Functional connectivity of cognition-related brain networks in adults with fetal alcohol syndrome.

BACKGROUND: Fetal alcohol syndrome (FAS) can result in cognitive dysfunction. Cognitive functions affected are subserved by few functional brain networks. Functional connectivity (FC) in these networks can be assessed with resting-state functional MRI (rs-fMRI). Alterations of FC have been reported in children and adolescents prenatally exposed to alcohol. Previous reports varied substantially regarding the exact nature of findings. The purpose of this study was to assess FC of cognition-related networks in young adults with FAS. METHODS: Cross-sectional rs-fMRI study in participants with FAS (n = 39, age: 20.9 ± 3.4 years) and healthy participants without prenatal alcohol exposure (n = 44, age: 22.2 ± 3.4 years). FC was calculated as correlation between cortical regions in ten cognition-related sub-networks. Subsequent modelling of overall FC was based on linear models comparing FC between FAS and controls. Results were subjected to a hierarchical statistical testing approach, first determining whether there is any alteration of FC in FAS in the full cognitive connectome, subsequently resolving these findings to the level of either FC within each network or between networks based on the Higher Criticism (HC) approach for detecting rare and weak effects in high-dimensional data. Finally, group differences in single connections were assessed using conventional multiple-comparison correction. In an additional exploratory analysis, dynamic FC states were assessed. RESULTS: Comparing FAS participants with controls, we observed altered FC of cognition-related brain regions globally, within 7 out of 10 networks, and between networks employing the HC statistic. This was most obvious in attention-related network components. Findings also spanned across subcomponents of the fronto-parietal control and default mode networks. None of the single FC alterations within these networks yielded statistical significance in the conventional high-resolution analysis. The exploratory time-resolved FC analysis did not show significant group differences of dynamic FC states. CONCLUSIONS: FC in cognition-related networks was altered in adults with FAS. Effects were widely distributed across networks, potentially reflecting the diversity of cognitive deficits in FAS. However, no altered single connections could be determined in the most detailed analysis level. Findings were pronounced in networks in line with attentional deficits previously reported.

Probing the relevance of the hippocampus for conflict-induced memory improvement.

The hippocampus plays a key role for episodic memory. In addition, a small but growing number of studies has shown that it also contributes to the resolution of response conflicts. It is less clear how these two functions are related, and how they are affected by hippocampal lesions in patients with mesial temporal lobe epilepsy (MTLE). Previous studies suggested that conflict stimuli might be better remembered, but whether the hippocampus is critical for supporting this interaction between conflict processing and memory formation is unknown. Here, we tested 19 patients with MTLE due to hippocampal sclerosis and 19 matched healthy controls. Participants performed a face-word Stroop task during functional magnetic resonance imaging (fMRI) followed by a recognition task for the faces. We tested whether memory performance and activity in brain regions implicated in long-term memory were modulated by conflict during encoding, and whether this differed between MTLE patients and controls. In controls, we largely replicated previous findings of improved memory for conflict stimuli. While MTLE patients showed response time slowing during conflict trials as well, they did not exhibit a memory benefit. In controls, neural activity of conflict resolution and memory encoding interacted within a hippocampal region of interest. Here, left hippocampal recruitment was less efficient for memory performance in incongruent trials than in congruent trials, suggesting an intrahippocampal competition for limited resources. They also showed an involvement of precuneus and posterior cingulate cortex during conflict resolution. Both effects were not observed in MTLE patients, where activation of the precuneus and posterior cingulate cortex instead predicted later memory. Further research is needed to find out whether our findings reflect widespread functional reorganization of the episodic memory network due to hippocampal dysfunction.

Medical education too: sexual harassment within the educational context of medicine - insights of undergraduates.

BACKGROUND: Assessment of the presence and characteristics of sexual harassment in academic medicine is a global issue. Only limited international data are available so far. METHODS: Aim: To assess the extent of sexual harassment and identify the perpetrators in the student population of the medical school of Münster, Germany. A survey was undertaken, using the Medical Women's International Association sexual harassment questionnaire translated into German. The anonymous online questionnaire was sent as a link to all medical undergraduates at Münster Medical School via a mailing list between 1 October and 30 November 2018. Identifying or potentially identifying data were not collected. Data were analysed by descriptive statistical methods such as categorical variables. Baseline characteristics, e.g. answers by male or female medical students, were correlated with their individual sexual harassment experiences and perpetrator groups by means of univariate analysis. RESULTS: A total of 2162 medical students were asked to participate, with 623 (28.8%) completing the survey. Sexual harassment is a significant issue among medical students at Münster Medical School with over half (58.9%) of all undergraduates being exposed to sexually harassing behaviour. In total, 31.8% of all participants reported having experienced unwanted physical sexual contact such as unwanted physical touching, with 87.6% of the victims being female. Overall, 41.3% personally experienced verbal sexual harassment of which 87.4% were female. Furthermore, 8.5% of undergraduates faced forced sexual contact such as oral, anal or vaginal penetration, intercourse and rape, with all victims being female. Perpetrators in these cases were mostly male medical superiors (7.0%) and male patients (18.3%). In general, most perpetrators were patients, followed by medical superiors and educators, and less frequently by colleagues. CONCLUSIONS: Sexual harassment in medical education and the medical workplace is a significant problem in a German medical school. Most students experiencing sexual harassment are females. Female students also experience the more serious forms of sexual harassment more often.

Reduced hippocampal recruitment during response conflict resolution in mesial temporal lobe epilepsy.

Recent evidence suggests that the human hippocampus (HC) is not only involved in the processing of motivationally relevant approach-avoidance conflicts but is also engaged in the resolution of more general response conflicts as measured in the Stroop paradigm. Here we investigated whether neural activity in the HC is necessary for successful response conflict resolution. We compared hippocampal recruitment during an auditory Stroop paradigm in 20 patients with mesial temporal lobe epilepsy (MTLE) due to hippocampal sclerosis and 20 age-matched healthy controls using functional magnetic resonance imaging (fMRI). We analyzed hippocampal activation and behavioral performance in conflict trials relative to non-conflict trials. Moreover, functional connectivity (FC) analyses with left and right HCs as seeds were performed. Subjects' regional gray matter volumes were analyzed based on high-resolution T2-weighted MRI scans. The current study replicated previous results showing increased activation in left HC during the processing of conflict trials in healthy subjects. By contrast, MTLE patients showed higher behavioral costs of response conflict resolution and reduced conflict-related HC activation. In patients with left MTLE, left HC activation was predictive of faster conflict-related response times (RTs). By contrast, right HC activation was related to RT slowing, suggestive of a maladaptive compensation attempt in MTLE patients. Our results provide evidence that left hippocampal activation is required for the successful resolution of response conflicts.

Approaching altered inhibitory control in phenylketonuria: A functional MRI study with a Go-NoGo task in young female adults.

Subtle executive function deficits, particularly regarding inhibitory control, have been reported in patients with phenylketonuria (PKU) despite early dietary treatment. Purpose of this study was to assess whether young female adults with PKU exhibit altered neural activity underlying such deficits, particularly in a fronto-parietal cognitive control network (CCN). Behavioural data and functional magnetic resonance imaging (fMRI) data were acquired during a Go-NoGo task in 16 young adult patients with PKU and 17 control subjects. Hypothesis-driven analyses of behavioural and fMRI data in the CCN were supplemented by exploratory whole brain activation analyses. PKU patients exhibited a trend towards higher errors of commission. Patients exhibited marginally increased activation associated with inhibitory control in only one CCN core region (right middle frontal gyrus, p = .043). Whole brain analyses revealed widespread relatively increased activation in adults with PKU in the main task contrast (NoGo > Go). This increased activation was mainly observed outside the CCN and largely overlapped with the default mode network (DMN). In conclusion, only subtle inhibitory control deficits and associated brain activity differences were observed in young adults with PKU. Thus, this work adds to the notion that this particular population seems to be only slightly affected by such cognitive deficits. While there were also only minimal increases when compared to healthy subjects in brain activity in a cognitive control network, we observed more widespread activation increases outside this network. These results support the assumption of DMN dysfunction in PKU.

Subtle changes of gray matter volume in fibromyalgia reflect chronic musculoskeletal pain rather than disease-specific effects.

Fibromyalgia syndrome (FMS) is a chronic pain syndrome. Neuroimaging studies provided evidence of altered gray matter volume (GMV) in FMS but, similarly, in chronic pain of other origin as well. Therefore, the purpose of this study was to evaluate the disease specificity of GMV alterations in FMS by direct comparison. Structural MRI data of the brain were acquired in 25 females with FMS and two different control groups: 21 healthy subjects and 23 patients with osteoarthritis. Regional GMVs were compared by voxel-based morphometry and additional ROI-analyses. In conclusion, we did not identify significant GMV alterations in either FMS or OA patients compared to healthy controls when adopting a conservative statistical approach with multiple comparison correction. However, even under a more liberal approach no FMS-specific GMV changes were found because both pain groups presented increased gray matter volumes in the precentral gyrus and decreased GMV in the angular gyrus/middle occipital gyrus and middle temporal gyrus in comparison with healthy controls. Since no differences between both pain groups could be detected cortical GMV changes in FMS should not be interpreted as FMS-specific but might rather reflect changes in chronic pain in general. This previously held notion is confirmed in this study by direct comparison with a control group consisting of another pain disorder.

Effects of Cognitive Behavioral Therapy on Neural Processing of Agoraphobia-Specific Stimuli in Panic Disorder and Agoraphobia.

BACKGROUND: Patients suffering from panic disorder and agoraphobia are significantly impaired in daily life due to anxiety about getting into a situation due to apprehension about experiencing a panic attack, especially if escape may be difficult. Dysfunctional beliefs and behavior can be changed with cognitive behavioral therapy; however, the neurobiological effects of such an intervention on the anticipation and observation of agoraphobia-specific stimuli are unknown. METHODS: We compared changes in neural activation by measuring the blood oxygen level-dependent signal of 51 patients and 51 healthy controls between scans before and those after treatment (group by time interaction) during anticipation and observation of agoraphobia-specific compared to neutral pictures using 3-T fMRI. RESULTS: A significant group by time interaction was observed in the ventral striatum during anticipation and in the right amygdala during observation of agoraphobia-specific pictures; the patients displayed a decrease in ventral striatal activation during anticipation from pre- to posttreatment scans, which correlated with clinical improvement measured with the Mobility Inventory. During observation, the patients displayed decreased activation in the amygdala. These activational changes were not observed in the matched healthy controls. CONCLUSIONS: For the first time, neural effects of cognitive behavioral therapy were shown in patients suffering from panic disorder and agoraphobia using disorder-specific stimuli. The decrease in activation in the ventral striatum indicates that cognitive behavioral therapy modifies anticipatory anxiety and may ameliorate abnormally heightened salience attribution to expected threatening stimuli. The decreased amygdala activation in response to agoraphobia-specific stimuli indicates that cognitive behavioral therapy can alter the basal processing of agoraphobia-specific stimuli in a core region of the fear network.

Diagnostic classification of unipolar depression based on resting-state functional connectivity MRI: effects of generalization to a diverse sample.

In small, selected samples, an approach combining resting-state functional connectivity MRI and multivariate pattern analysis has been able to successfully classify patients diagnosed with unipolar depression. Purposes of this investigation were to assess the generalizability of this approach to a large clinically more realistic sample and secondarily to assess the replicability of previously reported methodological feasibility in a more homogeneous subgroup with pronounced depressive symptoms. Two independent subsets were drawn from the depression and control cohorts of the BiDirect study, each with 180 patients with and 180 controls without depression. Functional connectivity either among regions covering the gray matter or selected regions with known alterations in depression was assessed by resting-state fMRI. Support vector machines with and without automated feature selection were used to train classifiers differentiating between individual patients and controls in the entire first subset as well as in the subgroup. Model parameters were explored systematically. The second independent subset was used for validation of successful models. Classification accuracies in the large, heterogeneous sample ranged from 45.0 to 56.1% (chance level 50.0%). In the subgroup with higher depression severity, three out of 90 models performed significantly above chance (60.8-61.7% at independent validation). In conclusion, common classification methods previously successful in small homogenous depression samples do not immediately translate to a more realistic population. Future research to develop diagnostic classification approaches in depression should focus on more specific clinical questions and consider heterogeneity, including symptom severity as an important factor.

Distraction From Itch Shows Brainstem Activation Without Reduction in Experimental Itch Sensation.

The central processing of itch is not completely understood. This is the first study to use functional magnetic resonance imaging (fMRI) to examine the central modulation by distraction of experimentally induced itch. A total of 33 healthy volunteers were examined with fMRI. Periods of itch induction without distraction and itch with distraction by a Stroop task (psychological test, where the participants have to decide if the colour of the writing corresponds to the written word, for example if "red" is written in red or not) were counterbalanced during the scanning to examine task-specific changes in blood oxygenation level dependent-signal. The intensity of the subjects' itch sensation, desire to scratch and pain sensation were evaluated. Distraction by a Stroop task did not reduce itch intensity or urge to scratch. However, the Stroop task led to significantly higher activation of the left brainstem when it followed the "pure" itch sensation. Itch and pain seem to have similar inhibition pathways, particularly concerning brainstem activation during distraction. But as itch sensation, in contrast to pain, could not be sufficiently reduced by distraction, both entities might have different modulation systems.

Coordinate-based (ALE) meta-analysis of brain activation in patients with fibromyalgia.

There are an increasing number of neuroimaging studies that allow a better understanding of symptoms, neural correlates and associated conditions of fibromyalgia. However, the results of these studies are difficult to compare, as they include a heterogeneous group of patients, use different stimulation paradigms, tasks, and the statistical evaluation of neuroimaging data shows high variability. Therefore, this meta-analytic approach aimed at evaluating potential alterations in neuronal brain activity or structure related to pain processing in fibromyalgia syndrome (FMS) patients, using quantitative coordinate-based "activation likelihood estimation" (ALE) meta-analysis. 37 FMS papers met the inclusion criteria for an ALE analysis (1,264 subjects, 274 activation foci). A pooled ALE analysis of different modalities of neuroimaging and additional analyses according functional and structural changes indicated differences between FMS patients and controls in the insula, amygdala, anterior/mid cingulate cortex, superior temporal gyrus, the primary and secondary somatosensory cortex, and lingual gyrus. Our analysis showed consistent results across FMS studies with potential abnormalities especially in pain-related brain areas. Given that similar alterations have already been demonstrated in patients with other chronic pain conditions and the lack of adequate control groups of chronic pain subjects in most FMS studies, it is not clear however, whether these findings are associated with chronic pain in general or are unique features of patients with FMS. Hum Brain Mapp 37:1749-1758, 2016. © 2016 Wiley Periodicals, Inc.

Major depressive disorder: Findings of reduced homotopic connectivity and investigation of underlying structural mechanisms.

Depression has been associated with various alterations in magnetic resonance imaging (MRI) derived resting-state functional connectivity. Recently, homotopic connectivity, defined as functional connectivity between homotopic regions across hemispheres, has been reported to be reduced in patients with major depressive disorder (MDD). However, little is known about structural factors underlying alterations of homotopic connectivity, which would contribute to the understanding of the altered neurophysiological architecture in patients with MDD. We compared 368 patients with MDD and 461 never-depressed controls regarding voxel-mirrored homotopic connectivity (VMHC) and potential underlying mechanisms such as the structural connectivity of the corpus callosum, measured by DTI-derived fractional anisotropy (FA), and left-right symmetries in homotopic gray matter volumes. Compared to controls, patients with MDD exhibited reduced VMHC in the cuneus, putamen, superior temporal gyrus, insula, and precuneus. Within these regions, no differences in left-right symmetries in homotopic gray matter volumes were evident across cohorts. FA of the corpus callosum correlated with VMHC in the entire sample. However, patients with MDD and controls did not differ with regard to callosal FA. The findings indicate that MDD is associated with a loss of interhemispheric synchrony in regions known to be implicated in self-referential and reward processing. They also suggest that additional mechanisms are implicated in altered homotopic connectivity of patients with MDD, other than direct callosal fiber pathways or asymmetries in homotopic gray matter volumes.

Itch Perception and Skin Reactions as Modulated by Verbal Suggestions: Role of Participant's and Investigator's Sex.

This study investigated sex-specific differences in itch perception and skin reactions, as modulated by verbal suggestions, and the role of the investigator's sex. Healthy volunteers (50 males, 50 females), divided into 4 groups, were tested by male and female investigators. Itch was induced via prick testing with sodium chloride and histamine in 4 runs; 2 control conditions (with no exaggerated verbal comments about expected itch) and 2 experimental conditions (with exaggerated verbal comments). After 5 min, wheal and flare reactions were measured and itch intensity was rated by subjects on a numerical rating scale. Exaggerated verbal suggestions resulted in higher itch intensity ratings in the sodium chloride and histamine condition, and higher unpleasantness ratings and a wheal of greater extent in the sodium chloride condition, as well as a flare of greater extent in the histamine condition. The magnitude of the differences between the exaggerated verbal suggestion conditions and respective control conditions was only significantly different between male and female investigators concerning flare size in the histamine condition. There were no differences between male and female participants. Therefore, sex differences may play only a minor role in nocebo-induced itch perception.

Therapygenetics: anterior cingulate cortex-amygdala coupling is associated with 5-HTTLPR and treatment response in panic disorder with agoraphobia.

Variation in the 5'-flanking promoter region of the serotonin transporter gene SLC6A4, the 5-HTT-linked polymorphic region (5-HTTLPR) has been inconclusively associated with response to cognitive-behavioural therapy (CBT). As genomic functions are stronger related to neural than to behavioural markers, we investigated the association of treatment response, 5-HTTLPR and functional brain connectivity in patients with panic disorder with agoraphobia (PD/AG). Within the national research network PANIC-NET 231 PD/AG patients who provided genetic information underwent a manualized exposure-based CBT. A subset of 41 patients participated in a functional magnetic resonance imaging (fMRI) add-on study prior to treatment applying a differential fear conditioning task. Neither the treatment nor the reduced fMRI sample showed a direct effect of 5-HTTLPR on treatment response as defined by a reduction in the Hamilton Anxiety Scale score ≥50 % from baseline to post assessment. On a neural level, inhibitory anterior cingulate cortex (ACC)-amygdala coupling during fear conditioning that had previously been shown to characterize treatment response in this sample was driven by responders with the L/L genotype. Building upon conclusive evidence from basic and preclinical findings on the association of the 5-HTTLPR polymorphism with emotion regulation and related brain connectivity patterns, present findings translate these to a clinical sample of PD/AG patients and point towards a potential intermediate connectivity phenotype modulating response to exposure-based CBT.

Health-Related Quality of Life in Chronic Pruritus: An Analysis Related to Disease Etiology, Clinical Skin Conditions and Itch Intensity.

BACKGROUND: It is unknown if health-related quality of life (HRQoL) differs between diseases associated with chronic pruritus (CP). OBJECTIVE: To analyze HRQoL in relation to age, gender, skin lesions (primary vs. scratch-induced secondary) and itch intensity. METHODS: Consecutive patients of our itch clinic were assessed with the Dermatology Life Quality Index (DLQI) and visual analogue scale (VAS). RESULTS: In 510 CP patients (282 females; median age, 61.4 years), DLQI scores and VAS values were highly correlated, irrespective of the type of skin lesion. Overall, women had a lower HRQoL compared to men (females: 10.7 ± 6.7, males: 8.9 ± 6.7), but female gender was only associated with worse quality of life in patients <65 years old. CONCLUSION: HRQoL impairment in CP is highly influenced by pruritus intensity but not to the visible skin lesion or underlying cause. With limitations to item bias, DLQI is a suitable instrument for estimating quality of life impairment by CP.

Facing the challenges of chronic pruritus: a report from a multi-disciplinary medical itch centre in Germany.

The complex nature and difficult-to-establish aetiology of chronic pruritus (CP) makes it challenging to provide medical care for patients with CP. This challenge can only be met with a multidisciplinary approach. The first multidisciplinary Itch Centre in Germany was established at the University of Münster in 2002 to meet the needs of this patient population. More than 2,500 outpatients and 400 inpatients are diagnosed and receive treatment each year. To ensure evidence-based medical care, an electronic system for medical documentation and patient-reported outcomes was established. Automated data transfer to a research database enables comprehensive data analysis. Our translational research has characterized peripheral and central itch mechanisms, provided novel clustering of CP patients, and identified novel target-specific therapies (e.g. neurokinin 1 receptor-antagonist). The multidisciplinary approach, combined with basic, clinical and translational research, enables comprehensive medical care of patients as well as implementation of high-quality experimental and clinical studies.

Internal focus of attention in anxiety-sensitive females up-regulates amygdale activity: an fMRI study.

Cognitive behavioral models of panic disorder (PD) stress the importance of an increased attentional focus towards bodily symptoms in the onset and maintenance of this debilitating anxiety disorder. In this fMRI mental tracking paradigm, we looked at the effects of focusing one's attention internally (interoception) vs. externally (exteroception) in a well-studied group at risk for PD-that is anxiety-sensitive females (AS-high). We hypothesized that AS-high subjects compared to control subjects will present higher arousal and decreased valence scores during interoception and parallel higher activity in brain areas which are associated with fear and interoception. 24 healthy female students with high levels of anxiety sensitivity and 24 healthy female students with normal levels of anxiety sensitivity serving as control group were investigated by 3 T fMRI. Subjects either focused their attention on their heartbeats (internal condition) or on neutral tones (external condition). Task performance was monitored by reporting the number of heartbeats or tones after each block. State of arousal and emotional valence were also assessed. The high anxiety-sensitive group reported higher arousal scores compared to controls during the course of the experiment. Simultaneously, fMRI results indicated higher activation in anxiety-sensitive participants than in controls during interoception in a network of cortical and subcortical brain regions (thalamus, amygdala, parahippocampus) that overlaps with known fear circuitry structures. In particular, the activity of the right amygdala was up-regulated. Future prospective-longitudinal studies are needed to validate the role of the amygdala for transition to disorder. Attention to internal body functions up-regulates the activity of interoceptive and fear-relevant brain regions in anxiety-sensitive females, a high-risk group for the development of anxiety disorders.

Neural correlates of procedural variants in cognitive-behavioral therapy: a randomized, controlled multicenter FMRI study.

BACKGROUND: Cognitive behavioral therapy (CBT) is an effective treatment for panic disorder with agoraphobia (PD/AG). It is unknown, how variants of CBT differentially modulate brain networks involved in PD/AG. This study was aimed to evaluate the effects of therapist-guided (T+) versus self-guided (T-) exposure on the neural correlates of fear conditioning in PD/AG. METHOD: In a randomized, controlled multicenter clinical trial in medication-free patients with PD/AG who were treated with 12 sessions of manualized CBT, functional magnetic resonance imaging (fMRI) was used during fear conditioning before (t1) and after CBT (t2). Quality-controlled fMRI data from 42 patients and 42 healthy subjects (HS) were obtained. Patients were randomized to two variants of CBT (T+, n = 22, and T-, n = 20). RESULTS: The interaction of diagnosis (PD/AG, HS), treatment group (T+, T-), time point (t1, t2) and stimulus type (conditioned stimulus: yes, no) revealed activation in the left hippocampus and the occipitotemporal cortex. The T+ group demonstrated increased activation of the hippocampus at t2 (t2 > t1), which was positively correlated with treatment outcome, and a decreased connectivity between the left inferior frontal gyrus and the left hippocampus across time (t1 > t2). CONCLUSION: After T+ exposure, contingency-encoding processes related to the posterior hippocampus are augmented and more decoupled from processes of the left inferior frontal gyrus, previously shown to be dysfunctionally activated in PD/AG. Linking single procedural variants to neural substrates offers the potential to inform about the optimization of targeted psychotherapeutic interventions.

Seeing more than the Tip of the Iceberg: Approaches to Subthreshold Effects in Functional Magnetic Resonance Imaging of the Brain.

Many functional magnetic resonance imaging (fMRI) studies and presurgical mapping applications rely on mass-univariate inference with subsequent multiple comparison correction. Statistical results are frequently visualized as thresholded statistical maps. This approach has inherent limitations including the risk of drawing overly-selective conclusions based only on selective results passing such thresholds. This article gives an overview of both established and newly emerging scientific approaches to supplement such conventional analyses by incorporating information about subthreshold effects with the aim to improve interpretation of findings or leverage a wider array of information. Topics covered include neuroimaging data visualization, p-value histogram analysis and the related Higher Criticism approach for detecting rare and weak effects. Further examples from multivariate analyses and dedicated Bayesian approaches are provided.

Elevated accuracy in recognition of subliminal happy facial expressions in patients with panic disorder after psychotherapy.

Background: Individuals with anxiety disorders (ADs) often display hypervigilance to threat information, although this response may be less pronounced following psychotherapy. This study aims to investigate the unconscious recognition performance of facial expressions in patients with panic disorder (PD) post-treatment, shedding light on alterations in their emotional processing biases. Methods: Patients with PD (n=34) after (exposure-based) cognitive behavior therapy and healthy controls (n=43) performed a subliminal affective recognition task. Emotional facial expressions (fearful, happy, or mirrored) were displayed for 33 ms and backwardly masked by a neutral face. Participants completed a forced choice task to discriminate the briefly presented facial stimulus and an uncovered condition where only the neutral mask was shown. We conducted a secondary analysis to compare groups based on their four possible response types under the four stimulus conditions and examined the correlation of the false alarm rate for fear responses to non-fearful (happy, mirrored, and uncovered) stimuli with clinical anxiety symptoms. Results: The patient group showed a unique selection pattern in response to happy expressions, with significantly more correct "happy" responses compared to controls. Additionally, lower severity of anxiety symptoms after psychotherapy was associated with a decreased false fear response rate with non-threat presentations. Conclusion: These data suggest that patients with PD exhibited a "happy-face recognition advantage" after psychotherapy. Less symptoms after treatment were related to a reduced fear bias. Thus, a differential facial emotion detection task could be a suitable tool to monitor response patterns and biases in individuals with ADs in the context of psychotherapy.