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Background: Musicians' dystonia (MD) is a movement disorder with several established risk factors, but the exact pathophysiology remains unknown. Recent research suggests dysfunction in sensory-motor, basal ganglia, cerebellar, and limbic loops as potential causes. Adverse childhood experiences are also considered risk factors., Objective: This study aimed to investigate whether MD patients have experienced more childhood trauma, leading to increased stress reactivity and neural vulnerability to movement disorders., Methods: Using functional magnetic resonance imaging and the Montreal Imaging Stress Task, 40 MD patients were compared with 39 healthy musicians (HMs). Whole-brain analysis and regions of interest analysis were performed. Parameter estimates and subjective stress levels were compared between groups and correlated with the Childhood Trauma Questionnaire., Results: MD patients reported significantly higher childhood trauma scores than healthy control subjects, but they did not differ in their subjective stress experiences. Stress-related activity of limbic areas was neither found in the whole sample nor between the two groups. Instead, increased activity of visual association and temporal areas was observed, but this activation did not differ between patients and HMs. However, patients showed a tendency toward reduced precuneus activity under stress. Adverse childhood experiences were negatively correlated with precuneus, thalamus, and substantia nigra activity across all participants., Conclusions: Overall, MD patients and HMs had similar subjective and neurological reactions to stress but differed in childhood trauma experiences and precuneus activity under stress. Further research about the functional connectivity between precuneus, cerebellum, thalamus, and basal ganglia in musicians is needed. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Grapheme-color synesthesia is a normal and healthy variation of human perception. It is characterized by the association of letters or numbers with color perceptions. The etiology of synesthesia is not yet fully understood. Theories include hyperconnectivity in the brain, cross-activation of adjacent or functionally proximate sensory areas of the brain, or various models of lack of inhibitory function in the brain. The growth factor brain-derived neurotrophic (BDNF) plays an important role in the development of neurons, neuronal pathways, and synapses, as well as in the protection of existing neurons in both the central and peripheral nervous systems. ELISA methods were used to compare BDNF serum concentrations between healthy test subjects with and without grapheme-color synesthesia to establish a connection between concentration and the occurrence of synesthesia. The results showed that grapheme-color synesthetes had an increased BDNF serum level compared to the matched control group. Increased levels of BDNF can enhance the brain's ability to adapt to changing environmental conditions, injuries, or experiences, resulting in positive effects. It is discussed whether the integration of sensory information is associated with or results from increased neuroplasticity. The parallels between neurodegeneration and brain regeneration lead to the conclusion that synesthesia, in the sense of an advanced state of consciousness, is in some cases a more differentiated development of the brain rather than a relic of early childhood., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Eckardt, Sinke, Bleich, Lichtinghagen and Zedler.)

Meta-analyses suggest a sustained alleviation of depressive symptoms through glabellar botulinum toxin (BTX) injections. This can be explained by the disruption of facial feedback loops, which may moderate and reinforce the experience of negative emotions. Borderline personality disorder (BPD) is characterized by excessive negative emotions. Here, a seed-based resting-state functional connectivity (rsFC) analysis following BTX (N = 24) or acupuncture (ACU, N = 21) treatment in BPD is presented on areas related to the motor system and emotion processing. RsFC in BPD using a seed-based approach was analyzed. MRI data were measured before and 4 weeks after treatment. Based on previous research, the rsFC focus was on limbic and motor areas as well as the salience and default mode network. Clinically, after 4 weeks both groups showed a reduction of borderline symptoms. However, the anterior cingulate cortex (ACC) and the face area in the primary motor cortex (M1) displayed aberrant rsFC after BTX compared to ACU treatment. The M1 showed higher rsFC to the ACC after BTX treatment compared to ACU treatment. In addition, the ACC displayed an increased connectivity to the M1 as well as a decrease to the right cerebellum. This study shows first evidence for BTX-specific effects in the motor face region and the ACC. The observed effects of BTX on rsFC to areas are related to motor behavior. Since symptom improvement did not differ between the two groups, a BTX-specific effect seems plausible rather than a general therapeutic effect., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Persistent Genital Arousal Disorder (PGAD) is a rare condition-mostly in women-where patients perceive prolonged genital arousal without any sexual desire or stimulation. Etiopathological considerations reach from peripheral to central issues over local disturbance of the pudendal nerve to neuropathy, psychosocial, and pharmacological theories. Since well controlled clinical studies about PGAD in conjunction with a mental and somatic health status are missing, this study is a detailed clinical investigation of PGAD patients compared to healthy controls. 26 women who fulfilled diagnostic criteria for PGAD were compared to 26 age matched healthy controls. Investigations included comparison of vegetative, gynaecological and sexual history, psychiatric features as well as a (neuro-)radiological, neurophysiological and gynaecological examination. Moreover, a detailed clinical characterisation of PGAD symptoms was performed. PGAD symptoms were mostly characterised as tingling or prickling and were permanently present. In over 80%, PGAD symptoms were located in the clitoris. Almost 70% reported radiations to other regions of the body. Most frequent trigger factors were tight clothes, mental stress, driving a car/bus/bicycle and sexual intercourse. Relieving factors were mainly distraction, relaxation, physical exercise, masturbation and swimming. In group comparisons, PGAD presented with significant higher rates of sexual dysfunctions, spontaneous orgasms, swelling of the genitals, extraordinary lubrication as well as higher rates in depression, agoraphobia, generalized anxiety disorder and lifetime panic disorder. Significantly more PGAD patients were diagnosed with restless legs symptoms. In contrast childhood traumatization, somatization disorder, suicidality, gynaecological as well as neurophysiological examination of the pudendal nerve were not different between the groups. MRI of the brain, pelvis and spinal cord was unsuspicious and incidental findings - including Tarlov cysts or pelvic venous congestion - were equally distributed among the groups. In summary, our study provides a careful characterization of women with PGAD highlighting a serious mental burden, most probably as a consequence of PGAD. With the current set of clinical investigations there was no evidence of a clear causal relationship to a specific clinical finding as it has been previously discussed. Future studies and additional techniques will have to further explore where and how in the peripheral or central nervous systems PGAD develops., (© 2023. The Author(s).)

Learning to play an instrument at an advanced age may help to counteract or slow down age-related cognitive decline. However, studies investigating the neural underpinnings of these effects are still scarce. One way to investigate the effects of brain plasticity is using resting-state functional connectivity (FC). The current study compared the effects of learning to play the piano (PP) against participating in music listening/musical culture (MC) lessons on FC in 109 healthy older adults. Participants underwent resting-state functional magnetic resonance imaging at three time points: at baseline, and after 6 and 12 months of interventions. Analyses revealed piano training-specific FC changes after 12 months of training. These include FC increase between right Heschl's gyrus (HG), and other right dorsal auditory stream regions. In addition, PP showed an increased anticorrelation between right HG and dorsal posterior cingulate cortex and FC increase between the right motor hand area and a bilateral network of predominantly motor-related brain regions, which positively correlated with fine motor dexterity improvements. We suggest to interpret those results as increased network efficiency for auditory-motor integration. The fact that functional neuroplasticity can be induced by piano training in healthy older adults opens new pathways to countervail age related decline., (© 2023. The Author(s).)

Multisensory, as opposed to unisensory processing of stimuli, has been found to enhance the performance (e.g., reaction time, accuracy, and discrimination) of healthy individuals across various tasks. However, this enhancement is not as pronounced in patients with schizophrenia (SZ), indicating impaired multisensory integration (MSI) in these individuals. To the best of our knowledge, no study has yet investigated the impact of MSI deficits in the context of working memory, a domain highly reliant on multisensory processing and substantially impaired in schizophrenia. To address this research gap, we employed two adopted versions of the continuous object recognition task to investigate the effect of single-trail multisensory encoding on subsequent object recognition in 21 schizophrenia patients and 21 healthy controls (HC). Participants were tasked with discriminating between initial and repeated presentations. For the initial presentations, half of the stimuli were audiovisual pairings, while the other half were presented unimodal. The task-relevant stimuli were then presented a second time in a unisensory manner (either auditory stimuli in the auditory task or visual stimuli in the visual task). To explore the impact of semantic context on multisensory encoding, half of the audiovisual pairings were selected to be semantically congruent, while the remaining pairs were not semantically related to each other. Consistent with prior studies, our findings demonstrated that the impact of single-trial multisensory presentation during encoding remains discernible during subsequent object recognition. This influence could be distinguished based on the semantic congruity between the auditory and visual stimuli presented during the encoding. This effect was more robust in the auditory task. In the auditory task, when congruent multisensory pairings were encoded, both participant groups demonstrated a multisensory facilitation effect. This effect resulted in improved accuracy and RT performance. Regarding incongruent audiovisual encoding, as expected, HC did not demonstrate an evident multisensory facilitation effect on memory performance. In contrast, SZs exhibited an atypically accelerated reaction time during the subsequent auditory object recognition. Based on the predictive coding model we propose that this observed deviations indicate a reduced semantic modulatory effect and anomalous predictive errors signaling, particularly in the context of conflicting cross-modal sensory inputs in SZ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ghaneirad, Borgolte, Sinke, Čuš, Bleich and Szycik.)

Aim: Compulsive Sexual Behavior Disorder (CSBD) is a new category in ICD-11. Research examining underlying brain mechanisms is sparse. Research into neurobiological differences can be helpful in advancing the possibilities of new diagnostic approaches and therapeutic methods. The present study aimed to examine brain matter volume and resting state functional connectivity (rs-FC) in CSBD., Methods: Structural and rs-FC magnetic resonance imaging and data from questionnaires were collected in 30 men with CSBD and 32 age- and education-matched controls. Whole brain voxel based morphometry (VBM) and seed based rs-FC in a-priori defined seeds were analyzed., Results: Structural analyses showed that men with CSBD had significantly increased gray matter volume in the right cerebellum, middle occipital and superior frontal lobe. No differences in rs-FC could be detected when using these brain structures as seed regions in rs-FC. In contrast, literature based rs-FC analysis revealed decreased rs-FC between the right orbital middle frontal cortex (mOFC) and the right gyrus rectus, as well as between left pallidum and right post/precentral gyrus in men with CSBD. In the left amygdala we observed increased rs-FC with precuneus in this group. In addition, most of these measures correlated with symptom severity., Conclusion: Structural findings may underscore the idea that the cerebellum plays an important role in sexual arousal and CSBD. Perhaps, a simultaneous activation of the left amygdala and the precuneus reflects a constant sexual occupation of men with CSBD. Furthermore, lower connectivity between mOFC and gyrus rectus in CSBD may support the assumption that sexual stimuli are evaluated more positively because inhibition is decreased.

The hypothalamus regulates sexual behavior and is simultaneously associated with aggression and violence. Consequently, this brain region is relevant in research of pedophilia and child sexual offenses (CSO). The distinction between these two phenomena is of great importance and was the object of consideration of this study. We analyzed exclusively men, including 73 pedophilic offenders who committed CSO, an equal number of people with pedophilia but without such offenses, and 133 non-pedophilic, non-offending subjects who formed the control group. All data were collected in a multicenter in vivo study and analyzed using a semi-automated segmentation algorithm for 3-Tesla magnetic resonance images. Men with pedophilia who committed CSO on average had a 47 mm 3 smaller hypothalamus per side than people without committed CSO. This effect was driven by both the group of non-offending people with pedophilia and the control group. By contrast, the exploratory comparison of pedophilic persons without CSO with the control group showed no significant difference. The present study demonstrates a deviant hypothalamic structure as a neurobiological correlate of CSO in pedophiles, but not in people with pedophilia who have not committed CSO. Thus, it strengthens the argument to distinguish between sexual offending and paraphilic sexual preferences., (© 2022. The Author(s).)

Introduction: Little is known about cognitive control in adults with high-functioning forms of autism spectrum disorder because previous research focused on children and adolescents. Cognitive control is crucial to monitor and readjust behavior after errors to select contextually appropriate reactions. The congruency effect and conflict adaptation are measures of cognitive control. Post-error slowing, error-related negativity and error positivity provide insight into behavioral and electrophysiological correlates of error processing. In children and adolescent with autism spectrum disorder deficits in cognitive control and error processing have been shown by changes in post-error slowing, error-related negativity and error positivity in the flanker task., Methods: We performed a modified Eriksen flanker task in 17 adults with high-functioning autism spectrum disorder and 17 healthy controls. As behavioral measures of cognitive control and error processing, we included reaction times and error rates to calculate congruency effects, conflict adaptation, and post-error slowing. Event-related potentials namely error-related negativity and error positivity were measured to assess error-related brain activity., Results: Both groups of participants showed the expected congruency effects demonstrated by faster and more accurate responses in congruent compared to incongruent trials. Healthy controls exhibited conflict adaptation as they obtained performance benefits after incongruent trials whereas patients with autism spectrum disorder did not. The expected slowing in reaction times after errors was observed in both groups of participants. Individuals with autism spectrum disorder demonstrated enhanced electrophysiological error-processing compared to healthy controls indicated by increased error-related negativity and error positivity difference amplitudes., Discussion: Our findings show that adults with high-functioning autism spectrum disorder do not show the expected upregulation of cognitive control in response to conflicts. This finding implies that previous experiences may have a reduced influence on current behavior in these patients which possibly contributes to less flexible behavior. Nevertheless, we observed intact behavioral reactions after errors indicating that adults with high-functioning autism spectrum disorder can flexibly adjust behavior in response to changed environmental demands when necessary. The enhancement of electrophysiological error-processing indicates that adults with high-functioning autism spectrum disorder demonstrate an extraordinary reactivity toward errors reflecting increased performance monitoring in this subpopulation of autism spectrum disorder patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Möde, Borgolte, Ghaneirad, Roy, Sinke, Szycik, Bleich and Wiswede.)

Background and Aims: Hypersexual disorder is characterized by recurrent and intense sexual fantasies, sexual urges, or sexual behaviors that can lead to clinically relevant levels of distress and adverse consequences for affected individuals. Earlier research has established a connection between sexual phenomena, such as compulsive sexual behavior, and personality features. The aim of the present study was to gain further insights into the associations of personality maladjustment and HD., Methods: The present study applied the dimensional approach of personality maladjustment presented in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) to connect compulsive sexual behavior to personality maladjustment. We investigated 47 men suffering from HD (age: M = 36.51, SD = 11.47) and 38 matched men without HD (age: M = 37.92, SD = 12.33) regarding personality maladjustment using a 100-item version of the Personality Inventory for DSM-5 (PID-5-BF)., Results: The men with HD showed higher levels of personality maladjustment regarding all PID-5-BF domains (negative affect, detachment, psychoticism, antagonism, and disinhibition) and significantly differentiated from men without HD in the level of subordinate facets. However, no domain of personality differentiated significantly between groups using a binary stepwise logistic regression analysis., Discussion and Conclusions: In sum, the findings of the study underline the extent of personality maladjustment in men with HD. Interpersonal difficulties which men with HD frequently experience can contribute to clinically relevant levels of distress and adverse consequences reported by affected individuals.

In everyday verbal communication, auditory speech perception is often disturbed by background noise. Especially in disadvantageous hearing conditions, additional visual articulatory information (e.g., lip movement) can positively contribute to speech comprehension. Patients with schizophrenia (SZs) demonstrate an aberrant ability to integrate visual and auditory sensory input during speech perception. Current findings about underlying neural mechanisms of this deficit are inconsistent. Particularly and despite the importance of early sensory processing in speech perception, very few studies have addressed these processes in SZs. Thus, in the present study, we examined 20 adult subjects with SZ and 21 healthy controls (HCs) while presenting audiovisual spoken words (disyllabic nouns) either superimposed by white noise (-12 dB signal-to-noise ratio) or not. In addition to behavioral data, event-related brain potentials (ERPs) were recorded. Our results demonstrate reduced speech comprehension for SZs compared to HCs under noisy conditions. Moreover, we found altered N1 amplitudes in SZ during speech perception, while P2 amplitudes and the N1-P2 complex were similar to HCs, indicating that there may be disturbances in multimodal speech perception at an early stage of processing, which may be due to deficits in auditory speech perception. Moreover, a positive relationship between fronto-central N1 amplitudes and the positive subscale of the Positive and Negative Syndrome Scale (PANSS) has been observed.

Musical training can improve fine motor skills and cognitive abilities and induce macrostructural brain changes. However, it is not clear whether the changes in motor skills occur simultaneously with changes in cognitive and neurophysiological parameters. In this study, 156 healthy, musically naïve and right-handed older adults were recruited and randomly assigned to a piano training or a music listening group. Before, after 6 and 12 months, participants were scanned using MRI and assessed for fine motor skills, auditory working memory and processing speed. A Bayesian multilevel modelling approach was used to examine behavioural and neurophysiological group differences. The relationships between motor and cognitive and between motor and neurophysiological parameters were determined using latent change score models. Compared with music listening, practicing piano resulted in greater improvement in fine motor skills and probably working memory. Only in the piano group, unimanual fine motor skills and grey matter volume of the contralateral M1 changed together during the 6-12-month period. Additionally, M1 co-developed with ipsilateral putamen and thalamus. Playing piano induced more prevalent coupling between the motor and cognitive domains. However, there is little evidence that fine motor control develops concurrently with cognitive functions. Playing an instrument promotes motor, cognitive and neural development into older age. During the learning process, the consolidation of piano skills appears to take place in sensorimotor networks, enabling musicians to perform untrained motor tasks with higher acuity. Relationships between the development of motor acuity and cognition were bidirectional and can be explained by a common cause as well as by shared resources with compensatory mechanisms., (© 2023 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Introduction: The Attention Training Technique (ATT) developed as part of metacognitive therapy is a psychotherapeutic treatment method used to enhance top-down attentional flexibility and control. This study investigated potential neurocognitive changes due to ATT and its underlying neural mechanisms using pre-to-post functional magnetic resonance imaging (fMRI)., Materials and Methods: Fifty-four healthy participants were subjected to a randomized, sham-controlled attention training and evaluated using a neurocognitive test battery that partly took place in an fMRI environment. Participants received two doses ATT or sham ATT daily for 1 week. On day eight, all subjects completed the neurocognitive test battery again., Results: After the training, the ATT group showed a significant improvement in reaction times regarding attentional disengagement compared to the sham ATT group. fMRI data showed decreased levels of activation in the anterior cingulate cortex (ACC) when comparing the ATT group to the sham ATT group during attentional disengagement post intervention. No ATT > sham ATT effects were found regarding selective auditory attention, working memory performance and inhibitory control., Discussion: These findings putatively indicate that ATT facilitates faster attention allocation and increased attentional flexibility in healthy subjects. The fMRI results suggest this ATT-dependent improvement is accompanied by reduced ACC activity, indicating a more flexible attentional state., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jahn, Sinke, Kayali, Krug, Leichter, Peschel, Müller, Burak, Krüger, Kahl and Heitland.)

The menstrual cycle is characterized by various hormonal alterations and associations with mental and physical conditions have been postulated. Among endocrine factors, the androgen system has been a target of major interest in males and to a lesser extent in females and may influence emotion, cognition, behavior and somatic factors. Only few studies investigated alterations of these parameters throughout the menstrual cycle and there is a lack of studies exploring a link towards epigenetic and genetic regulation. This multisite longitudinal study examines behavioral parameters including affectivity, stress perception and various diary parameters of mental and physical well-being in conjunction with testosterone and LH plasma levels in 87 menstruating women. Additionally, Cysteine-Adenenine-Guanin (CAG) repeat length and methylation of the androgen receptor gene collected at four time points across two cycles comprising the menstrual, pre-ovulatory, mid-luteal and premenstrual phase were assesed. There was a significant increase of LH and testosterone plasma levels during the pre-ovulatory phase as well as a decrease of methylation of the androgen receptor at mid-luteal phase. Subjective ratings of physical condition and sexual interest peaked during the pre-ovulatory phase and the former correlated negatively with the androgen receptor gene methylation level. This longitudinal study shows alterations of the androgen system including epigenetic measurements throughout the menstrual cycle. While a link between peripheral testosterone and sexual activity and between increased physical condition and an upregulation of testosterone receptor protein expression can be assumed, the majority of parameters remained unchanged. These initial findings need validation by subsequent studies., Competing Interests: Declaration of Competing Interest All authors report none., (Copyright © 2022. Published by Elsevier Inc.)

Previous studies have indicated that glabellar botulinum toxin (BTX) injections may lead to a sustained alleviation of depression. This may be accomplished by the disruption of a facial feedback loop, which potentially mitigates the experience of negative emotions. Accordingly, glabellar BTX injection can attenuate amygdala activity in response to emotional stimuli. A prototypic condition with an excess of negative emotionality and impulsivity accompanied by elevated amygdala reactivity to emotional stimuli is borderline personality disorder (BPD). In order to improve the understanding of how glabellar BTX may affect the processing of emotional stimuli and impulsivity, we conducted a functional magnetic resonance imaging (fMRI) study. Our hypotheses were (1) glabellar BTX leads to increased activation in prefrontal areas during inhibition performance and (2) BTX decreases amygdala activity during the processing of emotional stimuli in general. Using an emotional go-/no-go paradigm during fMRI, the interference of emotion processing and impulsivity in a sample of n = 45 women with BPD was assessed. Subjects were randomly assigned to BTX treatment or serial acupuncture (ACU) of the head. After 4 weeks, both treatments led to a reduction in the symptoms of BPD. However, BTX treatment was specifically associated with improved inhibition performance and increased activity in the motor cortex. In addition, the processing of negative emotional faces was accompanied by a reduction in right amygdala activity. This study provides the first evidence that glabellar BTX injections may modify central neurobiological and behavioural aspects of BPD. Since the control treatment produced similar clinical effects, these neurobiological findings may be specific to BTX and not a general correlate of symptomatic improvement., (© 2022. The Author(s).)

Morphological differences in the auditory brain of musicians compared to nonmusicians are often associated with life-long musical activity. Cross-sectional studies, however, do not allow for any causal inferences, and most experimental studies testing music-driven adaptations investigated children. Although the importance of the age at which musical training begins is widely recognized to impact neuroplasticity, there have been few longitudinal studies examining music-related changes in the brains of older adults. Using magnetic resonance imaging, we measured cortical thickness (CT) of 12 auditory-related regions of interest before and after 6 months of musical instruction in 134 healthy, right-handed, normal-hearing, musically-naive older adults (64-76 years old). Prior to the study, all participants were randomly assigned to either piano training or to a musical culture/music listening group. In five regions-left Heschl's gyrus, left planum polare, bilateral superior temporal sulcus, and right Heschl's sulcus-we found an increase in CT in the piano training group compared with the musical culture group. Furthermore, CT of the right Heschl's gyrus could be identified as a morphological substrate supporting speech in noise perception. The results support the conclusion that playing an instrument is an effective stimulator for cortical plasticity, even in older adults., (© 2022 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals LLC on behalf of New York Academy of Sciences.)

While aging is characterized by neurodegeneration, musical training is associated with experience-driven brain plasticity and protection against age-related cognitive decline. However, evidence for the positive effects of musical training mostly comes from cross-sectional studies while randomized controlled trials with larger sample sizes are rare. The current study compares the influence of six months of piano training with music listening/musical culture lessons in 121 musically naïve healthy elderly individuals with regard to white matter properties using fixel-based analysis. Analyses revealed a significant fiber density decline in the music listening/musical culture group (but not in the piano group), after six months, in the fornix, which is a white matter tract that naturally declines with age. In addition, these changes in fiber density positively correlated to episodic memory task performances and the amount of weekly piano training. These findings not only provide further evidence for the involvement of the fornix in episodic memory encoding but also more importantly show that learning to play the piano at an advanced age may stabilize white matter microstructure of the fornix., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jünemann, Marie, Worschech, Scholz, Grouiller, Kliegel, Van De Ville, James, Krüger, Altenmüller and Sinke.)

Background: Inhibition of frowning via injections of botulinum toxin A (BTX) into the glabellar region has shown beneficial effects in the treatment of major depression. Preliminary research suggests that improvements in the affective domain are not depression-specific, but may also translate to other psychiatric disorders., Aim: This 16-week, single-blind, two-center randomized controlled trial investigated the influence of BTX on clinical symptoms of borderline personality disorder (BPD)., Methods: Fifty-four patients with BPD were randomly assigned to treatment with BTX (n  = 27) or a minimal acupuncture (ACU) control condition ( n  = 27). Clinical outcomes were followed at 2, 4, 6, 8, 12, and 16 weeks. Primary endpoint was the relative score change on the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD) 8 weeks after baseline relative to the control group and adjusted for treatment center. Secondary and additional outcome variables were self-rated borderline symptoms, comorbid symptoms of depression, psychological distress, and clinical global impression., Results: Participants showed significant improvements at the primary efficacy endpoint in both treatment groups (BTX: M  = -0.39, SD  = 0.39; ACU: M  = -0.35, SD  = 0.42), but no superior effect of the BTX condition in comparison with the control intervention was found- F (1,5323) = 0.017, p  = 0.68). None of the secondary or additional outcomes yielded significant group differences. Side effects were mild and included headache, transient skin or muscle irritations, and dizziness., Conclusion: Evidence regarding the efficacy of BTX for BDP remains limited, and the design of adequate control conditions presents an opportunity for further research. ClinicalTrials.gov registry : Botulinum Toxin A for Emotional Stabilization in Borderline Personality Disorder (BPD), NCT02728778, https://clinicaltrials.gov/ct2/show/NCT02728778.

Numerous studies have shown associations between anomalies of the serotonergic system and impulsive behavior, depression, or traumatic life events. However, it is currently unknown, whether pedophilia or child sexual offending (CSO) is also related to alterations of the serotonergic system. Using a two by two factorial paradigm within a multisite consortium (NeMUP*) study cohort, we analyzed whether the SLC6A4-linked polymorphic region (SLC6A4LPR) or the SLC6A4 (transporter) and HTR3A (receptor) promotor methylation rates differed with regard to a pedophilic preference and/or child sexual offending. Methylation rates of HTR3A showed significant differences between child sexual offenders and non-offenders, with child sexual offenders showing lower methylation rates. Moreover, HTR3A methylation rates showed significant negative correlations with the Child Trauma Questionnaire (CTQ) subscale "sexual violence", and the number of sexual offenses committed. Interestingly, we also found pedophilia-related alterations in 5HT 3A as well as SLC6A4 methylation rates. For HTR3A we detected significant higher methylation rates in subjects with a pedophilic sexual preference, whereas for SLC6A4 methylation rates were reduced, indicating a possible downregulation of the serotonergic system in total. Although there were no significant group differences concerning the SLC6A4LPR, we found a significant correlation of the SLC6A4 methylation rate with this polymorphism in pedophilia. The present study suggests an involvement of epigenetic alterations of the serotonergic system in pedophilia and child sexual offending as well as own experience of sexual violence. While such an environmental factor may account for the epigenetic changes seen in child sexual offending, this was not seen in pedophilia. These findings will hopefully inspire further research in this underinvestigated field which should aim at validating and extending these initial results., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Deficits in audiovisual speech perception have consistently been detected in patients with Autism Spectrum Disorder (ASD). Especially for patients with a highly functional subtype of ASD, it remains uncertain whether these deficits and underlying neural mechanisms persist into adulthood. Research indicates differences in audiovisual speech processing between ASD and healthy controls (HC) in the auditory cortex. The temporal dynamics of these differences still need to be characterized. Thus, in the present study we examined 14 adult subjects with high-functioning ASD and 15 adult HC while they viewed visual (lip movements) and auditory (voice) speech information that was either superimposed by white noise (condition 1) or not (condition 2). Subject's performance was quantified by measuring stimulus comprehension. In addition, event-related brain potentials (ERPs) were recorded. Results demonstrated worse speech comprehension for ASD subjects compared to HC under noisy conditions. Moreover, ERP-analysis revealed significantly higher P2 amplitudes over parietal electrodes for ASD subjects compared to HC., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Understanding speech in background noise poses a challenge in daily communication, which is a particular problem among the elderly. Although musical expertise has often been suggested to be a contributor to speech intelligibility, the associations are mostly correlative. In the present multisite study conducted in Germany and Switzerland, 156 healthy, normal-hearing elderly were randomly assigned to either piano playing or music listening/musical culture groups. The speech reception threshold was assessed using the International Matrix Test before and after a 6 month intervention. Bayesian multilevel modeling revealed an improvement of both groups over time under binaural conditions. Additionally, the speech reception threshold of the piano group decreased during stimuli presentation to the left ear. A right ear improvement only occurred in the German piano group. Furthermore, improvements were predominantly found in women. These findings are discussed in the light of current neuroscientific theories on hemispheric lateralization and biological sex differences. The study indicates a positive transfer from musical training to speech processing, probably supported by the enhancement of auditory processing and improvement of general cognitive functions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Worschech, Marie, Jünemann, Sinke, Krüger, Großbach, Scholz, Abdili, Kliegel, James and Altenmüller.)

Synaesthesia is a multimodal phenomenon in which the activation of one sensory modality leads to an involuntary additional experience in another sensory modality. To date, normal multisensory processing has hardly been investigated in synaesthetes. In the present study we examine processes of audiovisual separation in synaesthesia by using a simultaneity judgement task. Subjects were asked to indicate whether an acoustic and a visual stimulus occurred simultaneously or not. Stimulus onset asynchronies (SOA) as well as the temporal order of the stimuli were systematically varied. Our results demonstrate that synaesthetes are better in separating auditory and visual events than control subjects, but only when vision leads.

Botulinum toxin (BTX) treatment of glabellar frown lines is one of the most common procedures in aesthetic medicine. In addition to its cosmetic effect, the neurotoxin has been shown to have a positive influence on mood and affect. Several randomized clinical trials (RCTs) have examined the effect of botulinum toxin on the treatment of depression. Combining the results of the five RCTs in a random effects meta-analysis revealed that patients treated with BTX showed a more intense improvement of depressive symptoms in comparison to subjects that received placebo injections (d = 0.98). Despite methodological limitations, the results of this study emphasize the effectiveness of BTX in the treatment of depression and therefore pave the way for its use in the field of psychiatry., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Recent data suggest that musical practice prevents age-related cognitive decline. But experimental evidence remains sparse and no concise information on the neurophysiological bases exists, although cognitive decline represents a major impediment to healthy aging. A challenge in the field of aging is developing training regimens that stimulate neuroplasticity and delay or reverse symptoms of cognitive and cerebral decline. To be successful, these regimens should be easily integrated in daily life and intrinsically motivating. This study combines for the first-time protocolled music practice in elderly with cutting-edge neuroimaging and behavioral approaches, comparing two types of musical education., Methods: We conduct a two-site Hannover-Geneva randomized intervention study in altogether 155 retired healthy elderly (64-78) years, (63 in Geneva, 92 in Hannover), offering either piano instruction (experimental group) or musical listening awareness (control group). Over 12 months all participants receive weekly training for 1 hour, and exercise at home for ~ 30 min daily. Both groups study different music styles. Participants are tested at 4 time points (0, 6, and 12 months & post-training (18 months)) on cognitive and perceptual-motor aptitudes as well as via wide-ranging functional and structural neuroimaging and blood sampling., Discussion: We aim to demonstrate positive transfer effects for faculties traditionally described to decline with age, particularly in the piano group: executive functions, working memory, processing speed, abstract thinking and fine motor skills. Benefits in both groups may show for verbal memory, hearing in noise and subjective well-being. In association with these behavioral benefits we anticipate functional and structural brain plasticity in temporal (medial and lateral), prefrontal and parietal areas and the basal ganglia. We intend exhibiting for the first time that musical activities can provoke important societal impacts by diminishing cognitive and perceptual-motor decline supported by functional and structural brain plasticity., Trial Registration: The Ethikkomission of the Leibniz Universität Hannover approved the protocol on 14.08.17 (no. 3604-2017), the neuroimaging part and blood sampling was approved by the Hannover Medical School on 07.03.18. The full protocol was approved by the Commission cantonale d'éthique de la recherche de Genève (no. 2016-02224) on 27.02.18 and registered at clinicaltrials.gov on 17.09.18 ( NCT03674931 , no. 81185).

Background: Attentional control has been observed to play an important role in affective disorders by impacting information processing, the ability to exert top-down control in response to distracting stimuli, and by affecting emotional regulation. Prior studies demonstrated an association between attentional control and response to psychotherapy, thereby identifying attentional control as an interesting prognostic pre-treatment factor. Improving attentional control and flexibility is a cornerstone in metacognitive therapy (MCT), which is trained by the use of the Attentional Training Technique (ATT). However, as of yet, it remains unclear if pre-treatment attentional control is related to the effect of ATT., Methods: An aggregated sample of 139 healthy participants [study 1: 85 participants, mean age 23.7 years, previously published (Barth et al., 2019); study 2: 54 participants, mean age 33.7 years, not previously published] performed an attentional performance test battery before and after applying ATT. Before ATT was administered, attentional control was measured using a well-established self-report instrument, i.e., the Attentional Control Scale (ACS; Derryberry and Reed, 2002). ATT was given in 2, 4, or 15 doses and compared to sham ATT. The test battery comprised a selection of established neurocognitive tasks: emotional dot probe, Stroop, 2-back, and dichotic listening., Results: Sham ATT showed no interaction with ACS score on performance outcome in all tests. At four doses of ATT, ACS score was associated with training response, i.e., subjects with high self-reported attentional control before training showed the largest improvements post-training (all P -values <0.05; see Figure 3). At 2 and 15 doses of ATT, the ACS score was unrelated to training response., Conclusion: This is a first attempt in understanding the optimal dosage in which ATT should be administered dependent on the individual characteristics of each subject pre-training. The current data suggest self-reported attentional control pre-training as a marker to determine an optimal individual ATT training profile. Future studies should investigate if other domains of metacognitions also interact with training outcome and evaluate the extent to which this relationship transfers to clinical samples. If successful, assessing attentional control prior to treatment in clinical samples could be of use regarding personalized therapy plans and treatment outcome., (Copyright © 2020 Heitland, Barth, Winter, Jahn, Burak, Sinke, Krüger and Kahl.)

Our ability to integrate multiple sensory-based representations of our surrounding supplies us with a more holistic view of our world. There are many complex algorithms our nervous system uses to construct a coherent perception. An indicator to solve this 'binding problem' are the temporal characteristics with the specificity that environmental information has different propagation speeds (e.g., sound and electromagnetic waves) and sensory processing time and thus the temporal relationship of a stimulus pair derived from the same event must be flexibly adjusted by our brain. This tolerance can be conceptualized in the form of the cross-modal temporal binding window (TBW). Several studies showed the plasticity of the TBW and its importance concerning audio-visual illusions, synesthesia, as well as psychiatric disturbances. Using three audio-visual paradigms, we investigated the importance of length (short vs. long) as well as modality (uni- vs. multimodal) of a perceptual training aiming at reducing the TBW in a healthy population. We also investigated the influence of the TBW on speech intelligibility, where participants had to integrate auditory and visual speech information from a videotaped speaker. We showed that simple sensory trainings can change the TBW and are capable of optimizing speech perception at a very naturalistic level. While the training-length had no different effect on the malleability of the TBW, the multisensory trainings induced a significantly stronger narrowing of the TBW than their unisensory counterparts. Furthermore, a narrowing of the TBW was associated with a better performance in speech perception, meaning that participants showed a greater capacity for integrating informations from different sensory modalities in situations with one modality impaired. All effects persisted at least seven days. Our findings show the significance of multisensory temporal processing regarding ecologically valid measures and have important clinical implications for interventions that may be used to alleviate debilitating conditions (e.g., autism, schizophrenia), in which multisensory temporal function is shown to be impaired., (Copyright © 2019 Zerr, Freihorst, Schütz, Sinke, Müller, Bleich, Münte and Szycik.)

Audiovisual (AV) integration deficits have been proposed to underlie difficulties in speech perception in Asperger's syndrome (AS). It is not known, if the AV deficits are related to alterations in sensory processing at the level of unisensory processing or at levels of conjoint multisensory processing. Functional Magnetic-resonance images (MRI) was performed in 16 adult subjects with AS and 16 healthy controls (HC) matched for age, gender, and verbal IQ as they were exposed to disyllabic AV congruent and AV incongruent nouns. A simple semantic categorization task was used to ensure subjects' attention to the stimuli. The left auditory cortex (BA41) showed stronger activation in HC than in subjects with AS with no interaction regarding AV congruency. This suggests that alterations in auditory processing in unimodal low-level areas underlie AV speech perception deficits in AS. Whether this is signaling a difficulty in the deployment of attention remains to be demonstrated., (Copyright © 2019 Tietze, Hundertmark, Roy, Zerr, Sinke, Wiswede, Walter, Münte and Szycik.)

Background: Several lines of evidence support the hypothesis of an autoimmune origin of Gilles de la Tourette-Syndrome (GTS). Accordingly, in a recent study we detected positive oligoclonal bands (OCB) in cerebrospinal fluid (CSF) in >30% of adult patients indicating an intrathecal antibody synthesis. However, until today no corresponding antibodies could be identified. The aims of this study were to replicate our findings of positive OCB in an independent sample and to detect CSF autoantibodies. Methods: In this prospective study, 20 adult patients with GTS (male: female = 18:2, median age 36.1 years ± 14.34 SD) were included. All patients were thoroughly clinically characterized. Magnetic Resonance Imaging (MRI) and CSF standard measurements were performed. Isoelectric focusing on polyacrylamide gels with silver staining was used to detect OCB. To examine specific and unspecified autoantibodies, we used transfected Human Embryonic Kidney (HEK) cells expressing different surface antigens (NMDA-, CASPR2-, LGI1-, AMPA-, or GABAB1/B), indirect immunofluorescence on different brain tissue sections, and enzyme-linked visualization. Additionally, we differentiated Glioma stem cells SY5Y (human neuroblastoma) using retinoic acid and astrocytes (rat). Results: CSF analyses showed positive OCB (type 2) in 4/20 patients (20%). Using transfected HEK cells we did not find specific surface-autoantibodies. Immunohistochemistry on tissue-sections, SY5Y Glioma stem-cells, and astrocytes showed no specific binding patterns either. Conclusions: Our results corroborate previous findings and demonstrate positive OCB in a substantial number of patients with GTS (prevalence in healthy controls: 5%). Although this is the largest study investigating CSF autoantibodies in GTS using several techniques, we failed to detect any specific or unspecified autoantibodies.

High prevalence of child sexual offending stand in contradiction to low conviction rates (one-tenth at most) of child sexual offenders (CSOs). Little is known about possible differences between convicted and non-convicted pedophilic CSOs and why only some become known to the judicial system. This investigation takes a closer look at the two sides of "child sexual offending" by focusing on clinical and neurobiological characteristics of convicted and non-convicted pedophilic CSOs as presented in the Neural Mechanisms Underlying Pedophilia and sexual offending against children (NeMUP)*-study. Seventy-nine male pedophilic CSOs were examined, 48 of them convicted. All participants received a thorough clinical examination including the structured clinical interview (SCID), intelligence, empathy, impulsivity, and criminal history. Sixty-one participants (38 convicted) underwent an inhibition performance task (Go/No-go paradigm) combined with functional magnetic resonance imaging (fMRI). Convicted and non-convicted pedophilic CSOs revealed similar clinical characteristics, inhibition performances, and neuronal activation. However, convicted subjects' age preference was lower (i.e., higher interest in prepubescent children) and they had committed a significantly higher number of sexual offenses against children compared to non-convicted subjects. In conclusion, sexual age preference may represent one of the major driving forces for elevated rates of sexual offenses against children in this sample, and careful clinical assessment thereof should be incorporated in every preventive approach.

Background and Aims: Despite the high prevalence of perceived problems relating to symptoms of hypersexual disorder (HD), important aspects remain underinvestigated. This study examines symptoms of depression, symptoms of problematic cybersex, and coercive sexual behavior in a large online sample from a German-speaking population., Methods: In an online survey, N  = 1,194 ( n  = 564 women) participated in this study and completed measures including self-report questionnaires to assess depressive symptoms (PHQ-9), HD (HBI-19), symptoms of problematic cybersex (s-IATsex), as well as questions characterizing participants sexually, including fantasies and actual sexual coercive behaviors., Results: Men reported increased levels of HD symptom severity, pornography consumption, masturbation, and partnered sexual activity. Moreover, 59% of men and 18% of women reported fantasies of sexual coercion, whereas 21% of men and 4% of women reported acts of sexual coercion. Moderated regression analyses showed that symptoms of depression as well as sexual coercive fantasies and behaviors were associated with levels of HD symptom severity. Problematic cybersex, total sexual outlet (TSO), pornography consumption, and number of sexual partners were also associated with HD symptom severity. Interaction effects indicated that, in women, the connection of TSO as well as pornography was more strongly associated with levels of HD symptom severity than in men., Conclusions: This survey indicated that levels of HD symptom severity are often associated with severe intra- and interpersonal difficulties. Furthermore, the amount of sexual activity seems to be more strongly connected to levels of HD symptom severity in women than in men.