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Models of eye-movement control distinguish between different control levels, ranging from automatic (bottom-up, stimulus-driven selection) and automatized (based on well-learned routines) to voluntary (top-down, goal-driven selection, e.g., based on instructions). However, one type of voluntary control has yet only been examined in the manual and not in the oculomotor domain, namely free-choice selection among arbitrary targets, that is, targets that are of equal interest from both a bottom-up and top-down processing perspective. Here, we ask which features of targets (identity- or location-related) are used to determine such oculomotor free-choice behavior. In two experiments, participants executed a saccade to one of four peripheral targets in three different choice conditions: unconstrained free choice, constrained free choice based on target identity (color), and constrained free choice based on target location. The analysis of choice frequencies revealed that unconstrained free-choice selection closely resembled constrained choice based on target location. The results suggest that free-choice oculomotor control is mainly guided by spatial (location-based) target characteristics. We explain these results by assuming that participants tend to avoid less parsimonious recoding of target-identity representations into spatial codes, the latter being a necessary prerequisite to configure oculomotor commands.
Epigenetic signatures such as methylation of the monoamine oxidase A (MAOA) gene have been found to be altered in panic disorder (PD). Hypothesizing temporal plasticity of epigenetic processes as a mechanism of successful fear extinction, the present psychotherapy-epigenetic study for we believe the first time investigated MAOA methylation changes during the course of exposure-based cognitive behavioral therapy (CBT) in PD. MAOA methylation was compared between N=28 female Caucasian PD patients (discovery sample) and N=28 age- and sex-matched healthy controls via direct sequencing of sodium bisulfite-treated DNA extracted from blood cells. MAOA methylation was furthermore analyzed at baseline (T0) and after a 6-week CBT (T1) in the discovery sample parallelized by a waiting time in healthy controls, as well as in an independent sample of female PD patients (N=20). Patients exhibited lower MAOA methylation than healthy controls (P<0.001), and baseline PD severity correlated negatively with MAOA methylation (P=0.01). In the discovery sample, MAOA methylation increased up to the level of healthy controls along with CBT response (number of panic attacks; T0-T1: +3.37±2.17%), while non-responders further decreased in methylation (-2.00±1.28%; P=0.001). In the replication sample, increases in MAOA methylation correlated with agoraphobic symptom reduction after CBT (P=0.02-0.03). The present results support previous evidence for MAOA hypomethylation as a PD risk marker and suggest reversibility of MAOA hypomethylation as a potential epigenetic correlate of response to CBT. The emerging notion of epigenetic signatures as a mechanism of action of psychotherapeutic interventions may promote epigenetic patterns as biomarkers of lasting extinction effects.