Bernd Weber

Semi-quantitative analysis of hippocampal internal architecture (HIA) on MRI has been shown to be a reliable predictor of the side of seizure onset in patients with temporal lobe epilepsy (TLE). In the present study, we investigated the relationship between postoperative seizure outcome and preoperative semi-quantitative measures of HIA. We determined HIA on high in-plane resolution preoperative T2 short tau inversion recovery MR images in 79 patients with presumed unilateral mesial TLE (mTLE) due to hippocampal sclerosis (HS) who underwent amygdalohippocampectomy and postoperative follow up. HIA was investigated with respect to postoperative seizure freedom, neuronal density determined from resected hippocampal specimens, and conventionally acquired hippocampal volume. HIA ratings were significantly related to some neuropathological features of the resected hippocampus (e.g. neuronal density of selective CA regions, Wyler grades), and bilaterally with preoperative hippocampal volum...

Autoantibodies against glutamic acid decarboxylase (GAD) and the voltage-gated potassium channel (VGKC) complex are associated with distinct subtypes of limbic encephalitis regarding clinical presentation, response to therapy, and outcome. The aim of this study was to investigate white matter changes in these two limbic encephalitis subtypes by means of diffusion tensor imaging (DTI). Diffusion data were obtained in 14 patients with GAD antibodies and 16 patients with VGKC-complex antibodies and compared with age- and gender-matched control groups. Voxelwise statistical analysis was carried out using tract-based spatial statistics. The results were furthermore compared with those of 15 patients with unilateral histologically confirmed hippocampal sclerosis and correlated with verbal and figural memory performance. We found widespread changes of fractional anisotropy and all diffusivity parameters in GAD-associated limbic encephalitis, whereas no changes were found in VGKC-complex-as...

The proneness to minor errors and slips in everyday life as assessed by the Cognitive Failures Questionnaire (CFQ) constitutes a trait characteristic and is reflected in stable features of brain structure and function. It is unclear, however, how dynamic interactions of large-scale brain networks contribute to this disposition. To address this question, we performed a high model order independent component analysis (ICA) with subsequent dual regression on resting-state fMRI data from 71 subjects to extract temporal time courses describing the dynamics of 17 resting-state networks (RSN). Dynamic network interactions between all 17 RSN were assessed by linear correlations between networks' time courses. On this basis, we investigated the relationship between subject-level RSN interactions and the susceptibility to everyday cognitive failure. We found that CFQ scores were significantly correlated with the interplay of the cingulo-opercular network (CON) and a posterior parietal network which unifies clusters in the posterior cingulate, precuneus, intraparietal lobules and middle temporal regions. Specifically, a higher positive functional connectivity between these two RSN was indicative of higher proneness to cognitive failure. Both the CON and posterior parietal network are implicated in cognitive functions, such as tonic alertness and executive control. Results indicate that proper checks and balances between the two networks are needed to protect against cognitive failure. Furthermore, we demonstrate that the study of temporal network dynamics in the resting state is a feasible tool to investigate individual differences in cognitive ability and performance.

Target Audience: Epileptologists; MR Image Analysists; Neuroimaging Scientists; Neurologists; Neurosurgeons. Purpose: Temporal lobe epilepsy (TLE) is the most common medically intractable epilepsy disorder, and neurosurgery to relieve refractory seizures is most commonly performed for patients with TLE. Surgery will render approximately 60-70% patients seizure free two years postoperatively. The reasons for why some patients continue to experience seizures after surgery are unknown. In the present study, we applied a series of automated mapping techniques to T1-weighted MR images in patients with TLE who underwent temporal lobe surgery to determine the presurgical imaging correlates of postoperative persistent seizures (PPS). Methods: 87 patients with unilateral TLE (55 left, 32 right) and ipsilateral hippocampal sclerosis (HS) were studied. All patients underwent comprehensive presurgical investigation, including MR imaging on a 3 T Siemens system, amygdalohippocampectomy, and stan...

Rationale: Up to 70% of patients with intractable temporal lobe epilepsy(TLE) and hippocampal sclerosis(HS) continue to experience complex partial seizures(CPS) after temporal lobe surgery when followed up two years post-surgery.1This figure falls to 48% ten years post-surgery.2Why some patients continue to experience postsurgical seizures despite being excellent surgical candidates is unknown. In this study, we sought to investigate whether regional atrophy of the hippocampus on presurgical MRI is associated with postsurgical CPS. We hypothesised that posterior ipsilateral and contralateral hippocampal atrophy would be associated with postsurgical CPS based on previous work.3 Methods: We analysed T1-weighted MRI data(Magnetom Trio, Siemens) of 86 patients with TLE(mean age 42 yrs, SD 14; 57 left, 29 right) with neuroradiological evidence of ipsilateral HS. All patients had comprehensive routine presurgical investigations4 and underwent standardised amygdalohippocampectomy. HS was c...

Functional connections between brain regions constitute the substrate of the human functional connectome, whose topography has been discussed as an endophenotype for psychiatric disorders. Genetic influences on the entire connectome, however, have been rarely investigated so far. We tested for connectome-wide influences of the val158met (rs4860) polymorphism on the catechol-O-methyltransferase (COMT) gene by applying formal network analysis and eigenvector centrality mapping on the voxel level to resting-state functional magnetic imaging data. This approach finds brain regions that are central in the network by aggregating local and global connectivity patterns, most importantly without the requirement to select regions or networks of interest. The COMT variant linked to high enzyme activity increased network centrality in distributed brain areas that are known to constitute the brain's default mode network. Further results also indicated a COMT influence on areas implicated in ...

Antibody-associated limbic encephalitis (LE) is an increasingly recognized cause of mostly adult-onset temporal lobe epilepsy. Magnetic resonance imaging (MRI) typically shows volume and signal changes of the mesiotemporal structures. However, recent studies indicate that imaging characteristics depend on the type of the associated antibody. The aim of the present study was to investigate early and chronic gray matter (GM) volume changes in LE by means of voxel-based morphometry (VBM). Optimized VBM analysis was applied to altogether 73 MRI volumes of 55 patients with antibody-associated LE. Based on the time point of MRI acquisition, patients were split into two separate groups to enable the evaluation of early (≤2 years after LE onset) and chronic (>2 years after LE onset) GM volume changes. In addition, separate analyses for the two most common LE subtypes in our study cohort, that is, glutamic acid decarboxylase (GAD)-associated LE and voltage-gated potassium channel (VGKC)-c...

Apart from everyday duties, such as doing the laundry or cleaning the house, there are tasks we do for pleasure and enjoyment. We do such tasks, like solving crossword puzzles or reading novels, without any external pressure or force; instead, we are intrinsically motivated: we do the tasks because we enjoy doing them. Previous studies suggest that external rewards, i.e., rewards from the outside, affect the intrinsic motivation to engage in a task: while performance-based monetary rewards are perceived as controlling and induce a business-contract framing, verbal rewards praising one's competence can enhance the perceived self-determination. Accordingly, the former have been shown to decrease intrinsic motivation, whereas the latter have been shown to increase intrinsic motivation. The present study investigated the neural processes underlying the effects of monetary and verbal rewards on intrinsic motivation in a group of 64 subjects applying functional magnetic resonance imag...

Previous trials have often defined genotype 2 and 3 patients as an "easy to treat" group and guidelines recommend similar management. The present study looks for differences between the two genotypes and analyzes predictive factors for SVR. Prospective, community-based cohort study involving 421 physicians throughout Germany. The analysis includes 2,347 patients with untreated chronic HCV genotype 2 (n = 391) and 3 (n = 1,956) infection treated with PEG-IFN α-2a plus ribavirin between August 2007 and July 2012. When compared with genotype 2 patients, those with genotype 3 were younger, had a shorter duration of infection, lower values of total cholesterol, LDL cholesterol and BMI, a higher frequency of drug use as infection mode and male gender (p<0.0001, respectively), and a higher APRI score (p<0.005). SVR was higher in genotype 2 when compared with genotype 3 (64.7% vs. 56.9%, p = 0.004). By multivariate analysis of genotype 2 patients, low baseline γ -GT and RVR ...

Neural representations of specific stimuli rely on activity patterns in distributed neural assemblies [1-4]. According to one influential view, these assemblies are characterized by synchronized gamma-band activity (GBA) [5-11] that reflects stimulus-specific representations [12-14]. However, recent studies have shown that GBA is closely correlated with the overall amount of cellular activity and may be detrimental for precise representations of specific stimuli [15, 16]. Until now, the role of GBA for the formation of dynamically changing representations has been unknown. Here, we applied representational similarity analysis (RSA) [17] to intracranial electroencephalogram (iEEG) data from ten presurgical epilepsy patients to identify stimulus-specific neural representations. Patients first learned and then retrieved their paths through virtual houses. Dynamic representations were identified by the rapidly changing distributions of frequency-specific global (spatial) activity patter...

The investigation of the interaction of genes and environment in the context of mental health and personality yields important new insights for a better understanding of human nature. Both antenatal and postnatal environmental factors have been considered as potential modulators of genetic activity. Antenatally, especially smoking or alcohol drinking habits of the mother dramatically influence the health of the child during pregnancy and even later on in life. In the present study we would like to introduce a more "distant" factor that is not under the control of the becoming mother but that nevertheless plays a potential role for the health of the unborn child later on in adulthood. Here, we retrospectively investigate the influence of solar activity (while the child is still in the uterus of the becoming mother) on brain structure (with a focus on hippocampus and amygdala volume) and personality in adulthood. We observe an interaction of a genetic variant (rs41423247) of...

The present study focuses on the neurostructural foundations of the human personality. In a large sample of 227 healthy human individuals (168 women and 59 men), we used MRI to examine the relationship between personality traits and both regional gray and white matter volume, while controlling for age and sex. Personality was assessed using the German version of the NEO Five-Factor Inventory that measures individual differences in the 'Big Five of Personality': extraversion, neuroticism, agreeableness, conscientiousness, and openness to experience. In contrast to most previous studies on neural correlates of the Big Five, we used improved processing strategies: white and gray matter were independently assessed by segmentation steps before data analysis. In addition, customized sex-specific diffeomorphic anatomical registration using exponentiated lie algebra templates were used. Our results did not show significant correlations between any dimension of the Big Five and regional gray matter volume. However, among others, higher conscientiousness scores correlated significantly with reductions in regional white matter volume in different brain areas, including the right insula, putamen, caudate, and left fusiformis. These correlations were driven by the female subsample. The present study suggests that many results from the literature on the neurostructural basis of personality should be reviewed carefully, considering the results when the sample size is larger, imaging methods are rigorously applied, and sex-related and age-related effects are controlled.

ABSTRACT Fragestellung: Die limbische Enzephalitis (LE) ist eine autoimmunentzündliche Erkrankung, die typischerweise im Erwachsenenalter beginnt und mit Temporallappenanfällen, mnestischen Defiziten und affektiver Symptomatik einhergeht. Im MRT finden sich im akuten Stadium häufig hyperintense und volumenvermehrte temporo-mesiale Strukturen. In einigen Fällen sind die bildmorphologischen Veränderungen jedoch diskret, was die Diagnose erschwert. Mit dem Ziel, ein objektives Maß für diese Volumenvermehrung zu erhalten und die diagnostische Sensitivität und Spezifität des MRTs zu verbessern, führten wir eine volumetrische Analyse temporo-mesialer Strukturen bei Patienten mit neu aufgetretener, Antikörper-positiver (Ak-pos) LE durch und verglichen diese mit einer Normdatenbank. Methoden: Wir schlossen 12 Patienten mit Ak-pos LE ein, deren erstes MRT inklusive 3D-T1-Datensatz innerhalb des ersten Jahres nach Erkrankungsbeginn durchgeführt wurde. Die Normdatenbank setzte sich aus 100 gesunden Probanden zusammen, die hinsichtlich Alter und Geschlechtsverteilung an das Patientenkollektiv angepasst wurde. Die volumetrische Analyse von Hippokampus (HC) und Amygdala (AM) wurde mit FreeSurfer (4.5.0) durchgeführt und manuell korrigiert (geblindeter Auswerter, Dauer der manuellen Korrektur pro Individuum ca. 45min). Aufgrund der progredienten Hirnatrophie mit zunehmendem Lebensalter wurden die Volumina als prozentualer Anteil am individuellen Gesamthirnvolumen ausgegeben (keine signifikante Korrelation mit dem Lebensalter). Ergebnisse: Insgesamt konnte bei 11 der 12 untersuchten Patienten eine signifikante Zunahme dieses Wertes im Bereich der temporo-mesialen Strukturen als Hinweis auf eine akute Entzündung beobachtet werden, wobei die AM (10/12)häufiger betroffen war als der HC (3/10). Eine signifikante Abnahme des prozentualen Wertes als Hinweis auf eine bereits abgelaufene Entzündung beobachteten wir bei insgesamt 3 Patienten (1xAM, 2xHC). Eine Korrelation mit dem EEG und der neuropsychologischen Testung ergab, dass bei jeweils 9 der 12 Patienten die Seite der größten Abweichung vom Normkollektiv mit der Seite des EEG-Fokus bzw. der neuropsychologischen Defizite übereinstimmte. Schlussfolgerungen: Die semiautomatische volumetrische Analyse bietet ein objektives Maß für Volumenänderungen der temporo-mesialen Strukturen, die häufig bei der LE beobachtet werden und kann zur Verbesserung der bildmorphologischen Diagnostik bei dieser Erkrankung beitragen

Social norms, such as treating others fairly regardless of kin relations, are essential for the functioning of human societies. Their existence may explain why humans, among all species, show unique patterns of prosocial behaviour. The maintenance of social norms often depends on external enforcement, as in the absence of credible sanctioning mechanisms prosocial behaviour deteriorates quickly. This sanction-dependent prosocial behaviour suggests that humans strategically adapt their behaviour and act selfishly if possible but control selfish impulses if necessary. Recent studies point at the role of the dorsolateral prefrontal cortex (DLPFC) in controlling selfish impulses. We test whether the DLPFC is indeed involved in the control of selfish impulses as well as the strategic acquisition of this control mechanism. Using repetitive transcranial magnetic stimulation, we provide evidence for the causal role of the right DLPFC in strategic fairness. Because the DLPFC is phylogenetically one of the latest developed neocortical regions, this could explain why complex norm systems exist in humans but not in other social animals.

Vicarious embarrassment (VE) is an emotion triggered by the observation of others' pratfalls or social norm violations. Several explanatory approaches have been suggested to explain the source of this phenomenon, including perspective taking abilities or ingroup identification. Knowledge about its biological bases, however, is scarce. To gain a better understanding, the present study investigated neural activation patterns in response to video clips from reality TV shows. Reality TV is well known for presenting social norm violations, flaws and pratfalls of its protagonists in real life situations thereby qualifying as an ecological valid trigger for VE. N=60 healthy participants viewed stand stills from previously watched video clips taken from German reality TV-shows while undergoing functional magnetic resonance imaging. The clips were preselected for high versus low VE content in a pilot study. Besides the investigation of differences in brain activation elicited by VE versus control stand stills (blocked design contrast), we performed additional exploratory functional connectivity analyses (psychophysiological interaction; PPI) to detect VE related brain networks. Compared to the low VE condition, participants in the high VE condition showed a higher activation in the middle temporal gyrus, the supramarginal gyrus, the right inferior frontal gyrus and the gyrus rectus. Functional connectivity analyses confirmed increased connectivity of these regions with the anterior cingulate in the VE condition. Moreover, self-ratings of VE and brain activity were correlated positively. Reality TV formats with high VE content activate brain regions associated with Theory of Mind, but also with empathic concern and social identity. Therefore, our results support the idea that the ability to put oneself in other person's shoes is a major prerequisite for VE.

The present study investigates the link between volumetric hemispheric ratios (VHRs) and personality measures in N=267 healthy participants using Eysenck's Personality Inventory-Revised (EPQ-R) and the BIS/BAS scales. A robust association between extraversion and VHRs was observed for gray matter in males but not females. Higher gray matter volume in the left than in the right hemisphere was associated with higher extraversion in males. The results are discussed in the context of positive emotionality and laterality of the human brain.

Recent functional imaging studies that examined functional connectivity in the resting brain have demonstrated various intrinsic connectivity networks (ICNs). Certain patterns of over- and underactivity in various ICNs have been hypothesized to form the neural basis of psychiatric disorders. Furthermore, activity in the ICNs does not reflect ongoing mental activity but the maintenance of neural circuits in a ready state suggesting not only relationships between ICNs and disorders but also correlations between ICNs and personality. In the present study, we assess the relationship between trait anxiety, a well established endophenotype of anxiety disorders, and functional connectivities within the insular salience ICN in a sample of healthy female subjects. Based on a previous study that demonstrated the functional relevance of the insular salience ICN for state anxiety, we used the harm avoidance scale from the Temperament and Character Inventory (TCI) as a trait marker to demonstrate increased functional connectivity within the insular salience ICN. Specifically, the functional connectivity between the anterior insula and the anterior cingulate and between the anterior insula and the dorsolateral prefrontal cortex were positively correlated with individual harm avoidance scores. The results fit into previous work, provide evidence for a potential biomarker of anxiety disorders and, most importantly, demonstrate a direct neural correlate of the personality trait harm avoidance in the absence of external stimulation.