Title:	Rhythmic Sensory Stimulation and the Role of Phase Synchronization in Fear Conditioning
Authors:	Plog, Elena
ORCID of the author:	https://orcid.org/0000-0002-2396-1811
Thesis advisor:	Prof. Dr. Ursula Stockhorst
Thesis referee:	Prof. Dr. Thomas Gruber
Abstract:	Understanding the complexity of memory processing in the brain is a major element of research in biopsychology and neuroscience. Advantages of animal studies comprise various ways to directly manipulate neural activity in memory-processing brain areas with high temporal and spatial precision. In contrast, human studies are often correlational in nature via assessing brain oscillations occurring during different stages of memory processing. Causal experimental approaches addressing the relevant associations are still sparse. As one promising line of research for causal inference in humans, external rhythmic stimulation via technical device or frequencymodulated sensory stimuli is suitable. It can be used to directly modulate brain oscillations and therefore opens the possibility of assessing the causal role of brain rhythms. In the present thesis this rhythmic sensory stimulation is used in fear conditioning which is a valid model for aversive learning and memory. It aims at 1) investigating visuocortical tunings towards a threat-predictive stimulus and, importantly, addressing its persistence over different phases of fear conditioning and 2) for the first time testing the causal role of phase-synchronization in different low frequency bands for the association of an initially neutral visual stimulus with an auditory threat cue in both a laboratory and in a web-based fear conditioning paradigm. In line with these aims, the three empirical studies were designed to use either unimodal or multimodal rhythmic stimulation to modulate oscillatory activity in a generalization fear conditioning paradigm, covering the learning phases habituation, fear acquisition, and extinction on day 1 (Studies 1 to 3), and delayed recall on day 2 (Studies 1, 2). In Study 1, we examined the visuocortical engagement in fear conditioning with a special focus on its persistence across an extinction and delayed recall phase. To account for the very early sensory processing, we assessed steady-state visual responses (as an indicator of visuocortical engagement) that were evoked via rhythmic visual stimulation in an alpha rhythm. We found visuocortical tuning to the threatpredictive stimulus as a result of fear acquisition, while extinction learning prompted rapid changes in orientation tuning: Here, conditioned visuocortical engagement and skin conductance responses to the fear-associated stimulus were strongly reduced. Importantly, delayed recall revealed a brief but precise return-of-tuning to the threat-stimulus in the visual cortex accompanied by a brief, more generalized return-of-fear in skin conductance. In sum, early visual processing shows response patterns that are consistent with memory consolidation and spontaneous recovery. In Study 2, we extended our rhythmic stimulation paradigm from being unimodal to multimodal. This served to manipulate phase-synchronization between an initially neutral visual stimulus and an auditory threat cue in a memory-relevant theta frequency, and thus to address the associative nature of fear conditioning. We compared the effects of a synchronous (in-phase) condition with an asynchronous (out-of-phase) condition on fear acquisition, extinction learning, and delayed recall. Phase synchronization improved contingency knowledge and facilitated discrimination in terms of rated valence and arousal. However, synchronization did not modify conditioned responding in skin conductance responses and steady-state visually evoked potentials during acquisition, although both measures demonstrated the greatest response to the threat-predictive stimulus. Together, these data support a causal role of theta-phase synchronization in affective evaluation and contingency knowledge during fear acquisition. In Study 3 we extended the modulation of phasesynchronization from a theta to a slower delta rhythm and moreover, transferred our procedure into a web-based fear conditioning paradigm (due to the COVID-19 pandemic). In accordance with Study 2, phase-synchronization augmented the discrimination of generalization stimuli in contingency knowledge. However, it did not affect valence and arousal ratings. Interestingly, the effect of synchronization occurred independent of frequency, i.e., occurred after both theta and delta rhythm. Moreover, and as a prerequisite of Study 3, we proved the ability to successfully conduct complex generalization fear conditioning in an online setting. Together, our data of phase synchronization studies supports a causal role of phase synchronization in the declarative knowledge of contingency for low frequencies rather than in the specific theta frequency. In sum, the current thesis provides the promising approach of using rhythmic sensory stimulation to modulate very early sensory processing as well as to directly manipulate the precise timing of to-be-associated stimuli in an aversive fear conditioning paradigm. Both methods emphasize the importance of oscillatory brain activity by offering non-invasive ways of direct modulations in order to modify selected stages of the fear learning and memory (e.g., fear acquisition, extinction, and delayed recall).
URL:	https://doi.org/10.48693/328 https://osnadocs.ub.uni-osnabrueck.de/handle/ds-202305059034
Subject Keywords:	Fear Conditioning; Rhythmic Sensory Stimulation; Phase Synchronization; Associative Learning
Issue Date:	5-May-2023
License name:	Attribution-NonCommercial-NoDerivs 3.0 Germany
License url:	http://creativecommons.org/licenses/by-nc-nd/3.0/de/
Type of publication:	Dissertation oder Habilitation [doctoralThesis]
Appears in Collections:	FB08 - E-Dissertationen

This item is licensed under a Creative Commons License