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Improving executive functioning in patients with Mild Cognitive Impairment by transcranial alternate current brain stimulation

Projectomschrijving

Mensen met een milde cognitieve stoornis (MCS) kunnen problemen ervaren met functies als mentale flexibiliteit of het vermogen tot plannen en organiseren, die samen ook wel het executief functioneren worden genoemd. Problemen met het executief functioneren vergroten de kans op het ontwikkelen van dementie. Transcranial alternating current stimulation (tACS) is een methode zonder bekende bijwerkingen om hersenactiviteit te beïnvloeden.

Doel

In dit project wordt onderzocht of stimulatie van de frontale en pariëtale hersengebieden het executief functioneren bij mensen met MCS verbetert. Ook willen de onderzoekers de effectiviteit van de behandeling onderzoeken door de hersenactiviteit voor en na de behandeling te vergelijken, gemeten met een functionele MRI (hersenscan) en een EEG (hersenfilmpje). Dit zal leiden tot meer kennis over het gebruik van hersenstimulatie als behandeling voor problemen met uitvoerende taken bij mensen met MCS en daarmee het voorkomen dat zij dementie ontwikkelen.

Verslagen


Samenvatting van de aanvraag

A hallmark of Mild Cognitive Impairment (MCI) and Alzheimer’s disease (AD) is impaired cognitive function, most notably in the domains of memory and executive functioning (EF). EF concerns a set of skills involved in the coordination and control of cognitive processes essential for daily functioning, such as managing time or switching focus. This includes working memory, in which information is consciously maintained and manipulated for brief periods of time. An example is converting centiliters to milliliters by heart during cooking while at the same time pouring water in a bowl. On the brain level, impaired short-term EF are associated with altered activation and synchronization of the fronto-parietal brain network. It has been shown that deficiencies EF as well as of impaired low frequency (theta) brain oscillations may be predictive of progression from MCI to dementia. Finding an effective and patient-friendly treatment for such cognitive impairment is important for MCI patients as it may improve quality of life on the short term and may postpone conversion to dementia on the long term. Transcranial alternating electrical current brain stimulation (tACS) is a novel application of transcranial stimulation that may provide such a treatment. Given the deficiencies in low frequency brain oscillations in MCI, it is very appealing that tACS can directly target relevant oscillations by the application of a weak alternating current to specific parts of the brain. Brain oscillations here refer to electrical activity from large neuronal ensembles as measured by electroencephalography (EEG) in specific frequency bands. These frequencies or oscillations, are associated with specific cognitive brain functions. In particular EF are associated with low frequency (theta) oscillations [1]. Indeed, preliminary evidence has been published implying that tACS can improve aspects of EF in MCI patients and healthy people [2-4]. Therefore, We hypothesize that synchronous tACS in the theta range will increase fronto-parietal brain synchronization and improve EF of MCI patients, potentially delaying conversion to dementia. Notably, tACS is a safe technique that is painless and well tolerated by patients. Of importance for future clinical application is that tACS can be delivered in patients’ homes, and potentially by remotely controlled self-treatment. We base our particular stimulation paradigms on previous studies in healthy participants. As theta oscillations are associated with working memory and application of synchronous theta stimulation in healthy people resulted in better reaction times [3], the first stimulation paradigm that we will use will employ synchronous theta stimulation. In addition, the interplay between theta and gamma oscillations seems to be reflective of cognitive processes. Specifically, the theta/gamma power ratio seems to be related to working memory. Since Vosskhul et al. [4] applied stimulation at the theta/gamma subject specific frequency and found increased EEG synchronization and improved cognitive performance, the second stimulation paradigm that we propose to use involves theta/gamma stimulation. In our study, we will thus apply two types of tACS with the aim to increase synchronization of the fronto-parietal network during an executive functioning task. We will monitor changes in EF up to one year after treatment. This will also be the first study to measure brain activation and connectivity before and after tACS treatment in MCI patients. This will yield important information about the possible mechanism of action. In total, 60 amnestic MCI patients will randomly receive either one of the two types of tACS or placebo. We will maximize the potential effect of the treatment by repeating the treatment for two weeks. Two experts by experience (ervaringsdeskundigen) will advise on the contents and feasibility of the study, on information for the patients and they will help in organizing informative seminars for MCI and dementia patients and patient organizations. Our our research team combines a long-standing high-level expertise in applying brain stimulation in patient populations and assessing cognitive function and brain connectivity, with tACS expertise and neurological expertise of dementia. We are therefore confident that we have the combined knowledge and experience to assess the applicability and efficiency of tACS for the treatment of cognitive dysfunction in MCI patients and to contribute to the development of highly needed novel treatment strategies.

Kenmerken

Projectnummer:
733050836
Looptijd: 94%
Looptijd: 94 %
2018
2024
Onderdeel van programma:
Gerelateerde subsidieronde:
Projectleider en penvoerder:
B - Ćurčić-Blake
Verantwoordelijke organisatie:
Universitair Medisch Centrum Groningen