Search Results (402)

Parkinson’s disease (PD) involves progressive basal ganglia dysfunction, with hyperexcitability of striatal indirect-pathway D2 medium spiny neurons (D2-MSNs) linked to motor impairment. Neuromotor rehabilitation is an important therapy, but its efficacy varies across interventions. This thematic review examines eleven rehabilitative strategies for PD, spanning forced and voluntary exercise (FE and VE respectively), non-invasive brain stimulation (rTMS, tDCS), and technology-based approaches such as exoskeletons, augmented reality, and dual-task training, within a framework distinguishing striatal recalibration from compensation via alternative motor networks. To formalize this distinction, a Bayesian ranking framework combines neurobiological plausibility with clinical evidence quality, identifying three functional clusters: a high-recalibration cluster (FE, p ≈ 0.80; LSVT BIG, p ≈ 0.62), an intermediate-uncertainty cluster (rTMS, HIIT, tDCS, treadmill, resistance training, Tai Chi/dance; 0.40–0.56), and a bypass/compensatory cluster (augmented reality, exoskeletons, dual-task training; p ≤ 0.33). This distinction between direct modulation of basal ganglia circuitry and recruitment of alternative motor networks, including the lateral premotor cortex, parieto-premotor circuits, and cerebello-thalamo-cortical pathways, supports a precision rehabilitation approach in PD. Full article

In the central nervous system, the neuropeptide oxytocin stimulates neural networks that regulate social behaviors, including social attachment, aggression, and complex social cognition. Perturbations in oxytocin and/or oxytocin receptor expression results in social behavioral deficits and are associated with a number of psychopathologies including autism spectrum disorder, schizophrenia, anxiety, and depression. In rodent models of autism spectrum disorder, oxytocin is effective at improving social behavior. However, limited translatability between animal models and human physiology has hindered successful translation of these findings into human therapeutics. Oxytocin variant-induced cellular signaling pathways and G-protein coupling have largely been investigated in HEK and CHO heterologous expression systems; however, cellular context is crucial, and these profiles likely differ from intact neurons. This project assessed oxytocin variants in in vitro human-derived neuron-like SH-SY5Y cells that endogenously express the oxytocin receptor. Results demonstrated that the naturally occurring oxytocin variants Leu⁸-OT, Pro⁸-OT and Val³-Pro⁸-OT activated intracellular signaling pathways and promoted neuronal differentiation-associated responses, including calcium mobilization, membrane hyperpolarization, and neurite outgrowth in a concentration-dependent manner. Knowledge of how oxytocin variants alter cellular structure and function has the potential to both identify mechanisms that produce social dysfunction and to inform the development of therapeutic agents. Full article

Spinal cord stimulation (SCS) is an established neuromodulatory therapy for refractory chronic pain; however, the timing of SCS initiation has received relatively little attention. In some patients requiring spine surgery, the indication for SCS is already present at the time of surgery. Percutaneous leads combine reversibility with low invasiveness, allowing the timing of SCS introduction to be matched to clinical need. We describe a technical approach for simultaneous percutaneous SCS lead placement during spine surgery and present a retrospective case series of five illustrative cases. This report discusses the significance of this approach from the perspective of SCS timing, invasiveness, and reversibility. In two patients, the therapeutic objective was achieved during the acute postoperative period, and the leads were electively removed without recurrence. In three patients, continued stimulation benefit was observed, and an implantable pulse generator was placed for permanent use. No procedure-related adverse events occurred. Simultaneous percutaneous SCS lead placement during spine surgery may allow neuromodulation to be delivered at the time it is needed, for the duration it is required, and at the relevant spinal level. Full article

Persistent post-concussion syndrome (PPCS) develops in 10 to 30 percent of patients following mild traumatic brain injury (mTBI), yet the most effective management approach remains an open question. This report describes a 37-year-old female who sustained a motor vehicle collision and was followed prospectively over 27 months. Structured evaluation at baseline identified dysfunction across oculomotor, vestibular, autonomic, cognitive, and neurophysiological domains. An intensive multimodal rehabilitation programme was associated with an 86 percent reduction in symptom burden (Post-Concussion Symptom Scale: 80 to 11) by the six-month mark. Thereafter, symptoms gradually returned in spite of continued treatment, and at 27 months the patient still reported moderate-to-severe headache (6 to 7 out of 10), persistent dizziness (5 to 6 out of 10), and meaningful functional limitations. The trajectory observed here, marked by initial gains followed by progressive relapse, illustrates the fluctuating and often incomplete recovery seen in a subgroup of PPCS patients. Clinicians should anticipate this pattern and frame outcome expectations accordingly, while building sustained, adaptive management strategies into long-term care plans. Full article

Background/Objectives: Reconstructed three-dimensional (3D) endoscopic visualization is believed to improve depth perception and surgical performance compared with conventional two-dimensional (2D) systems. However, evidence supporting its use in unilateral biportal endoscopic (UBE) spine surgery remains limited. The objective was to compare procedural performance, task completion times, and subjective workload between 3D and 2D visualization in simulated biportal lumbar endoscopy. Methods: This randomized crossover pilot feasibility ex vivo study enrolled 6 neurosurgeons (3 residents, 3 seniors) who each completed a standardized UBE lumbar discectomy simulation (UpSurgeOn Lumbar SpineBox) under both 3D and 2D visualization in randomized sequence. The primary outcome was composite procedural performance (0–100 scale) assessed using a multi-item checklist encompassing technical success, quality, and safety. Secondary outcomes included task completion times for 7 procedural steps and subjective workload. Linear mixed-effects models adjusted for expertise level, spinal segment, operative side, and session order. Within-participant effect sizes (Cohen’s d) and a sensitivity power analysis were calculated. Results: All participants completed both conditions (24 procedures). Composite performance was high with both modalities, with no significant difference for the unweighted (adjusted difference 0.64 points, 95% CI −3.67 to 4.96, p = 0.76, d = 0.13) or weighted score (1.67 points, 95% CI −4.04 to 7.37, p = 0.55, d = 0.26). Subjective workload also did not differ (p = 0.67, d = 0.19). Effect sizes were negligible to small for most outcomes but reached medium magnitude for subjective fatigue (d = 0.54) and situational stress (d = 0.56). Exploratory expertise-stratified comparisons suggested faster lamina drilling with 3D among seniors (p = 0.04) and slower dura identification with 3D among residents (p = 0.02), based on only 3 participants per subgroup. The sample afforded 80% power to detect only very large effects (d ≈ 1.43). Conclusions: 3D visualization was feasible and well tolerated but did not significantly improve procedural performance, task completion time, or subjective workload in UBE simulation. Because the study was powered to detect only very large effects, these nonsignificant results reflect limited power rather than equivalence, and the medium effect-size signals for fatigue and situational stress are hypothesis-generating. Adequately powered trials are needed to confirm task-specific or expertise-dependent benefits. Full article

Purpose: To examine the association between diaphragmatic thickness and upper arm muscle area (AMA), as a surrogate of nutritional status, in children and adolescents with cerebral palsy (CP) stratified by gross motor function severity. Methods: In this cross-sectional study, participants were stratified into ambulatory (Gross Motor Function Classification System [GMFCS] I–III) and non-ambulatory (GMFCS IV–V) groups. AMA was estimated from anthropometric measurements, and diaphragmatic thickness was assessed by B- and M-mode ultrasonography; between-group comparisons used the Mann–Whitney U test and associations were examined using Spearman’s rank correlation coefficient (ρ). Results: Fifty children aged 2–12 years with a confirmed CP diagnosis were evaluated (14 ambulatory, 36 non-ambulatory). In the non-ambulatory group, diaphragmatic thickness showed significant positive correlations with AMA during inspiration (ρ = 0.50; p = 0.002) and expiration (ρ = 0.67; p < 0.001). These subgroup-specific associations should be interpreted as exploratory, as the AMA × GMFCS interaction did not reach statistical significance. No significant correlations were observed in ambulatory participants. Moderate muscle mass deficits were prevalent among non-ambulatory children, and approximately 63% of the total sample presented adipose tissue deficit or risk thereof. Conclusions: In children with severe CP, a significant association between peripheral muscle reserve and diaphragmatic thickness suggests a possible functional link between nutritional status and respiratory muscle morphology. These preliminary findings support further investigation of diaphragmatic ultrasonography as a non-invasive tool for combined nutritional and respiratory monitoring in pediatric neurorehabilitation. Full article

Autism Spectrum Disorder (ASD) is characterized by deficits in communication, socialization, and restricted behavioral patterns. Valproic acid (VPA) is a teratogen that, through epigenetic mechanisms, induces ASD-like phenotypes in animal models. The zebrafish (Danio rerio) represents an ideal model for evaluating these alterations due to its complex behavioral repertoire. This study analyzed the longitudinal effect of an enriched environment (EE) on VPA-induced behavioral alterations in juvenile and adult stages (n = 72; n = 18 per group: CTRL-SE, CTRL-EE, VPA-SE, and VPA-EE). Subjects were evaluated across the novel tank, mirror test, and social interaction tests. The results reveal a selective, stage-dependent modulation: in the novel tank test, VPA fish housed in EE presented a significant reduction in erratic movements (stereotypies) and increased time spent in the upper zone (reduced anxiety), whereas specific modifications in shoal approach were observed in the social interaction test. These modulating effects were evident from the juvenile stage and consolidated in adulthood across specific locomotor and exploratory metrics. It is concluded that the enriched environment may act as a neuromodulatory strategy capable of mitigating selective aspects of the autism-like behavioral phenotype in zebrafish. Full article

Alzheimer’s disease (AD) classification from structural magnetic resonance imaging (MRI) may benefit from weak supervision that uses clinically meaningful but imperfect supervisory signals. We evaluated a weakly supervised framework in which a multilayer perceptron (MLP) trained on age, sex, and Mini-Mental State Examination (MMSE) scores generated clinical pseudo-labels to initialize a patch-based fully convolutional network (FCN). For 260 Alzheimer’s Disease Neuroimaging Initiative (ADNI) training participants, subsequent refinement combined 80% of the preceding MRI-model probability with 20% of the participant’s ground-truth diagnostic label. This design preserves a dominant pseudo-label/self-training component while using partial diagnostic guidance to stabilize refinement. The FCN generated whole-brain probability maps, and selected voxel probabilities were classified by a second MLP. The framework was developed using ADNI (n = 417). Using ADNI validation data only, iteration 3 and a classification threshold of 0.5 were selected and then applied unchanged to the held-out ADNI test set and the external AIBL (n = 182), FHS (n = 102), and NACC (n = 265) cohorts. The selected model achieved F1 scores of 0.853 in ADNI, 0.707 in AIBL, 0.765 in FHS, and 0.807 in NACC. These results support the feasibility and cross-cohort transferability of clinical pseudo-label-based weak supervision for MRI classification. The framework is not intended to be label-free; rather, it provides a transparent strategy for integrating imperfect clinical pseudo-labels with partially weighted diagnostic guidance during training. Full article

Responsive neurostimulation (RNS) is a neuromodulation option for treatment of drug-resistant epilepsy (DRE). There is limited data reviewing bilateral thalamic and corticothalamic RNS therapy response. We performed a retrospective analysis of 21 patients undergoing RNS implantation with either bilateral thalamic (n = 17) or corticothalamic (n = 4) leads and ≥6 months of follow-up. Patients were classified as responders (≥50% seizure frequency reduction) vs. non-responders (<50% seizure frequency reduction). Among the bilateral thalamic cohort, 12/17 (70.6%) patients were responders, and 15/17 (88.2%) patients reported reduction in seizure severity. Pre-RNS seizure frequency was higher in bilateral thalamic nonresponders, although not found to be significant (median 13 vs. 30 seizures per month, p = 0.20). Among the corticothalamic cohort, 3/4 (75.0%) patients were responders, and all patients demonstrated improvement in seizure severity. These findings suggest that although bilateral thalamic targets were selected at our center more often, both bilateral thalamic and corticothalamic RNS approaches provided seizure frequency reduction. The majority of patients, including non-responders, reported seizure severity alleviation. Full article

Parkinson’s disease (PD) is a neurodegenerative disorder caused by the loss of dopaminergic neurons. Its symptoms affect both motor functions—such as bradykinesia, rigidity, resting tremor, and postural instability—and non-motor functions, including neuropsychiatric issues, sleep disorders, and constipation. Drawing on the literature, the following topics were developed and presented: Pathophysiology; Treatment; Neuropsychiatric and Cognitive Function; Sleep Challenges; Exercise and Movement; Striving for Wellness; and Obstacles/Paths Forward. These seven categories form the foundation of this review, which centers on four main areas related to PD: dopamine biology and pathophysiology; management of key motor and non-motor symptoms; strategies for achieving wellness; and unresolved issues in PD. The complexity of PD’s clinical features is highlighted by describing patient–healthcare provider interactions, elucidating disease mechanisms, managing motor and non-motor symptoms, highlighting the benefits of exercise, emphasizing the importance of sleep, addressing mental health challenges and cognitive changes, fostering a hopeful and resilient mindset, potentially slowing disease progression, treating comorbidities, and promoting overall wellness. Although there have been tremendous advances in the basic science and clinical management of PD in recent years, PD remains incurable. Thus, we describe several roadblocks that have hindered progress in understanding PD. Only by integrating historical insights with the latest PD advances can we acquire the knowledge needed to change the disease’s trajectory. Finally, this review aims to provide a meaningful summary for healthcare professionals (and students) caring for patients with PD. Full article

Background: Neurocognitive testing in neuro-oncological patients often relies on time-intensive batteries with limited feasibility in this patient cohort. We evaluated the feasibility of the Bonn Leistungs Tracking Test (BLTT), a time-efficient screening tool assessing episodic memory, semantic memory, and executive functions in patients with high-grade temporal lobe gliomas. Methods: Twenty patients undergoing resection of temporal high-grade glioma between 2019 and 2022 underwent preoperative cognitive assessment using either the BLTT or a comprehensive neuropsychological battery routinely applied in temporal lobe epilepsy surgery. Results: Twelve patients (60%) underwent the BLTT, and eight (40%) underwent the standard neuropsychological test battery. The BLTT was feasible in all 12 individuals (0% drop-out), whereas only four of eight patients (50% drop-out) were able to complete the standard battery. The mean BLTT total score was 69.3 (SD 4.5), indicating impaired neurocognitive performance relative to normative data. The BLTT provided evaluable domain-specific measures across episodic memory, semantic memory, and executive functioning despite the high discontinuation rate observed with standard testing. Conclusions: The BLTT showed high feasibility for preoperative neurocognitive testing in patients with temporal high-grade gliomas. Its brief administration time and consistent applicability across relevant cognitive domains support its utility for routine neurocognitive assessment. Full article

Menopause represents a major neuroendocrine transition characterized by substantial hormonal, metabolic, vascular, and inflammatory changes that may increase vulnerability to cognitive decline and neurodegenerative disease. Declining estrogen levels during the menopausal transition influence multiple neural processes, including synaptic plasticity, cerebral glucose metabolism, mitochondrial function, neuroinflammatory signaling, and cerebrovascular regulation. Women account for nearly two-thirds of individuals diagnosed with Alzheimer’s disease, and mounting evidence suggests that menopause may represent a period of heightened neurological vulnerability. Physical exercise has emerged as one of the most promising non-pharmacological strategies for preserving cognitive health and reducing neurodegeneration risk in aging women. Current evidence demonstrates that exercise interventions after menopause are associated with improvements in executive function, memory performance, attention, and global cognition. These benefits appear to result from converging biological mechanisms that include enhanced neurotrophic signaling, increased brain-derived neurotrophic factor (BDNF) expression, improved cerebrovascular function, reduced systemic inflammation, improved insulin sensitivity, enhanced metabolic regulation, and preservation of structural brain integrity. Neuroimaging studies further demonstrate exercise-associated increases in hippocampal volume, cortical thickness, functional connectivity, and cerebral blood flow. Different exercise modalities appear to produce distinct but complementary neurological benefits. Aerobic exercise is strongly associated with improved cerebrovascular function and hippocampal integrity, resistance training demonstrates favorable effects on executive function and white matter preservation, and multimodal interventions combining aerobic, resistance, balance, and cognitively engaging activities appear to produce the broadest cognitive benefits. Emerging evidence further suggests that the timing of exercise initiation relative to menopause may influence outcomes, with earlier interventions potentially conferring greater neuroprotection. This review synthesizes current evidence regarding the effects of exercise on cognitive function in postmenopausal women, with emphasis on biological mechanisms, neuroimaging findings, exercise modality, timing considerations, and implications for neurodegeneration prevention. Understanding these relationships provides a scientific rationale for positioning exercise as a foundational strategy for preserving cognitive health and reducing neurodegenerative disease burden in postmenopausal women. Full article

Perfusion impairment is one of the major barriers to using machine perfusion to prepare brain tissue for research and clinical applications. As ischemia progresses, multiple mechanisms, including intravascular obstructions, perivascular cellular edema, mural cell contraction, and vessel wall breakdown, progressively limit the uniform delivery of preservative solutions. This problem is particularly important for connectomics, wherein successful preservation requires both widespread distribution of preservative chemicals and the maintenance of the cellular ultrastructure needed for circuit reconstruction. We conducted a narrative review of interventions used to ameliorate perfusion impairment across multiple fields, including organ transplantation, resuscitation medicine, forensic pathology, embalming, and neuroscience. We evaluated the evidence for these approaches in their original contexts and considered their potential application for brain banking aimed at preserving tissue for connectome reconstruction. We classify interventions into several categories, including anticoagulants, fibrinolytics, vasodilators, washout solutions, surfactants, osmotic agents, colloids, hypothermia, and perfusion pressure optimization. Many of these interventions have the potential to improve perfusion, but each also carries tradeoffs that may adversely affect tissue preservation. As connectomics advances toward profiling larger volumes of human brain tissue, overcoming perfusion impairment is likely to become an increasingly important challenge. This review provides a mechanistic framework for evaluating existing interventions and guiding the development of future perfusion protocols. Full article

Malpighia mexicana has been traditionally used in Mexican ethnomedicine for the treatment of central nervous systems disorders. Previous studies have demonstrated neuropharmacological activity of crude extracts, but the contribution of enriched phytochemical fractions remains unclear. A phenolic-enriched fraction (G4) obtained from the aerial parts of M. mexicana was evaluated for antidepressant-like and anticonvulsant activities in mice. Antidepressant-like effects were assessed using the forced swimming test (FST) and tail suspension test (TST), while locomotor activity was evaluated in the open field test. Anticonvulsant activity was determined using the pentylentetrazole (PTZ)-induced seizure model. The phytochemical profile of G4 was characterized by HPLC-DAD analysis. G4 (50 and 200 mg/kg, p.o.) significantly reduced immobility time in both FST and TST compared to the vehicle group (p < 0.05) without affecting locomotor activity in the OFT, suggesting a specific antidepressant-like effect. In the PTZ model, G4 significantly increased latency to clonic and tonic seizures and reduced seizure severity. HPLC-DAD analysis revealed the presence of phenolic compounds, with kaempferol and p-coumaric acid as major constituents. The phenolic-enriched G4 fraction from M. mexicana exhibits antidepressant-like and anticonvulsant effects in murine models, supporting its traditional use. These findings suggest that phenolic constituents, particularly kaempferol and p-coumaric acid, may contribute to the observed neuropharmacological activity. However, since only the G4 fraction was pharmacologically evaluated and not the isolated compounds, the specific role of each constituent remains to be established. Further studies are required to elucidate the underlying mechanisms of action and the contribution of individual compounds and potential synergistic interactions. Full article