Structural learning in feedforward and feedback control

For smooth and efficient motor control, the brain needs to make fast corrections during the movement to resist possible perturbations. It also needs to adapt subsequent movements to improve future performance. It is important that both feedback corrections and feedforward adaptation need to be made based on noisy and often ambiguous sensory data. Therefore, the initial response of the motor system, both for online corrections and adaptive responses, is guided by prior assumptions about the likely structure of perturbations. In the context of correcting and adapting movements perturbed by a force field, we asked whether these priors are hard wired or whether they can be modified through repeated exposure to differently shaped force fields. We found that both feedback corrections to unexpected perturbations and feedforward adaptation to a new force field changed, such that they were appropriate to counteract the type of force field that participants had experienced previously. We then investigated whether these changes were driven by a common mechanism or by two separate mechanisms. Participants experienced force fields that were either temporally consistent, causing sustained adaptation, or temporally inconsistent, causing little overall adaptation. We found that the consistent force fields modified both feedback and feedforward responses. In contrast, the inconsistent force field modified the temporal shape of feedback corrections but not of the feedforward adaptive response. These results indicate that responses to force perturbations can be modified in a structural manner and that these modifications are at least partly dissociable for feedback and feedforward control.

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Learning feedback and feedforward control in a mirror-reversed visual environment

Journal of Neurophysiology ◽

10.1152/jn.00096.2015 ◽

2015 ◽

Vol 114 (4) ◽

pp. 2187-2193 ◽

Cited By ~ 10

Author(s):

Shoko Kasuga ◽

Sebastian Telgen ◽

Junichi Ushiba ◽

Daichi Nozaki ◽

Jörn Diedrichsen

Keyword(s):

Feedback Control ◽

Visual Information ◽

Feedforward Control ◽

Control Policy ◽

Movement Direction ◽

Common Mechanism ◽

Central Target ◽

Online Corrections ◽

Online Feedback ◽

Initial Movement

When we learn a novel task, the motor system needs to acquire both feedforward and feedback control. Currently, little is known about how the learning of these two mechanisms relate to each other. In the present study, we tested whether feedforward and feedback control need to be learned separately, or whether they are learned as common mechanism when a new control policy is acquired. Participants were trained to reach to two lateral and one central target in an environment with mirror (left-right)-reversed visual feedback. One group was allowed to make online movement corrections, whereas the other group only received visual information after the end of the movement. Learning of feedforward control was assessed by measuring the accuracy of the initial movement direction to lateral targets. Feedback control was measured in the responses to sudden visual perturbations of the cursor when reaching to the central target. Although feedforward control improved in both groups, it was significantly better when online corrections were not allowed. In contrast, feedback control only adaptively changed in participants who received online feedback and remained unchanged in the group without online corrections. Our findings suggest that when a new control policy is acquired, feedforward and feedback control are learned separately, and that there may be a trade-off in learning between feedback and feedforward controllers.

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Differential effects of cerebellar degeneration on feedforward versus feedback control across speech and reaching movements

10.1101/2021.04.05.438454 ◽

2021 ◽

Author(s):

Benjamin Parrell ◽

Hyosub Kim ◽

Assaf Breska ◽

Arohi Saxena ◽

Rich Ivry

Keyword(s):

Feedback Control ◽

Speech Production ◽

Neural Circuit ◽

Feedforward Control ◽

Cerebellar Degeneration ◽

Adaptive Responses ◽

Compensatory Response ◽

Domain Specific ◽

Specific Manner ◽

Online Corrections

AbstractErrors that result from a mismatch between predicted movement outcomes and sensory afference are used to correct ongoing movements through feedback control and to adapt feedforward control of future movements. The cerebellum has been identified as a critical part of the neural circuit underlying implicit adaptation across a wide variety of movements (reaching, gait, eye movements, and speech). The contribution of this structure to feedback control is less well understood: although it has recently been shown in the speech domain that individuals with cerebellar degeneration produce even larger online corrections for sensory perturbations than control participants, similar behavior has not been observed in other motor domains. Currently, comparisons across domains are limited by different population samples and potential ceiling effects in existing tasks. To assess the relationship between changes in feedforward and feedback control associated with cerebellar degeneration across motor domains, we evaluated adaptive (feedforward) and compensatory (feedback) responses to sensory perturbations in reaching and speech production in individuals with cerebellar degeneration and neurobiologically healthy controls. As expected, the cerebellar group demonstrated impaired adaptation in both reaching and speech. In contrast, the groups did not differ in their compensatory response in either domain. Moreover, compensatory and adaptive responses in the cerebellar group were not correlated within or across motor domains. Together, these results point to a general impairment in feedforward control with spared feedback control in cerebellar degeneration. However, the magnitude of feedforward impairments and potential changes in feedback-based control manifest in a domain-specific manner across individuals.Significance StatementThe cerebellum contributes to feedforward updating of movement in response to sensory errors, but its role in feedback control is less understood. Here, we tested individuals with cerebellar degeneration (CD), using sensory perturbations to assess adaptation of feedforward control and feedback gains during reaching and speech production tasks. The results confirmed that CD leads to reduced adaption in both domains. However, feedback gains were unaffected by CD in either domain. Interestingly, measures of feedforward and feedback control were not correlated across individuals within or across motor domains. Together, these results indicate a general impairment in feedforward control with spared feedback control in CD. However, the magnitude of feedforward impairments manifests in a domain-specific manner across individuals.

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Hydration Free Energies of Organic Molecules in the FreeSolv Database Calculated with Polarized Atom In Molecules Atomic Charges and the GAFF Force Field.

10.26434/chemrxiv.6015611.v1 ◽

2018 ◽

Author(s):

Maximiliano Riquelme ◽

Alejandro Lara ◽

David L. Mobley ◽

Toon Vestraelen ◽

Adelio R Matamala ◽

...

Keyword(s):

Force Field ◽

Functional Groups ◽

Electrostatic Interactions ◽

Organic Molecules ◽

Force Fields ◽

Chemical Elements ◽

Atomic Charges ◽

Free Energies ◽

Molecular Systems ◽

Solvent Model

<div>Computer simulations of bio-molecular systems often use force fields, which are combinations of simple empirical atom-based functions to describe the molecular interactions. Even though polarizable force fields give a more detailed description of intermolecular interactions, nonpolarizable force fields, developed several decades ago, are often still preferred because of their reduced computation cost. Electrostatic interactions play a major role in bio-molecular systems and are therein described by atomic point charges.</div><div>In this work, we address the performance of different atomic charges to reproduce experimental hydration free energies in the FreeSolv database in combination with the GAFF force field. Atomic charges were calculated by two atoms-in-molecules approaches, Hirshfeld-I and Minimal Basis Iterative Stockholder (MBIS). To account for polarization effects, the charges were derived from the solute's electron density computed with an implicit solvent model and the energy required to polarize the solute was added to the free energy cycle. The calculated hydration free energies were analyzed with an error model, revealing systematic errors associated with specific functional groups or chemical elements. The best agreement with the experimental data is observed for the MBIS atomic charge method, including the solvent polarization, with a root mean square error of 2.0 kcal mol<sup>-1</sup> for the 613 organic molecules studied. The largest deviation was observed for phosphor-containing molecules and the molecules with amide, ester and amine functional groups.</div>

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QUBEKit: Automating the Derivation of Force Field Parameters from Quantum Mechanics

10.26434/chemrxiv.7247045.v2 ◽

2019 ◽

Cited By ~ 1

Author(s):

Joshua Horton ◽

Alice Allen ◽

Leela Dodda ◽

Daniel Cole

Keyword(s):

Quantum Mechanics ◽

Force Field ◽

Organic Molecules ◽

Force Fields ◽

Liquid Density ◽

Small Organic Molecules ◽

Automated Generation ◽

Energy Of Hydration ◽

Novel Method ◽

Force Field Parameters

<div><div><div><p>Modern molecular mechanics force fields are widely used for modelling the dynamics and interactions of small organic molecules using libraries of transferable force field parameters. For molecules outside the training set, parameters may be missing or inaccurate, and in these cases, it may be preferable to derive molecule-specific parameters. Here we present an intuitive parameter derivation toolkit, QUBEKit (QUantum mechanical BEspoke Kit), which enables the automated generation of system-specific small molecule force field parameters directly from quantum mechanics. QUBEKit is written in python and combines the latest QM parameter derivation methodologies with a novel method for deriving the positions and charges of off-center virtual sites. As a proof of concept, we have re-derived a complete set of parameters for 109 small organic molecules, and assessed the accuracy by comparing computed liquid properties with experiment. QUBEKit gives highly competitive results when compared to standard transferable force fields, with mean unsigned errors of 0.024 g/cm3, 0.79 kcal/mol and 1.17 kcal/mol for the liquid density, heat of vaporization and free energy of hydration respectively. This indicates that the derived parameters are suitable for molecular modelling applications, including computer-aided drug design.</p></div></div></div>

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QUBEKit: Automating the Derivation of Force Field Parameters from Quantum Mechanics

10.26434/chemrxiv.7247045 ◽

2019 ◽

Cited By ~ 1

Author(s):

Joshua Horton ◽

Alice Allen ◽

Leela Dodda ◽

Daniel Cole

Keyword(s):

Quantum Mechanics ◽

Force Field ◽

Organic Molecules ◽

Force Fields ◽

Liquid Density ◽

Small Organic Molecules ◽

Automated Generation ◽

Energy Of Hydration ◽

Novel Method ◽

Force Field Parameters

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A Transferable, Polarisable Force Field for Ionic Liquids

10.26434/chemrxiv.8845526.v1 ◽

2019 ◽

Author(s):

Kateryna Goloviznina ◽

José N. Canongia Lopes ◽

Margarida Costa Gomes ◽

Agilio Padua

Keyword(s):

Ionic Liquids ◽

Force Field ◽

Force Fields ◽

Dipole Moments ◽

Van Der Waals Interactions ◽

First Principles Calculations ◽

Ion Diffusion ◽

Fixed Integer ◽

Molecular Compounds ◽

Induced Dipoles

A general, transferable polarisable force field for molecular simulation of ionic liquids and their mixtures with molecular compounds is developed. This polarisable model is derived from the widely used CL\&P fixed-charge force field that describes most families of ionic liquids, in a form compatible with OPLS-AA, one of the major force fields for organic compounds. Models for ionic liquids with fixed, integer ionic charges lead to pathologically slow dynamics, a problem that is corrected when polarisation effects are included explicitly. In the model proposed here, Drude induced dipoles are used with parameters determined from atomic polarisabilities. The CL\&P force field is modified upon inclusion of the Drude dipoles, to avoid double-counting of polarisation effects. This modification is based on first-principles calculations of the dispersion and induction contributions to the van der Waals interactions, using symmetry-adapted perturbation theory (SAPT) for a set of dimers composed of positive, negative and neutral fragments representative of a wide variety of ionic liquids. The fragment approach provides transferability, allowing the representation of a multitude of cation and anion families, including different functional groups, without need to re-parametrise. Because SAPT calculations are expensive an alternative predictive scheme was devised, requiring only molecular properties with a clear physical meaning, namely dipole moments and atomic polarisabilities. The new polarisable force field, CL\&Pol, describes a broad set set of ionic liquids and their mixtures with molecular compounds, and is validated by comparisons with experimental data on density, ion diffusion coefficients and viscosity. The approaches proposed here can also be applied to the conversion of other fixed-charged force fields into polarisable versions.<br>

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Faculty Opinions recommendation of RNA force field with accuracy comparable to state-of-the-art protein force fields.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.732583614.793546916 ◽

2018 ◽

Author(s):

Alan Chen

Keyword(s):

Force Field ◽

State Of The Art ◽

Force Fields ◽

Protein Force Fields

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Measurements of periodically perturbed dewetting force fields and their consequences on the symmetry of the resulting patterns

Scientific Reports ◽

10.1038/s41598-021-92544-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Konstantinos Roumpos ◽

Sarah Fontaine ◽

Thomas Pfohl ◽

Oswald Prucker ◽

Jürgen Rühe ◽

...

Keyword(s):

Force Field ◽

Driving Force ◽

Force Fields ◽

Contact Lines ◽

Polymer Flow ◽

Circular Symmetry ◽

Pillar Array ◽

Restoring Forces ◽

Micro Pillars ◽

Circular Contact

AbstractWe studied the origin of breaking the symmetry for moving circular contact lines of dewetting polymer films suspended on a periodic array of pillars. There, dewetting force fields driving polymer flow were perturbed by elastic micro-pillars arranged in a regular square pattern. Elastic restoring forces of deformed pillars locally balance driving capillary forces and broke the circular symmetry of expanding dewetting holes. The observed envelope of the dewetting holes reflected the symmetry of the underlying pattern, even at sizes much larger than the characteristic period of the pillar array, demonstrating that periodic perturbations in a driving force field can establish a well-defined pattern of lower symmetry. For the presented system, we succeeded in squaring the circle.

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Combining experimental and simulation data of molecular processes via augmented Markov models

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1704803114 ◽

2017 ◽

Vol 114 (31) ◽

pp. 8265-8270 ◽

Cited By ~ 53

Author(s):

Simon Olsson ◽

Hao Wu ◽

Fabian Paul ◽

Cecilia Clementi ◽

Frank Noé

Keyword(s):

Force Field ◽

Structural Changes ◽

Markov Models ◽

Force Fields ◽

Divide And Conquer ◽

Simulation Data ◽

Wide Range ◽

Simulation And Experiment ◽

Kinetics Of

Accurate mechanistic description of structural changes in biomolecules is an increasingly important topic in structural and chemical biology. Markov models have emerged as a powerful way to approximate the molecular kinetics of large biomolecules while keeping full structural resolution in a divide-and-conquer fashion. However, the accuracy of these models is limited by that of the force fields used to generate the underlying molecular dynamics (MD) simulation data. Whereas the quality of classical MD force fields has improved significantly in recent years, remaining errors in the Boltzmann weights are still on the order of a few kT, which may lead to significant discrepancies when comparing to experimentally measured rates or state populations. Here we take the view that simulations using a sufficiently good force-field sample conformations that are valid but have inaccurate weights, yet these weights may be made accurate by incorporating experimental data a posteriori. To do so, we propose augmented Markov models (AMMs), an approach that combines concepts from probability theory and information theory to consistently treat systematic force-field error and statistical errors in simulation and experiment. Our results demonstrate that AMMs can reconcile conflicting results for protein mechanisms obtained by different force fields and correct for a wide range of stationary and dynamical observables even when only equilibrium measurements are incorporated into the estimation process. This approach constitutes a unique avenue to combine experiment and computation into integrative models of biomolecular structure and dynamics.

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