Mechanisms of action of oscillatory transcranial direct current stimulation during sleep on electrophysiological correlates and memory consolidation – assessed via presurgically implanted electrodes in patients with epilepsy

• Applicant: Professorin Dr. Agnes Flöel
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology ; Human Cognitive and Systems Neuroscience
• Term: from 2019 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 413459402

The main aim of this study is to elucidate the mechanisms underlying sleep-dependent memory consolidation. We will evaluate patients implanted presurgically with intracranial electrodes for treatment of pharmacorefractory epilepsy. In a balanced cross-over design, we will apply either slow oscillatory transcranial anodal direct current stimulation (sotDCS) or sham stimulation during a 90 min nap. During sleep, we will record slow cortical oscillations (SO), spindles, and ripples, using surface EEG and invasive EEG. Moreover, several memory tasks will be learned before sleep, and sleep-dependent memory consolidation will be evaluated after sleep as a function of the stimulation condition. The following questions will be addressed: a) Is the hierarchical coupling between SO-to- spindles, and spindles-to-ripples in the hippocampus, associated with the ability to consolidate novel memories? b) What is the impact of so-tDCS on hippocampal-thalamo-cortical networks, and particularly hippocampal ripple-activity? c) Is the modulation of coupling of SO-to-spindles, and spindles-to-ripples, associated with the ability to consolidate novel memories? d) Does the so-tDCS-Effects on SO, spindles, and ripples persist after end of stimulation, and do the after-effects depend on entrainment? Combination of a perturbation approach with so-tDCS, and intracranial recordings in epilepsy patients offers the unique possibility to assess subcortical oscillations including hippocampal ripple-activity with regard to their causal relevance for successful memory consolidation. In addition to furthering basic neuroscientific knowledge, the study will allow us to evaluate and to improve the therapeutic potential of sot-DCS with regard to improving sleep-dependent memory consolidation in aging and in incipient neurodegenerative disease. So-tDCS, as a non-invasive and low-risk treatment approach that targets sleep and its neurophysiological correlates, may convey symptomatic (memory consolidation) and possibly even causal (amyloid-clearance) benefit to patients, an issue of great clinical relevance. However, before testing this approach in larger clinical studies in relevant patient cohorts, it is paramount to optimize the intervention, on the basis of a more thorough understanding of the underlying mechanisms that will result from the present study.

• DFG Programme: Research Grants
• Co-Investigator: Julia Ladenbauer, Ph.D.