Improvements in cognition during ageing require neural resource mobilisation through effective training interventions. We hypothesize that neural resource mobilisation can be optimized by adapting the task demands relative to the current ability. We refer to the gap between demand and ability (functional task difficulty) as the Ability Prediction Error (APE). Using computational modelling and longitudinal quantitative MRI (qMRI), we aim to explore how training using experimentally manipulated APEs (underload, optimal load, overload) control sensorimotor performance improvements, behavioural transfer and neural resource mobilization at macro- and micro-structural brain levels in a defined (pre-) frontal brain circuit.
Prof. Dr. Marco Taubert
Marco Taubert is the head of the Cognition and Action Research group and chair for Training Science at the Otto-von Guericke University Magdeburg. His research focusses on training-induced structural and functional brain plasticity in humans. His expertise is in motor learning, the time course of tissue-specific plasticity and non-invasive brain imaging and transcranial stimulation methods.
Dr. Gabriel Ziegler
Gabriel Ziegler is heading the modelling and neuroprognosis group at the Institute of Cognitive Neurology and Dementia Research (IKND). His work focusses on state-of-the art statistical approaches such as latent variable modelling of brain-behavioral relationships, longitudinal brain changes, and disease progression in ageing and dementia research using MRI. He has made innovative contributions in developmental cognitive neuroscience using multivariate, kernel methods, Gaussian Processes, dynamical systems and Bayesian inference. His working group implements MR-based predictive models for memory performance and develops multivariate functional and structural indices of brain maintenance. He is part of the in-vivo histology (hMRI) working group that establishes new analysis techniques for quantitative multi-modal MRI.
Dr. Nico Lehmann
I’m a research associate in the lab of Marco Taubert at Otto von Guericke University (Department of Sport Science). My research focusses on the effects of physical exercise (cardiovascular and balance training) on motor learning and cognition, and the mediating role of structural and functional brain plasticity in this relationship.
I am working as a PhD student in the C01 project of the CRC on dynamic modelling of structural brain alterations and changes in functional abilities during learning. My goal as a researcher is to help understand how changing environments induce neuroplasticity. This understanding may help to inform future interventions that aim to mobilise neural resources in aged humans. As a basis for that, I am also interested in ongoing improvements in quantitative MRI.
Affiliation: Faculty of Human Sciences, Institute III, Department of Sport Science (Training science with focus on cognition and action), Otto von Guericke University
Research interests: My research interests include understanding the neurobiological mechanisms involved in the process of motor learning and the relationship between brain structure and behaviour. As part of the C01 project, my goal is to explore the factors that promote exercise-induced neuroplasticity through response optimised balance training in the elderly.
Expansion-renormalisation model of plasticity
According to the expansion-renormalisation model, learning-induced structural brain changes often follow a sequence of expansion, selection and renormalisation. Human learning may involve an initial but transient phase of increase in grey matter volume followed by a partial or even complete return to baseline once a behaviourally optimal neural circuitry has been selected (Wenger et al., 2017). The expansion-renormalisation model assumes that transfer effects of training to other related tasks are most likely at or just before volume expansion has reached its peak, motivating closer inspection of the temporal characteristics of plasticity and its relationship to CRC-defined neural resource properties. Depending on the particular phase of plasticity (i.e. grey matter expansion, grey matter renormalisation), the engaged neural circuit may be more or less susceptible to positive or negative transfer to similar learning tasks (Richards & Frankland, 2017).
The match of task demands and ability
It has been hypothesised that training intensity, defined as the mismatch (or gap) between an individual’s current ability and the requested task demand (Lövdén et al., 2010; Lindenberger, 2016), influences the trajectories of brain plasticity and its associated behavioural capacities (specific task-related performance improvements and its potential transfer). It is therefore expected that task demands need to be within the range of functional capacity (underload < optimum > overload) in order to optimally trigger plasticity (Lövdén et al., 2010). Model-based prediction errors are increasingly used in computational neuroscience, reinforcement learning and modelling trial-by-trial decision processes (Dayan, 2005). In this project, we aim to test the above hypothesis by experimentally manipulating Ability Prediction Errors (APEs), i.e. the quantitative mismatch of the required task demands and the subject’s current ability (estimate) in the learning process. APEs will play a central role in our development of a computational model of neural resource mobilisation that predicts multimodal structural MRI patterns of training-induced plasticity in a frontal cortex network.
Quantitative magnetic resonance imaging (qMRI) is a promising tool to study training-induced plasticity in humans due to its sensitivity to (often called “micro-structural”) brain tissue properties such as axon, myelin, and iron at millimetre resolution (Weiskopf et al., 2015, Tardif et al., 2016, Tabelow et al., 2019, Ziegler et al., 2018, 2019). In this particular line of research, “micro-structural” refers to quantitative aspects of the brain tissue (e.g. myelin density per volume) and is independent of the actual image resolution which is used to map it spatially (e.g. meso- or macroscale in this CRC). qMRI goes beyond traditional brain morphometry characterising volume differences or tissue expansion which is traditionally referred to as “macro-structural”. Longitudinal qMRI training studies which aim to analyse micro-structural contributions to macro-structural expansion and renormalisation cycles are still lacking.
The goals of our project
This project develops a computational brain-behavioural model for frontal neurocognitive circuit reorganisation serving performance improvements to match demands of a novel task. We assess brain changes during training that integrates macro- and multiple (micro-) structural imaging modalities (MT, R2* & DTI/NODDI). We study a CRC cohort (Z03-Düzel/Maass/Kreißl) subsample of 60 older participants’ learning trajectories using dynamical system modelling and hierarchical Bayesian inference. We hypothesize that experimentally manipulated APEs predict specific brain-behavioural adaptations. The dynamical model parameters represent (1) the ‘update rules’ (or dynamics) of week-wise individual performance and the (2) ‘microstructural cortical updates’ underlying these performance improvements during learning. Each participant acquiring the sensorimotor ability has an initial brain-behavioural starting point (a given raw ability/resource), adapts according to mechanisms via manipulated APEs and ends at a final state reflecting individual limitations of plasticity. We finaally study the individual differences and the contribution of hidden pathological conditions (such as amyloid) to training-induced brain and performance changes.
Imaging pilot study
In a test-retest reliability pilot study, we assessed multi-parameter maps (MPM) for qMRI as well as diffusion-tensor imaging (DTI) plus neurite orientation dispersion and density imaging (NODDI) parameters for N=30 subjects at two measurement occasions one month apart and derived intraclass correlation coefficients (ICC). Specifically, voxel-based reliability for advanced imaging markers (MPMs and NODDI parameters) was promising (Lehmann et al., 2021, Aye et al., under review), supporting the application of this imaging protocol to map frontal circuit changes under training in the proposed project.
We aim to extend previous balance training paradigm (Sehm et al., 2014) and develop an ability testing protocol for APE manipulation during training. First, we set the stage towards a fine-grained assessment of the subject’s current ability during each learning session using mechanical sensors. Task difficulty is then adaptively regulated via additional board weights across training and clamped to manipulate functional task difficulty according to each participant’s current balance ability from a testing session. Using this stabilometer paradigm and response-optimisation strategy, we will manipulate task difficulty over six training sessions and across individuals (N = 30 older participants between 60 – 75 years of age). We assess motor task improvements and transfer task performance using neuropsychological testing.
Longitudinal neuroimaging study
We will perform an intervention study with 60 healthy older participants (60-75 years of age) from CRC’s central cohort (Z03). Participants will be randomly allocated in main experimental groups with response-optimized vs. suboptimal APEs during training. Recent developments of MRI technology allow us to go beyond morphometric assessments to realize Multi-Parameter Mapping (MPM) of (MT, R1, R2*, PD) and combine the strength of qMRI with advanced diffusion MRI (NODDI). We are involved in the software development of state-of-the-art processing routines for quantitative imaging data in an international team (www.hmri.info; see Tabelow et al., 2019). Based on 6 weekly observations we will test for neural resource mobilisation in a frontal brain network comprising primary motor cortex (Taubert et al., 2016), pre-SMA/SMA, dorsolateral prefrontal cortex, anterior prefrontal cortex and hippocampus as well as adjacent white matter fibre tracts (Taubert et al., 2010, 2011; Sehm et al., 2014; Lehmann et al., 2019).
Computational model of brain-behavioral plasticity
We will extend previous work on dynamical modelling (Ziegler et al. 2017, Johnson/Ziegler et al.. 2021) to build a quantitative model of macro- and microstructural brain plasticity induced by learning the new sensorimotor (balance) task. We will focus on a hypothesised neurocognitive circuit (regions of interest) including the motor, pre-motor and anterior prefrontal cortex areas. A dynamical system with (macro- and microstructural states) captures multipametric MRI measurement and parameters of interest are estimated on a single subject and group level using Bayesian inference. Evidence-based model comparison will be performed to compare the dynamic model to more traditional polynomial models. The training-induced non-linear brain changes and cross-modal interactions of different processes are captured by model parameters, allowing us to study the interplay of myelination/iron changes and volume expansion-renormalisation during training for the first time.
In the long run, the project aims at (1) developing a behavioural intervention strategy to promote neural resource mobilisation at an optimal cost-benefit relationship (costs = training time; benefits = mobilised neural resources of cognition). Furthermore, the project develops (2) an increased understanding of the key determinants underlying structural brain plasticity studied with state-of-the-art neuroimaging. Our research agenda focusses on overcoming the descriptive nature of previous research on training-induced plasticity. In contrast to previous work where brain changes were induced and ‘just’ observed, we will follow the vision of building a new generation of generative models that incorporate a quantitative representation of the hypothesised drivers of neural changes on various levels, e.g. the behavioural deficit causing tissue property changes (resulting from a demand-ability mismatch during an interaction with the environment).
Publications of the project C01
Emrah Düzel, Gabriel Ziegler, David Berron, Anne Maass, Hartmut Schütze, Arturo Cardenas-Blanco, Wenzel Glanz, Coraline Metzger, Laura Dobisch, Martin Reuter, Annika Spottke, Frederic Brosseron, Klaus Fliessbach, Michael T Heneka, Christoph Laske, Oliver Peters, Josef Priller, Eike Jakob Spruth, Alfredo Ramirez,…
Hippocampal vascularization patterns exert local and distant effects on brain structure but not vascular pathology in old age
Niklas Vockert, Valentina Perosa, Gabriel Ziegler, Frank Schreiber, Anastasia Priester, Marco Spallazzi, Berta Garcia-Garcia, Merita Aruci, Hendrik Mattern, Aiden Haghikia, Emrah Düzel, Stefanie Schreiber, Anne Maass Brain Communications (2021)