Neural mechanisms of memory stability and flexibility in the human brain
<p>The brain has the remarkable capacity to acquire, store, and reinstate memories. On the one hand, memories can be stored safely, free from interference. On the other hand, new memories are acquired daily, and can be used to update previously stored information. To safely store memories, a s...
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| Format: | Thesis |
| Language: | English |
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2022
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| _version_ | 1811141209828098048 |
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| author | Koolschijn, RS |
| author2 | O'Reilly, J |
| author_facet | O'Reilly, J Koolschijn, RS |
| author_sort | Koolschijn, RS |
| collection | OXFORD |
| description | <p>The brain has the remarkable capacity to acquire, store, and reinstate memories. On the one hand, memories can be stored safely, free from interference. On the other hand, new memories are acquired daily, and can be used to update previously stored information. To safely store memories, a stable memory system is required, while for new learning flexibility and plasticity are needed. This means that the brain operates along a trade-off between memory stability and flexibility. In this thesis, I investigated the neural mechanisms that support stable and flexible memory, probing neocortical, hippocampal and neuromodulatory contributions. To study these different contributions, I have used techniques that measure and modulate cortical excitation and inhibition, in combination with behavioural and neural readouts of memory, with the aim to understand how neurochemistry and neural representations influence memory formation, storage and recall.</p>
<p>First, I asked whether neuromodulators might set the trade-off between stability and flexibility during learning by modulating the balance between excitation and inhibition (E/I). I manipulated the concentration of the neuromodulator noradrenaline during learning through administration of a single dose of the drug atomoxetine, and measured the effect of this intervention on cortical inhibition and behavioural and neural measures of overgeneralisation. I found that increased noradrenaline led to a decrease in neocortical inhibition, which predicted an increase in neural markers of excitability, which in turn predicted behavioural signatures of memory overgeneralisation.</p>
<p>Second, I went on to look at the mechanisms that protect stored memories from interference. By combining functional MRI (fMRI) with transcranial direct current stimulation (tDCS) to lower cortical inhibition, I showed that two distinct mechanisms prevent overlapping memories from interference: hippocampus separates overlapping memories using a relational code, while in neocortex, inhibition prevents co-activation of overlapping memories.</p>
<p>Third, I investigated the hippocampal and neocortical contributions to memory recall. By applying a novel MR sequence that interleaves fMRI with functional MR Spectroscopy (fMRS), I found that recall of a visual cue resulted in a transient increase in E/I balance in visual cortex, which was predicted by activity in hippocampus. Taken together, these three studies reveal the contributions of hippocampus and cortical E/I balance in memory-related processes, where hippocampus represents the relational structure of a memory and where neural inhibition gates reactivation of memories and sets the trade-off between stability and flexibility during memory formation. Together, the hippocampus and cortical E/I balance play a key role in the neural computations that underlie flexible behaviour.</p> |
| first_indexed | 2024-09-25T04:34:15Z |
| format | Thesis |
| id | oxford-uuid:eaf5b766-5281-4ac2-aab9-6223cb1c3ee2 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-09-25T04:34:15Z |
| publishDate | 2022 |
| record_format | dspace |
| spelling | oxford-uuid:eaf5b766-5281-4ac2-aab9-6223cb1c3ee22024-09-09T17:53:55ZNeural mechanisms of memory stability and flexibility in the human brainThesishttp://purl.org/coar/resource_type/c_db06uuid:eaf5b766-5281-4ac2-aab9-6223cb1c3ee2NeurosciencesEnglishHyrax Deposit2022Koolschijn, RSO'Reilly, JBarron, H<p>The brain has the remarkable capacity to acquire, store, and reinstate memories. On the one hand, memories can be stored safely, free from interference. On the other hand, new memories are acquired daily, and can be used to update previously stored information. To safely store memories, a stable memory system is required, while for new learning flexibility and plasticity are needed. This means that the brain operates along a trade-off between memory stability and flexibility. In this thesis, I investigated the neural mechanisms that support stable and flexible memory, probing neocortical, hippocampal and neuromodulatory contributions. To study these different contributions, I have used techniques that measure and modulate cortical excitation and inhibition, in combination with behavioural and neural readouts of memory, with the aim to understand how neurochemistry and neural representations influence memory formation, storage and recall.</p> <p>First, I asked whether neuromodulators might set the trade-off between stability and flexibility during learning by modulating the balance between excitation and inhibition (E/I). I manipulated the concentration of the neuromodulator noradrenaline during learning through administration of a single dose of the drug atomoxetine, and measured the effect of this intervention on cortical inhibition and behavioural and neural measures of overgeneralisation. I found that increased noradrenaline led to a decrease in neocortical inhibition, which predicted an increase in neural markers of excitability, which in turn predicted behavioural signatures of memory overgeneralisation.</p> <p>Second, I went on to look at the mechanisms that protect stored memories from interference. By combining functional MRI (fMRI) with transcranial direct current stimulation (tDCS) to lower cortical inhibition, I showed that two distinct mechanisms prevent overlapping memories from interference: hippocampus separates overlapping memories using a relational code, while in neocortex, inhibition prevents co-activation of overlapping memories.</p> <p>Third, I investigated the hippocampal and neocortical contributions to memory recall. By applying a novel MR sequence that interleaves fMRI with functional MR Spectroscopy (fMRS), I found that recall of a visual cue resulted in a transient increase in E/I balance in visual cortex, which was predicted by activity in hippocampus. Taken together, these three studies reveal the contributions of hippocampus and cortical E/I balance in memory-related processes, where hippocampus represents the relational structure of a memory and where neural inhibition gates reactivation of memories and sets the trade-off between stability and flexibility during memory formation. Together, the hippocampus and cortical E/I balance play a key role in the neural computations that underlie flexible behaviour.</p> |
| spellingShingle | Neurosciences Koolschijn, RS Neural mechanisms of memory stability and flexibility in the human brain |
| title | Neural mechanisms of memory stability and flexibility in the human brain |
| title_full | Neural mechanisms of memory stability and flexibility in the human brain |
| title_fullStr | Neural mechanisms of memory stability and flexibility in the human brain |
| title_full_unstemmed | Neural mechanisms of memory stability and flexibility in the human brain |
| title_short | Neural mechanisms of memory stability and flexibility in the human brain |
| title_sort | neural mechanisms of memory stability and flexibility in the human brain |
| topic | Neurosciences |
| work_keys_str_mv | AT koolschijnrs neuralmechanismsofmemorystabilityandflexibilityinthehumanbrain |