Thalamus, Cortex & Cognition
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Funded by Wellcome Trust and MRC
Prof. Anna S Mitchell
How do subcortical and cortical brain structures interact to support complex cognition?
We focus on how different subdivisions of the dorsal thalamus interact with the frontal lobes and cingulate/retrosplenial cortex to support our ability to learn new information, remember and make decisions.
Our group focuses on how our brain works when we learn new information, navigate and make adaptive, rapid decisions. Our particular interest is with the dorsal thalamus and its interactions with cortex (thalamo-cortical networks and transthalamic loops). We use behavioural and cognitive neuroscience methods to understand how the medial thalamus and interconnected cortical regions contribute to learning new information, remembering, navigation and decision-making as well as other cognitive processes (e.g. planning).
One of our focuses is on the mediodorsal thalamus (it is the largest subdivision of the dorsal medial thalamus) and its interactions with the prefrontal cortex and structures in the medial temporal lobes. The functions of the mediodorsal thalamus are still not yet well defined and its role in many neurological disorders and psychiatric diseases remains speculative.
We have recently shown using neuroimaging in non-human primates that, in the healthy brain, learning to discriminate complex visuospatial information induces remarkable connectivity changes between dorsal medial thalamus and cortical structures, and in key fronto-temporal regions, at both the structural (anatomical connections) and the functional (temporally correlated signal) level. Subsequently, in the same brains after damage to the fornix, that disconnected the extended hippocampal system, different (almost opposite) connectivity profiles were found. These findings shed light on experience- and damage-related brain plasticity (Pelekanos, et al., 2020, J Neurosci, doi: 10.1523/JNEUROSCI.0364-20.2020).
Previously, we have provided the first causal evidence of the importance of interactions between the mediodorsal thalamus and prefrontal cortex during learning complex information on a trial-by-trial basis and during performing a value-based decision-making task in primates (Browning, Chakraborty, Mitchell, 2015, Cerebral Cortex) and identified the causal contribution of the magnocellular mediodorsal thalamus in value-based decision-making in primates (Mitchell, Baxter, Gaffan, 2007, J Neurosci).
Other recent findings show the critical role of the mediodorsal thalamus in updating reward-guided learning in uncertain or changing environments (Chakraborty, Kolling, Walton, Mitchell, 2016, eLife). We also have further causal behavioural evidence to demonstrate that the integrity of the mediodorsal thalamus is critical in supporting the prefrontal cortex during tasks involving cognitive flexibility, including documenting neuroimaging changes after damage to the mediodorsal thalamus.
Our other main focus concerns interactions between the retrosplenial cortex and the anterior thalamic nuclei (also located within the medial thalamus) with our latest research in rats highlighting newly identified thalamocortical subcircuits between the anterior thalamus and retrosplenial cortex (Lomi et al, 2021, bioRxiv https://doi.org/10.1101/2021.06.11.448056). Further work in non-human primates demonstrates the critical role for the retrosplenial cortex in supporting our ability to retain previously acquired information (Buckley and Mitchell, 2016, Cerebral Cortex).
We use a multidisciplinary approach to advancing fundamental knowledge about the interactions between nuclei of the medial thalamus and their cortical targets during performing cognitive processes and navigation. We combine cognitive and behavioural neuroscience techniques including electrophysiology, neuroimaging, neurocognitive testing, disruption to selective brain targets in animals, neuroanatomy and immunohistochemistry. We also assess cognitive and behavioural changes in patients with medial thalamic strokes or neurological diseases using neuropsychological testing and neuroimaging.
Some of our work is conducted in humans, while other studies involve us investigating our hypotheses using animal models (rodents and non-human primates).
Dr Mitchell's group also incorporate evaluations of 3Rs refinements into their research with non-human primates. Her group has recently developed a primate protective head cap that supports wound healing after cranial implant surgeries (Perry et al., 2021 J Neurosci Methods, doi: 10.1016/j.jneumeth.2020.108992). This device won the UK Institute for Animal Technologies best refinement award in 2020. We have also identified effective strategies for training primates for neuroscience techniques (Mason et al., 2019, J Neurosci Methods, doi: 10.1016/j.jneumeth.2019.02.001).
You can explore our non-human primate lab via a virtual tour here http://www.labanimaltour.org/ . For this work, we were awarded the 2017 Understanding Animals in Research Public Engagement Award.
Dr Mitchell explains why she uses non-human primates to answer some of her research questions via an interview with the Wellcome Trust here https://www.facebook.com/wellcometrust/videos/608674132916002
Dr Mitchell and her lab have provided an online virtual tour of their primate lab showcasing some of their primate welfare refinements and their research results at recent UK Science Festivals
Dr Mitchell has also recently contributed to the discussion about the importance of animal research including primate research in neuroscience, its importance for advancing our fundamental understanding about brain functions that in some cases can support the discovery of ways to treat serious conditions, and the ways in which animal welfare is safeguarded. http://metro.co.uk/2018/03/20/why-are-primates-still-used-in-uk-experiments-7367751/
Dr Mitchell is Co-Editor in Chief of Current Research in Neurobiology ; she is a member of the Understanding Animal Research Board; and she is the scientific representative on the Animal Welfare Ethical Review Panel at the UK Centre for Macaques.
- Dr Elsie Premereur - Visiting Senior Fellow from KU Leuven
- Dr Vassilis Pelekanos - Postdoctoral Researcher now in Nottingham University
- Dr Subhojit Chakraborty – Postdoctoral Researcher now in UCL London