Dynamic Neuromodulation
Lead Research Organisation:
University of Oxford
Department Name: Clinical Neurosciences
Abstract
It is estimated that 4% of UK's population suffer from essential tremor while approximately 127,000 people live with Parkinson's disease, making long-term treatment of these conditions one of the key challenges facing the healthcare system. Deep brain stimulation is a commonly used therapeutic intervention, which involves electrical stimulation of key brain regions. State of the art stimulation patterns attenuate brain activity that drives disease symptoms and lead to symptom suppression. However, stimulation also suppresses brain activity not linked with motor symptoms of Parkinson's disease and essential tremor, inducing side effects in up to 50 % of the patients treated with deep brain stimulation. I believe developing therapeutic strategies that selectively target brain activity driving disease symptoms could reduce stimulation-induced side effects and significantly improve patients' quality of life.
This proposal emerges from a clinical need to improve stimulation specificity in order to reduce side effects experienced by patients, and to expand the use of this powerful therapeutic intervention to other difficult to treat neurological disorders. The first aim of the proposal is to selectively suppress disease related brain activity by carefully timing stimulation. Critically, I aim to achieve state-dependent deep brain stimulation, which adjusts key aspects of the therapy (e.g. how much stimulation is delivered and pattern of stimulation) dynamically according to patients' symptom severity. Neuromodulation can be used not only to suppress brain activities driving disease symptoms but also to enhance neural activity that play a critical role in controlling our every day actions. I aim to develop stimulation techniques in order to selectively enhance neural processes believed to contribute to behaviors such as response inhibition and action selection. The possibility of promoting neural activity to compensate for impairment may play an important role in the future for managing treatment-refractory disorders such as obsessive-compulsive disorder and impulsivity.
The second aim of the proposal is to learn from fundamental neural processes in order to design more "natural" therapeutic interventions. Brain activity driving motor symptoms of Parkinson's disease and essential tremor can be spontaneously suppressed. For instance, when patients with tremor make a movement, tremor amplitude reduces significantly. Therapeutic interventions inspired by natural processes that take place in our brains even during disease, may provide an effective method for reducing disease symptoms while sparing brain activity not linked to disease processes.
This research programme will generate exciting theoretical and experimental tools, which could be used to understand how different brain regions communicate and control behavior. Critically, the notion of mimicking the way our brains readily control disease related neural activity through stimulation is an innovative path that could lead to the development of new types of therapeutic interventions not only for Parkinson's disease and essential tremor but also for other movement and psychiatric disorders driven by similar types of brain activity.
This proposal emerges from a clinical need to improve stimulation specificity in order to reduce side effects experienced by patients, and to expand the use of this powerful therapeutic intervention to other difficult to treat neurological disorders. The first aim of the proposal is to selectively suppress disease related brain activity by carefully timing stimulation. Critically, I aim to achieve state-dependent deep brain stimulation, which adjusts key aspects of the therapy (e.g. how much stimulation is delivered and pattern of stimulation) dynamically according to patients' symptom severity. Neuromodulation can be used not only to suppress brain activities driving disease symptoms but also to enhance neural activity that play a critical role in controlling our every day actions. I aim to develop stimulation techniques in order to selectively enhance neural processes believed to contribute to behaviors such as response inhibition and action selection. The possibility of promoting neural activity to compensate for impairment may play an important role in the future for managing treatment-refractory disorders such as obsessive-compulsive disorder and impulsivity.
The second aim of the proposal is to learn from fundamental neural processes in order to design more "natural" therapeutic interventions. Brain activity driving motor symptoms of Parkinson's disease and essential tremor can be spontaneously suppressed. For instance, when patients with tremor make a movement, tremor amplitude reduces significantly. Therapeutic interventions inspired by natural processes that take place in our brains even during disease, may provide an effective method for reducing disease symptoms while sparing brain activity not linked to disease processes.
This research programme will generate exciting theoretical and experimental tools, which could be used to understand how different brain regions communicate and control behavior. Critically, the notion of mimicking the way our brains readily control disease related neural activity through stimulation is an innovative path that could lead to the development of new types of therapeutic interventions not only for Parkinson's disease and essential tremor but also for other movement and psychiatric disorders driven by similar types of brain activity.
Technical Summary
I aim to utilize dynamic changes in neural synchrony to selectively modulate neural networks underlying oscillopathies such as essential tremor and Parkinson's disease. Specifically,
1) I will develop an on-line tracking system that a) determines the extent of cerebello-thalamo-cortical synchrony underlying essential tremor from peripheral measurements, and b) maps muscle activity to principal movement axis, in order to control the timing and pattern of stimulation delivered to thalamus according to the dynamic state of the tremor network.
2) Utilizing the fact that neural synchrony can be selectively enhanced or suppressed with phase specific deep brain stimulation, I will modulate transient synchrony between the medio pre-frontal cortex and subthalamic nucleus, implicated in decision making, in order to determine whether physiological transient synchrony is causally linked to behavior or epiphenomenal.
3) I will a) identify cortical lamina specific processes related to spontaneous suppression of pathological neural oscillations observed during Parkinson's disease, and b) replicate aspects of these interactions through stimulation in 6-OHDA-rat model of Parkinson's disease in order to establish the causal importance of lamina specific processes in termination of pathological neural oscillations and in motor impairment.
4) I will combine OPM-MEG and EMG in order to explore cortical dynamics impacting the severity of tremor. Detailed models of the thalamo-cortical circuit will be utilized in order to determine neural dynamics underlying tremor suppression during voluntary movement with the view to harness these dynamic changes to develop selective neuromodulation strategies in the future.
1) I will develop an on-line tracking system that a) determines the extent of cerebello-thalamo-cortical synchrony underlying essential tremor from peripheral measurements, and b) maps muscle activity to principal movement axis, in order to control the timing and pattern of stimulation delivered to thalamus according to the dynamic state of the tremor network.
2) Utilizing the fact that neural synchrony can be selectively enhanced or suppressed with phase specific deep brain stimulation, I will modulate transient synchrony between the medio pre-frontal cortex and subthalamic nucleus, implicated in decision making, in order to determine whether physiological transient synchrony is causally linked to behavior or epiphenomenal.
3) I will a) identify cortical lamina specific processes related to spontaneous suppression of pathological neural oscillations observed during Parkinson's disease, and b) replicate aspects of these interactions through stimulation in 6-OHDA-rat model of Parkinson's disease in order to establish the causal importance of lamina specific processes in termination of pathological neural oscillations and in motor impairment.
4) I will combine OPM-MEG and EMG in order to explore cortical dynamics impacting the severity of tremor. Detailed models of the thalamo-cortical circuit will be utilized in order to determine neural dynamics underlying tremor suppression during voluntary movement with the view to harness these dynamic changes to develop selective neuromodulation strategies in the future.
Planned Impact
1) Patients suffering from Parkinson's disease and essential tremor
Approximately 12.5M people live with a neurological condition in the UK, which poses a significant burden both on the individual and the society as a whole. Essential tremor and Parkinson's disease are two common neurological disorders, making long-term treatment of these conditions one of the key challenges facing the healthcare system. Deep brain stimulation is an effective treatment technique, which involves high frequency electrical stimulation of key brain regions. Clinically used stimulation patterns are not specific to essential tremor and Parkinson's disease pathophysiology, which may induce side effects in up to 50% of the implanted patients. Moreover, key stimulation parameters such as stimulation intensity and pattern are not dynamically adjusted according to patient's symptom severity and state of the pathological network.
An important property of the motor circuit is that symptom suppression could be achieved transiently: e.g. essential and parkinsonian tremor is dampened during voluntary movement. Learning from these natural processes, provides the potential to modulate neural systems in a more finessed "physiological" fashion.
I have recently provided the first proof of concept for a novel stimulation strategy, which selectively targets tremor pathophysiology through delivery of well timed stimuli to key brain regions - phase specific deep brain stimulation. The proposed research programme aims to address several critical challenges faced in the neuromodulation research field. Specifically I aim to (1) dynamically alter phase specific deep brain stimulation patterns according to the state of the pathological network in order to achieve sustained symptom suppression and reduce treatment side-effects; (2) determine how our brains naturally keep pathological neural activity under control in order to develop novel neuromodulation strategies inspired by nature. Such improvements would increase patients' overall quality of life by reducing side effects of treatment and therefore making this proposal of immediate interest to patient groups such as Parkinson's disease and essential tremor.
2) Benefit to other patient groups
State-dependent deep brain stimulation would aim to adjust stimulation parameters according to the dynamic state of the disease network and patient's symptom severity. Several other patient groups, currently being treated with deep brain stimulation, may potentially benefit from state-dependent deep brain stimulation, such as dystonia, dyskinesia, obsessive-compulsive disorder and epilepsy. Neuromodulation techniques developed in this proposal to selectively control physiological neural synchrony could also potentially be used to manage symptoms of other disorders not currently treated with deep brain stimulation such as impulsivity.
3) Healthcare industry
Enclosed research proposal is relevant for medical device companies, developing brain pacemakers (Medtronic, St. Jude and Boston Scientific). Critically, stimulation based modulation of the nervous system is gathering interest from other industries such as the pharmaceutical industry, as evident from the recent investment by Google and GlaxoSmithKline into bioelectrical medicine and establishment of Galvani bioelectronics. Galvani bioelectronics will aim to restore health through electrical stimulation of nerve fibers. As such, dynamic neuromodulation is of direct relevance for a broad range of industries.
4) Wider Public
Outlined projects would be of interest to the wider public as it demonstrates how translational research could improve therapeutic interventions. Critically, as a multidisciplinary researcher with an engineering background, I believe this type of research would interest young students and demonstrate broad range of research one could conduct after pursuing a science degree.
Approximately 12.5M people live with a neurological condition in the UK, which poses a significant burden both on the individual and the society as a whole. Essential tremor and Parkinson's disease are two common neurological disorders, making long-term treatment of these conditions one of the key challenges facing the healthcare system. Deep brain stimulation is an effective treatment technique, which involves high frequency electrical stimulation of key brain regions. Clinically used stimulation patterns are not specific to essential tremor and Parkinson's disease pathophysiology, which may induce side effects in up to 50% of the implanted patients. Moreover, key stimulation parameters such as stimulation intensity and pattern are not dynamically adjusted according to patient's symptom severity and state of the pathological network.
An important property of the motor circuit is that symptom suppression could be achieved transiently: e.g. essential and parkinsonian tremor is dampened during voluntary movement. Learning from these natural processes, provides the potential to modulate neural systems in a more finessed "physiological" fashion.
I have recently provided the first proof of concept for a novel stimulation strategy, which selectively targets tremor pathophysiology through delivery of well timed stimuli to key brain regions - phase specific deep brain stimulation. The proposed research programme aims to address several critical challenges faced in the neuromodulation research field. Specifically I aim to (1) dynamically alter phase specific deep brain stimulation patterns according to the state of the pathological network in order to achieve sustained symptom suppression and reduce treatment side-effects; (2) determine how our brains naturally keep pathological neural activity under control in order to develop novel neuromodulation strategies inspired by nature. Such improvements would increase patients' overall quality of life by reducing side effects of treatment and therefore making this proposal of immediate interest to patient groups such as Parkinson's disease and essential tremor.
2) Benefit to other patient groups
State-dependent deep brain stimulation would aim to adjust stimulation parameters according to the dynamic state of the disease network and patient's symptom severity. Several other patient groups, currently being treated with deep brain stimulation, may potentially benefit from state-dependent deep brain stimulation, such as dystonia, dyskinesia, obsessive-compulsive disorder and epilepsy. Neuromodulation techniques developed in this proposal to selectively control physiological neural synchrony could also potentially be used to manage symptoms of other disorders not currently treated with deep brain stimulation such as impulsivity.
3) Healthcare industry
Enclosed research proposal is relevant for medical device companies, developing brain pacemakers (Medtronic, St. Jude and Boston Scientific). Critically, stimulation based modulation of the nervous system is gathering interest from other industries such as the pharmaceutical industry, as evident from the recent investment by Google and GlaxoSmithKline into bioelectrical medicine and establishment of Galvani bioelectronics. Galvani bioelectronics will aim to restore health through electrical stimulation of nerve fibers. As such, dynamic neuromodulation is of direct relevance for a broad range of industries.
4) Wider Public
Outlined projects would be of interest to the wider public as it demonstrates how translational research could improve therapeutic interventions. Critically, as a multidisciplinary researcher with an engineering background, I believe this type of research would interest young students and demonstrate broad range of research one could conduct after pursuing a science degree.
Organisations
- University of Oxford (Lead Research Organisation)
- UNIVERSITY OF OXFORD (Collaboration)
- Francis Crick Institute (Collaboration)
- Max Planck Society (Collaboration)
- University College London (Collaboration)
- University of Luxembourg (Collaboration)
- Queen's Hospital (Collaboration)
- Radboud University Nijmegen (Collaboration)
- Medical Research Council (MRC) (Collaboration)
- IMPERIAL COLLEGE LONDON (Collaboration)
- Imperial College London (Fellow)
People |
ORCID iD |
Hayriye Cagnan (Principal Investigator / Fellow) |
Publications
Fleming JE
(2023)
From dawn till dusk: Time-adaptive bayesian optimization for neurostimulation.
in PLoS computational biology
Holt AB
(2019)
Phase-Dependent Suppression of Beta Oscillations in Parkinson's Disease Patients.
in The Journal of neuroscience : the official journal of the Society for Neuroscience
Jafarian A
(2020)
Comparing dynamic causal models of neurovascular coupling with fMRI and EEG/MEG.
in NeuroImage
Katsanevaki C
(2022)
Attentional effects on local V1 microcircuits explain selective V1-V4 communication
Parr T
(2019)
Dynamic Causal Modelling of Active Vision.
in The Journal of neuroscience : the official journal of the Society for Neuroscience
Pedrosa DJ
(2018)
A functional micro-electrode mapping of ventral thalamus in essential tremor.
in Brain : a journal of neurology
Reis C
(2019)
Thalamocortical dynamics underlying spontaneous transitions in beta power in Parkinsonism.
in NeuroImage
Reis C
(2021)
Essential tremor amplitude modulation by median nerve stimulation.
in Scientific reports
Description | 1st year Biomedical course |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Influenced training of practitioners or researchers |
Impact | I have given two lectures on neural modelling to a group of students who are enrolled in the Biomedical Undergraduate Degree at the University of Oxford. |
Description | Academy of Finland |
Geographic Reach | Europe |
Policy Influence Type | Participation in a guidance/advisory committee |
Description | Academy of Finland |
Geographic Reach | Europe |
Policy Influence Type | Participation in a guidance/advisory committee |
Description | Donders Cognition Brain and Technology School |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Influenced training of practitioners or researchers |
Impact | This course is aimed towards PhD students, early career researchers and industry. |
Description | EC |
Geographic Reach | Local/Municipal/Regional |
Policy Influence Type | Membership of a guideline committee |
Impact | Through the Executive Committee, we aim to impact education of our unit members together with decisions on public engagement, knowledge transfer and day-to-day operation of the unit. |
Description | EDI |
Geographic Reach | Local/Municipal/Regional |
Policy Influence Type | Membership of a guideline committee |
Impact | Through best practices into "Equality, Diversity and Inclusivity", we are aiming to improve education of our workforce. |
Description | EngSci - 3YP |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Influenced training of practitioners or researchers |
Impact | Students taking part in this course design new medical devices in groups of four, getting hands on experience on device design together with extensive mentoring from experts in the field. |
Description | EngSci - 3YP |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Influenced training of practitioners or researchers |
Impact | Students taking part in this course design new medical devices in groups of four, getting hands on experience on device design together with extensive mentoring from experts in the field. |
Description | EngSci - 3YP |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Influenced training of practitioners or researchers |
Impact | Students taking part in this course design new medical devices in groups of four, getting hands on experience on device design together with extensive mentoring from experts in the field. |
Description | GSC |
Geographic Reach | Local/Municipal/Regional |
Policy Influence Type | Membership of a guideline committee |
Description | MSC in Neuroscience |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Influenced training of practitioners or researchers |
Impact | I have given a lecture on Basal Ganglia pathophysiology to a group of students who are enrolled in the MSc in Neuroscience programme at the University of Oxford. Majority of students who attended the lecture are currently undertaking research on this topic. |
Description | MSc Neuroscience |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Influenced training of practitioners or researchers |
Impact | Majority of students who attended the lecture are currently undertaking research on brain stimulation strategies and theoretical neural modelling. |
Description | MSc Neuroscience |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Influenced training of practitioners or researchers |
Impact | Majority of students who attended the lecture are currently undertaking research on brain stimulation strategies and theoretical neural modelling. |
Description | MSc in Neuroscience |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Influenced training of practitioners or researchers |
Impact | I have given a lecture on brain stimulation strategies and theoretical neural modelling to a group of students who are enrolled in the MSc in Neuroscience programme at the University of Oxford. Majority of students who attended the lecture are currently undertaking research on these topics. |
Description | MSc in Neuroscience 2020 |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Influenced training of practitioners or researchers |
Impact | I have given a lecture on Basal Ganglia pathophysiology and an other one on theoretical neural modelling to a group of students who are enrolled in the MSc in Neuroscience programme at the University of Oxford. Majority of students who attended the lecture are currently undertaking research on these topics. |
Description | OA |
Geographic Reach | Local/Municipal/Regional |
Policy Influence Type | Membership of a guideline committee |
Impact | We are aiming to educate our workforce on best practices for open access publishing and reproducible science. |
Description | SPM course 2018 |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Influenced training of practitioners or researchers |
Impact | I organised the SPM 2018 course which had 24 attendees from around the world . Main topics covered during the course were how to analyse and model neuroimaging data with extensive theoretical and practical segments . |
Description | inBrain |
Geographic Reach | Europe |
Policy Influence Type | Participation in a guidance/advisory committee |
Description | Biological Technologies Grant |
Amount | $896,863 (USD) |
Organisation | Defense Advanced Research Projects Agency (DARPA) |
Sector | Public |
Country | United States |
Start | 04/2020 |
End | 09/2021 |
Description | Changing rhythms in Parkinson's disease: development of motor and non-motor digital progression biomarkers based on continuous, real-life monitoring |
Amount | $850,000 (USD) |
Funding ID | MJFF-020425 |
Organisation | Radboud University Nijmegen Medical Center |
Sector | Academic/University |
Country | Netherlands |
Start | 11/2021 |
End | 05/2024 |
Description | ISSF |
Amount | Ā£65,000 (GBP) |
Organisation | University of Oxford |
Sector | Academic/University |
Country | United Kingdom |
Start | 03/2021 |
End | 08/2022 |
Description | Medical and Life Sciences Translational Fund |
Amount | Ā£75,000 (GBP) |
Organisation | University of Oxford |
Sector | Academic/University |
Country | United Kingdom |
Start | 10/2020 |
End | 09/2021 |
Description | NeuroMod+: Co-creation for next-generation neuromodulation therapeutics |
Amount | Ā£1,265,848 (GBP) |
Funding ID | EP/W035057/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 11/2022 |
End | 10/2025 |
Description | Travel Grant |
Amount | Ā£1,000 (GBP) |
Organisation | Guarantors of Brain |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 10/2019 |
End | 10/2019 |
Title | Theoretical model of motor cortex |
Description | This paper accompanies our recently published paper on "When do bursts matter in the primary motor cortex? Investigating changes in the intermittencies of beta rhythms associated with movement states" |
Type Of Material | Computer model/algorithm |
Year Produced | 2023 |
Provided To Others? | Yes |
Impact | This model has already been requested by other researchers for further use. |
URL | https://zenodo.org/record/7509926#.ZA805y-l2X0 |
Title | Theoretical model of stimulating at the right time |
Description | This model accompanies our recently published paper on "Stimulating at the right time to recover network states in a model of the cortico-basal ganglia-thalamic circuit" |
Type Of Material | Computer model/algorithm |
Year Produced | 2022 |
Provided To Others? | Yes |
Impact | This model has already been requested by other researchers for further use. |
URL | https://doi.org/10.5281/zenodo.5971846 |
Title | Theoretical model of tremor |
Description | This theoretical model aims to characterise the interaction between key brain regions implicated in pathological tremor. |
Type Of Material | Computer model/algorithm |
Year Produced | 2020 |
Provided To Others? | Yes |
Impact | This theoretical model is being utilised to explore different types of stimulation strategies for effective treatment of tremor. The enclosed link is updated as the model is developed by my research team. A manuscript detailing this work is currently under preparation and the final model will be shared via GitHub and the MRC BNDU data sharing platform. |
URL | https://github.com/cagnan-lab/PeripheralStim_ABC |
Title | Transient changes in biomarkers of Parkinson's disease |
Description | This model explores brief changes in the cortico-thalamic-basal ganglia network which underlie spontaneous changes in beta power. It is important to understand these dynamic changes since patient symptom severity is linked to power in the beta frequency band. This model is also used to determine the efficacy of novel stimulation strategies and how these depend on the dynamic state of the brain circuit. |
Type Of Material | Computer model/algorithm |
Year Produced | 2020 |
Provided To Others? | Yes |
Impact | The enclosed link is updated as the model is developed by my research team. The paper describing the model is currently in submission and final model will be made freely available via GitHub and the MRC BNDU database. |
URL | https://github.com/cagnan-lab/ABC_Inference_Neural_Paper |
Description | 6OHDA lesion animal model - Peter Magill (MRC BNDU) |
Organisation | University of Oxford |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | I have developed a data analysis pipeline, which has been used to analyse simultaneously recorded electrophysiological data. My PhD student Carolina Reis extended these analysis techniques to different parts of the disease circuit implicated in Parkinsonism. My postdoc Timothy West developed computational models of Parkinsonism with the aim of using these models to test novel therapies in silico. |
Collaborator Contribution | Prof Pete Magill has provided the archival simultaneously recorded electrophysiological data, obtained from the 6-OHDA lesioned rodent model of Parkinson's disease. |
Impact | Three journal publications (Cagnan et al 2019, Reis et al 2019, West et al 2022) and one thesis chapter (Reis 2021) have been published. This research blends together theoretical neuroscience, electrophysiology and biomedical informatics to explore information exchange during Parkinson's disease. Techniques developed have enabled us to explore information exchange across multiple brain regions and novel treatment strategies. By using archival data, we are reducing the use of animals as part of our commitment to the 3Rs. The research carried out is multi-disciplinary and spans disciplines such as physics, mathematics, and basic neuroscience. |
Start Year | 2018 |
Description | 6OHDA lesioned animal model of PD - Dr Andrew Sharott |
Organisation | Medical Research Council (MRC) |
Department | MRC Brain Network Dynamics Unit at the University of Oxford (BNDU) |
Country | United Kingdom |
Sector | Public |
PI Contribution | I have developed a data analysis pipeline, which is currently being used to analyse electrophysiological data, obtained from the unilaterally lesioned 6-OHDA rodent model of Parkinson's disease. I am currently co-supervising a PhD student who is extending this work to explore cognitive symptoms of Parkinson's disease. |
Collaborator Contribution | Dr Andrew Sharott has provided the archival electrophysiological data, obtained from the unilaterally lesioned 6-OHDA rodent model of Parkinson's disease and contributed to the development of the data analysis pipeline. My collaborators is also co-supervising the PhD student who has been recruited to extend our work to explore cognitive symptoms of Parkinson's disease. |
Impact | This collaboration has resulted in a conference proceeding presented at the Neuroscience 2015 Conference in Chicago and Neuroscience 2017 Conference in Washington DC. Additionally, the work has been presented during various workshops and talks such as the MRC Brain Network Dynamics Unit Science Day. Three journal publications (Cagnan et al 2019, Reis et al 2019, West et al 2022) and one thesis chapter (Reis 2021) have been published. This research blends together electrophysiology and biomedical informatics to explore information exchange during Parkinson's disease. The techniques developed have enabled us to explore information exchange across multiple brain regions that play a key role in both disease pathophysiology and treatment. This collaboration has resulted in recruitment of one PhD student who will extend this work to explore cognitive symptoms of Parkinson's disease. |
Start Year | 2015 |
Description | ASAP collaboration |
Organisation | Francis Crick Institute |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | I am contributing to the study design and grant proposal. |
Collaborator Contribution | My collaborators are contributing to the study design and grant proposal. |
Impact | This collaboration aims to explore longitudinal changes in Parkinson's disease with a specific focus on disease circuits. Our hypothesis is that differences in disease progression can be linked to whole brain microstructure, circuit dynamics and cellular pathways. A grant application was submitted to support this new line of research, which was unfortunately not successful at the final application stage. |
Start Year | 2020 |
Description | ASAP collaboration |
Organisation | Max Planck Society |
Department | Max Plank Institute for Human Cognitive and Brain Sciences |
Country | Germany |
Sector | Academic/University |
PI Contribution | I am contributing to the study design and grant proposal. |
Collaborator Contribution | My collaborators are contributing to the study design and grant proposal. |
Impact | This collaboration aims to explore longitudinal changes in Parkinson's disease with a specific focus on disease circuits. Our hypothesis is that differences in disease progression can be linked to whole brain microstructure, circuit dynamics and cellular pathways. A grant application was submitted to support this new line of research, which was unfortunately not successful at the final application stage. |
Start Year | 2020 |
Description | ASAP collaboration |
Organisation | University College London |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | I am contributing to the study design and grant proposal. |
Collaborator Contribution | My collaborators are contributing to the study design and grant proposal. |
Impact | This collaboration aims to explore longitudinal changes in Parkinson's disease with a specific focus on disease circuits. Our hypothesis is that differences in disease progression can be linked to whole brain microstructure, circuit dynamics and cellular pathways. A grant application was submitted to support this new line of research, which was unfortunately not successful at the final application stage. |
Start Year | 2020 |
Description | Morpheus, Magneto and Dexterity - Timothy Denison |
Organisation | University of Oxford |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | I have contributed to study design and preparation of grant proposals for additional funding. |
Collaborator Contribution | Prof Denison has contributed to study design and preparation of grant proposals for additional funding. |
Impact | This collaboration aims to apply our expertise in stimulation strategies: (1) to characterise the impact of stimulation on patient's sleep quality and alertness - Morpheus (2) to develop a novel transcranial magnetic stimulation device - Magneto (3) to develop a noninvasive stimulation device for treatment of tremor - Dexterity This partnership has resulted in additional research funding for all three streams of research. I am a co-investigator on two and a principal investigator on one of these proposals. Our work brings together the following expertise: device development, biomedical engineering, neuroscience. We have recruited two PhD students and several fourth year engineering students as a result of this collaboration. While technical development is still on going for all three projects, patient and data collection was on hold due to Covid-19 up to late 2021. This will have significant impact on project timeline and output. We are currently preparing a funding application for the third stream and are in the beginning stages of collecting patient data for stream two (ethics completed). |
Start Year | 2018 |
Description | Neuromod + |
Organisation | Imperial College London |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Contributed to a grant application for an EPSRC/MRC Network + creation |
Collaborator Contribution | Contributed to a grant application for an EPSRC/MRC Network + creation |
Impact | The EPSRC & MRC NEUROMOD+ Network is a new UK network aiming to build capacity and bring together multidisciplinary stakeholder groups to support the co-creation of novel neuromodulation therapies. NEUROMOD+ will promote and facilitate discussion between stakeholders, and instigate new collaborative research partnerships, through a range of activities including co-creation events, workshops and funding calls. We have recently launched the network and had our first event. |
Start Year | 2022 |
Description | Optically Pumped Magnetometers - Gareth Barnes and Simon Farmer (University College London) |
Organisation | University College London |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | This project involves the use of a novel neuroimaging system, optically pumped magnetometers, to better understand the disease circuit underlying pathological tremor (e.g. Essential Tremor and Parkinson's disease). My research team has contributed to the study design and has completed the ethics application, which has been approved by the local ethics committee. Marielle Stam and Deniz Kucukahmetler who worked as interns in my research group designed the task which will be used in these experiments in collaboration with my postdoctoral research associate Timothy West. Timothy West is also building a new theoretical model of the tremor circuit which will be used to further explore this dataset. |
Collaborator Contribution | Prof Barnes and Prof Farmer contributed to study design, and Prof Farmer will be identifying patients recruited for the study. |
Impact | This collaboration is bringing together the following fields: neuroscience, engineering and medicine. This project has resulted in the recruitment of two interns (Marielle Stam and Deniz Kucukahmetler). Due to Covid-19, patient recruitment and recording have been on hold for a significant period of time and further delays were experienced for research approvals (linked to pandemic related backlog), which has significantly impacted the project timeline. This is in particular a significant set-back for my postdoc Timothy West who needed an extension of his contract in order to complete this project. We are currently writing up this work. |
Start Year | 2018 |
Description | Optically Pumped Magnetometers - Gareth Barnes and Simon Farmer (University College London) |
Organisation | University College London |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | This project involves the use of a novel neuroimaging system, optically pumped magnetometers, to better understand the disease circuit underlying pathological tremor (e.g. Essential Tremor and Parkinson's disease). My research team has contributed to the study design and has completed the ethics application, which has been approved by the local ethics committee. Marielle Stam and Deniz Kucukahmetler who worked as interns in my research group designed the task which will be used in these experiments in collaboration with my postdoctoral research associate Timothy West. Timothy West is also building a new theoretical model of the tremor circuit which will be used to further explore this dataset. |
Collaborator Contribution | Prof Barnes and Prof Farmer contributed to study design, and Prof Farmer will be identifying patients recruited for the study. |
Impact | This collaboration is bringing together the following fields: neuroscience, engineering and medicine. This project has resulted in the recruitment of two interns (Marielle Stam and Deniz Kucukahmetler). Due to Covid-19, patient recruitment and recording have been on hold for a significant period of time and further delays were experienced for research approvals (linked to pandemic related backlog), which has significantly impacted the project timeline. This is in particular a significant set-back for my postdoc Timothy West who needed an extension of his contract in order to complete this project. We are currently writing up this work. |
Start Year | 2018 |
Description | Personalised Parkinson's Project |
Organisation | Radboud University Nijmegen |
Country | Netherlands |
Sector | Academic/University |
PI Contribution | My research group has developed an analysis pipeline for further exploration of this unique dataset which follows 500 patients diagnosed with Parkinson's disease patients longitudinally. |
Collaborator Contribution | My collaborators are sharing data collected from patients together with contributing to scientific direction. |
Impact | This collaboration will enable us to study longitudinal changes in patient's symptoms based on wearable sensors. We will aim to classify patients into different groups based on their symptom manifestation and use these insights to explore underlying neural dynamics at the group level. This research brings together bioinformatics and clinical neuroscience and aims to leverage modern analysis techniques for handling large datasets in order to better understand variabilities in disease manifestation across patient populations. As a result of this collaboration, we have recently secured additional funding from the Michael J Fox Foundation and are currently planning to make an additional grant application. |
Start Year | 2020 |
Description | Phasic DBS - Jorge Goncalves |
Organisation | University of Luxembourg |
Country | Luxembourg |
Sector | Academic/University |
PI Contribution | This collaboration aims to investigate whether patients' own tremor could be used to control stimulation patterns in order to improve the efficacy and efficiency of deep brain stimulation. I have contributed to experimental design, data collection, and development of the analysis pipeline used to determine efficacy of this novel stimulation strategy with respect to conventional high frequency deep brain stimulation (Cagnan et al 2017). This collaboration focuses on further testing this stimulation strategy and exploring stability of therapy. |
Collaborator Contribution | Jorge Goncalves will contribute to identification of patients for recruitment. |
Impact | The research carried out is multi-disciplinary and spans disciplines such as physics, electronics engineering, neurology and basic neuroscience. Data collection was on hold due to restrictions posed by Covid-19. This will significantly impact project timeline and output. This collaboration has resulted in recruitment of a PhD student to University of Luxembourg, who has recently defended their thesis. |
Start Year | 2018 |
Description | Phasic DBS - Queen's Hospital Functional Neurosurgery |
Organisation | Queen's Hospital |
Country | United Kingdom |
Sector | Hospitals |
PI Contribution | This collaboration aims to investigate whether patients' own tremor could be used to control stimulation patterns in order to improve the efficacy and efficiency of deep brain stimulation. I have contributed to experimental design, data collection, and development of the analysis pipeline used to determine efficacy of this novel stimulation strategy with respect to conventional high frequency deep brain stimulation (Cagnan et al 2017). This collaboration focuses on further testing this stimulation strategy and exploring stability of therapy. |
Collaborator Contribution | Queen's Hospital Functional Neurosurgery has contributed to identification of patients for recruitment. |
Impact | This collaboration has resulted in a poster presentation by my PhD student Carolina Reis - who attended the Society for Neuroscience meeting in 2019. The research carried out is multi-disciplinary and spans disciplines such as physics, electronics engineering, neurology and basic neuroscience. Patient recruitment was on hold due to Covid-19. A manuscript detailing the outcome of this study is currently in preparation using the limited data set acquired prior to the pandemic. However, we anticipate potential challenges which may influence the impact of the study outcome. |
Start Year | 2018 |
Description | Phasic DBS - Unit of Functional Neurosurgery |
Organisation | University College London |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | This collaboration aims to investigate whether patients' own tremor could be used to control stimulation patterns in order to improve the efficacy and efficiency of deep brain stimulation. I have contributed to experimental design, data collection, and development of the analysis pipeline used to determine efficacy of this novel stimulation strategy with respect to conventional high frequency deep brain stimulation (Cagnan et al 2017). This collaboration focuses on further testing this stimulation strategy and exploring stability of therapy. |
Collaborator Contribution | Unit of Functional Neurosurgery has contributed to identification of patients for recruitment. |
Impact | This research demonstrated for the first time the feasibility and efficacy of tremor phase locked stimulation. In some patients, this novel stimulation strategy could suppress patients' symptoms comparable to suppression levels observed with the state of the art high frequency stimulation yet with less than 20% of the power demanded by conventional stimulation. Our aim is to maximise efficacy and selectivity of novel treatment strategies in order to reduce stimulation induced side effects. This collaboration has resulted in a journal publication, detailing the efficacy of tremor phase locked stimulation, and numerous oral presentations. The research carried out is multi-disciplinary and spans disciplines such as physics, electronics engineering, neurology and basic neuroscience. Patient recruitment was on hold due to Covid-19. |
Start Year | 2015 |
Description | Phasic DBS and peripheral stimulation - Prof Peter Brown |
Organisation | Medical Research Council (MRC) |
Department | MRC Brain Network Dynamics Unit at the University of Oxford (BNDU) |
Country | United Kingdom |
Sector | Public |
PI Contribution | This collaboration aims to investigate whether patients' own tremor could be used to control stimulation patterns in order to improve the efficacy and efficiency of deep brain stimulation. I have contributed to experimental design, data collection, and development of the analysis pipeline used to determine efficacy of this novel stimulation strategy with respect to conventional high frequency deep brain stimulation (Cagnan et al 2017). This collaboration now focuses on further testing the new deep brain stimulation protocol and exploring stability of therapy. This collaboration has also been extended to application of the same core stimulation principle via peripheral stimulators and recruitment of two PhD students, who are extending the deep brain stimulation work to development of non-invasive stimulation strategies for tremor patients. I have also contributed to writing a grant application and securing additional funding to support this new research direction. |
Collaborator Contribution | Prof Peter Brown has contributed to experimental design and patient recruitment for the deep brain stimulation study. He has also been involved with experimental design and patient recruitment for the phasic peripheral stimulation study. |
Impact | This research demonstrated for the first time the feasibility and efficacy of tremor phase locked stimulation. In some patients, this novel stimulation strategy could suppress patients' symptoms comparable to suppression levels observed with the state of the art high frequency stimulation yet with less than 20% of the power demanded by conventional stimulation. Our aim is to maximise efficacy and selectivity of novel treatment strategies in order to reduce stimulation induced side effects. The research carried out is multi-disciplinary and spans disciplines such as physics, electronics engineering, neurology and basic neuroscience. This collaboration has resulted in a conference paper, describing the use of peripheral sensors to control implanted stimulators, two publications (detailing the efficacy of tremor phase locked stimulation and the future of deep brain stimulation (Cagnan et al 2017 and Cagnan et al 2019)), and numerous oral presentations. This work has lead to recruitment of one PhD student (Carolina Reis). An additional journal publication is currently in preparation highlighting utility of this new stimulation protocol during movement. The follow up work on peripheral stimulation has lead to recruitment of an other PhD student (Beatriz Arruda) in 2019. There are two manuscripts which are currently under revision (Reis et al and Arruda et al), detailing this new research direction. This collaboration has also resulted in securing additional funding for the development of a peripheral stimulator which can be used to optimise therapy from home. |
Start Year | 2015 |
Description | 4th motor control workshop |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Postgraduate students |
Results and Impact | I have organised the 4th motor control workshop. The main aim was to discuss recent advancements made in motor control, bringing together multiple key collaborators across the University of Oxford and providing the opportunity to postgraduate students to share their recent analysis. Senior researchers provided feedback to postgraduate students and determined key areas for future collaborations. My team members presented during this event. |
Year(s) Of Engagement Activity | 2018 |
Description | BNDU 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 | Unit staff and students welcomed pupils and teachers from local state-funded schools as they visited to learn more about STEM (Science, Technology, Engineering and Mathematics) and medical research at the Unit. During their visits, pupils in small groups talked informally to Unit members about key concepts and challenges in brain research, as well as what it is like working in STEM. Special emphasis was also placed on giving pupils the opportunity to see real working instruments and laboratories for themselves. After a group discussion on the use of animals in medical research, engagement activities were coordinated around 4 'knowledge stations', at which pupils could experience some of the Unit's core research themes, including: the activity and structure of the brain in health and disease; human brain stimulation; computer modelling of brain function; and brain-machine interfaces. At the end of the visit, pupils were given souvenirs to take home. |
Year(s) Of Engagement Activity | 2022 |
URL | https://www.mrcbndu.ox.ac.uk/news/schools-open-day-2022 |
Description | BluePrint |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Other audiences |
Results and Impact | I was interviewed for the BluePrint which is the Staff magazine for the University of Oxford - regarding shared parental leave and achieving work/life balance. |
Year(s) Of Engagement Activity | 2020 |
Description | Cafe Scientifique |
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 | Public/other audiences |
Results and Impact | We took part in Cafe Scientifique in Reading where Prof Paul Bolam gave a presentation on Parkinson's disease . After the talk, we answered questions from the audience about Parkinson's disease and general neuroscience. |
Year(s) Of Engagement Activity | 2018 |
Description | DBS Summit |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | My team members (Carolina Reis and Tim West) have successfully showcased their work at the 2nd DBS Summit in Wurzburg. |
Year(s) Of Engagement Activity | 2022 |
Description | Fall School |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | I was the keynote speaker at the 1st Biennial Fall School of the Collaborative Research Centre TRR 295 ReTune and also gave a talk on career development and important considerations for career progression . This organisation covers 9 international research institutes focusing on neurological conditions and their treatment. |
Year(s) Of Engagement Activity | 2021 |
URL | https://twitter.com/Retune_CRC/status/1450864099458433025 |
Description | JundiaĆ, Brazil |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Schools |
Results and Impact | My PhD student, Beatriz, gave two talks to primary and high school students in Jundiaí, her hometown, in Brazil (22/3/2021 and 13/4/2021). |
Year(s) Of Engagement Activity | 2021 |
Description | MIT Tech review |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Media (as a channel to the public) |
Results and Impact | I was interviewed by the MIT Technology Review regarding recent research on neuromodulation and asked to comment regarding importance of such work. |
Year(s) Of Engagement Activity | 2023 |
Description | MRC BNDU Science Day 2020 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Postgraduate students |
Results and Impact | My group members and I have presented during the MRC BNDU Science Day. These events are organised to enable discussion across different research groups within the MRC BNDU together and to receive input from invited external speakers, who are leaders in related research fields. |
Year(s) Of Engagement Activity | 2020 |
Description | MRC BNDU Science Day December 2019 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | I have organised the MRC BNDU December 2019 Science day which aimed to bring together different research groups within the MRC BNDU, providing an opportunity to postgraduate students to present their latest work, and receive feedback from senior researchers and invited distinguished speakers. My team members presented during this event. |
Year(s) Of Engagement Activity | 2019 |
Description | MRC BNDU Science Day Summer - Winter 2021 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | My group members and I have presented during the bi-annual MRC BNDU Science Day. These events are organised to enable discussion across different research groups within the MRC BNDU together and to receive input from invited external speakers, who are leaders in related research fields. |
Year(s) Of Engagement Activity | 2021 |
URL | https://www.mrcbndu.ox.ac.uk/news/unit-science-day-winter-2021 |
Description | MRC BNDU Training Day 2021 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Postgraduate students |
Results and Impact | I have organised the annual MRC BNDU Training day as part of my role within the BNDU Training, Career Development and Capacity Building Committee. This event aimed at addressing issues related to conducting research during the Covid-19 pandemic and effective grant writing. |
Year(s) Of Engagement Activity | 2021 |
Description | MRC BNDU Training Event 2020 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Postgraduate students |
Results and Impact | I have organised the annual MRC BNDU Training day as part of my role within the BNDU Training, Career Development and Capacity Building Committee and gave a talk on shared parental leave and levelling the playing field for female researchers in STEM. |
Year(s) Of Engagement Activity | 2020 |
URL | https://www.mrcbndu.ox.ac.uk/news/unit-training-and-careers-development-event-2020 |
Description | NTF |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Patients, carers and/or patient groups |
Results and Impact | I have given a talk during the Essential Tremor Webinar on "different electrical stimulation-based therapies for Essential Tremor with a particular focus on current research towards the next generation of non-invasive therapies". This event was streamed online and widely participated in by patients and their carers. |
Year(s) Of Engagement Activity | 2021 |
URL | https://tremor.org.uk/events/neta/essential-tremor-webinar |
Description | NeuroTales |
Form Of Engagement Activity | Engagement focused website, blog or social media channel |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | My PhD student spoke in the event, during which she shared her personal trajectory that led her to pursue a career in research. |
Year(s) Of Engagement Activity | 2020 |
Description | Oxford Sparks |
Form Of Engagement Activity | Engagement focused website, blog or social media channel |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | My Phd student delivered a live Q&A about Parkinson's disease research through Oxford Sparks on 26/5/2020. The event was held through YouTube. She talked briefly about her research and answered questions from the public. |
Year(s) Of Engagement Activity | 2020 |
Description | School visit (Oxford) |
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 | We visited a local school , where we demonstrated various scientific concepts from the field of neuroscience to 38 year 6 children. During our visit , we received a lot of questions from the students, and students engaged in a lively discussion after the demonstration. |
Year(s) Of Engagement Activity | 2018 |
URL | https://www.mrcbndu.ox.ac.uk/news/unit-returns-local-school-mrc-festival-medical-research |
Description | 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 | My research group has taken part in the in2science initiative as mentors. The main aim of this initiative is to allow high school students to gain hands on research experience to encourage them to pursue a career in STEM. |
Year(s) Of Engagement Activity | 2019,2020 |
URL | https://in2scienceuk.org |