Universität zu Köln

Sildatke, Elena (2022). Extending the knowledge on performance monitoring in obsessive-compulsive disorder: Insights gained by electrophysiological recordings and deep brain stimulation. PhD thesis, Universität zu Köln.

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Abstract

Obsessive-compulsive disorder (OCD) is characterized by alterations in frontostriatal circuits and associated impairments in performance monitoring. The overactivity of the performance monitoring system is reflected by enhanced electrophysiological correlates during decision conflict (conflict-theta) and error processing (error-theta and error-related negativity, ERN). Besides the mediofrontal cortex, composing the source of these correlates, further brain structures are fundamentally involved in these cognitive processes. Particularly, the anterior limb of internal capsule (ALIC) and nucleus accumbens (NAc) are not only involved in performance monitoring but show partially also altered activity in OCD. Despite the importance of ALIC/NAc in performance monitoring observation of its electrophysiological activity during decision conflict and error processing are limited. Notably, ALIC/NAc has been established as target region for deep brain stimulation (DBS) for treatment resistant OCD and has proved to be clinically effective. Although, it is still unknown whether stimulation of the ALIC/NAc affects the aforementioned cortical correlates. In the first part of the present dissertation, electrophysiological activity during decision conflict and error processing from the cortex and the ALIC/NAc (by means of local-filed potentials, LFP) was investigated in patients with OCD (LFP-study). As expected, previous findings were successfully replicated cortical correlates of decision conflict (conflict-theta) and error processing (error-theta and ERN) were observed. Additionally, it was hypothesized that LFPs from the ALIC/NAc also comprises correlates of decision conflict (LFP-conflict-theta) and error processing (LFP-error-theta and LFP-ERN). Indeed, all three performance monitoring modulations were observed in the ALIC/NAc. Accordingly, ALIC/NAc seems to be involved in processes associated with monitoring of decision conflict and performance errors. Presumably, it provides the signal for the need of increased cognitive control to resolve the conflict and of behavioral adaptation to improve performance, respectively. Although, it was expected to find increased frontostriatal connectivity during decision conflict and error monitoring, this was not confirmed. Putatively, this could be explained by increased connectivity between both structures irrespective of cognitive control demands in OCD. Finally, possible interrelations between striatal correlates and symptom severity or symptom improvement by DBS in OCD were explored. Our results indicated an association of patients who exhibited smaller error signals (LFP-error-theta and LFP-ERN) with lesser symptom severity and with greater DBS efficacy. This links ALIC/NAc performance monitoring modulations to OCD symptomatology, possibly reflecting hyperactive performance monitoring, and connect this to attenuated response to DBS. In the second part of the present dissertation, the modulatory effect of DBS on cortical correlates of decision conflict (conflict-theta) and error processing (ERN) was investigated by comparing the correlates from pre-DBS state with stimulation on and stimulation off (Stimulation-study). It was hypothesized that acute DBS reduces conflict-theta and the ERN and that these effects would rebound after cessation of stimulation. In line with our hypotheses, the correlates were decreased by acute stimulation, indicating DBS-induced reduction of the pathologically overactive performance monitoring system. Contrary to our hypotheses, the rebound effect after cessation of stimulation was not observed for conflict-theta but at trend level for the ERN. Likely, DBS has only acute and no long-term effects on the performance monitoring system, which might become clearer by extending the stimulation off phase. Finally, possible interrelations between clinical efficacy of DBS with pre-DBS conflict-theta and the ERN and their changes through stimulation were explored. Our results associated patients who exhibited smaller pre-DBS ERN with greater DBS efficacy. In conclusion, this dissertation provides new insights on electrophysiological correlates of performance monitoring in OCD derived from ALIC/NAc and on the modulation of their cortical pendants by DBS. Further investigations, particularly involving long-term acquisition of LFPs, are required to further characterize ALIC/NAc activity during performance monitoring and its association with the pathophysiology of DBS. Also, additional studies are needed to confirm the interrelation between electrophysiological correlates and clinical parameters with regard to clinical applications in the future. Particularly, it should be further explored whether increased cortical and striatal error signals point toward a hyperactive performance monitoring system and are also related to attenuated clinical efficacy.

Item Type:	Thesis (PhD thesis)
Creators:	Creators Email ORCID ORCID Put Code Sildatke, Elena UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-633321
Date:	2022
Language:	English
Faculty:	Faculty of Medicine
Divisions:	Faculty of Medicine > Psychiatrie und Psychotherapie > Klinik und Poliklinik für Psychiatrie und Psychotherapie
Subjects:	Medical sciences Medicine
Uncontrolled Keywords:	Keywords Language Obsessive-compulsive disorder English Deep brain stimulation UNSPECIFIED EEG UNSPECIFIED
Date of oral exam:	2022
Referee:	Name Academic Title Grefkes, Christian Prof.Dr. Dafsari, Haidar PD Dr. Daun, Silvia Prof. Dr.
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/63332