Frontal cortical mechanisms and interactions during learning and decision making

Lead Research Organisation: University of Oxford
Department Name: Experimental Psychology

Abstract

The aim of the current proposal is to look at the neural mechanisms of learning and decision making. Learning, the acquisition of new behaviours and information, and decision making, the ability to act on that information, are two of the most fundamental cognitive operations that are called into play throughout our lives. Impairments in learning and decision making are often central to psychiatric conditions; maladaptive choices are not just made in the first place but they are also not adjusted as a result of experience. It is important to emphasize that not only do we investigate basic aspects of learning and decision making but, for example, we also attempt to understand such processes in the social domain.
Learning and decision making do not depend on a single brain region but on the interactions that occur between many regions. Our aim is to investigate these interactions in five key circuits. The focus will be on the parts of the five circuits that are located in the frontal lobes of the brain and the aim is to test whether and how the frontal components of these circuits regulate activity in the rest of the circuits of which they are parts.
The interactions within brain circuits will be investigated in two principal ways. First, we will attempt to manipulate and alter activity in one component of each circuit and then record the consequences for behaviour and for activity recorded in other parts of the circuits. This can be done by making a selective lesion in a brain area and for this reason it is necessary to use animal models. In the current case the brain areas are only present in a few species and so the macaque is the model species. The lesion?s effect on other parts of the network can be investigated by using a non-invasive brain scanner technique, functional magnetic resonance imaging (fMRI), to record the blood oxygen level dependent (BOLD) signal that provides an index of brain activity. The second way that we can look at brain circuits is by using the brain scanner to acquire a different type of MRI data, diffusion weighted MRI (DW-MRI). DW-MRI scans provide information about the white matter pathways that run between different component parts of brain circuits. We plan to look at how the pathways linking brain circuits change during learning to make decisions in the most effective manner possible.

Technical Summary

Prefrontal and anterior cingulate cortex (PFC and ACC) play fundamental roles in voluntary or goal-guided behaviour. They are essential for decision making and learning. Changes and biases in such cognitive processes are central to the behavioural alterations seen in psychiatric illnesses.


The aim of the current proposal is twofold. First, we intend to uncover the mechanisms of operation of PFC and ACC by using computational approaches to describe the effects of selective brain lesions and patterns of brain activity recorded with functional magnetic resonance imaging (fMRI). Second, we intend to uncover the manner in which these brain areas are able to perform such functions through their interactions with other brain regions. Combined lesion-fMRI studies will address this second aim. The work will be carried out using a macaque model and will employ the Oxford MRC-funded macaque MRI facilities.
The focus is on five brain regions.


It is hypothesized that ventromedial frontal cortex is essential making value-guided decisions because it rapidly focuses on key choice options; after a lesion it is hypothesized that activity in other brain regions will no longer be correlated with the values of the key choice options that might be taken. It is hypothesized that lateral orbitofrontal cortex and dopamine make distinctive contributions to the learning of stimulus-reward associations; while the former learns precise associations the latter reinforces choices in proportion to their proximity to reward regardless of the exact nature of any contingency. Third, it is hypothesized that frontopolar cortex has a special contribution to make to learning because it mediates counterfactual learning; the ability to learn not from experience but from observation of consequences of choices not taken. Fourth, it is suggested that the anterior cingulate sulcus has a role in assigning value to the component stages of a course of action that determines how primates engage in, start, and stop courses of actions. Fifth, it is suggested that the anterior cingulate gyrus has a role in the valuation of social information that is related not just to the manner in which the social status of conspecifics is perceived but to the manner in which an individual expresses social status. Finally it is hoped that provision of the resources requested will make it possible to continue a programme of work using diffusion weighted MRI to compare anatomical structure in humans and macaques and investigating individual differences in learning induced changes in anatomical connexions.
 
Description Federation of European Neuroscience Societies (FENS) Committee on Animal Research Ethics (CARE)
Geographic Reach Europe 
Policy Influence Type Membership of a guideline committee
Impact Review of EU directive 2010/63 (Animals in Science) on animal research in science
 
Description Federation of European Neuroscience Societies Committee on Animal Research Ethics
Geographic Reach Europe 
Policy Influence Type Implementation circular/rapid advice/letter to e.g. Ministry of Health
Impact policy and practicce in relation to European Directive 2010/63/EU on animal research
 
Description Wellcome Trust Senior Investigator Award
Amount £1,851,544 (GBP)
Funding ID WT100973AIA 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2013 
End 09/2020
 
Description Wellcome Trust Strategic Award
Amount £4,955,047 (GBP)
Funding ID WT101092MA 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2013 
End 12/2020
 
Description Wellcome Trust Studentship
Amount £100,000 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2012 
End 09/2015
 
Description Wellcome Trust Studentships
Amount £200,000 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2006 
End 09/2010
 
Description Wellcome Trust Stundentship
Amount £100,000 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2008 
End 09/2011
 
Title Delineations of cortical areas for use in MRI scanning experiments 
Description Delineations of cortical areas for use in MRI scanning experiments 
Type Of Material Data analysis technique 
Year Produced 2009 
Provided To Others? Yes  
Impact Tomassini V, Jbabdi S, Klein JC, Behrens TE, Pozzilli C, Matthews PM, Rushworth MF, Johansen-Berg H. Diffusion-weighted imaging tractography-based parcellation of the human lateral premotor cortex identifies dorsal and ventral subregions with anatomical and functional specializations. J Neurosci. 2007 Sep 9;27(38):10259-69. 
 
Title resting state fMRI data bases 
Description macaque resting state functional magnetic resonance imaging data sets 
Type Of Material Biological samples 
Year Produced 2014 
Provided To Others? Yes  
Impact papers published by other research groups: Kumar V, Croxson PL, Simonyan K (2016) Structural Organization of the Laryngeal Motor Cortical Network and Its Implication for Evolution of Speech Production. J Neurosci 36:4170-4181. Mitchell DJ, Bell AH, Buckley MJ, Mitchell AS, Sallet J, Duncan J (2016) A Putative Multiple-Demand System in the Macaque Brain. J Neurosci 36:8574-8585. 
 
Description Integrated neural networks in the primate brain 
Organisation University of Oxford
Country United Kingdom 
Sector Academic/University 
PI Contribution Investigation of frontal cortical brain mechanisms
Collaborator Contribution neuroimaging and neurosurgical expertise
Impact 23924609; 23884933; 23754406
Start Year 2013
 
Description Neural mechanisms for foraging in an uncertain environment 
Organisation Wellcome Trust
Department KEMRI-Wellcome Trust Research Programme
Country Kenya 
Sector Multiple 
PI Contribution principal applicant
Collaborator Contribution The Wellcome Trust provided funding
Impact Wellcome Trust Senior Investigator Award to principal investigator
Start Year 2013
 
Description Federation of European Neurosciences Socieities Committee on Animal Research and Ethics 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact coordinating the policies of the Federation of European Neuroscience Socieities and their national affiliates in relation to animal research. Engaging with the European parliament in the review of animal research directives. Promoting openness and transparency in animal research
Year(s) Of Engagement Activity 2014,2015,2016,2017,2018
 
Description Radio interview 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact radio interview about animal research
Year(s) Of Engagement Activity 2017
 
Description Research presentation at SKOL foundation workshop 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Health professionals
Results and Impact presentation of research into decision making to social entrepreneur
Year(s) Of Engagement Activity 2011
 
Description School visit (Oxford) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Type Of Presentation Workshop Facilitator
Geographic Reach Local
Primary Audience Schools
Results and Impact 30 children attended talks and participated in brain related workshops

children learned about brains
Year(s) Of Engagement Activity 2012
 
Description Understanding Animal Research Lab Tour 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Understanding Animal Research lab tours provides an easily accessible web resource that allows members of the general public to visit and navigate through a primate neuroscience research facility
Year(s) Of Engagement Activity 2017
URL http://www.labanimaltour.org/
 
Description interview for national news 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Intereviews in national newspapers and scientific journals relating to ultrasound stimulation experiments (eg http://blog.pnas.org/2019/03/journal-club-low-intensity-focused-ultrasound-shows-promise-as-tool-to-probe-deep-brain-function/)
Year(s) Of Engagement Activity 2019
 
Description media interest 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact bbc interviews and newspaper coverage

press office reported changes in opions and attitudes
Year(s) Of Engagement Activity 2014
 
Description presentation at Science Oxford 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact presented research in neuroscience, on neural plasticity, in animal models to general audience

increased knowledge of neuroscience
Year(s) Of Engagement Activity 2011