Biological Psychiatry Cognitive Neuroscience and Neuroimaging, Год журнала: 2024, Номер 10(3), С. 258 - 266
Опубликована: Окт. 30, 2024
Язык: Английский
Biological Psychiatry Cognitive Neuroscience and Neuroimaging, Год журнала: 2024, Номер 10(3), С. 258 - 266
Опубликована: Окт. 30, 2024
Язык: Английский
Chaos Solitons & Fractals, Год журнала: 2023, Номер 171, С. 113442 - 113442
Опубликована: Апрель 17, 2023
Язык: Английский
Процитировано
56Proceedings of the National Academy of Sciences, Год журнала: 2025, Номер 122(10)
Опубликована: Март 3, 2025
Understanding the key drivers of brain aging is essential for effective prevention and treatment neurodegenerative diseases. Here, we integrate human physiological data to investigate underlying mechanisms. Functional MRI analyses across four large datasets (totaling 19,300 participants) show that networks not only destabilize throughout lifetime but do so along a nonlinear trajectory, with consistent temporal "landmarks" starting in midlife (40s). Comparison metabolic, vascular, inflammatory biomarkers implicate dysregulated glucose homeostasis as driver mechanism these transitions. Correlation between brain's regionally heterogeneous patterns gene expression further supports findings, selectively implicating GLUT4 (insulin-dependent transporter) APOE (lipid transport protein). Notably, MCT2 (a neuronal, glial, ketone emerges potential counteracting factor by facilitating neurons' energy uptake independently insulin. Consistent results, an interventional study 101 participants shows ketones exhibit robust effects restabilizing networks, maximized from ages 40 60, suggesting "critical window" early metabolic intervention.
Язык: Английский
Процитировано
2Imaging Neuroscience, Год журнала: 2024, Номер 2, С. 1 - 14
Опубликована: Апрель 23, 2024
Aging is associated with impaired signaling between brain regions when measured using resting-state fMRI. This age-related destabilization and desynchronization of networks reverses itself the switches from metabolizing glucose to ketones. Here, we probe mechanistic basis for these effects. First, confirmed their robustness across measurement modalities two datasets acquired EEG (
Язык: Английский
Процитировано
5Chaos Solitons & Fractals, Год журнала: 2024, Номер 184, С. 114993 - 114993
Опубликована: Май 17, 2024
Язык: Английский
Процитировано
5Chaos Solitons & Fractals, Год журнала: 2024, Номер 183, С. 114967 - 114967
Опубликована: Май 11, 2024
Язык: Английский
Процитировано
4PLoS Computational Biology, Год журнала: 2024, Номер 20(7), С. e1012283 - e1012283
Опубликована: Июль 18, 2024
All fields of science depend on mathematical models. Occam’s razor refers to the principle that good models should exclude parameters beyond those minimally required describe systems they represent. This is because redundancy can lead incorrect estimates model from data, and thus inaccurate or ambiguous conclusions. Here, we show how deep learning be powerfully leveraged apply parameters. Our method, FixFit, uses a feedforward neural network with bottleneck layer characterize predict behavior given its input FixFit has three major benefits. First, it provides metric quantify original model’s degree complexity. Second, allows for unique fitting data. Third, an unbiased way discriminate between experimental hypotheses add value versus do not. In use cases, demonstrate broad applicability this method across scientific domains. To validate using known system, recover composite Kepler orbit dynamic blood glucose regulation. latter, ability fit latent real illustrate applied less well-established fields, identify multi-scale brain reduce search space viable candidate mechanisms.
Язык: Английский
Процитировано
3Scientific Reports, Год журнала: 2025, Номер 15(1)
Опубликована: Март 14, 2025
Enhanced activity of inhibitory neurons, which is often used to suppress behaviors pyramidal neurons treat brain diseases, whereas can enhance spiking a mixed-mode bursting (MMB) in recent experiments on migraine and seizure. The MMB contains phase with high level membrane potential/extracellular potassium concentration ([K+]o), propagate form spreading depolarization (SD) wave. Different from the common view that MMB/SD induced by enhanced positive effect or [K+]o, present paper, dynamics conditions for uncommon evoked synaptic current are obtained theoretical model. Firstly, addition well-known threshold across effect, neuron exhibits novel negative low [K+]o MMB. A long strong stimulation suppresses silence via saddle-node bifurcation an invariant circle at first then run threshold, triggering feedback potential levels enough, resulting Secondly, coupling model, interneuron conductance synapse, neuron, favorable Then, reducing these activities parameters measures prevent Finally, network induce SD results explanation MMB/SD, counterintuitive function interneuron, diseases.
Язык: Английский
Процитировано
0Regular and Chaotic Dynamics, Год журнала: 2024, Номер 29(1), С. 100 - 119
Опубликована: Янв. 1, 2024
Язык: Английский
Процитировано
1bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown
Опубликована: Май 11, 2023
Abstract Aging is associated with impaired signaling between brain regions when measured using resting-state fMRI. This age-related destabilization and desynchronization of networks reverses itself the switches from metabolizing glucose to ketones. Here, we probe mechanistic basis for these effects. First, established their neuronal two datasets acquired EEG ( Lifespan: standard diet, 20-80 years, N = 201; Metabolic: individually weight-dosed calorically-matched ketone ester challenge, μ age 26.9 ± 11.2 36). Then, multi-scale Larter-Breakspear neural mass model, identified unique set parameters consistent our clinical data. Together, results implicate potassium (K + ) gradient dysregulation as a mechanism its reversal ketosis, latter finding which direct measurement ion channels.
Язык: Английский
Процитировано
1Biological Psychiatry Cognitive Neuroscience and Neuroimaging, Год журнала: 2024, Номер 10(3), С. 258 - 266
Опубликована: Окт. 30, 2024
Язык: Английский
Процитировано
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