlPFC) stimulation and the integration of complementary therapies for optimizing treatment efficacy.

The exact cause of nigral cell death in Parkinson's disease (PD) is still unknown. However, research on MPTP-induced experimental parkinsonism has significantly advanced our understanding. In this model, it is widely accepted that mitochondrial respiratory failure is the primary mechanism of cell death. Studies have shown that a toxic metabolite of MPTP inhibits Complex I and alpha-ketoglutarate dehydrogenase activities in mitochondria. Since then, many research groups have focused on mitochondrial dysfunction in PD, identifying deficiencies in Complex I or III in PD patients' brains, skeletal muscle, and platelets. There is some debate about the decline in mitochondrial function in peripheral organs. However, since α-synuclein, the main component protein of Lewy bodies, accumulates in peripheral organs, it is reasonable to consider PD a systemic disease. Additionally, mutant mitochondrial DNA with a 4,977 base pair deletion has been found in the brains of PD patients, suggesting that age-related accumulation of deleted mtDNA is accelerated in the striatum and may contribute to the pathophysiology of PD. While the cause of PD remains unknown, mitochondrial dysfunction is undoubtedly a factor in cell death in PD. In addition, the causative gene for familial PD, parkin (now PRKN), and PTEN-induced putative kinase 1 (PINK1), both gene products are also involved in mitochondrial quality control. Moreover, we have successfully isolated and identified CHCHD2, which is involved in the mitochondrial electron transfer system. There is no doubt that mitochondrial dysfunction contributes to cell death in PD.

Essential tremor (ET) is characterized by upper limbs action tremor, sometimes extending to other body parts. However, ET can present with additional neurological features known as "soft signs." These signs of uncertain clinical significance are not sufficient to suggest an alternative neurological diagnosis, and include, among others, questionable dystonia and subtle voluntary movement alterations, i.e., bradykinesia and related features. This study aimed to explore the prevalence and relationship between questionable dystonia and subtle bradykinesia features in ET. Forty ET patients were video-recorded during clinical examination. Five movement disorder experts reviewed the videos to identify soft motor signs, i.e., dystonia and movement alterations during finger-tapping namely, (i) bradykinesia (reduced velocity), (ii) dysrhythmia, and (iii) sequence effect. Inter-rater agreement was quantified using the Fleiss' Kappa index. Data analysis was performed using nonparametric tests. We found a fair inter-rater agreement for upper limb dystonia (Fleiss' K = 0.27). Inter-rater agreement was higher (moderate) for head dystonia (Fleiss' K = 0.49) and finger-tapping assessment (Fleiss' K = 0.45). Upper limb dystonia was identified in 70% of patients, head dystonia in 35%, and finger-tapping alterations (in variable combinations) were observed in 95% of individuals (P < 0.001 by Fisher's exact test), including subtle bradykinesia and related features. No significant concordance or correlation was found between the soft signs. Subtle bradykinesia and related features are the most easily identifiable and frequent soft signs in ET, appearing in a higher percentage of patients than subtle dystonia. These findings provide insights into the clinical and pathophysiological understanding of ET.

The crucial role of steroid hormones in health and diseases merits their high-throughput, accurate and affordable measurements in biological specimens. Despite advances in analytical methods, sensing and quantifying steroid hormones remains challenging. Immunoassays offer excellent sensitivity but are inherently labour-intensive, costly, and prone to false positives. Mass spectrometry (MS) has been increasingly utilised, with the main hurdle being the isobaric tendencies of similar analytes, which complicates their separation and accurate quantification. This study compares ultrahigh-performance supercritical fluid chromatography separation (UHPSFC) and ultra-high-performance liquid chromatography (UHPLC) for MS detection. It optimises the column chemistry, temperature, and pressure to provide an operational protocol for the resolution and quantification of analytes. It presents the systematic characterisation of UHPSFC-MS performance by investigating spiked blood samples using Solid-Phase Extraction (SPE) and describes the matrix effects associated with MS measurements. Although both separation methods showed adequate resolution, specificity, and retention time, UHPSFC-MS was superior for five out of seven columns tested. With added high-throughput capacities, UHPSFC-MS, thus, offers an optimal solution for the analysis of steroid hormones for research, medical chemistry, and clinical diagnostics.

This multicentre, prospective, single-arm study evaluated safinamide as add-on therapy to levodopa in Korean patients with Parkinson's disease (PD) with motor fluctuations with ≥ 1.5 h of "off" time daily, who took levodopa ≥ 3 times/day (n = 199). Baseline levodopa and dopamine agonist doses were maintained without escalation during the 18-week treatment period. Participants received safinamide 50 mg/day for 2 weeks and 100 mg/day thereafter. PD diaries and questionnaires (Parkinson's Disease Questionnaire, PDQ-39; Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale, MDS-UPDRS part 3 and part 4; King's Parkinson's Disease Pain Scale, KPPS; Mini-Mental State Examination, MMSE) were assessed at baseline and at week 18. Treatment-emergent adverse events (TEAEs) were recorded. Mean disease duration was 6.6 years, and mean levodopa equivalent daily dose was 721.1 mg/day. At week 18, significant improvements from baseline were seen for the co-primary endpoints, mean daily "off" time (- 1.3 ± 2.4 h, p < 0.001) and quality of life (QoL) based on PDQ-39 summary index (- 2.7 ± 10.3, p < 0.001), Moreover, significant improvements were seen in motor symptoms and motor complications (MDS-UPDRS part 3 and 4), daily "on" time without dyskinesia (all p < 0.001) and pain (KPPS; p = 0.013). TEAEs occurred in 40.2% of patients, with most being mild in severity. In conclusion, safinamide at a dosage of 100 mg/day significantly improved motor symptoms, QoL, and pain, and demonstrated a favourable safety profile without levodopa dosage escalation during the 18-week treatment period in Korean patients with PD.Trial registration number and date: NCT05312632, First Posted: April 5, 2022.

Alzheimer's dementia is the main cause of cognitive impairment in people over the age of 65, with Alzheimer's disease starting presumably 10-15 years before the onset of clinical symptoms. It is therefore important to recognize dementia at an early stage and identify possible predictors. The existing methods, like different parameters of ß-Amyloid and Tau quantification in cerebrospinal fluid (CSF) or the living brain by measure of PET, are invasive and expensive. Therefore, the present study investigates the predictive value of a battery of clinical, neuropsychological, and blood parameters as well as two neurophysiological methods (functional near-infrared spectroscopy [fNIRS] and vagus somatosensory evoked potentials [VSEP]) which are easy to perform, less invasive and cost-efficient, for developing cognitive impairments in the elderly.In this longitudinal, prospective study, we enrolled 604 healthy participants between 70 and 77 years of age. The participants were invited back after a mean time interval of 3 years and 11 months, and after 7 years and 8 months, and their cognitive impairments were determined.Here we show that the development of cognitive impairments after approximately 8 years can be predicted not only by previously known risk factors such as ApoE4 risk alleles, dysosmia, or poor cognitive performance at baseline but that latency prolongation in the VSEP and altered functional activation patterns measured by NIRS at baseline also provide additional predictive value.We therefore suggest that both neurophysiological parameters, VSEP and NIRS, should be included in future studies, investigating the prediction of dementia. Dementia ClinicalTrials.gov Identifier: NCT02224326.

Exposure to stress is known to affect biological aging as well as individuals' susceptibility to a wide variety of mental illnesses, such as schizophrenia. There is an established relationship between the onset of schizophrenia spectrum disorders (SSD) and biological aging. On the other hand, epigenetic modifications, such as DNA methylation (DNAm), are used as biomarkers for biological aging and were previously proven to be altered in schizophrenia. However, previous research did not consider the effect of psychosocial resilience to stress and its effect on aging in schizophrenia, which is what our study aims to address. For our pilot study, 65 schizophrenia patients were recruited and stress exposure and perception levels were assessed using the Social Readjustment Rating Scale (SRRS) and Perceived Stress Scale (PSS), respectively. Moreover, DNA was extracted from venous blood samples and 850,000 CpG loci were assessed for DNA methylation analysis. Average age of participants was 43.15 ± 13.32 years (55.4% male, 44.6% female). Linear regression plots showed significant correlation between SRRS and PSS scores as well as between biological and chronological ages (p < 0.05). The residuals from the two regression models were defined as the psychosocial resilience and DNAm age acceleration, respectively. Interestingly, DNAm age acceleration was inversely correlated with resilience to stress (p < 0.05). In conclusion, it appears that epigenetic age acceleration is associated with reduced resilience to stress in schizophrenia patients. Future studies should focus on establishing resilience effect on disease prognosis.

Tools for the early diagnosis of neurocognitive disorders (NCD) both accessible, fast, fun and efficient are currently needed. A digit-tracking technique (Digitrack) has been developed based on the exploration of blurred images on a tablet with the finger, related to the exploration of images during eye-tracking. The present study aimed at assessing the objective usability and the subjective User eXperience (UX) of the Digitrack by older adults according to the presence and the severity of NCD. A total of 135 patients were included in a geriatric acute care unit. Objective usability was assessed through the number of patients able to complete the Digitrack's training (3 images) and evaluation (20 images) phases. UX was measured through standard questionnaires (AttrakDiff and meCUE), and through the description of engagement behaviors following an internally developed scale which included 5 levels (interactive, constructive, active, passive and disengaged behaviors). The success rate of the device was 94.1%. The Digitrack had a very good overall attractiveness, standard hedonic and pragmatic qualities, and the emotions perceived were predominantly positive. These findings were not homogeneously observed in the whole studied population. Patients highly impaired due to NCD tended to rate the device with more neutral scores and to perceive more negative emotions. The participants mainly demonstrated active behaviors, but patients with severe major NCD were mostly passive. The study showed promising results regarding the usability and acceptability of a digit-tracking technique within older adults. Further studies should evaluate the potential of this novel methods to make a cognitive diagnosis.

TDCS is one of the most widely used non-invasive neuromodulation techniques, which changes the excitability of local cortical tissue by applying weak continuous direct current to the scalp, effectively improves the attention and concentration of ADHD children, and improves the impulse disorder of patients, but related research is still in its infancy. Based on a review of a large number of existing literatures and an analysis of the pathogenesis and principle of ADHD, this paper summarized the research on tDCS in the treatment of ADHD in recent years from the aspects of treatment mechanism, safety and stimulation parameters, and simply compared the application of tDCS with other non-traumatic neuromodulation techniques in the treatment of ADHD. The future development direction of this technology is further discussed.