Declarative memory refers to memories that can be consciously recalled and verbalized, such as facts and life events in contrast to procedural (or implicit) memory. Declarative memory is heavily dependent on hippocampal structures. The famous case of patient H.M. had his both temporal lobes (including hippocampi) surgically removed as a cure for severe epilepsy. Since the surgery, he was not able to form any new declarative memories while his ability to form new motor skill was not that much affected. Deficit of declarative memories is also a paramount symptom of Alzheimer’s disease and other conditions that cause functional deficits in the medial temporal lobe.
Based on the animal work, it is known that hippocampal theta (6-7 Hz) oscillation is intimately related to memory trace formation in hippocampus-dependent (or, in human terms, declarative) learning. Theta oscillation is affected by manipulations of the neurotransmitter acetylcholine, which is also in direct causal relationship with declarative learning. Scopolamine is an anticholinergic agent and it reduces the amount hippocampal theta and in humans, produce changes is EEG/MEG that resemble those usually seen in Alzheimer’s patients. In fact, scopolamine administration to healthy subjects has been suggested to mimic the loss of cholinergic cells characteristic to AD patients.
Showing that brain activity related to formation of declarative memory traces could be recorded noninvasively in humans would directly connect the knowledge gained with the animal model to humans. Because of very detailed knowledge about the interplay between cholinergic system, its oscillatory counterpart and learning in animals, it is possible to formulate the criteria for an oscillatory surrogate marker of declarative memory in humans. So far, we have made pilot experiments on this in with EEG and found that frontal theta responses to the learning-related stimuli correlates with learning rate in humans, but the neural phenomenon in question could also be a more complex one, such as functional connectivity of the oscillation between brain areas. The purpose of this project is to identify those oscillatory phenomena that are related to good learning performance by recording MEG/EEG while manipulating the participants’ ability to form new declarative memories with scopolamine.

Project team