Using computer simulations for predicting interventions restoring healthy patterns of neural activity
Lead Research Organisation:
University of Oxford
Department Name: UNLISTED
Abstract
In many neurological disorders, the neurons change how they respond. For example, in Parkinson’s disease, the neurons in brain regions involved in initiation of movements start to produce oscillations in their activity. These oscillations make transmission of information more difficult and some of them are causing shaking of hands. One treatment for Parkinson’s disease involves electrical stimulation of the brain through implanted electrodes. The research in our unit aims in refining treatments like this one by making the stimulation dependent of the ongoing pattern of neural activity. The aim of this research programme is to use computer simulations to investigate how and when (in relation to ongoing activity) to provide the electrical stimulation to minimize the symptoms of the disease. Through simulations and analyses of mathematical models of brain networks, we will suggest ways of stimulations, which will be subsequently tested. We hope that the developed methods could be also applied to other neurological disorders.
Technical Summary
Many neurological disorders are characterized by abnormal patterns of oscillations in neural activity. However, due to the complexity of the circuits these oscillations originate from, it is often unclear how they are generated, and how to best control them. To understand dynamics of complex systems, mathematical and computational methods are routinely employed in more established areas of science and engineering, and they have been proved critical for developing effective mechanisms for control of oscillations. This programme will develop methodology for using computer simulations of neural circuits affected by neurological disorders to predict interventions optimally restoring healthy patterns of activity. It will initially focus on Parkinson’s disease, because the basal ganglia circuits producing abnormal activity in this disorder are relatively well understood. Computational models of the basal ganglia will be developed that will describe how it generates the pathological dynamics and how it responds to deep brain stimulation (DBS) and optogenetic stimulation. The unique aspect of these models is that they will be constrained by a wide range of the high quality experimental data directly available in the MRC Unit, and optimized to maximize their ability to predict responses to novel stimulation protocols. The models will be used to rapidly test candidate versions of closed-loop DBS in silico, and to identify how and when with respect to ongoing activity the stimulation should be provided to optimally restore neural activity normally present in healthy basal ganglia. The suggested closed-loop intervention protocols will be tested within the MRC Unit, and results will be iteratively used to further refine the procedure. Moreover, the programme will investigate how the developed methodology and theory can be generalized to other neurological disorders (e.g. essential tremor) and to other neural systems (e.g. hippocampus).
Publications
Bogacz R
(2020)
Dopamine role in learning and action inference.
in eLife
Bogacz R
(2017)
A tutorial on the free-energy framework for modelling perception and learning.
in Journal of mathematical psychology
Bogacz R
(2019)
Dopamine role in learning and action inference
Bogacz R
(2016)
Properties of Neurons in External Globus Pallidus Can Support Optimal Action Selection.
in PLoS computational biology
Chan MC
(2016)
Pharmacological targeting of the HIF hydroxylases--A new field in medicine development.
in Molecular aspects of medicine
Cieslak PE
(2018)
Selective Effects of the Loss of NMDA or mGluR5 Receptors in the Reward System on Adaptive Decision-Making.
in eNeuro
Duchet B
(2021)
Optimizing deep brain stimulation based on isostable amplitude in essential tremor patient models.
in Journal of neural engineering
Duchet B
(2020)
Phase-dependence of response curves to deep brain stimulation and their relationship: from essential tremor patient data to a Wilson-Cowan model.
in Journal of mathematical neuroscience
Duchet B
(2021)
Average beta burst duration profiles provide a signature of dynamical changes between the ON and OFF medication states in Parkinson's disease.
in PLoS computational biology
Related Projects
Project Reference | Relationship | Related To | Start | End | Award Value |
---|---|---|---|---|---|
MC_UU_12024/1 | 01/04/2015 | 31/03/2020 | £3,057,940 | ||
MC_UU_12024/2 | Transfer | MC_UU_12024/1 | 01/04/2015 | 31/03/2020 | £1,597,940 |
MC_UU_12024/3 | Transfer | MC_UU_12024/2 | 01/04/2015 | 31/03/2020 | £1,830,940 |
MC_UU_12024/4 | Transfer | MC_UU_12024/3 | 01/04/2015 | 31/03/2020 | £2,545,940 |
MC_UU_12024/5 | Transfer | MC_UU_12024/4 | 01/04/2015 | 31/03/2020 | £1,287,940 |
Description | Computational models of dynamics in brain networks underlying action selection |
Amount | £1,280,000 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 04/2020 |
End | 03/2025 |
Description | Evaluation of costs and benefits of actions in the basal ganglia |
Amount | £689,119 (GBP) |
Funding ID | BB/S006338/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 01/2020 |
End | 12/2023 |
Title | Behaviour and pupillometry in a bandit task |
Description | Behavioural data and pupil diliation obtained from humans performing learning and decision making task. |
Type Of Material | Database/Collection of data |
Year Produced | 2021 |
Provided To Others? | Yes |
Impact | No impact yet |
URL | https://data.mrc.ox.ac.uk/data-set/behaviour-and-pupillometry-bandit-task |
Title | Computer model of neural circuits affected by Parkinson's disease |
Description | The computer model describes neural circuits involved in generating pathological oscillations in Parkinson's disease. |
Type Of Material | Computer model/algorithm |
Year Produced | 2015 |
Provided To Others? | Yes |
Impact | The model allows other researchers to observe how the changes in parameters in the network affects the neural activity and oscillations in the simulated networks. |
URL | https://senselab.med.yale.edu/modeldb/ShowModel.cshtml?model=184491 |
Title | Effects of hunger on model-based and model-free decision-making |
Description | Behavioural data from an experiment investigating effects of hunger on contributions of different neural systems to decision making. |
Type Of Material | Database/Collection of data |
Year Produced | 2021 |
Provided To Others? | Yes |
Impact | No impact yet. |
URL | https://data.mrc.ox.ac.uk/data-set/effects-hunger-model-based-and-model-free-decision-making |
Title | Human LFP recordings from STN during sequential conflict task |
Description | Local field potentials recorded from human subthalamic nucleus in a sequential decision making paradigm. |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
Impact | No impact yet. |
URL | https://data.mrc.ox.ac.uk/data-set/human-lfp-recordings-stn-during-sequential-conflict-task |
Title | Model of learning in cortical neural networks |
Description | This computer model allows simulating learning in hierarchically organised neural circuits. The model is able to learn very efficiently (achieving equally good performance in image classification as top algorithms used in artificial intelligence). The code of Model is provided in Matlab, and is very easy to understand. |
Type Of Material | Computer model/algorithm |
Year Produced | 2017 |
Provided To Others? | Yes |
Impact | The model allows researches interested in cortical circuits to easily simulate learning in models of brain networks. |
URL | https://senselab.med.yale.edu/modeldb/ShowModel.cshtml?model=218084 |
Title | Simulations of the effects of deep brain stimulation |
Description | Online simulations showing how closed-loop deep brain stimulation affects amplitude of oscillations generated by the Kuramoto model (a computational model often used to study neural synchronisation). |
Type Of Material | Computer model/algorithm |
Year Produced | 2018 |
Provided To Others? | Yes |
Impact | This tool has been used multiple times during talks on conferences, as well public engagement events. |
URL | https://data.mrc.ox.ac.uk/data-set/kuramoto |
Title | The effects of hunger on experiential and explicit risk-taking |
Description | Set of behavioural data from an experiment investigating effects of hunger on risk taking. |
Type Of Material | Database/Collection of data |
Year Produced | 2021 |
Provided To Others? | Yes |
Impact | No impact yet. |
URL | https://data.mrc.ox.ac.uk/data-set/effects-hunger-experiential-and-explicit-risk-taking |
Title | Tremor data measured from essential tremor patients subjected to phase-locked deep brain stimulation |
Description | This data is from the study of Cagnan et al. where phase-locked DBS was delivered according to the tremor measured by an accelerometer attached to a patient's hand. Stimulation was delivered over a set of trials, with each trial consisting of 12 blocks of 5 second phase-locked stimulation at a randomly chosen phase from a set of 12. Each block of phase-locked stimulation was also separated by a 1 second interblock of no stimulation. The data consists of a signal and trigger time series, which corresponds to the accelerometer data for the dominant tremor axis and the stimulation triggers, respectively. The triggers are signals sent to the stimulation device. |
Type Of Material | Database/Collection of data |
Year Produced | 2019 |
Provided To Others? | Yes |
Impact | A unique dataset has been made available to a community of researchers, and will be of great interest to computational modellers. |
URL | https://data.mrc.ox.ac.uk/ |
Description | Computational modelling of confirmation bias in reinforcement learning |
Organisation | University of Oxford |
Department | Department of Experimental Psychology |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Develop mathematical models of confirmation bias in reinforcement learning |
Collaborator Contribution | Professor Chris Sumerfield related computational models to data from humans in learning tasks |
Impact | The collaboration resulted in a joint publication (PMID: 34758486). This is an interdisciplinary collaborabion which combines: - Computational neuroscience (Rafal Bogacz) - Psychology (Chris Summerfield) |
Start Year | 2020 |
Description | Neural bases of risky decision making |
Organisation | University of Oxford |
Department | Nuffield Department of Clinical Neurosciences |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Developing computational models of brain decision circuits predicting human behaviour during decision making involving risky option |
Collaborator Contribution | Prof Sanjay Manohar designed and supervised experimental studies testing predicitions of computational models. |
Impact | Outputs include 3 datasets from performed experiments which have been made available on the MRC Brain Network Dynamics Data Sharing Platform. The collaboration resulted in a joint publications: van Swieten, M. M., Bogacz, R., & Manohar, S. G. (2021). Hunger improves reinforcement-driven but not planned action. Cognitive, Affective, & Behavioral Neuroscience, 21(6), 1196-1206. Moeller, M., Grohn, J., Manohar, S., & Bogacz, R. (2021). An association between prediction errors and risk-seeking: Theory and behavioral evidence. PLoS computational biology, 17(7), e1009213. Moeller, M., Manohar, S., & Bogacz, R. (2022). Uncertainty-guided learning with scaled prediction errors in the basal ganglia. PLoS Computational Biology, 18(5), e1009816. This is an interdisciplinary collaborabion which combines: - Computational neuroscience (Rafal Bogacz) - Clinical Neuroscience (Sanjay Manohar) |
Start Year | 2020 |
Description | Using computational models to investigate the effects of dopaminergic receptors on decision making |
Organisation | Polish Academy of Sciences |
Country | Poland |
Sector | Public |
PI Contribution | Analysis of experimental data with computational models |
Collaborator Contribution | Performing experiments investigating effects of knocking out dopaminergic receptors on decision making |
Impact | Publication: Cieslak, P. E., Ahn, W. Y., Bogacz, R., & Parkitna, J. R. (2018). Selective effects of the loss of NMDA or mGluR5 receptors in the reward system on adaptive decision-making. eNeuro, 5(4). |
Start Year | 2017 |
Description | Using computational models to investigate the effects of dopaminergic receptors on decision making |
Organisation | Seoul National University |
Country | Korea, Republic of |
Sector | Academic/University |
PI Contribution | Analysis of experimental data with computational models |
Collaborator Contribution | Performing experiments investigating effects of knocking out dopaminergic receptors on decision making |
Impact | Publication: Cieslak, P. E., Ahn, W. Y., Bogacz, R., & Parkitna, J. R. (2018). Selective effects of the loss of NMDA or mGluR5 receptors in the reward system on adaptive decision-making. eNeuro, 5(4). |
Start Year | 2017 |
Description | Generating Genius School Visit during MRC Festival Week (commencing week 20 June 2016) |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Schools |
Results and Impact | Generating Genius, http://www.generatinggenius.org.uk/ a charity that works with high-achieving secondary school students from disadvantaged backgrounds to help them acquire the skills they need to win places on STEM courses at top universities. 22 Students from two schools attended the open day on 22 June 2016. A group of bright GCSE students from the pre-16 strand of the programme called Junior Genius. A range of hands-on practical sessions, lab tours and talks will be run by Unit members at all levels to provide the children with an insight into the nature and benefits of medical/brain research, and inspire them to pursue a career in science. |
Year(s) Of Engagement Activity | 2016 |
URL | http://www.generatinggenius.org.uk/ |
Description | Longwick Church of England Combined School Visit - October 2018 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | Longwick Church of England Combined School visited by myself and Peter Brown's PhD student Saed Khawaldeh. Together with Saed Khawaldeh we met with about 50 pupils from Years 5 and 6. During the visit, Saed and I led the pupils in discussions about how the brain is built and how it controls movements. The pupils experimented with brain-computer interfaces, and explored how a robotic arm can be controlled by electrical signals in muscles that are triggered by the brain. The pupils were also given opportunities to build pipecleaner models of nerve cell networks, and to see some of the Unit's brain tissue archive. Year 5 teacher Ms Emma Pughe commented: "The children really enjoyed the visit and were very inspired to hear about the research. We invited the parents into school on Friday so that the children could share what they had learnt in Science Week. I could hear lots of the children telling their parents about the brains and robotic arms." |
Year(s) Of Engagement Activity | 2018 |
URL | https://www.mrcbndu.ox.ac.uk/news/units-researchers-visit-local-primary-school-longwick |
Description | MRC Festival Medical Research Parkinsons Disease Open Day visit (19 June 2018) |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Patients, carers and/or patient groups |
Results and Impact | 27 Lay members of the Oxford, Banbury and Reading groups of the charity Parkinson's UK visited MRC, BNDU for an Open Day visit to learn more about the Unit's research on the causes and treatment of Parkinson's disease. Two short presentations on "Deep Brain Stimulation as a therapy for Parkinson's" and "Use of animals in Parkinson's research". Followed by tour of the Unit's laboratories and microscope facilities. For those who were not able to attend the lab tours were treated to a live demonstration of Transcranial Magnetic Stimulation of the brain. The visit concluded with a final Q & A session, and a chance for the visitors to give their feedback. The Unit also took the opportunity to promote its local networks for Patient and Public Involvement (PPI) in research which resulted in half of the attendees signing up for PPI. |
Year(s) Of Engagement Activity | 2018 |
URL | http://www.mrcbndu.ox.ac.uk/news |
Description | STEM placements for local school pupils (in2science) |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | Each year our group hosts 1 or 2 pupils from local schools in Oxford. The placement scheme was tailored for pupils from local state-funded schools to support their progress into university degrees and careers in science, technology, engineering and mathematics (STEM). During their time in the Unit, the pupils worked alongside Unit scientists and received personalised mentoring to gain a wide variety of practical experiences and learn more about key concepts and challenges in neuroscience and medical research. In a series of integrated workshops with in2scienceUK, the pupils also received guidance on university applications, wider information about STEM careers, and training in transferable skills. The pupils recorded their experiences and progress in blogs and images. |
Year(s) Of Engagement Activity | 2016,2017,2018,2019,2022 |
URL | https://www.mrcbndu.ox.ac.uk/news/unit-hosts-school-pupils-fourth-year-stem-placement-scheme |
Description | STEM placements for local school pupils (in2science) (2016) |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Postgraduate students |
Results and Impact | Hosted 5 pupils from 4 local schools in Oxford. The placement scheme hosted at the Unit was a first for Oxford, and was tailored for pupils from local state-funded schools to support their progress into university degrees and careers in science, technology, engineering and mathematics (STEM). During their time in the Unit, the pupils worked alongside Unit scientists and received personalised mentoring to gain a wide variety of practical experiences and learn more about key concepts and challenges in neuroscience and medical research. In a series of integrated workshops with in2scienceUK, the pupils also received guidance on university applications, wider information about STEM careers, and training in transferable skills. The pupils recorded their experiences and progress in blogs and images. |
Year(s) Of Engagement Activity | 2016 |
URL | http://www.mrcbndu.ox.ac.uk/news |
Description | STEM placements for local school pupils (in2science) (2017) |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | A group of 5 students from local schools within the Oxfordshire area was enrolled on a 2-week programme (non-residential) during which they were given: - Personalised mentoring from scientists - Opportunities to gain a wide variety of practical experiences as well as exposure to key concepts and challenges in research - Integrated workshops with in2scienceUK, where the pupils receive guidance on university applications, wider information about STEM careers, and training in transferable skills. In2science partners with academic institutions to give sixth-form students from low income backgrounds the opportunity to work alongside STEM scientists, with a view to inspiring/coaching them to get into top universities. |
Year(s) Of Engagement Activity | 2017 |
URL | http://in2scienceuk.org/ |
Description | STEM placements for local school pupils (in2science) (2018) |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Postgraduate students |
Results and Impact | Hosted 3 pupils from 3 local schools in Oxford. The placement scheme hosted at the Unit was a first for Oxford, and was tailored for pupils from local state-funded schools to support their progress into university degrees and careers in science, technology, engineering and mathematics (STEM). During their time in the Unit, the pupils worked alongside Unit scientists and received personalised mentoring to gain a wide variety of practical experiences and learn more about key concepts and challenges in neuroscience and medical research. In a series of integrated workshops with in2scienceUK, the pupils also received guidance on university applications, wider information about STEM careers, and training in transferable skills. The pupils recorded their experiences and progress in blogs and images. |
Year(s) Of Engagement Activity | 2018 |
URL | https://www.mrcbndu.ox.ac.uk/news?page=1 |
Description | School Open Day - 16 March 2017 |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | 120 GCSE/A level students from 8 local schools within Oxfordshire area attended the school open day. A range of hands-on practical sessions, lab tours and talks ran by Unit members at all levels to provide the children with an insight into the nature and benefits of medical/brain research, and inspire them to pursue a career in science. Also in attendance were local County Cllr Lorraine Lindsay-Gale , City Councillors Pat Kennedy and Louise Upton. |
Year(s) Of Engagement Activity | 2017 |
URL | http://www.mrcbndu.ox.ac.uk/news |
Description | School Open Day - 17 March 2016 |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | 140 GCSE/A level students from 12 local schools within Oxfordshire area attended the school open day. A range of hands-on practical sessions, lab tours and talks ran by Unit members at all levels to provide the children with an insight into the nature and benefits of medical/brain research, and inspire them to pursue a career in science. Also in attendance were local Oxfordshire MP (Rt. Hon Mr Andrew Smith) and Councillor (Mr Bob Price) attended the school open day. |
Year(s) Of Engagement Activity | 2016 |
URL | http://www.mrcbndu.ox.ac.uk/outreach |
Description | Schools Open Day |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | Each year around 70 GCSE/A level students from 6 local schools within Oxfordshire area attended the school open day. A range of hands-on practical sessions, lab tours and talks ran by Unit members at all levels to provide the children with an insight into the nature and benefits of medical/brain research, and inspire them to pursue a career in science. Also in attendance in 2018 were the Mrs Jean Fooks - Lord Mayor of Oxford, Cllr Chris Wright - Chair of Garsington Parish Council and Cllr Elizabeth Gillespie - South Oxfordshire District Council. |
Year(s) Of Engagement Activity | 2016,2017,2018,2022 |
URL | http://www.mrcbndu.ox.ac.uk/news |
Description | Visit to St Joseph Primary School - September 2016 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | On 20 September 2016, I visited St Joseph's Primary School in Oxford to give a talk and did some activities explaining how neurons learn by forming connections. During the school visit introduction to the brain and research conducted by MRC Brain Network Dynamics Unit was given to 60 students. There was a lot of questions and discussion after the presentation. The goal of the visit was to inspire the students and encourage them to consider choosing a career in science. |
Year(s) Of Engagement Activity | 2016 |