Unified probabilistic modelling of adaptive spatial-temporal structures in the human brain

Lead Research Organisation: University of Birmingham
Department Name: School of Computer Science

Abstract

Learning from experience and adapting our behaviour to new situations is a fundamental skill for our everyday interactions. But what are the brain plasticity mechanisms that mediate an individual's ability to make progress during training on complex tasks? What is it that differentiates `good' from `poor' learners in their ability to adapt? Recent advances in functional brain imaging technology provide us with the unique opportunity to study how the human brain changes with learning. However, the existing methods focus predominantly on modelling brain activity data within a single session rather than across training sessions. As such, these methods are not capable of capturing larger scale dependencies emerging in brain activity as training progresses. We will develop a novel methodology that allows holistic unified modelling of a series of brain imaging data measured during the course of learning. Using this methodology we will study brain changes that result from extensive training on complex visual tasks. Our work will offer scientists and practitioners advanced tools for using brain activity measurements to understand the brain learning mechanisms and how they improve our ability to make complex decisions. The proposed methodology may have predictive power for making inferences about 'prototypical' learning patterns that can be used to predict adaptive behaviour in individuals with different learning strategies and design training schemes tailored to the individuals' abilities and needs. Hence our findings have potential implications for the design of dedicated training programmes that take into account an individual's learning capacity. Such programmes may have applications in education or intervention and rehabilitation in normal and pathological development and ageing (e.g. stroke, neurodegenerative disorders).

Technical Summary

Conventional methods for the analysis of functional MRI data have been instrumental in revealing the human brain architecture, allowing us to identify cortical areas involved in processing sensory information, as well as circuits engaged in higher cognitive functions. However, characterising the link between activity in these networks and adaptive behaviour remains an open challenge in cognitive neuroscience. In particular, understanding how the brain circuits and functions change with experience is fundamental for unravelling the plasticity of the human brain. Yet, we are still lacking principled methods for modelling and analysing in a unified framework the dependencies of brain activity across stages of training (within and across multiple sessions) that mediate our ability to make progress in learning complex tasks. We propose to develop a novel methodology based on generative probabilistic modelling for holistic analysis of complex brain imaging data measured during multiple sessions and across stages of training. The model is formed by a set of coupled hidden process models, one for each session. To stabilise the parameter fitting and enhance interpretability of the model, the hidden process models will be constrained by 1) probabilistic pooling of voxels into spatially contiguous groups of common parametrised hemodynamic response; 2) reducing the uncertainty in the onset time of hidden processes by concurrent fMRI and EEG measurements. We will test and validate our methodology in a large set of controlled experiments using synthetic data, as well as real data measured in participants trained to perform complex visual decision tasks. The proposed work will provide advanced methodological tools for studying the human brain plasticity mechanisms that mediate our ability to train and improve in complex tasks and novel theoretical insights into the functional plasticity signatures of learning in the individual human brain.

Planned Impact

Most of the current functional brain imaging research is concerned with understanding neural mechanisms involved in cognitive processes as revealed by single session scans. However, investigating neural mechanisms in the human brain that mediate our ability to train and improve in complex tasks requires a new set of tools capable of capturing dependencies in the brain imaging data across multiple sessions characterising different stages of learning. The proposed project will deliver a novel methodology for a unified systematic processing and analysis of such complex data. The work has a strong potential for building and enhancing interdisciplinary, high-end research in cognitive neuroscience in the UK. This basic research on learning and brain plasticity has the potential to improve the quality of life through applications in public health, education and policy. Who will benefit from this research? The main beneficiaries outside the academic community will be the general population engaged in everyday activities entailing training in complex tasks as well as individuals with learning difficulties of different kinds, professionals from health and social services working with them and policy makers. Further, we will exploit opportunities for applied research and knowledge transfer: companies developing advanced tools for brain imaging research, designing educational software or brain training games. How will they benefit from this research? Our findings will advance our understanding of the link between activity in cortical areas involved in the processing of sensory information, as well as circuits engaged in higher cognitive functions (attention, memory, decision making) and adaptive behaviour. Delineating brain learning mechanisms is critical for the design of learning programmes for education or intervention that are tailored, accessible and beneficial to people of all ages and conditions. What will be done to ensure that they have the opportunity to benefit from this research? We will disseminate our work to the public, third and private sector through: 1. project-specific website and links to collaborators' sites 2. keeping participants in our research informed about findings and applications 3. the University and BBSRC Press Office (e.g. National and local media, Science Festival). 4. activities for the public organised by the University and the Alumni Office: presentations at Open Days, lay-reports for magazines. 5. Workshops through the Bridging the Gap programme engaging scientists, practitioners, participants in our studies, and the general public.

Publications

10 25 50
 
Description We continue to work on extracting spatiotemporal features from fMRI data. Our recent work aims at extracting task-relevant fMRI features and the task is to discriminate patients with Mild Cognitive Impairment (MCI) from healthy controls. For a given ROI, spatiotemporal information encoded in the fMRI data is simply represented by a correlation matrix whose elements measure zero-lag cross-correlation between two fMRI time series from every pair of voxels in that ROI. Such matrix is called graph matrix. Traditionally, fMRI data in a ROI is summarised by a single number, the so-called percent signal change (PSC). This number actually measures the overall activation intensity of the brain in a cognitive task. Compared to PSC, each element in the graph matrix is a functional connectivity measure and independent of the activation intensity on each of the two voxels. Usually, the graph matrix is a large matrix and we first reduce it to a much smaller graph matrix by functional clustering of contiguous voxels into a small set of nodes. Each element of the reduced matrix measures the averaged connectivity between two nodes. After that, the graph matrix is further reduced to a single number in a supervised fashion by employing so-called matrix-based Linear Discriminant Analysis (2D-LDA) algorithm. We call the number as fMRI graph feature. Along with these features from individual MCI patients and healthy controls, we also obtain a set of node pairs. They represent the connections that are most relevant to the discrimination task.

The developed methodology has been applied to the fMRI data collected from a cohort of MCI patients and healthy controls that participated a probabilistic sequence-learning task. For each participant, we have 6 data sets from two fMRI scan sessions (before and after training) and from three ROIs (1 frontal ROI, 1 cerebellar ROI, and 1 subcortical ROI). For the discrimination task, we employed Generalised Matrix Learning Vector Quantisation (GMLVQ) classifiers. The training of such classifiers also provides the relative importance weights of the classifiers' inputs, that is, six PSC features or six graph features. Our analysis suggests that (1) when overall fMRI signal is used as inputs to the classifier, the post-training session is most relevant and (2) when the graph feature reflecting underlying spatiotemporal fMRI pattern is used, the pre-training session is most relevant.

Furthermore, we adopted a "Learning with privileged information (PI)" approach to combine cognitive and fMRI data for the classification task. The resulting classifier operates solely on the cognitive data (that is, the cognitive profiles that measure the participants' ability of working memory, cognitive inhibition, divided attention, and selective attention) but it does incorporate the fMRI data as privileged information during training. This novel classifier is of practical use as the collection of brain imaging data is not always possible with old patients and participants. Our results show that the PI guided GMLVQ classifiers outperform the baseline classifier that only used the cognitive data. In addition, we found that for the baseline classifier, divided attention is the only relevant cognitive feature to the discrimination task. When PI was incorporated, divided attention remained the most relevant feature while cognitive inhibition became also relevant for the task.
We further present our key findings obtained from a behavioral and fMRI study of how humans learn sequential structures that are probabilistically encoded in temporal sequences of visual stimuli. In this study, such structures need to be extracted for predicting upcoming stimuli in the sequences. These findings are of significance because human behavior is guided by our expectations about the future. Often, we make predictions by monitoring how event sequences unfold and extracting event structures in the variable environment.
First, we investigate the dynamics of structure learning by tracking human responses to temporal sequences that change in structure unbeknownst to the participants. Participants were asked to predict the upcoming item following a probabilistic sequence of symbols. Using a Markov process, we created a family of sequences, from simple frequency statistics (e.g., some symbols are more probable than others) to context-based statistics (e.g., symbol probability is contingent on preceding symbols). We demonstrate the dynamics with which individuals adapt to changes in the environment's statistics-that is, they extract the behaviorally relevant structures to make predictions about upcoming events. Further, we show that this structure learning relates to individual decision strategy; faster learning of complex structures relates to selection of the most probable outcome in a given context (maximizing) rather than matching of the exact sequence statistics. Our findings provide evidence for alternate routes to learning of behaviorally relevant statistics that facilitate our ability to predict future events in variable environments.

Second, we investigate the brain mechanisms that mediate our ability to adapt to the environment's statistics and predict upcoming events. By combining behavioral training and multisession fMRI in human participants (male and female), we track the cortico-striatal mechanisms that mediate learning of temporal sequences as they change in structure complexity. We show that the two decision strategies engage distinct human brain regions: maximizing engages dorsolateral prefrontal, cingulate, sensory-motor regions, and basal ganglia (dorsal caudate, putamen), whereas matching engages occipito-temporal regions (including the hippocampus) and basal ganglia (ventral caudate). Our findings provide evidence for distinct cortico-striatal mechanisms that facilitate our ability to extract behaviorally relevant statistics to make predictions.

Third, we investigate whether changes in the processing and connectivity of functional brain networks due to training relate to our ability to learn temporal regularities. By combining behavioral training and functional brain connectivity analysis, our fMRI results demonstrate that learning-dependent changes in functional connectivity between brain networks relate to individual variability in strategy. In particular, extracting the exact sequence statistics (i.e., matching) relates to changes in brain networks known to be involved in memory and stimulus-response associations, while selecting the most probable outcomes in a given context (i.e., maximizing) relates to changes in frontal and striatal networks. Thus, our findings provide evidence that dissociable brain networks mediate individual ability in learning behaviorally relevant statistics. We have now also managed to push the work in the direction of the final goal - full probabilistic modelling of fMRI signals across several levels of spatial and temporal scales. This has been achieved by linking together data from subjects trained on a hierarchy of increasingly complex temporal tasks. Besides behavioural data, fMRI was measured before and after training at each level of the task complexity. We applied behavioural models in conjunction with our probabilistic spatial-temporal fMRI models to extract signatures of neuro-cortical activations distinguishing slow and fast learners.

Finally, we have been recently able to go beyond the original aims of this proposal (paper in final stages of preparation). We have extended the core models for unified probabilistic modelling of behavioural and brain imaging data by formulating a hierarchy of population models. In this way we were able to discover cortical signatures related to decision making in behaviourally different groups of participants (in our context - weak and strong learners in noisy prediction tasks under shallow memory). This enables the users to draw principled model based conclusions from joint behavioural and brain imaging experiments, eliminating the need to use largely heuristics based methods and rely mainly on extensive statistical testing.
Exploitation Route The methodology we have developed could be evaluated using a much larger cohort of MCI patients. This would allow us to further develop our methodology. We are working on this. Our recent model extensions will be able to unify in a principled way behavioural and brain imaging data collected while subjects are in the process of learning a cognitive task - thus potentially helping us to better understand the spatial temporal changes of cortical representations underpinning learning.
Sectors Education,Healthcare

 
Description A multi-disciplinary approach to understanding the immunological basis and potential prevention of graft versus host disease
Amount £1,680,092 (GBP)
Funding ID MR/K021192/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 04/2013 
End 03/2017
 
Description ABC: Adaptive Brain Computations
Amount £3,800,000 (GBP)
Funding ID FP7-PEOPLE-2011-1-1-ITN 
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 10/2011 
End 09/2016
 
Description Adaptive decision templates in the human brain. Wellcome Trust Investigator Award.
Amount £1,344,200 (GBP)
Funding ID 205067/Z/16/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2017 
End 09/2022
 
Description Alan Turing Fellowship
Amount £103,981 (GBP)
Funding ID TU/B/000095 
Organisation Alan Turing Institute 
Sector Academic/University
Country United Kingdom
Start 10/2017 
End 09/2019
 
Description BBSRC IAA
Amount £15,000 (GBP)
Funding ID BB/S506710/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 08/2018 
End 10/2018
 
Description Flexible perception: functional plasticity mechanisms in the human brain.
Amount £497,801 (GBP)
Funding ID BB/P021255/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 01/2018 
End 12/2020
 
Description Global Public Health: Partnership Awards. Pictures of ageing in Uganda: A partnership to explore demography, phenotype and self-perception in a community of older people in Uganda.
Amount £199,908 (GBP)
Funding ID AH/R005990/1 
Organisation Arts & Humanities Research Council (AHRC) 
Sector Public
Country United Kingdom
Start 01/2018 
End 12/2019
 
Description Learning and brain plasticity across the lifespan
Amount £28,347 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start  
 
Description Learning and brain plasticity for perceptual decisions
Amount € 5,000,000 (EUR)
Organisation Research Foundation - Flanders (FWO) 
Sector Charity/Non Profit
Country Belgium
Start 09/2012 
End 08/2017
 
Description Learning and brain plasticity: understanding individual variability across the lifespan
Amount £44,637 (GBP)
Funding ID RF-2011-378 
Organisation The Leverhulme Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2011 
End 10/2014
 
Description Model-based decoding of the individual brain
Amount £19,697 (GBP)
Funding ID EPSRC 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start  
 
Description Personalised Medicine through Learning in the Model Space
Amount £1 (GBP)
Funding ID EP/L000296/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 05/2013 
End 04/2016
 
Description ProMoS- Probabilistic Models in Pseudo-Euclidean Spaces
Amount € 221,606 (EUR)
Funding ID 327791 
Organisation European Commission 
Department Seventh Framework Programme (FP7)
Sector Public
Country European Union (EU)
Start 01/2014 
End 12/2015
 
Title Unified probabilistic model of fMRI data across scales 
Description We have developed and fully coded a probabilistic prototype-based model for consistent treatment of fMRI data across scales. The results have been reported in Y. Shen, S.D. Mayhew, Z. Kourtzi, P. Tino: Spatial-temporal modelling of fMRI data through spatially regularized mixture of hidden process models. Neuroimage, 84(1), pp. 657-671, 2014. 
Type Of Material Model of mechanisms or symptoms - human 
Provided To Others? No  
Impact We have not yet provided the tool for general use, but plan to do so. It is a complex piece of software that needs to be documented in a detailed manner. The tool was used to analyse fMRI and the work was reported in a prestigious journal (Neuroimage). 
 
Title Behavioural and brain imaging dataset 
Description We have created a unique dataset of participants trained on a carefully designed hierarchy of sequence prediction tasks with increasing complexity. Concurrent fMRI measurements were performed on at the beginning and end of training. This data involves 62 undergraduate students. All participants were naive to the aim of the study, had normal or corrected-to-normal vision and gave written informed consent. This study was approved by the University of Birmingham Ethics Committee 
Type Of Material Database/Collection of data 
Provided To Others? No  
Impact We will make the data set available once initial analysis and modelling is finished. Two major journal papers resulting from this study are under submission, the third one is being written. 
 
Description Invited Talk at IJCAI-15 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited Talk as part of the Machine Learning Track at IJCAI-15
Year(s) Of Engagement Activity 2015
 
Description Brain Imaging in cognitive ageing 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Invited talk at Age Well Conference 2010

no actual impacts realised to date
Year(s) Of Engagement Activity 2010
 
Description Cambridge BRAINfest 2017 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Cambridge BRAINfest is a free interactive public festival, and this was its inaugural event. Cambridge BRAINFest brings together neuroscientists from across Cambridge, to present ground breaking research through interactive exhibits, film, art, neurotheatre and Q&A with Cambridge experts at Café Scientifique. The Adaptive Brain Lab held a stall over the weekend, entitled 'How we learn to see' about how the brain learns and how the brain perceives depth'. This stall used optical illusions, tablet-based games, posters and a model brain stimulator to help the visitors to think about how the brain uses the visual cues it detects to make predictions about depth based on visual information alone.In addition, Zoe Kourtzi gave a one hour talk entitled 'What next? Learning to predict the future from the past', which included a lively discussion with the audience. Feedback on the event was extremely positive, with Prof. Kourtzi being named by one attendee as the best thing about the event. Other benefits highlighted by attendees included: 'Opportunities to learn about the researchers, talking to scientists and hands on for kids', 'The amount of expertise and the way it was showing science's applications to people's lives.' and 'Enthusiastic presenters. Current research-very inspiring. Best educational event I have been to.'
Year(s) Of Engagement Activity 2017
URL https://www.neuroscience.cam.ac.uk/brainfest
 
Description Cambridge Science Festival 2017 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact The Cambridge Science Festival is a city-wide event which showcases to the general public the variety of science going on across Cambridge. The Adaptive Brain Lab had a stall which gave an opportunity for visitors to experience a range of visual illusions, and to discover the science behind their creation. In addition to the basic science, we also demonstrated some of the methods and approaches used in the lab. Feedback on the day was very positive, and we have been invited back next year.
Year(s) Of Engagement Activity 2014,2017
URL https://www.sciencefestival.cam.ac.uk/
 
Description Cambridge Science Festival 2018 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact "Cambridge Science Festival gives the public the opportunity to explore Cambridge Science.
The Science Festival provides the public with opportunities to explore and discuss issues of scientific interest and concern and to raise aspirations by encouraging young people to consider a career in science, technology, engineering or mathematics.
Each year, the Cambridge Science Festival welcomes visitors to hundreds of events and receives extensive national and local media coverage.
This was our second year participating in the Science Festival. Prof. Zoe Kourtzi give a talk entitled 'How do brains learn about the world around us?', which about 150 people attended. The lab also held a day-long stall entitled 'Don't believe everything you see' which included optical illusions, language games, stereovision games, and the chance to learn firsthand from researchers. Local press (the Cambridge News) cited Prof. Kourtzi's talk as a 'highlight' of the entire two-week festival. The organisers are in the process of collating feedback.
Year(s) Of Engagement Activity 2018
URL https://www.sciencefestival.cam.ac.uk/
 
Description Evolutionary algorithms 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Participants in your research or patient groups
Results and Impact Invited talk at 7th International Summer School on Pattern Recognition

no actual impacts realised to date
Year(s) Of Engagement Activity 2011
 
Description Imaging plasticity in the young and ageing brain 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Participants in your research and patient groups
Results and Impact Invited talk at Marie Curie FP7 Advanced Training Course,

Brain imaging and its applications.

no actual impacts realised to date
Year(s) Of Engagement Activity 2010
 
Description Imaging visual perception 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Participants in your research or patient groups
Results and Impact Invited talk at Visual Neuroscience Summer School

no actual impacts realised to date
Year(s) Of Engagement Activity 2010
 
Description Imaging visual perception and learning in the human brain 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Participants in your research or patient groups
Results and Impact Invited talk at the opening of the University of Bristol Imaging Centre

no actual impacts realised to date
Year(s) Of Engagement Activity 2011
 
Description Invited talk at the Science Festival, Bradford, UK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact The talk inspired lively discussions about rehabilitation programmes in healthy ageing and disease

Follow up talks were requested on the topic of cognitive ageing
Year(s) Of Engagement Activity 2011
 
Description Learning for flexible decisions in the human brain. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Invited talk at Baylor College of Medicine, Houston, USA.

no actual impacts realised to date
Year(s) Of Engagement Activity 2012
 
Description Roche schools event (GenerationeXt) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact Members of the Adaptive Brain Lab delivered an interactive workshop as part of Roche's GenerationNext event in November 2017. This event targets 16-18 year olds who are studying science and thinking of their options for further education and careers and is designed to help them consider all the options available to them within STEM, and encourage and excite them about studying within a STEM subject. This workshop used optical illusions, tablet-based games and a model brain stimulator to help the students to think about how the brain uses the visual cues it detects to make predictions about depth based on visual information alone, and how researchers can study this. The workshop was bookended with information about how to access a career in research, and discussion of this was positive. The URL below provides an example of the feedback received from an attendee. As part of this event, the lab also gave a presentation to staff members of Roche. This was open to all staff from all departments at Roche, so the audience was diverse. The talk, entitled 'Extracting the structure of the world around us: Lifelong Learning and brain plasticity' explained how we address this challenge using an interdisciplinary approach that combines behavioural paradigms, movement recording, multimodal brain imaging (MRI, EEG, MEG, TMS) and state-of-the-art computational methods. A lively Q&A session followed, and feedback on the day was very positive. The talk was given twice, to a total of 40 Roche members.
Year(s) Of Engagement Activity 2017
URL https://www.facebook.com/RocheGenerationeXt/videos/10159924056330727/
 
Description Tutorial at IJCNN 2015 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact 2 hour Tutorial on Learning in Indefinite Proximity Spaces at IJCNN 2015 (Int Joint Conf on Neural Networks), Killarney, Ireland.
Year(s) Of Engagement Activity 2015
 
Description Tutorial at IJCNN 2015 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact 2 hour Tutorial on Dynamical Systems and Learning in the Model Space at IJCNN 2015, Killarney, Ireland.
Year(s) Of Engagement Activity 2015
 
Description Tutorial at AI 2013 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact 4 hour Tutorial on Theory and Applications of State Space Models for
Time Series Data at AI 2013 (Australasian Conference on Artificial
Intelligence), 3-6 December, 2013, Dunedin, New Zealand
Year(s) Of Engagement Activity 2013
 
Description Visual learning for perceptual decisions in the human brain 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach international
Primary Audience Participants in your research or patient groups
Results and Impact Invited talk at the Washington University Imaging Centre

no actual impacts realised to date
Year(s) Of Engagement Activity 2011
 
Description What drives learning and plasticity in the human brain? 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Participants in your research and patient groups
Results and Impact Invited talk at British Science Festival 2011

no actual impacts realised to date
Year(s) Of Engagement Activity 2011