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Neural oscillations - a code for memory

Periodic Reporting for period 4 - Code4Memory (Neural oscillations - a code for memory)

Reporting period: 2020-04-01 to 2020-07-31

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 sets specific oscillatory mechanisms 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 hypothesis 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).
In the first 18 months of this project significant progress has been made on three work packages (A, B, and D), being well in line with the projected deliverables. Note that work package C is not due to start until month 24 of the project. Two highly talented team members have been hired (Dr F. Roux and B. Griffiths) and all major pieces of equipment have been purchased set up and configured. Concerning work package A we were able to successfully record single and multi unit data in 7 out of a total of 11 patients, which is slightly more than I have projected at this stage. We succeeded in finding specific neurons that code for specific concepts well known to the patients. These 7 datasets allow us to address the question of whether the firing of single neurons in the hippocampus is synchronized to theta and gamma oscillations in the service of memory. First analysis suggests that there is indeed significant synchronization of neurons in these frequency bands. Unexpectedly, we did also find synchronization in other frequency bands (i.e. beta oscillations) which has not been described before. Additionally, we recorded 7 datasets in patients which allow us to address the question of how cortical desynchronization and hippocampal synchronization interacts. The results from the first 6 patients look very promising and fully support the Synchronization Desynchronization Framework, in showing that cortical desynchronization correlates with hippocampal synchronization during memory formation. Concerning work package B we were able to finish data collection for a combined EEG-fMRI experiment and are in the process of finishing data collection for an MEG experiments. First results in both experiments support the idea that cortical desynchronization is a mechanism via which the cortex represents information. Additionally, an EEG study has been published showing a link between alpha power decreases and the reinstatement of sensory information in memory. Concerning work package D we finished a first version of a computational model, i.e. the Synchronization Desynchronization Memory Model, which implements memory formation and retrieval via a synchronized hippocampus and a desynchronized neocortex.
Code4Memory will have significant impact on the scientific community by re-defining how brain oscillations underlie human memory. The socio-economic impact of this project is difficult to assess at this stage, but I assume the results of this project to inform clinical research on mental disorders showing aberrant memory function (e.g. dementia, schizophrenia, PTSD). At this stage of the project the focus is on data collection and analysis of the first experiments. Nevertheless, in these first 18 months we have published a theoretical paper, which was the first paper that spells out specific mechanisms for oscillatory interactions between the neocortex and hippocampus in the service of memory. This paper has been received very well and has already attracted 23 citations. In an EEG study we have found evidence for desynchronized neocortical alpha/beta oscillations to represent information in memory during retrieval, which we published in PLoS Biology (2 citations). These results have been followed up by a simultaneous EEG-fMRI study which is currently being analysed. Importantly, so far the data fully supports the conclusions of this previous paper. In addition we published several other papers related to project which lend ecological validity to our lab based findings, and investigate the effectivity of different oscillatory stimulation procedures for perturbing brain oscillations, which will inform the stimulation studies envisioned in the third work package.