Periodic Reporting for period 1 - COMEDM (Common mechanisms for decision-making and working memory in health and old age)
Reporting period: 2021-01-18 to 2023-01-17
We are regularly required to keep recently encountered information about the world in mind, and to use that information to make appropriate decisions. These essential cognitive functions, known as working memory (WM) and decision-making (DM), respectively, have typically been studied separately. Yet, recent developments in theoretical and systems neuroscience suggest that both WM and DM could emerge from a shared set of neural mechanisms. This is an exciting proposal, as it points to a new, integrative view on the neural basis of higher cognition; a view through which the multifaceted changes in WM and DM behaviour present in psychological and neuropsychiatric disorders affecting millions worldwide may be localized to single, potentially treatable loci of neural dysfunction.
With this project, hosted by Trinity College Dublin, we aimed to interrogate the extent to which WM and DM are reliant on shared mechanisms in the human brain. We employed a suite of cutting-edge approaches in cognitive neuroscience to provide strong convergent support for this idea. We also took initial steps toward applying insights from these investigations to assess a possible shared neural basis for the WM and DM deficits that are known to exist in a large portion of the global population: healthy older adults. As such, our research both offers a new, unified perspective on fundamental building blocks of cognition, and points to ways in which this can be exploited to understand conditions of brain change and disorder.
With this project, hosted by Trinity College Dublin, we aimed to interrogate the extent to which WM and DM are reliant on shared mechanisms in the human brain. We employed a suite of cutting-edge approaches in cognitive neuroscience to provide strong convergent support for this idea. We also took initial steps toward applying insights from these investigations to assess a possible shared neural basis for the WM and DM deficits that are known to exist in a large portion of the global population: healthy older adults. As such, our research both offers a new, unified perspective on fundamental building blocks of cognition, and points to ways in which this can be exploited to understand conditions of brain change and disorder.
The project has generated compelling convergent evidence that maintenance (subserving WM) and integration (subserving DM) of information over time are implemented in shared neural circuits. We used recurrent neural network (RNN) modelling to provide initial proof-of-principle that a single circuit, with characteristics matching those of a specific class of neurobiologically plausible models (‘ring attractors’), can produce both robust WM and flexible information integration depending on the task context. We used non-invasive scalp electroencephalography (EEG) combined with state-of-the-art multivariate decoding methods to show that human participants performing WM and DM tasks appear to exploit this same shared-circuit solution. We also demonstrated that while the human participants successfully adapted across WM and DM contexts, their behaviour in both was contaminated by shared sources of noise and bias that likely originate within the shared memory/decision circuit. Furthermore, we succeeded in identifying an apparently prominent role for pupil-linked arousal systems in adaptation of the shared circuit across WM vs DM contexts. Altogether, these findings amount to a fundamental new insight into the neural basis and close relationship between two higher cognitive functions. They have been received very well at scientific conferences and we are currently preparing them for publication.
Over the course of the project, the researcher has also published two research articles in collaboration with international laboratories, both of which addressed questions relevant to the project. Work with collaborators at Leiden University further illuminated the role of pupil-linked arousal systems in higher cognition – in this case, in the implementation of ‘cognitive control’ on the classic Stroop task (Tromp, Nieuwenhuis & Murphy, 2022, Computational Brain & Behavior). Other work with collaborators at UKE Hamburg assessed how humans flexibly switch between distinct sensory-motor mapping rules during DM (van den Brink et al., 2022, Neuron).
Lastly, at time of writing we have also collected 60% of a behavioural/EEG/pupillometry dataset of older adults performing the same WM/DM paradigm used above, with the aim of exposing potential shared sources of age-related deficits in WM and DM. Preliminary analysis of these data indicate that degraded sensory encoding is a dominant source of age-related increase in WM and DM error. Data collection and analysis for this part of the project are ongoing; once complete, we will write up the results and submit them for publication.
Over the course of the project, the researcher has also published two research articles in collaboration with international laboratories, both of which addressed questions relevant to the project. Work with collaborators at Leiden University further illuminated the role of pupil-linked arousal systems in higher cognition – in this case, in the implementation of ‘cognitive control’ on the classic Stroop task (Tromp, Nieuwenhuis & Murphy, 2022, Computational Brain & Behavior). Other work with collaborators at UKE Hamburg assessed how humans flexibly switch between distinct sensory-motor mapping rules during DM (van den Brink et al., 2022, Neuron).
Lastly, at time of writing we have also collected 60% of a behavioural/EEG/pupillometry dataset of older adults performing the same WM/DM paradigm used above, with the aim of exposing potential shared sources of age-related deficits in WM and DM. Preliminary analysis of these data indicate that degraded sensory encoding is a dominant source of age-related increase in WM and DM error. Data collection and analysis for this part of the project are ongoing; once complete, we will write up the results and submit them for publication.
The integrative approach developed for the project generated a set of convergent results that together advance the development of a truly unified model of the neural implementation of WM and DM. In doing so they point to exciting new research directions that can be pursued in the coming years. Accordingly, my collaborators and I plan to elaborate on our insights from the project and push further beyond the state of the art in this field in the following ways: i) to use neuroimaging to localize the shared, potentially distributed circuit responsible for both information maintenance and integration; ii) to elaborate on the pupillometry results reported here by using neuroimaging and causal manipulations to delineate the roles of candidate ‘circuit modulators’ in flexibly tuning the circuit to suit different contexts; and iii) to use magnetic resonance spectroscopy (MRS) to assess how individual and regional differences in neurochemical composition shape circuit function. Collectively, these pursuits will fill key gaps in the unified model of WM and DM that is emerging as a consequence of the project research, and will represent a major advance in our understanding of the neural principles and processes underpinning the two functions.
Ultimately, a key function of this emerging model of WM and DM will be to generate testable hypotheses that relate individual loci of neural dysfunction to multifaceted consequences for behaviour. To complement this, the project research also established a rich set of behavioural and neurophysiological metrics that we hope can ultimately be used to help identify these loci. As such, the project research is expected to facilitate new insights into the many neuropsychological disorders that are characterized by joint WM/DM deficits (e.g. schizophrenia, attention deficit hyperactivity disorder), and to have translational impact on the developing fields of computational psychiatry and precision medicine. Our project work on cognitive aging represents important first steps in this direction that we hope ourselves and other researchers will continue making and elaborate on in the coming years.
Ultimately, a key function of this emerging model of WM and DM will be to generate testable hypotheses that relate individual loci of neural dysfunction to multifaceted consequences for behaviour. To complement this, the project research also established a rich set of behavioural and neurophysiological metrics that we hope can ultimately be used to help identify these loci. As such, the project research is expected to facilitate new insights into the many neuropsychological disorders that are characterized by joint WM/DM deficits (e.g. schizophrenia, attention deficit hyperactivity disorder), and to have translational impact on the developing fields of computational psychiatry and precision medicine. Our project work on cognitive aging represents important first steps in this direction that we hope ourselves and other researchers will continue making and elaborate on in the coming years.