Changing pattern in the basal ganglia: motor switching under reduced dopaminergic drive

Abstract Action selection in the basal ganglia is often described within the framework of a standard model, associating low dopaminergic drive with motor suppression. Whilst powerful, this model does not explain several clinical and experimental data, including varying therapeutic efficacy across movement disorders. We tested the predictions of this model in patients with Parkinson’s disease, on and off subthalamic deep brain stimulation (DBS), focussing on adaptive sensory-motor responses to a changing environment and maintenance of an action until it is no longer suitable. Surprisingly, we observed prolonged perseverance under on-stimulation, and high inter-individual variability in terms of the motor selections performed when comparing the two conditions. To account for these data, we revised the standard model exploring its space of parameters and associated motor functions and found that, depending on effective connectivity between external and internal parts of the globus pallidus and saliency of the sensory input, a low dopaminergic drive can result in increased, dysfunctional, motor switching, besides motor suppression. This new framework provides insight into the biophysical mechanisms underlying DBS, allowing a description in terms of alteration of the signal-to-baseline ratio in the indirect pathway, which better account of known electrophysiological data in comparison with the standard model.

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PAKEs: New Framework, New Techniques and More Efficient Lattice-Based Constructions in the Standard Model

Lecture Notes in Computer Science - Public-Key Cryptography – PKC 2020 ◽

10.1007/978-3-030-45374-9_14 ◽

2020 ◽

pp. 396-427

Author(s):

Shaoquan Jiang ◽

Guang Gong ◽

Jingnan He ◽

Khoa Nguyen ◽

Huaxiong Wang

Keyword(s):

Standard Model ◽

New Techniques ◽

The Standard Model ◽

New Framework

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#3101 Imbalanced basal ganglia connectivity is associated with motor deficits and apathy in Huntingtons disease: first evidence from human in vivo neuroimaging

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2021-bnpa.15 ◽

2021 ◽

Vol 92 (8) ◽

pp. A6.1-A6

Author(s):

Akshay Nair ◽

Adeel Razi ◽

Sarah Gregory ◽

Robb Rutledge ◽

Geraint Rees ◽

...

Keyword(s):

Basal Ganglia ◽

Bayesian Model ◽

Empirical Bayes ◽

Model Comparison ◽

De Novo ◽

Effective Connectivity ◽

Indirect Pathway ◽

Direct Pathway ◽

Bayesian Model Comparison

BackgroundThe gating of movement in humans is thought to depend on activity within the cortico-striato-thalamic loops. Within these loops, emerging from the cells of the striatum, run two opponent pathways the direct and indirect pathway. Both are complex and polysynaptic but the overall effect of activity within these pathways is to encourage and inhibit movement respectively. In Huntingtons disease (HD), the preferential early loss of striatal neurons forming the indirect pathway is thought to lead to disinhibition that gives rise to the characteristic motor features of the condition. But early HD is also specifically associated with apathy, a failure to engage in goal-directed movement. We hypothesised that in HD, motor signs and apathy may be selectively correlated with indirect and direct pathway dysfunction respectively.MethodsUsing a novel technique for estimating dynamic effective connectivity of the basal ganglia, we tested both of these hypotheses in vivo for the first time in a large cohort of patients with prodromal HD (n = 94). We used spectral dynamic casual modelling of resting state fMRI data to model effective connectivity in a model of these cortico-striatal pathways. We used an advanced approach at the group level by combining Parametric Empirical Bayes and Bayesian Model Reduction procedure to generate large number of competing models and compare them by using Bayesian model comparison.ResultsWith this fully Bayesian approach, associations between clinical measures and connectivity parameters emerge de novo from the data. We found very strong evidence (posterior probability > 0.99) to support both of our hypotheses. Firstly, more severe motor signs in HD were associated with altered connectivity in the indirect pathway and by comparison, loss of goal-direct behaviour or apathy, was associated with changes in the direct pathway component of our model.ConclusionsThe empirical evidence we provide here is the first in vivo demonstration that imbalanced basal ganglia connectivity may play an important role in the pathogenesis of some of commonest and disabling features of HD and may have important implications for therapeutics.

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A novel cost framework reveals evidence for competitive selection in the evolution of complex traits during plant domestication

10.1101/2020.10.30.362236 ◽

2020 ◽

Author(s):

Robin G Allaby ◽

Chris J Stevens ◽

Dorian Q Fuller

Keyword(s):

Grain Size ◽

Standard Model ◽

Complex Traits ◽

Selection Intensity ◽

Model Framework ◽

Competitive Selection ◽

The Standard Model ◽

Fundamental Insight ◽

Insight Into ◽

Over Time

AbstractMost models of selection incorporate some notion of an environmental degradation in which the majority of the population becomes less fit with respect to a character resulting in a pressure to adapt. Such models have been variously associated with an adaptation cost, the substitution load. Conversely, adaptative mutations that represent an improvement in fitness in the absence of environmental change have generally been assumed to be associated with negligible cost. However, such adaptations could represent a competitive advantage that diminishes resource availability for others and so induce a cost. This type of adaptation in the form of seedling competition has been suggested as a mechanism for increases in seed size during domestication. Here we present a novel cost framework for competitive selection that demonstrates significant differences in behaviour to environmental based selection in typical initial selection intensity and intensity over time. We show that selection intensity over time in grain size metrics of nine archaeological crops increases in one to several episodes fitting closely to the competitive selection model of single large effect alleles, but surprisingly in direct contrast to the expectations of the standard model of stabilizing selection. While size trait changes ultimately slow down in crops over time as expected from pleiotropic constraints expressed in the standard model, the mechanism outlined here shows possible complexities within the environmental based mode of shifting optimums in the standard model and a fundamental insight into the factors driving domestication.Significance statementWe present here a new model framework for selection based on direct competition between individuals rather than the more conventional approach of individual’s fitness being measured against an environmental gradient. The model explains patterns of increasing selection intensity seen in archaeological grain sizes of nine domesticated crops that otherwise contradict the expectations of shifting stabilising selection of complex traits. We show that grain size increases seen across domesticated crops are consistent with spontaneous competition between seedlings under cultivation for resources and so reveal a fundamental insight into the mechanism of plant adaptation to the human environment.

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GHOST-FREE HIGHER DERIVATIVE QUANTUM GRAVITY, THE HIERARCHY AND THE COSMOLOGICAL CONSTANT PROBLEMS

Modern Physics Letters A ◽

10.1142/s021773230903062x ◽

2009 ◽

Vol 24 (15) ◽

pp. 1193-1197 ◽

Cited By ~ 4

Author(s):

V. I. TKACH

Keyword(s):

Standard Model ◽

Quantum Gravity ◽

Cosmological Constant ◽

Higher Order ◽

Higher Derivative ◽

Higher Order Gravity ◽

The Standard Model ◽

New Framework

We propose a new solution to problems of the hierarchy and smallness of the cosmological constant using the TeV scale of the Standard Model in a new framework of the higher-order gravity.

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Indirect measurements in micro-space with the EM

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100139366 ◽

1995 ◽

Vol 53 ◽

pp. 598-599

Author(s):

Sterling P. Newberry

Keyword(s):

Electron Microscope ◽

Standard Model ◽

Particle Physics ◽

Information Storage ◽

Storage Space ◽

Indirect Measurements ◽

Storage And Retrieval ◽

Adequate Information ◽

Compelling Reason ◽

The Standard Model

At the 1958 meeting of our society, then known as EMSA, the author introduced the concept of microspace and suggested its use to provide adequate information storage space and the use of electron microscope techniques to provide storage and retrieval access. At this current meeting of MSA, he wishes to suggest an additional use of the power of the electron microscope.The author has been contemplating this new use for some time and would have suggested it in the EMSA fiftieth year commemorative volume, but for page limitations. There is compelling reason to put forth this suggestion today because problems have arisen in the “Standard Model” of particle physics and funds are being greatly reduced just as we need higher energy machines to resolve these problems. Therefore, any techniques which complement or augment what we can accomplish during this austerity period with the machines at hand is worth exploring.

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Phenomena Beyond the Standard Model: What Do We Expect for New Physics to Look Like?

10.3389/978-2-88963-990-8 ◽

2020 ◽

Keyword(s):

Standard Model ◽

New Physics ◽

Beyond The Standard Model ◽

The Standard Model

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An Interview with the Physicist that Her Head in the Universe and Both Feet on the Earth

10.31227/osf.io/mfv4e ◽

2019 ◽

Author(s):

Adib Rifqi Setiawan

Keyword(s):

Standard Model ◽

Particle Physics ◽

Space Time ◽

Additional Dimension ◽

The Earth ◽

The Standard Model ◽

The Universe

Put simply, Lisa Randall’s job is to figure out how the universe works, and what it’s made of. Her contributions to theoretical particle physics include two models of space-time that bear her name. The first Randall–Sundrum model addressed a problem with the Standard Model of the universe, and the second concerned the possibility of a warped additional dimension of space. In this work, we caught up with Randall to talk about why she chose a career in physics, where she finds inspiration, and what advice she’d offer budding physicists. This article has been edited for clarity. My favourite quote in this interview is, “Figure out what you enjoy, what your talents are, and what you’re most curious to learn about.” If you insterest in her work, you can contact her on Twitter @lirarandall.

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