Cortico-hippocampal mechanisms of short-term memory
Cognitive, Systems and Behavioural Neurobiology
Final Report Abstract
In this project we studied the large-scale cortico-subcortical mechanisms of short-term memory. During short-term memory, persistent activity in the prefrontal cortex encodes memorized information and shows oscillatory dynamics. What are the neuronal mechanisms underlying this memory information? The prefrontal cortex engages in recurrent interactions with subcortical brain regions such as the hippocampal complex and secondary thalamic nuclei. The central goal of this project was to investigate the hypothesis that these prefrontalsubcortical interactions underlie short-term memory in the primate brain. To address this question, we recorded neuronal activity in two Rhesus monkeys during a flexible short-term memory task. This task required memory of two types of information – either the spatial position or color of a visual cue. We implemented novel recording technologies including new microdrives, implants and software tools. For the first time, this allowed us to simultaneously record spiking activity and LFPs from more than 200 electrodes acutely implanted in 7 different cortical and subcortical brain regions. While we originally aimed to focus on prefrontal-hippocampal interactions, due to technical reasons, during the recordings, we decided to focus the project on the prefrontal-thalamic axis (mediodorsal thalamus and pulvinar). Furthermore, we added further simultaneous cortical targets (A46, A9/46d, A9/46v, FEF, LIP). We successfully performed these massively parallel recordings in both animals. In addition, we performed human-comparable EEG recordings during the same behavioral task in both animals. First, we found that both color and spatial short-term memory information was encoded in all fronto-parietal cortical regions as well as in the mediodorsal thalamus and pulvinar. The regional pattern of information was specific for the type of information and information dynamics differed between regions. Second, we found prominent phase-coupling within and between all recorded cortical and subcortical brain regions. Granger-causality analyses revealed directed and frequencyspecific interactions between prefrontal and thalamic regions that were most prominently expressed in the alpha band. Third, Muscimol microinjections in the mediodorsal thalamus efficiently and selectively suppressed local spiking in the thalamus. This inactivation caused a reduction of memory information in the prefrontal cortex. Together, these results support the hypothesis that oscillatory interactions between the prefrontal cortex and secondary thalamic nuclei subserve the prefrontal encoding of visual short-term memory information. Forth, we performed detailed analyses of the waveforms of extracellularly recorded spikes. This allowed us to dissociate four functionally distinct cell types based on spike shape. Finally, we developed a new analysis framework to integrate invasive electrophysiology in monkeys, monkey EEG and human MEG/EEG. We found that position and color memory information can be decoded from the monkey EEG. These findings establish a link between invasive recordings in monkeys and non-invasive human electrophysiology.
Publications
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(2018) Gradual progression from sensory to task-related processing in cerebral cortex. PNAS 115(30):E7202-E7211
Brincat SL, Siegel M, von Nicolai C, Miller EK
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(2019) Extracellular spike waveform dissociates four functionally distinct cell classes in primate cortex. Current Biology 29
Trainito C, von Nicolai C, Miller EK, Siegel M
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(2019) Monkey EEG links neuronal color and motion information across species and scales. eLife 8:e45645
Sandhaeger F, von Nicolai C, Miller EK, Siegel M
