Periodic Reporting for period 5 - Code4Memory (Neural oscillations - a code for memory)
Período documentado: 2020-08-01 hasta 2022-03-31
Code4Memory investigates the role of brain oscillations for the formation and retrieval of human episodic memories. Doing so it follows the Synchronization / De-synchronization Framework (Hanslmayr et al. 2016; Trends in Neurosciences) which postulates specific oscillatory mechanisms for memory formation and retrieval. Specifically, the framework assumes that there are two main modules underlying memory formation in the human brain, the neocortex and the hippocampus, which implement two different functions in the service of memory. These functions are (i) binding of information in the hippocampus and (ii) representing information in the neocortex. When performing these two functions two opposing synchronization behaviours can be observed, with the neocortex desynchronizing neural activity in order to represent information and the hippocampus synchronizing neural assemblies in order to bind information. Together, this project addresses the fundamental question of how the human brain forms and retrieves memories. The answer to this question is of tremendous importance for society because it advances our understanding of one of the most fundamental cognitive functions, i.e. memory, which shapes our personality, makes us who we are, and is affected in several mental diseases (i.e. dementia, schizophrenia, PTSD, etc.). The overall objective of this project is to test a specific set of hypothesis, guided by the Synchronization and Desynchronization Framework. These hypotheses will be tested in four work packages, ranging from single and multi-unit recordings in the human brain (WP A), multimodal EEG/MEG and EEG-fMRI recordings in healthy human subjects (WP B), brain stimulation studies in healhy humans (WP C), and computational modelling (WP D).
Code4Memory concluded in March 22 and was highly successful in achieving its objectives. The project set out to test whether synchronized theta and gamma oscillations in the hippocampus, and desynchronized alpha/beta oscillations in the neocortex underly memory. This fundamental question was addressed in four work packages using human local field potential and single unit recordings (WP A), large scale MEG/EEG and EEG-fMRI recordings (WP B), brain stimulation (WP C), and computational modelling (WP D). Below I highlight the main achievements. In WP A we have shown that synchronized gamma oscillations in the hippocampus interact with desynchronized alpha/beta oscillations in the neocortex during memory encoding and retrieval in a directionally specific way (Griffiths et al., 2019; PNAS). Furthermore, we were able to demonstrate that synchronized firing between pairs of neurons is mediated by theta and gamma oscillations, and that such synchronized firing correlates with memory formation (Roux et al., 2022; under review). Together, these two studies confirm our predictions that synchronized oscillations in the hippocampus are critical for memory and that they interact with neocortical desynchronized alpha/beta oscillations. In WP B we have demonstrated in three EEG and MEG studies that desynchronized alpha/beta oscillations represent information in memory. This has been demonstrated for memory encoding (Michelmann et al., 2018; J Cog Neuro), retrieval of movies and sounds (Michelmann et al., 2016; PLoS Biology), and retrieval of sequential multi-element episodes (Michelmann et al., 2019; Nat Hum Behav). Furthermore, we were able to show that the fidelity of the memory code correlates with the amount of alpha/beta power decrease using a combination of multi-variate fMRI and EEG (Griffiths et al., 2019; eLife). Finally, using MEG we were able to experimentally dissociate the role of hippocampal theta/gamma synchronization and neocortical alpha/beta desynchronization for memorizing multi-element episodes (Griffiths et al., 2021; NeuroImage). Together, these studies represent a strong body of evidence for the information representing role of alpha/beta desynchronization in the service of memory. In WP C we were able to demonstrate the causal role of theta synchronization for associating different elements (i.e. sounds and videos) in a memory episode (Clouter et al., 2017; Curr Biol; Wang et al., 2018; J Neurosci). Furthermore, we were able to show that low frequency stimulation of the left dorsolateral prefrontal cortex boosts alpha/beta power decreases and improves memory performance (van der PLas, et al., 2021; PLoS Biol). Finally, we were able to investigate the interaction between the neocortex and hippocampus with intracranial electrical single pulse stimulation (van der Plas et al., in prep). These results are currently being finalised for publication. Together the results from this work package demonstrate a causal role of theta synchronization and alpha/beta desynchronization for memory formation. Lastly, two computational models were constructed and published where we demonstrate the computational utility of neocortical desynchronization for information representation, and hippocampal synchronization for long-term potentiation (Parish et al., 2018; J Neurosci; Parish et al., 2021; Neuropsychologia).
Code4Memory has had a significant impact on the scientific community in reshaping our knowledge about the neurophysiological foundations of episodic memory. In particular, the project has delivered a number of results from various experiments that are consistent with the Sync/De-sync framework. Specifically, the studies could demonstrate a central role of neocortical alpha/beta power decreases for representing information, and of synchronized hippocampal theta and gamma oscillations for binding information in memory. These results could be of benefit for society by informing the development of neural stimulation devices or protocols that boost memory formation by targeting synchronized/desynchronized neural activity.