MRC Transition Support Award CSF Sanjay Manohar
Lead Research Organisation:
University of Oxford
Department Name: Clinical Neurosciences
Abstract
The fellowship aimed to answer four main questions:
1. Do dopamine agonists affect different types of motivation differentially?
2. Can anticholinergic drugs modulate motivation in healthy volunteers?
3. Are motivational changes following ventromedial prefrontal damage explainable as reduced context-sensitivity?
Question 1 constituted 3 experiments, which were completed and published.
We established that
- dynamic effects of motivation can be captured by online corrective feedback during a movement (Manohar et al. Neuropsychologia 2018),
- dopamine has opposing effects on two types of motivation (Grogan, Sandhu, Hu & Manohar, eLife 2020),
- we can predict impulse control disorders using pupillometry (Drew, Muhammed, Baig, ... Manohar*, Husain* et al. Brain 2020),
- dopamine improved cognitive fluency (Ang*, Manohar* et al. Curr Biol 2018)
- dopamine also has opposing effects on different aspects of working memory (Fallon, Kienast, ... Manohar & Husain , J. Psychopharmacol. 2019),
- the effect on working memory influences control over actions (Fallon, Drew, Muhammed, Manohar & Husain, Cortex 2018),
and
- I developed the first physiological model of working memory that also accounts for action control (Manohar et al. Neurosci Biobeh Rev. 2019). The surprising new principle here is that neural patterns change their meaning over seconds, calling for re-evaluation of much single-neuron data. This has been cited in 4 major reviews, led to invited talks (Zurich, Brown, UCL) and formed the basis for my Leverhulme grant.
This work has led to my being awarded the Thomas Willis Intermediate Career Researcher award.
The second two questions are left unanswered by this data:
1. Acetylcholine is a critical regulator of striatal dopamine release. Can cholinergic drugs modulate disorders of motivation?
2. Dopamine release may be controlled by medial prefrontal cortex. Do apathy and impulsivity arise after lesions to different subregions within this area?
The transition award will permit me to answer these questions. Data collection and recruitment have already begun. I aim to have these two key publications out by the time of applying for a Senior Fellowship in 2022.
1. Do dopamine agonists affect different types of motivation differentially?
2. Can anticholinergic drugs modulate motivation in healthy volunteers?
3. Are motivational changes following ventromedial prefrontal damage explainable as reduced context-sensitivity?
Question 1 constituted 3 experiments, which were completed and published.
We established that
- dynamic effects of motivation can be captured by online corrective feedback during a movement (Manohar et al. Neuropsychologia 2018),
- dopamine has opposing effects on two types of motivation (Grogan, Sandhu, Hu & Manohar, eLife 2020),
- we can predict impulse control disorders using pupillometry (Drew, Muhammed, Baig, ... Manohar*, Husain* et al. Brain 2020),
- dopamine improved cognitive fluency (Ang*, Manohar* et al. Curr Biol 2018)
- dopamine also has opposing effects on different aspects of working memory (Fallon, Kienast, ... Manohar & Husain , J. Psychopharmacol. 2019),
- the effect on working memory influences control over actions (Fallon, Drew, Muhammed, Manohar & Husain, Cortex 2018),
and
- I developed the first physiological model of working memory that also accounts for action control (Manohar et al. Neurosci Biobeh Rev. 2019). The surprising new principle here is that neural patterns change their meaning over seconds, calling for re-evaluation of much single-neuron data. This has been cited in 4 major reviews, led to invited talks (Zurich, Brown, UCL) and formed the basis for my Leverhulme grant.
This work has led to my being awarded the Thomas Willis Intermediate Career Researcher award.
The second two questions are left unanswered by this data:
1. Acetylcholine is a critical regulator of striatal dopamine release. Can cholinergic drugs modulate disorders of motivation?
2. Dopamine release may be controlled by medial prefrontal cortex. Do apathy and impulsivity arise after lesions to different subregions within this area?
The transition award will permit me to answer these questions. Data collection and recruitment have already begun. I aim to have these two key publications out by the time of applying for a Senior Fellowship in 2022.
Technical Summary
The fellowship aimed to answer four main questions:
1. Do dopamine agonists affect different types of motivation differentially?
2. Can anticholinergic drugs modulate motivation in healthy volunteers?
3. Are motivational changes following ventromedial prefrontal damage explainable as reduced context-sensitivity?
Question 1 constituted 3 experiments, which were completed and published.
We established that
- dynamic effects of motivation can be captured by online corrective feedback during a movement (Manohar et al. Neuropsychologia 2018),
- dopamine has opposing effects on two types of motivation (Grogan, Sandhu, Hu & Manohar, eLife 2020),
- we can predict impulse control disorders using pupillometry (Drew, Muhammed, Baig, ... Manohar*, Husain* et al. Brain 2020),
- dopamine improved cognitive fluency (Ang*, Manohar* et al. Curr Biol 2018)
- dopamine also has opposing effects on different aspects of working memory (Fallon, Kienast, ... Manohar & Husain , J. Psychopharmacol. 2019),
- the effect on working memory influences control over actions (Fallon, Drew, Muhammed, Manohar & Husain, Cortex 2018),
and
- I developed the first physiological model of working memory that also accounts for action control (Manohar et al. Neurosci Biobeh Rev. 2019) that formed the basis for my Leverhulme grant.
This work has led to my being awarded the Thomas Willis Intermediate Career Researcher award.
The second two questions are left unanswered by this data:
1. Acetylcholine is a critical regulator of striatal dopamine release. Can cholinergic drugs modulate disorders of motivation?
2. Dopamine release may be controlled by medial prefrontal cortex. Do apathy and impulsivity arise after lesions to different subregions within this area?
The transition award will permit me to answer these questions. Data collection and recruitment have already begun. I aim to have these two key publications out by the time of applying for a Senior Fellowship in 2022.
1. Do dopamine agonists affect different types of motivation differentially?
2. Can anticholinergic drugs modulate motivation in healthy volunteers?
3. Are motivational changes following ventromedial prefrontal damage explainable as reduced context-sensitivity?
Question 1 constituted 3 experiments, which were completed and published.
We established that
- dynamic effects of motivation can be captured by online corrective feedback during a movement (Manohar et al. Neuropsychologia 2018),
- dopamine has opposing effects on two types of motivation (Grogan, Sandhu, Hu & Manohar, eLife 2020),
- we can predict impulse control disorders using pupillometry (Drew, Muhammed, Baig, ... Manohar*, Husain* et al. Brain 2020),
- dopamine improved cognitive fluency (Ang*, Manohar* et al. Curr Biol 2018)
- dopamine also has opposing effects on different aspects of working memory (Fallon, Kienast, ... Manohar & Husain , J. Psychopharmacol. 2019),
- the effect on working memory influences control over actions (Fallon, Drew, Muhammed, Manohar & Husain, Cortex 2018),
and
- I developed the first physiological model of working memory that also accounts for action control (Manohar et al. Neurosci Biobeh Rev. 2019) that formed the basis for my Leverhulme grant.
This work has led to my being awarded the Thomas Willis Intermediate Career Researcher award.
The second two questions are left unanswered by this data:
1. Acetylcholine is a critical regulator of striatal dopamine release. Can cholinergic drugs modulate disorders of motivation?
2. Dopamine release may be controlled by medial prefrontal cortex. Do apathy and impulsivity arise after lesions to different subregions within this area?
The transition award will permit me to answer these questions. Data collection and recruitment have already begun. I aim to have these two key publications out by the time of applying for a Senior Fellowship in 2022.
Publications
Attaallah B
(2023)
Role of the hippocampus in decision making under uncertainty
Barber TR
(2023)
Reward insensitivity is associated with dopaminergic deficit in rapid eye movement sleep behaviour disorder.
in Brain : a journal of neurology
Bocincova A
(2022)
Neural signature of flexible coding in prefrontal cortex.
in Proceedings of the National Academy of Sciences of the United States of America
Doody M
(2022)
Model-based learning retrospectively updates model-free values.
in Scientific reports
Fallon S
(2023)
Effects of cholinesterase inhibition on attention and working memory in Lewy body dementias
in Brain Communications
Grima LL
(2022)
Correction to: Nucleus accumbens D1-receptors regulate and focus transitions to reward-seeking action.
in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
Grima LL
(2022)
Nucleus accumbens D1-receptors regulate and focus transitions to reward-seeking action.
in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
| Title | Trial triplet Representational Similarity Analysis |
| Description | This is a new analysis technique we developed to re-analyse neurophysiological data. In our paper we apply it to monkey single-neuron recordings, but it can be applied to any high-dimensional neural signal during certain tasks. Classical representational similarity analysis measures the amount of neural coding of a specific behavioural variable, by examining large numbers of trials, under the assumption that the neural code is stable over trials. Our new method looks for short-term representations over small numbers of trials and thereby detects even time-varying neural coding. |
| Type Of Material | Improvements to research infrastructure |
| Year Produced | 2021 |
| Provided To Others? | No |
| Impact | Paper is under review. We hope that this method will be used by several neurophysiology labs internationally. |
| URL | https://osf.io/fmxs4/ |
| Title | A common neural network architecture for visual search and working memory |
| Description | A computational model of visual search and working memory. |
| Type Of Material | Computer model/algorithm |
| Year Produced | 2021 |
| Provided To Others? | Yes |
| Impact | A general modelling framework that can be used to simulate many different results in the memory and attention literature. |
| URL | https://osf.io/6c9uj/ |