Dynamic facial emotion recognition and affective prosody recognition are associated in patients with temporal lobe epilepsy.

Deficits in facial emotion recognition have frequently been established in temporal lobe epilepsy (TLE). However, static, rather than dynamic emotion recognition paradigms have been applied. Affective prosody has been insufficiently studied in TLE, and there is a lack of studies investigating associations between auditory and visual emotion recognition. We wished to investigate potential deficits in a dynamic morph task of facial emotion recognition and in an affective prosody recognition task, as well as associations between both tasks. 25 patients with TLE and 24 healthy controls (CG) performed a morph task with faces continuously changing in their emotional intensity. They had to press a button, as soon as they were able to recognize the emotion expressed, and label it accordingly. In the auditory task, subjects listened to neutral sentences spoken in varying emotional tones, and labeled the emotions. Correlation analyses were conducted across both tasks. TLE patients showed significantly reduced prosody recognition compared to CG, and in the morph task, there was a statistical trend towards significantly reduced performance for TLE. Recognition rates in both tasks were significantly associated. TLE patients show deficits in affective prosody recognition, and they may also be impaired in a morph task with dynamically changing facial expressions. Impairments in basic social-cognitive tasks in TLE seem to be modality-independent.

[Five past twelve - the resistance situation in small ruminant gastrointestinal nematodes in Germany]. / Fünf nach zwölf ­ zur Resistenzlage gastrointestinaler Nematoden bei kleinen Wiederkäuern in Deutschland.

Anthelmintic resistance has reached alarming levels worldwide and already seriously threatens pasture-based small ruminant production in certain geographic regions. The situation in Europe has also dramatically deteriorated in the last decade. This review provides an overview of the occurrence of anthelmintic resistance in small ruminants with a particular focus on Germany and its neighbouring countries. It also covers mechanisms leading to the development and spread of anthelmintic resistance, and recommendations for a responsible use of anthelmintics in veterinary practice.

Affective Empathy, Theory of Mind and Social Functioning in Patients With Focal Epilepsy.

Objective: Social cognition comprises basic and more complex functions, such as theory of mind (ToM) and affective empathy. Although everyday social interactions may be impaired if such higher-order social cognitive functions are compromised, associations between social functioning and social cognition in people with focal epilepsy (PWFE) are still poorly understood. We used a novel, naturalistic approach to investigate ToM in PWFE by applying the Movie for the Assessment of Social Cognition (MASC). Furthermore, we studied affective empathy, the relationship between social cognitive parameters and measures of social functioning, as well as between epilepsy focus and ToM. Methods: Thirty patients with either temporal (TLE) or frontal lobe epilepsy (FLE) were compared to 29 healthy control subjects (HC). In addition to the MASC, we applied questionnaire measures assessing empathy and everyday social functioning. Results: PWFE, especially with FLE, performed significantly worse than HC on the MASC. Perceived social integration and social activities, but not affective empathy, were reduced in PWFE. Regression analyses revealed associations between perceived social integration, clinical group status, affective empathy and ToM. Conclusion: PWFE displayed ToM deficits during a naturalistic task, whereas affective empathy was unimpaired. FLE may be associated with especially compromised ToM performance. Social cognition and social functioning appear to be interrelated in PWFE, whose self-perceived levels of social integration and social activities are lower than those of HC. More research into the association between social cognition and social functioning in PWFE is needed, in order to develop tailored intervention programs for these patients.

Eye-movement patterns during emotion recognition in focal epilepsy: An exploratory investigation.

BACKGROUND: Eye-movement patterns during facial emotion recognition are under-researched in patients with focal epilepsy (PWFE). Previous studies including other neurological patients indicate that bilateral mesiotemporal damage could be associated with impaired emotion recognition and abnormal eye-movement patterns. AIMS: The current study addresses the question whether PWFE, in whom fronto-(mesio-)temporal networks are often disturbed, also show abnormal eye-movement patterns during facial emotion recognition. METHOD: 24 PWFE and a group of 29 healthy controls (HC) performed a facial emotion recognition task and a gender recognition task while eye movements were recorded with an eye-tracker. For this purpose, Areas of Interest (AOI) were defined in the presented faces: the eye region and the mouth region. In addition to the proportion of correctly recognized emotions, the following eye-tracking parameters were recorded: Relative fixation duration (FD)/fixation count (FC) in the mouth region/eye region (relative to the FD/FC on the entire screen). RESULTS: PFWE showed an emotion recognition deficit compared to HC, whereas gender recognition performance did not differ between groups. In addition, PWFE showed significantly fewer and shorter fixations in the mouth region than HC, in both the emotion recognition task and the gender recognition task. CONCLUSIONS: When looking at faces, PFWE show eye-movement patterns different from those of healthy controls. Behaviorally, PWFE are only impaired in emotion recognition. Hence, PWFE possibly scan facial regions that are relevant to successful emotion recognition more diffusely and less efficiently than healthy control subjects. Future studies should investigate the etiology of such abnormal eye-movement patterns in PWFE.

Effectiveness of Anthelmintic Treatments in Small Ruminants in Germany.

Widespread anthelmintic resistance is a concern for small ruminant health and production worldwide. The current situation regarding anthelmintic efficacy is, however, not very well studied in Germany. Thus, a nationwide field study was undertaken to assess the effectiveness of 253 treatments performed in 223 small ruminant flocks by faecal egg count reduction test (FECRT) using pooled samples and a modified McMaster method. The percentage of Haemonchus contortus and non-Haemonchus eggs was determined by fluorescence microscopy following peanut agglutinin-fluorescein isothiocyanate staining. Treatments were chosen and performed by farmers together with their local veterinarian, and potentially confounding factors for FECRT results were addressed as far as possible by rigorous inclusion criteria. Reduced effectiveness was observed for treatments with all examined anthelmintic classes, but treatments with benzimidazoles and moxidectin showed significantly poorer results than monepantel, a closantel and mebendazole combination, and levamisole. Low case numbers precluded reliable assessment of avermectins. Unsuccessful treatments were frequently associated with the survival of H. contortus, but this was also observed for non-Haemonchus genera. The results are highly concerning, and sustainable approaches to parasite control are urgently needed to prevent further deterioration of this situation.

Cognitive and behavioral effects of cannabidiol in patients with treatment-resistant epilepsy.

PURPOSE: Therapeutic use of cannabidiol (CBD) in intractable epilepsies has increased considerably over the last ten years. As more evidence for the potentially beneficial effects of CBD on different epilepsy types is emerging, it is important to monitor potential cognitive and behavioral side effects. So far, studies including standardized neuropsychological data in the context of treatment with CBD in epilepsy patients are sparse. The present open-label study examines cognitive and behavioral effects of CBD in children and adults with treatment resistant epilepsy. METHOD: Thirty-nine patients with treatment-resistant epilepsy completed the study protocol, i.e. they were tested at baseline (T0) and after three months of CBD treatment (T1). Patients completed standardized neuropsychological tests on memory, executive functions and attention if they were capable. For cognitively impaired patients who could not complete cognitive tests, caregiver interviews were conducted and caregiver questionnaires completed. RESULTS: Significant cognitive decline from T0 to T1 was observed on none of the included measures. There was a significant improvement on a measure of selective attention and on a caregiver-rated behavioral measure. More than 89% of all individual test results remained stable or showed reliable improvement from T0 to T1. Cognitive and behavioral changes from T0 to T1 were not significantly correlated with CBD dose. Improvements in short-term/working memory were significantly related to better therapy response. CONCLUSION: No adverse group-level effects of CBD treatment were detected. On an individual level, most test results remained stable or were improved. Cognitive change was not related to CBD dose. The present results show that, from a cognitive and behavioral point of view, CBD seems to have an encouraging side-effect profile. The results need to be replicated with larger samples.

Effects of hippocampus-sparing resections in the temporal lobe: Hippocampal atrophy is associated with a decline in memory performance.

OBJECTIVE: In patients with temporal lobe epilepsy (TLE) with a nonlesional and nonepileptogenic hippocampus (HC), in order to preserve functionally intact brain tissue, the HC is not resected. However, some patients experience postoperative memory decline, possibly due to disruption of the extrahippocampal memory network and secondary hippocampal volume (HV) loss. The purpose of this study was to determine the extent of hippocampal atrophy ipsilateral and contralateral to the side of the surgery and its relation to memory outcomes. METHODS: Hippocampal volume and verbal as well as visual memory performance were retrospectively examined in 55 patients (mean age ± standard deviation [SD] 30 ± 15 years, 25 female, 31 left) before and 5 months after surgery within the temporal lobe that spared the entire HC. HV was extracted based on prespecified templates, and resection volumes were also determined. RESULTS: HV loss was found both ipsilateral and contralateral to the side of surgery (P < .001). Postoperative left HV loss was a significant predictor of postoperative verbal memory deterioration after left-sided surgery (P < .01). Together with the preoperative verbal memory performance, postoperative left HV explained almost 60% of the variance (P < .0001). However, right HV was not a clear predictor of visual memory performance. Larger resection volumes were associated with smaller postoperative HV, irrespective of side of surgery (left: P < .05, right: P < .01). SIGNIFICANCE: A disruption of the memory network by any resection within the TL, especially within the language-dominant hemisphere, may lead to HC atrophy and memory decline. These findings may further improve the counseling of patients concerning their postoperative memory outcome before TL resections sparing the entire HC.

Association of NPSR1 gene variation and neural activity in patients with panic disorder and agoraphobia and healthy controls.

INTRODUCTION: The neurobiological mechanisms behind panic disorder with agoraphobia (PD/AG) are not completely explored. The functional A/T single nucleotide polymorphism (SNP) rs324981 in the neuropeptide S receptor gene (NPSR1) has repeatedly been associated with panic disorder and might partly drive function respectively dysfunction of the neural "fear network". We aimed to investigate whether the NPSR1 T risk allele was associated with malfunctioning in a fronto-limbic network during the anticipation and perception of agoraphobia-specific stimuli. METHOD: 121 patients with PD/AG and 77 healthy controls (HC) underwent functional magnetic resonance imaging (fMRI) using the disorder specific "Westphal-Paradigm". It consists of neutral and agoraphobia-specific pictures, half of the pictures were cued to induce anticipatory anxiety. RESULTS: Risk allele carriers showed significantly higher amygdala activation during the perception of agoraphobia-specific stimuli than A/A homozygotes. A linear group x genotype interaction during the perception of agoraphobia-specific stimuli showed a strong trend towards significance. Patients with the one or two T alleles displayed the highest and HC with the A/A genotype the lowest activation in the inferior orbitofrontal cortex (iOFC). DISCUSSION: The study demonstrates an association of the NPSR1rs324981 genotype and the perception of agoraphobia-specific stimuli. These results support the assumption of a fronto-limbic dysfunction as an intermediate phenotype of PD/AG.

Orexin in the anxiety spectrum: association of a HCRTR1 polymorphism with panic disorder/agoraphobia, CBT treatment response and fear-related intermediate phenotypes.

Preclinical studies point to a pivotal role of the orexin 1 (OX1) receptor in arousal and fear learning and therefore suggest the HCRTR1 gene as a prime candidate in panic disorder (PD) with/without agoraphobia (AG), PD/AG treatment response, and PD/AG-related intermediate phenotypes. Here, a multilevel approach was applied to test the non-synonymous HCRTR1 C/T Ile408Val gene variant (rs2271933) for association with PD/AG in two independent case-control samples (total n = 613 cases, 1839 healthy subjects), as an outcome predictor of a six-weeks exposure-based cognitive behavioral therapy (CBT) in PD/AG patients (n = 189), as well as with respect to agoraphobic cognitions (ACQ) (n = 483 patients, n = 2382 healthy subjects), fMRI alerting network activation in healthy subjects (n = 94), and a behavioral avoidance task in PD/AG pre- and post-CBT (n = 271). The HCRTR1 rs2271933 T allele was associated with PD/AG in both samples independently, and in their meta-analysis (p = 4.2 × 10-7), particularly in the female subsample (p = 9.8 × 10-9). T allele carriers displayed a significantly poorer CBT outcome (e.g., Hamilton anxiety rating scale: p = 7.5 × 10-4). The T allele count was linked to higher ACQ sores in PD/AG and healthy subjects, decreased inferior frontal gyrus and increased locus coeruleus activation in the alerting network. Finally, the T allele count was associated with increased pre-CBT exposure avoidance and autonomic arousal as well as decreased post-CBT improvement. In sum, the present results provide converging evidence for an involvement of HCRTR1 gene variation in the etiology of PD/AG and PD/AG-related traits as well as treatment response to CBT, supporting future therapeutic approaches targeting the orexin-related arousal system.

Cognitive-behavioral therapy effects on alerting network activity and effective connectivity in panic disorder.

Given the particular relevance of arousal and alerting in panic disorder (PD), here the alerting network was investigated (1) contrasting patients with PD and healthy controls, (2) as a function of anxiety sensitivity constituting a dimensional measure of panic-related anxiety, and (3) as a possible correlate of treatment response. Using functional magnetic resonance imaging (fMRI), 45 out-patients with PD (f = 34) and 51 matched healthy controls were investigated for brain activation patterns and effective connectivity (Dynamic Causal Modeling, DCM) while performing the Attention Network Task (ANT). Anxiety sensitivity was ascertained by the Anxiety Sensitivity Index (ASI). Forty patients and 48 controls were re-scanned after a 6 weeks cognitive-behavioral treatment (CBT) or an equivalent waiting time, respectively. In the alerting condition, patients showed decreased activation in fronto-parietal pathways including the middle frontal gyrus and the superior parietal lobule (MFG, SPL). In addition, ASI scores were negatively correlated with connectivity emerging from the SPL, the SFB and the LC and going to the MFG in patients but not in healthy controls. CBT resulted in an increase in middle frontal and parietal activation along with increased connectivity going from the MFG to the SPL. This change in connectivity was positively correlated with reduction in ASI scores. There were no changes in controls. The present findings point to a pathological disintegration of the MFG in a fronto-parietal pathway in the alerting network in PD which was observed to be reversible by a successful CBT intervention.

Flashbulb memories: Is the amygdala central? An investigation of patients with amygdalar damage.

Flashbulb memories (FM) are a subgroup of autobiographical memories referring to the circumstances in which a person first heard of a surprising, emotionally arousing event. Patients with temporal lobe epilepsy (TLE) have been reported to be impaired in FM recall. As emotional arousal is central to FM, various authors have suggested a crucial role of the amygdala. However, to date, no studies have directly addressed this hypothesis. In this study, 33 TLE patients and 20 healthy controls (HC) were tested on an FM task twice with a minimum interval of two months. FM recall quality was measured as consistency of the answers. Patients were grouped according to the presence as well as the lateralisation of amygdalar damage, using information of brain imaging and intracranial electroencephalography-recordings. Analyses revealed that, relative to HC, patients with amygdalar damage had significantly diminished FM recall quality, whereas patients with intact amygdalae did not. Particularly patients with amygdalar damage in the non-language-dominant hemisphere performed significantly worse than HC. Findings suggest a negative influence of amygdalar damage, possibly especially in the non-dominant hemisphere, on FM retrieval quality. Given the shocking character of events evoking FM, a rapid emotion detection system involving the right (i.e. non-dominant) amygdala could be influential to FM formation. Thus, the present findings support previous, not yet examined, hypotheses concerning a crucial role of the amygdala in FM.

Task Performance Changes the Amplitude and Timing of the BOLD Signal.

Translational studies comparing imaging data of animals and humans have gained increasing scientific interests. With this upcoming translational approach, however, identifying harmonized statistical analysis as well as shared data acquisition protocols and/or combined statistical approaches is necessary. Following this idea, we applied Bayesian Adaptive Regression Splines (BARS), which have until now mainly been used to model neural responses of electrophysiological recordings from rodent data, on human hemodynamic responses as measured via fMRI. Forty-seven healthy subjects were investigated while performing the Attention Network Task in the MRI scanner. Fluctuations in the amplitude and timing of the BOLD response were determined and validated externally with brain activation using GLM and also ecologically with the influence of task performance (i.e. good vs. bad performers). In terms of brain activation, bad performers presented reduced activation bilaterally in the parietal lobules, right prefrontal cortex (PFC) and striatum. This was accompanied by an enhanced left PFC recruitment. With regard to the amplitude of the BOLD-signal, bad performers showed enhanced values in the left PFC. In addition, in the regions of reduced activation such as the parietal and striatal regions, the temporal dynamics were higher in bad performers. Based on the relation between BOLD response and neural firing with the amplitude of the BOLD signal reflecting gamma power and timing dynamics beta power, we argue that in bad performers, an enhanced left PFC recruitment hints towards an enhanced functioning of gamma-band activity in a compensatory manner. This was accompanied by reduced parieto-striatal activity, associated with increased and potentially conflicting beta-band activity.

ADORA2A genotype modulates interoceptive and exteroceptive processing in a fronto-insular network.

Facilitated processing of interoceptive and exteroceptive information in the salience network is suggested to promote the development of anxiety and anxiety disorders. Here, it was investigated whether the adenosine 2 A receptor gene (ADORA2A) 1976T/C (rs5751876) variant - previously associated with anxiety disorders and anxiety-related phenotypes as well as general attentional efficiency -was involved in the regulation of this network. In detail, fMRI recordings of 65 healthy participants (female=35) were analyzed regarding ADORA2A genotype effects on brain connectivity related to (1) interoceptive processing in terms of functional connectivity resting-state fMRI, and (2) exteroceptive processing using dynamic causal modeling in task-based fMRI. In a subsample, cardiac interoceptive accuracy was furthermore measured via the Mental Tracking Task. ADORA2A genotype was found to modulate a fronto-insular network at rest (interoceptive processing) and while performing an executive control task (exteroceptive processing). Across both modalities, the ADORA2A TT risk genotype was associated with increased connectivity between the insula and the prefrontal cortex. The strength in connectivity correlated with interoceptive accuracy. It is concluded that alterations in fronto-insular connectivity are modulated by both the adenosinergic system and interoceptive accuracy. Thus, fronto-insular connectivity in synopsis with ADORA2A genotypic information could serve as combined biomarkers for personalized treatment approaches in anxiety disorders targeting exteroceptive and interoceptive dysfunction.

Inter-hemispheric connectivity in the fusiform gyrus supports memory consolidation for faces.

This study investigated how changes of functional connectivity over time accompany consolidation of face memories. Based on previous research, it was hypothesized that connectivity changes in networks initially active during face perception and face encoding would be associated with individual recognition memory performance. Resting-state functional connectivity was examined shortly before, shortly after and about 40 min after incidental learning of faces. Memory performance was assessed in a surprise recognition test shortly after the last resting-state session. Results reveal that memory performance-related connectivity between the left fusiform face area and other brain areas gradually changed over the course of the experiment. Specifically, the increase in connectivity with the contralateral fusiform gyrus, the hippocampus, the amygdala and the inferior frontal gyrus correlated with recognition memory performance. As the increase in connectivity in the two final resting-state sessions was associated with memory performance, the present results demonstrate that memory formation is not restricted to the incidental learning phase but continues and increases in the following 40 min. It is discussed that the delayed increase in inter-hemisphere connectivity between the left and right fusiform gyrus is an indicator for memory formation and consolidation processes.

Altered executive control network resting-state connectivity in social anxiety disorder.

OBJECTIVES: Research into the neural basis of social anxiety disorder (SAD) suggests alterations in prefrontal networks, which may in turn disrupt regulation of the limbic system. Better understanding of the disturbed interface between these networks may improve current pathogenic models of this disorder. METHODS: Applying group independent component analysis (ICA) to recordings of fMRI resting-state, connectivity in the executive control network was studied in 18 patients with SAD and 15 age- and sex-matched healthy controls. RESULTS: Results revealed a dissociation within the left executive control network, with SAD patients showing decreased connectivity of the orbitofrontal gyrus and increased connectivity of the middle frontal gyrus compared to healthy controls. In a subsequent seed-based functional connectivity analysis, patients with SAD displayed increased connectivity between the left orbitofrontal gyrus and the left amygdala. CONCLUSIONS: Findings suggest that hypo-connectivity in the executive control network and hyper-connectivity between the orbitofrontal cortex and the amygdala may reflect a disturbance in the balance between top-down and bottom-up control processes, potentially contributing to the development of SAD.

Emotional face expression modulates occipital-frontal effective connectivity during memory formation in a bottom-up fashion.

This study investigated the role of bottom-up and top-down neural mechanisms in the processing of emotional face expression during memory formation. Functional brain imaging data was acquired during incidental learning of positive ("happy"), neutral and negative ("angry" or "fearful") faces. Dynamic Causal Modeling (DCM) was applied on the functional magnetic resonance imaging (fMRI) data to characterize effective connectivity within a brain network involving face perception (inferior occipital gyrus and fusiform gyrus) and successful memory formation related areas (hippocampus, superior parietal lobule, amygdala, and orbitofrontal cortex). The bottom-up models assumed processing of emotional face expression along feed forward pathways to the orbitofrontal cortex. The top-down models assumed that the orbitofrontal cortex processed emotional valence and mediated connections to the hippocampus. A subsequent recognition memory test showed an effect of negative emotion on the response bias, but not on memory performance. Our DCM findings showed that the bottom-up model family of effective connectivity best explained the data across all subjects and specified that emotion affected most bottom-up connections to the orbitofrontal cortex, especially from the occipital visual cortex and superior parietal lobule. Of those pathways to the orbitofrontal cortex the connection from the inferior occipital gyrus correlated with memory performance independently of valence. We suggest that bottom-up neural mechanisms support effects of emotional face expression and memory formation in a parallel and partially overlapping fashion.

Modulation of prefrontal functioning in attention systems by NPSR1 gene variation.

Evidence has accumulated for a dysfunction of arousal and executive attention in anxiety. The neuropeptide S (NPS) system has been shown to play a pivotal role in the mediation of arousal and to be associated with anxiety/panic disorder. The present study aims at investigating the impact of functional neuropeptide S receptor (NPSR1) gene variation on neural attention patterns applying an imaging genetics approach. In an event-related functional magnetic resonance imaging (fMRI) setting, 47 healthy subjects (f=23) evenly pre-stratified for NPSR1 rs324981 A/T genotype were investigated for brain activation patterns while performing the Attention Network Task (ANT), simultaneously probing alerting and executive control functions. Anxiety sensitivity was ascertained by the Anxiety Sensitivity Index (ASI). In the alerting condition, NPSR1 TT homozygotes showed higher activations in the right prefrontal cortex and the locus coeruleus region as compared to A allele carriers. In the executive control condition, TT homozygotes displayed increased activations in fronto-parietal regions. Genotype-driven activation differences in the prefrontal cortex correlated with anxiety sensitivity, in both the alerting and the executive control system. The present results for the first time suggest NPSR1 gene variation to be associated with alterations of prefrontal functioning in the attentional functions alerting and executive control partly modulated by anxiety sensitivity. These findings may aid in unraveling the neurobiological underpinnings of distorted arousal and attention in anxiety and thereby possibly in the biomarker-guided development of preventive/therapeutic strategies targeting attention processes in anxiety disorders.

Arousal and the attentional network in panic disorder.

Although a great deal of information about the neurobiology of panic disorder is now available, there is a need for an updated etiological model integrating recent findings on the neurobiology of the arousal system and its relationship with higher cortical functions in panic disorder. The current mini-review presents psychophysiological, molecular biological/genetic and functional neuroimaging evidence for dysfunction in major arousal systems of the brain. Such dysfunction may influence the development of panic disorder by precipitating autonomic bodily symptoms and at the same time increasing vigilance to these sensations by modulating cortical attentional networks. A multilevel model of arousal, attention and anxiety-including the norepinephrine, orexin, neuropeptide S and caffeine-related adenosine systems-may be useful in integrating a range of data available on the pathogenesis of panic disorder.