Imaging the Limbic System in Parkinson’s Disease—A Review of Limbic Pathology and Clinical Symptoms

Brain Sciences, Journal Year: 2022, Volume and Issue: 12(9), P. 1248 - 1248

Published: Sept. 15, 2022

The limbic system describes a complex of brain structures central for memory, learning, as well goal directed and emotional behavior. In addition to pathological studies, recent findings using in vivo structural functional imaging the pinpoint vulnerability neurodegeneration Parkinson’s disease (PD) throughout course. Accordingly, dysfunction is critically related symptom which characterizes PD, including neuropsychiatric, vegetative, motor symptoms, their heterogeneity patients with PD. aim this systematic review was put spotlight on neuroimaging PD give an overview most important affected by disease, function, alterations, corresponding clinical manifestations. PubMed searched order identify studies that investigate help methods. First, neuropathological changes symptoms each region are reviewed, and, finally, network integration within pathology discussed.

Language: Английский

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Cortical phase-amplitude coupling is key to the occurrence and treatment of freezing of gait

Brain, Journal Year: 2022, Volume and Issue: 145(7), P. 2407 - 2421

Published: March 29, 2022

Abstract Freezing of gait is a debilitating symptom in advanced Parkinson’s disease and responds heterogeneously to treatments such as deep brain stimulation. Recent studies indicated that cortical dysfunction involved the development freezing, while evidence depicting specific role primary motor cortex multi-circuit pathology freezing lacking. Since abnormal beta-gamma phase-amplitude coupling recorded from patients with indicates parkinsonian state responses therapeutic stimulation, we hypothesized this metric might reveal unique information on understanding improving therapy for gait. Here, directly potentials using subdural electrocorticography synchronously captured optoelectronic motion-tracking systems 16 freely-walking who received subthalamic nucleus stimulation surgery. Overall, 451 timed up-and-go walking trials quantified 7073 s stable 3384 conditions on/off-stimulation with/without dual-tasking. We found (i) high was detected (i.e. contained freezing), but not non-freezing trials, caused by dual-tasking or lack movement; (ii) episodes within also demonstrated abnormally couplings, which predicted severity; (iii) reduced these couplings simultaneously improved freezing; (iv) were at similar levels, still lower severity than no-stimulation trials. These findings suggest elevated higher probabilities freezing. Therapeutic alleviates both decoupling oscillations enhancing resistance coupling. formalized novel ‘bandwidth model,’ specifies dysfunction, cognitive burden emergence By targeting key elements model, may develop next-generation approaches

Language: Английский

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Perspectives on adaptive dynamical systems

Chaos An Interdisciplinary Journal of Nonlinear Science, Journal Year: 2023, Volume and Issue: 33(7)

Published: July 1, 2023

Adaptivity is a dynamical feature that omnipresent in nature, socio-economics, and technology. For example, adaptive couplings appear various real-world systems, such as the power grid, social, neural networks, they form backbone of closed-loop control strategies machine learning algorithms. In this article, we provide an interdisciplinary perspective on systems. We reflect notion terminology adaptivity different disciplines discuss which role plays for fields. highlight common open challenges give perspectives future research directions, looking to inspire approaches.

Language: Английский

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Learning critically drives parkinsonian motor deficits through imbalanced striatal pathway recruitment

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(12)

Published: March 15, 2023

Dopamine (DA) loss in Parkinson’s disease (PD) causes debilitating motor deficits. However, dopamine is also widely linked to reward prediction and learning, the contribution of dopamine-dependent learning movements that are impaired PD—which often do not lead explicit rewards—is unclear. Here, we used two distinct tasks dissociate dopamine’s acute motoric effects vs. its long-lasting, learning-mediated effects. In dopamine-depleted mice, task performance gradually worsened with exposure. Task experience was critical, as mice remained home cage during same period were relatively unimpaired when subsequently probed on task. Repeated replacement treatments acutely rescued deficits induced long-term rescue persisted despite treatment withdrawal. Surprisingly, both parkinsonian decline specific, implicating learning. D1R activation potently consolidated into rescue. Conversely, reduced D2R decline. either or prevented decline, restored balanced direct indirect striatal pathways. These findings suggest reinforcement maintenance movements—even leading rewards—are fundamental functions provide potential mechanisms for hitherto unexplained “long-duration response” by dopaminergic therapies PD.

Language: Английский

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The intralaminar thalamus: a review of its role as a target in functional neurosurgery

Brain Communications, Journal Year: 2023, Volume and Issue: 5(3)

Published: Jan. 1, 2023

Abstract The intralaminar thalamus, in particular the centromedian-parafascicular complex, forms a strategic node between ascending information from spinal cord and brainstem forebrain circuitry that involves cerebral cortex basal ganglia. A large body of evidence shows this functionally heterogeneous region regulates transmission different cortical circuits, is involved variety functions, including cognition, arousal, consciousness processing pain signals. Not surprisingly, thalamus has been target area for (radio)surgical ablation deep brain stimulation (DBS) neurological psychiatric disorders. Historically, have explored patients with pain, epilepsy Tourette syndrome. Moreover, DBS used as an experimental treatment disorders movement In review, we provide comprehensive analysis underlying mechanisms nuclei, historical clinical evidence, more recent (experimental) studies animals humans to define present future role

Language: Английский

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Dopamine Signaling in Substantia Nigra and Its Impact on Locomotor Function—Not a New Concept, but Neglected Reality

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 1131 - 1131

Published: Jan. 17, 2024

The mechanistic influences of dopamine (DA) signaling and impact on motor function are nearly always interpreted from changes in nigrostriatal neuron terminals striatum. This is a standard practice studies human Parkinson’s disease (PD) aging related animal models PD aging-related parkinsonism. However, despite dozens indicating an ambiguous relationship between striatal DA phenotype, this perseverating focus striatum continues. Although release substantia nigra (SN) was first reported almost 50 years ago, assessment nigral relation to rarely considered. Whereas has been well-characterized at all five steps neurotransmission (biosynthesis turnover, storage, release, reuptake, post-synaptic binding) the pathway, depth such interrogations SN, outside cell counts, sparse. there sufficient evidence that these SN operational regulated autonomously present models. To complete our understanding how affects function, it past time include interrogation signaling. brief review highlights each step autonomous those alone can influence locomotor function. Accordingly, for full characterization activity, essential.

Language: Английский

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Experimental models of Parkinson’s disease: Challenges and Opportunities

European Journal of Pharmacology, Journal Year: 2024, Volume and Issue: 980, P. 176819 - 176819

Published: July 18, 2024

Language: Английский

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Oxidative stress and dysregulated long noncoding RNAs in the pathogenesis of Parkinson’s disease

Biological Research, Journal Year: 2025, Volume and Issue: 58(1)

Published: Jan. 27, 2025

Parkinson's disease (PD) is a progressive age-related neurodegenerative whose annual incidence increasing as populations continue to age. Although its pathogenesis has not been fully elucidated, oxidative stress shown play an important role in promoting the occurrence and development of disease. Long noncoding RNAs (lncRNAs), which are more than 200 nucleotides length, also involved PD at transcriptional level via epigenetic regulation, or post-transcriptional by participating physiological processes, including aggregation α-synuclein, mitochondrial dysfunction, stress, calcium stabilization, neuroinflammation. LncRNAs correlated during processes: affects expression multiple lncRNAs, while lncRNAs regulate many genes responses. Oxidative affect other processes associated with neurodegeneration, dysfunction increased neuroinflammation that lead neuronal death. Therefore, modulating levels specific may alleviate pathological damage have neuroprotective effects. This review discusses general mechanisms mechanism underlying PD, teases out through pathogenesis, well identifies possible lncRNAs. Reviewing published studies will help us further understand process identify potential therapeutic strategies for PD.

Language: Английский

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Spiking Patterns in the Globus Pallidus Highlight Convergent Neural Dynamics across Diverse Genetic Dystonia Syndromes

Annals of Neurology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 30, 2025

Objective Genetic dystonia is a complex movement disorder with diverse clinical manifestations resulting from pathogenic mutations in associated genes. A recent paradigm shift emphasizes the functional convergence among genes, hinting at shared pathomechanism. However, neural dynamics supporting this remain largely unexplored. Methods Herein, we analyzed microelectrode recordings acquired during pallidal deep brain stimulation surgery 31 patients AOPEP , GNAL KMT2B PANK2 PLA2G6 SGCE THAP1 TOR1A and VPS16 We identified 1,694 single units whose activity was characterized by broad set of features. Results displayed higher firing regularity, whereas large fraction bursting neurons (> 26.6%), significantly exceeding rate other genes constituted an intermediate group, bridging these 2 groups, due to having highest degree spiking irregularity. Hierarchical clustering algorithms based on confirmed results obtained first‐order comparisons. Interpretation Despite lacking common molecular pathways, share overlapping structures patterns, particular regularity activity. propose that desynchronization facilitated bursts may explain variability (DBS) globus pallidus internus (GPi) outcomes across genetic syndromes. Lastly, investigating effects low‐frequency could optimize personalized adaptive DBS treatments dystonia. ANN NEUROL 2025

Language: Английский

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A novel integrative multimodal classifier to enhance the diagnosis of Parkinson’s disease

Briefings in Bioinformatics, Journal Year: 2025, Volume and Issue: 26(2)

Published: March 1, 2025

Abstract Parkinson’s disease (PD) is a complex, progressive neurodegenerative disorder with high heterogeneity, making early diagnosis difficult. Early detection and intervention are crucial for slowing PD progression. Understanding PD’s diverse pathways mechanisms key to advancing knowledge. Recent advances in noninvasive imaging multi-omics technologies have provided valuable insights into underlying causes biological processes. However, integrating these data sources remains challenging, especially when deriving meaningful low-level features that can serve as diagnostic indicators. This study developed validated novel integrative, multimodal predictive model detecting based on derived from data, including hematological information, proteomics, RNA sequencing, metabolomics, dopamine transporter scan imaging, sourced the Progression Markers Initiative. Several architectures were investigated evaluated, support vector machine, eXtreme Gradient Boosting, fully connected neural networks concatenation joint modeling (FCNN_C FCNN_JM), encoder-based multi-head cross-attention (MMT_CA). The MMT_CA demonstrated superior performance, achieving balanced classification accuracy of 97.7%, thus highlighting its ability capture leverage cross-modality inter-dependencies aid analytics. Furthermore, feature importance analysis using SHapley Additive exPlanations not only identified biomarkers inform models this but also holds potential future research aimed at integrated functional analyses perspective, ultimately revealing targets required precision medicine approaches treatment down

Language: Английский

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