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Abstract: Objectives: The medial temporal lobe (MTL) is essential for declarative memory formation, but also a frequent source of seizures. To decrease the risk of amnestic impairments after temporal lobectomy, functional magnetic resonance imaging (fMRI) is increasingly used to establish pre-operative measures for a prognosis of postoperative memory performance. The present study addresses one of the major challenges in clinical fMRI, the interpretation of activation pattern in single subjects. Before investigating patients however, it must be first assessed to which extent the verbal memory paradigm can be used to determine the lateralization and the functional neuroanatomy of MTL-activity. Therefore, this study took a “step backwards” by first examining healthy subjects without known MTL pathology. Patients and methods: An implicit verbal encoding task was applied to a group of ten healthy volunteers using fMRI. Results: At the group level the MTL activation was strongly left-lateralized and separated into three distinct clusters. At the individual level, the lateralization of MTL-activity could be determined in 9 of 10 subjects. In contrast, its localization was inter-individually highly variable. In each case, only one of the three group activation clusters was detected. Conclusions: The present study shows that fMRI can be used to assess the lateralization of brain activity related to verbal encoding even in individual subjects. For the routine use in a clinical setting however, the results of verbal memory paradigms must at present be treated with care if they are used to support decisions as to how far the resection of one MTL can be extended. [Copyright &y& Elsevier]

Abstract: Objective: To improve the quality of TMS studies by developing a new sham condition. Methods: We describe a novel and easily arranged TMS set-up of two standard TMS coils and a magnetic shield, stacked like a sandwich. In a first step we compare the magnetic field in the sham and verum conditions. In a second step we ask six subjects to rate the stimulation intensity. Results: The magnetic field in the sham mode is reduced to about one eighth of that during verum stimulation. The attenuation of the magnetic field is not limited to the actual stimulation site but also effective at neighbouring brain areas, avoiding direct and indirect stimulation via connected neural pathways. This also minimizes stimulation of the skin, but as a consequence allows subjects to distinguish between verum and sham conditions when these are contrasted directly. The position of the coil system and the acoustic sensations are indistinguishable between sham and verum condition. Subjects are not able to discriminate TMS position and condition by external cues. Conclusions: The proposed TMS setup is simple and allows verum and sham TMS without interaction of the researcher. If used with the magnetic shield, the magnetic field in the brain is attenuated most. Significance: With the sandwich TMS coil system it is possible to improve the quality of TMS studies. [Copyright &y& Elsevier]

Background: The diathesis-stress model of major depressive disorder (MDD) predicts interactions of recent stressful life events (SLEs) in adulthood and early developmental risk factors. We tested, for the first time, the diathesis stress model on brain structure in a large group of MDD patients.Methods: Structural magnetic resonance imaging data of 1465 participants (656 with lifetime diagnosis MDD; 809 healthy controls) were analyzed using voxel-based morphometry to identify clusters associated with recent SLEs (Life Events Questionnaire). Those clusters were then examined for group (healthy/MDD) × early developmental risk (operationalized as childhood abuse [Childhood Trauma Questionnaire] and a major psychiatric disorder [i.e., MDD, bipolar disorder, schizophrenia, and schizoaffective disorder] in a first-degree relative) × recent SLEs three-way interactions on grey matter volume.Results: There was a group × childhood abuse × recent SLEs interaction on left medial orbitofrontal cortex grey matter volume. This three-way interaction arose because childhood abuse and recent SLEs interacted in MDD subjects but not in healthy subjects.Limitations: We are not able to draw conclusions about the cause and effect relationship due to our cross-sectional study design.Conclusions: Our data provides evidence for an interplay between orbitofrontal cortex structure, childhood abuse and recent SLEs. These factors have previously been linked to MDD and their complex interaction contributes to the pathogenesis of MDD. [ABSTRACT FROM AUTHOR]

Showing empathy is crucial for social functioning and empathy is related to group membership. The aim of the current study was to investigate the influence of experimentally generated groups on empathy for pain in a functional magnetic resonance imaging (fMRI) paradigm. Thirty healthy participants underwent a minimal group paradigm to create two groups. While BOLD contrast was measured using fMRI, subjects were instructed to empathize with ingroup and outgroup members, who were depicted in a picture paradigm of painful and neutral situations. Behavioral measure of state empathy was measured using a visual analog scale. Furthermore, self-reported trait empathy measures were obtained. Repeated-measures ANOVAs were conducted for fMRI and behavioral data. In addition to a main effect of pain in pain-related areas, a main effect of group in areas belonging to the visual cortex was found. Although there was no ingroup bias for empathy ratings, subjects showed altered neural activation in regions of the right fusiform gyrus, the cerebellum, the hippocampal and amygdala region during the pain×group interaction. Activation in the preceding structures, revealed by the interaction of pain by group, suggests that activation in the pallidum might reflect specific empathy for pain-related regulation processes. [ABSTRACT FROM AUTHOR]

Background: Learning by conditioning is a key ability of animals and humans for acquiring novel behavior necessary for survival in a changing environment. Aberrant conditioning has been considered a crucial factor in the etiology and maintenance of panic disorder with agoraphobia (PD/A). Cognitive-behavioral therapy (CBT) is an effective treatment for PD/A. However, the neural mechanisms underlying the effects of CBT on conditioning processes in PD/A are unknown. Methods: In a randomized, controlled, multicenter clinical trial in medication-free patients with PD/A who were treated with 12 sessions of manualized CBT, functional magnetic resonance imaging (fMRI) was used during fear conditioning before and after CBT. Quality-controlled fMRI data from 42 patients and 42 healthy subjects were obtained. Results: After CBT, patients compared to control subjects revealed reduced activation for the conditioned response (CS+ > CS–) in the left inferior frontal gyrus (IFG). This activation reduction was correlated with reduction in agoraphobic symptoms from t1 to t2. Patients compared to control subjects also demonstrated increased connectivity between the IFG and regions of the “fear network” (amygdalae, insulae, anterior cingulate cortex) across time. Conclusions: This study demonstrates the link between cerebral correlates of cognitive (IFG) and emotional (“fear network”) processing during symptom improvement across time in PD/A. Further research along this line has promising potential to support the development and further optimization of targeted treatments. [ABSTRACT FROM AUTHOR]

Abstract: One well-investigated division of attentional processes focuses on alerting, orienting and executive control, which can be assessed applying the attentional network test (ANT). The goal of the present study was to add further knowledge about the temporal dynamics of relevant neural correlates. As a right hemispheric dominance for alerting and orienting has previously been reported for intrinsic but not for phasic alertness, we additionally addressed a potential impact of this lateralization of attention by employing a lateralized version of the ANT, capturing phasic alertness processes. Sixteen healthy subjects underwent event-related functional magnetic resonance imaging (fMRI) while performing the ANT. Analyses of BOLD magnitude replicated the engagement of a fronto-parietal network in the attentional subsystems. The amplitudes of the attentional contrasts interacted with visual field presentation in the sense that the thalamus revealed a greater involvement for spatially cued items presented in the left visual field. Comparisons of BOLD latencies in visual cortices, first, verified faster BOLD responses following contra-lateral stimulus presentation. Second and more importantly, we identified attention-modulated activation in secondary visual and anterior cingulate cortices. Results are discussed in terms of bottom-up and lateralization processes. Although intrinsic and phasic alertness are distinct cognitive processes, we propose that neural substrates of intrinsic alertness may be accessed by phasic alertness provided that the attention-dominant (i.e., the right) hemisphere is activated directly by a warning stimulus. [Copyright &y& Elsevier]

Abstract: Body orientation and eye gaze influence how information is conveyed during face-to-face communication. However, the neural pathways underpinning the comprehension of social cues in everyday interaction are not known. In this study we investigated the influence of addressing vs. non-addressing body orientation on the neural processing of speech accompanied by gestures. While in an fMRI scanner, participants viewed short video clips of an actor speaking sentences with object- (O; e.g., shape) or person-related content (P; e.g., saying goodbye) accompanied by iconic (e.g., circle) or emblematic gestures (e.g., waving), respectively. The actor''s body was oriented either toward the participant (frontal, F) or toward a third person (lateral, L) not visible. For frontal vs. lateral actor orientation (F>L), we observed activation of bilateral occipital, inferior frontal, medial frontal, right anterior temporal and left parietal brain regions. Additionally, we observed activity in the occipital and anterior temporal lobes due to an interaction effect between actor orientation and content of the communication (PF>PL)>(OF>OL). Our findings indicate that social cues influence the neural processing of speech–gesture utterances. Mentalizing (the process of inferring the mental state of another individual) could be responsible for these effects. In particular, socially relevant cues seem to activate regions of the anterior temporal lobes if abstract person-related content is communicated by speech and gesture. These new findings illustrate the complexity of interpersonal communication, as our data demonstrate that multisensory information pathways interact at both perceptual and semantic levels. [Copyright &y& Elsevier]

Background Oxytocin has received much attention as a prosocial and anxiolytic neuropeptide. In human studies, the G-allele of a common variant (rs53576) in the oxytocin receptor gene ( OXTR ) has been associated with protective properties such as reduced stress response and higher receptiveness for social support. In contrast, recent studies suggest a detrimental role of the rs53576 G-allele in the context of childhood maltreatment. To further elucidate the role of OXTR, gene by maltreatment interactions on brain structure and function were investigated. Methods Three hundred nine healthy participants genotyped for OXTR rs53576 underwent structural as well as functional magnetic resonance imaging during a common emotional face-matching task. Childhood maltreatment was assessed with the Childhood Trauma Questionnaire (CTQ). Gray matter volumes were investigated by means of voxel-based morphometry across the entire brain. Results Structural magnetic resonance imaging data revealed a strong interaction of rs53576 genotype and CTQ scores, mapping specifically to the bilateral ventral striatum. GG homozygotes but not A-allele carriers showed strong gray matter reduction with increasing CTQ scores. In turn, lower ventral striatum gray matter volumes were associated with lower reward dependence, a prosocial trait. Furthermore, the G-allele was associated with increased amygdala responsiveness to emotional facial expressions. Conclusions The findings suggest that the G-allele constitutes a vulnerability factor for specific alterations of limbic brain structure in individuals with adverse childhood experiences, complemented by increased limbic responsiveness to emotional interpersonal stimuli. While oxytocinergic signaling facilitates attachment and bonding in supportive social environments, this attunement for social cues may turn disadvantageous under early adverse conditions. [ABSTRACT FROM AUTHOR]

Abstract: Speech may have evolved from earlier modes of communication based on gestures. Consistent with such a motor theory of speech, cortical orofacial and hand motor areas are activated by both speech production and speech perception. However, the extent of speech-related activation of the motor cortex remains unclear. Therefore, we examined if reading and listening to continuous prose also activates non-brachiofacial motor representations like the leg motor cortex. We found corticospinal excitability of bilateral leg muscle representations to be enhanced by speech production and silent reading. Control experiments showed that speech production yielded stronger facilitation of the leg motor system than non-verbal tongue–mouth mobilization and silent reading more than a visuo-attentional task thus indicating speech-specificity of the effect. In the frame of the motor theory of speech this finding suggests that the system of gestural communication, from which speech may have evolved, is not confined to the hand but includes gestural movements of other body parts as well. [Copyright &y& Elsevier]

We investigated three patients with partial cortical blindness after brain injury by means of functional magnetic resonance imaging (fMRI) before and after the application of a daily visual stimulation-therapy over a period of 6 months. Before therapy, fMRI data showed a severely reduced blood-oxygen-level-dependent (BOLD) signal in primary visual cortex when compared to healthy volunteers. Following several months of rehabilitative therapy a neuropsychological improvement of visual functions was accompanied by an increase in BOLD signal of residual perilesional regions whereas fMRI data of the control group remained unchanged. A high capacity of functional recovery and synaptic plasticity of surviving perilesional neuronal structures of primary visual cortex followed by an increased input into post-connected visual areas can be discussed as a basis for the reoccurrence of visual functions. [Copyright &y& Elsevier]

Abstract: Regional brain volumes were compared between 23 participants with obsessive–compulsive disorder (OCD) and 36 healthy controls using magnetic resonance imaging with voxel-based morphometry. A volumetric decrease in OCD was found in the right mediofrontal cortex. An increase was found in the left temporoparietal cortex. Volume alterations were related to symptom severity and age of onset. [Copyright &y& Elsevier]