Investigating the neural basis for checking, selective attention and working memory in obsessive compulsive disorder, through MEG and TMS

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We all seem to know someone who tends to check repeatedly whether the door is locked, the oven is off, the alarm is set, etc. Thorough checking may even be regarded as part of being conscientious and we accept the fact that some people 'slightly overdo it', which, however, in the extreme can take on the form of compulsive checking, clinically diagnosed as part of Obsessive Compulsive Disorder (OCD). Despite consistent reporting in the literature of the maladaptive nature of checking and the high rate of subclinical compulsive checking tendencies in the typical population (~15%), the involved cognitive and brain systems have not been thoroughly investigated so far. Our recent research led us to believe that individuals with compulsive checking tendencies are less able to suppress external distractions that are perceived as threatening and are less efficient at controlling internal thoughts that are distracting and evoke further fear, thus, promoting a vicious circle of anxiety and deficient control. Such a circle of perceived threat and control deficits affects the contents of the individual's short-term memory. We further suggest that deficits in the control and suppression of distractions might underlie in a similar neuropathological form other clinical syndromes, while the strongly debilitating influences and the observed knock-on effects of deficient control on memory functions in OCD emphasise this syndrome as an optimal starting point for research. Adopting a symptom-specific approach focused on compulsive checking will further help clarifying the inconsistent results with OCD patients so far that have been related to the heterogeneity in OCD phenotypes. By means of our well-developed experimental paradigms the primary goal of this project will therefore be to characterise the neural signatures of deficient suppression and control in attention and short-term memory tasks by comparing clinical OCD checkers to subclinical high checkers and to non-checkers. A substantial body of research by others and by our team suggests that brain waves (i.e. "rhythms" or "oscillations") are key to understanding how communication within large-scale brain networks is established. To this end, we will employ cutting-edge neuroimaging in form of Magnetoencephalography (MEG) and transcranial magnetic stimulation (TMS) with Electroencephalography (EEG) co-recordings. Besides characterising in detail the oscillatory biomarkers of deficient suppression and control beyond our particular paradigms and patient group (OCD) we will use the emerging new application of frequency-tuned TMS to mimic brain oscillations with the following two aims. First, by controlled entrainment of brain oscillations, frequency-tuned TMS-EEG will allow us to test which oscillatory signatures play a causal role in behaviour, providing biomarkers of control deficits and increased risk of OCD as well as new candidate endophenotypes. Second, if TMS-induced oscillations directly improve performance in high checkers then a proof of concept will be achieved for future therapeutic applications.