Hierarchical figures in which large (global) forms are constructed from smaller (local) forms (Navon, 1977) have proved valuable in studies of perceptual organisation and hemispheric specialisation in both healthy volunteers and a wide range of neurological and psychiatric patients. In studies using Navon figures, normal young adults typically identify global forms faster than local forms. When the global and local forms are incongruent (e.g., a large E made of smaller Rs), global forms often interfere with local form identification more than vice versa. In two conditions on the same subjects, we contrasted the performance of young (mean age 22 years) and older (mean age 58 years) healthy volunteers on global and local processing. In the directed attention task, subjects were instructed to detect a target letter that occurred at the prespecified local or global level. The young subjects showed, as expected, faster reaction times (RTs) to detect global targets. In contrast, the older subjects showed significantly faster RTs to the local targets. Likewise, in a divided attention task, in which subjects were instructed to detect a target letter that could occur at either the local or the global level, the young adults were slightly quicker to detect the global targets and the older subjects were significantly quicker to detect the local targets. Error rates were generally low and there was no significant speed/accuracy trade-off in either condition. The observed local precedence effects in healthy older subjects were unexpected and are discussed in reference to previous work on differential hemispheric aging. That work has suggested that the left hemisphere is preferentially biased toward local processing and ages relatively slowly while the right hemisphere is biased toward global processing and ages relatively quickly. The implications of such putative differential aging for the interpretation of pathological local/global processing in neurological and psychiatric diseases are also emphasised.

Evidence from studies in both animals and humans suggests that pharmacological stimulation of the noradrenergic system may modulate cortical excitability. However, the influence of such a modulation on the motor system remains unclear. We here explored the effects of noradrenergic stimulation on different motor tasks with increasing complexity and sensorimotor demands. Healthy human subjects received either reboxetine--a selective noradrenaline reuptake inhibitor--or placebo in a double-blind within-subject design. The analysis of movement kinematics revealed differential effects of RBX on subjects' motor performance. While isolated stereotypic finger movements and simple reach-to-grasp movements did not change under RBX stimulation (compared to placebo), subjects showed a significant gain in movement speed in visuomotor tasks requiring online-control of precision movements. The results suggest that stimulating the noradrenergic system via RBX does not influence motor performance in general, but rather supports neural circuits involved in visuomotor control of movements.

Hierarchically organized figures (for example, a large E made up of smaller N's) are frequently used to investigate directed and divided attention. Investigations of neurological and psychiatric patients, and also tachistoscopic and functional neuroimaging studies on healthy subjects, typically find the right hemisphere to be specialized for the processing of global stimuli and the left hemisphere to be specialized for the processing of local stimuli. In the current study, a group of 12 patients with visuo-spatial neglect (NP) after right hemisphere lesions and 12 age and sex-matched control subjects (CO) performed a directed and a divided attention task with hierarchically organized letters. As expected, faster reaction times were found for control subjects than for neglect patients, especially for the directed global attention task. Lower error rates were found for CO and NP for local than for global targets during the divided attention condition. Local on global interference was found for both groups in reaction times. These local processing advantages for older healthy adults have been reported previously. Additionally, an impairment in the divided attention task was found in both groups, but especially for global targets in NP. This impairment is consistent with other evidence of difficulty in disengaging attention shown by patients with visuo-spatial neglect.

Cognitive flexibility helps us to navigate through our ever-changing environment and has often been examined by reversal learning paradigms. Performance in reversal learning can be modeled using computational modeling which allows for the specification of biologically plausible models to infer psychological mechanisms. Although such models are increasingly used in cognitive neuroscience, developmental approaches are still scarce. Additionally, though most reversal learning paradigms have a comparable design regarding timing and feedback contingencies, the type of feedback differs substantially between studies. The present study used hierarchical Gaussian filter modeling to investigate cognitive flexibility in reversal learning in children and adolescents and the effect of various feedback types. The results demonstrate that children make more overall errors and regressive errors (when a previously learned response rule is chosen instead of the new correct response after the initial shift to the new correct target), but less perseverative errors (when a previously learned response set continues to be used despite a reversal) adolescents. Analyses of the extracted model parameters of the winning model revealed that children seem to use new and conflicting information less readily than adolescents to update their stimulus-reward associations. Furthermore, more subclinical rigidity in everyday life (parent-ratings) is related to less explorative choice behavior during the probabilistic reversal learning task. Taken together, this study provides first-time data on the development of the underlying processes of cognitive flexibility using computational modeling.

Our visual world is hierarchically organized. Hierarchical processing is frequently investigated using Navon figures (large letters made up of smaller ones). In young adults, many studies reported faster reaction times (RT) to target letters presented at the global level [i.e., global precedence (GP)]. Furthermore, an age-related decline of this GP has been reported. We tested whether deficits in perceptual grouping via Gestalt laws (Gestalt principles of Proximity and Continuity) might contribute to this decline. In a directed attention task with valid and invalid cues, 20 young (mean age 22) and 20 older (mean age 57) male subjects had to indicate whether a target letter appeared at the global or local level of a Navon figure. The number of local letters forming the global figure was modulated in 5 steps. As expected, during valid trials, young adults showed a GP that linearly increased with increasing numbers of local letters (i.e., GP enhancement). This suggests that GP is related to perceptual grouping via Gestalt laws. By contrast, the group of older subjects demonstrated no precedence effect in RT and a non-significant trend toward GP in error rates (ER). No GP enhancement with an increasing number of local elements was observed. Exploratory analysis revealed that individual insensitivity to the modulation of matrix density, as revealed by a lack of global RT acceleration, was restricted to subjects that showed an overall local precedence (LP). Because older subjects tended to more frequently display an insensitivity to matrix modulation and an LP, we conclude that deficient Gestalt detection as indicated by non-enhanced global RT might contribute to the RT-related decline of GP with age.

Mental strategies have been suggested to constitute a promising approach to improve motor abilities in both healthy subjects and patients. This behavioural effect has been shown to be associated with changes of neural activity in premotor areas, not only during movement execution, but also while performing motor imagery or action observation. However, how well such mental tasks are performed is often difficult to assess, especially in patients. We here used a novel mental training paradigm based on the serial prediction task (SPT) in order to activate premotor circuits in the absence of a motor task. We then tested whether this intervention improves motor-related performance such as sensorimotor transformation. Two groups of healthy young participants underwent a single-blinded five-day cognitive training schedule and were tested in four different motor tests on the day before and after training. One group (N=22) received the SPT-training and the other one (N=21) received a control training based on a serial match-to-sample task. The results revealed significant improvements of the SPT-group in a sensorimotor timing task, i.e. synchronization of finger tapping to a visually presented rhythm, as well as improved visuomotor coordination in a sensory-guided pointing task compared to the group that received the control training. However, mental training did not show transfer effects on motor abilities in healthy subjects beyond the trained modalities as evident by non-significant changes in the Jebsen-Taylor handfunctiontest. In summary, the data suggest that mental training based on the serial prediction task effectively engages sensorimotor circuits and thereby improves motor behaviour.

The interpretation of interpersonal gaze behavior requires the use of complex cognitive processes and guides social interactions. Among a variety of different gaze characteristics, gaze direction and gaze duration modulate crucially the meaning of the "social gaze". Nevertheless, prior neuroimaging studies disregarded the relevance of gaze duration by focusing on gaze direction only. The present functional magnetic resonance imaging (fMRI) study focused on the differentiation of these two gaze parameters. Therefore direct gaze displayed by virtual characters was contrasted with averted gaze and, additionally, systematically varied with respect to gaze duration (i.e., 1, 2.5 or 4 s). Consistent with prior findings, behavioral data showed that likeability was higher for direct than for averted gaze and increased linearly with increasing direct gaze duration. On the neural level, distinct brain regions were associated with the processing of gaze direction and gaze duration: (i) the comparison between direct and averted gaze revealed activations in bilateral occipito-temporal regions including the posterior superior temporal sulcus (pSTS); (ii) whereas increasing duration of direct gaze evoked differential neural responses in the medial prefrontal cortex (MPFC) including orbitofrontal and paracingulate regions. The results suggest two complementary cognitive processes related to different gaze parameters. On the one hand, the recruitment of multimodal sensory regions in the pSTS indicates detection of gaze direction via complex visual analysis. On the other hand, the involvement of the MPFC associated with outcome monitoring and mentalizing indicates higher-order social cognitive processes related to evaluation of the ongoing communicational input conveyed by direct gaze duration.

Congenital deafness modifies an individual's daily interaction with the environment and alters the fundamental perception of the external world. How congenital deafness shapes the interface between the internal and external worlds remains poorly understood. To interact efficiently with the external world, visuospatial representations of external target objects need to be effectively transformed into sensorimotor representations with reference to the body. Here, we tested the hypothesis that egocentric body-centred sensorimotor transformation is impaired in congenital deafness. Consistent with this hypothesis, we found that congenital deafness induced impairments in egocentric judgements, associating the external objects with the internal body. These impairments were due to deficient body-centred sensorimotor transformation per se, rather than the reduced fidelity of the visuospatial representations of the egocentric positions. At the neural level, we first replicated the previously well-documented critical involvement of the frontoparietal network in egocentric processing, in both congenitally deaf participants and hearing controls. However, both the strength of neural activity and the intra-network connectivity within the frontoparietal network alone could not account for egocentric performance variance. Instead, the inter-network connectivity between the task-positive frontoparietal network and the task-negative default-mode network was significantly correlated with egocentric performance: the more cross-talking between them, the worse the egocentric judgement. Accordingly, the impaired egocentric performance in the deaf group was related to increased inter-network connectivity between the frontoparietal network and the default-mode network and decreased intra-network connectivity within the default-mode network. The altered neural network dynamics in congenital deafness were observed for both evoked neural activity during egocentric processing and intrinsic neural activity during rest. Our findings thus not only demonstrate the optimal network configurations between the task-positive and -negative neural networks underlying coherent body-centred sensorimotor transformations but also unravel a critical cause (i.e. impaired body-centred sensorimotor transformation) of a variety of hitherto unexplained difficulties in sensory-guided movements the deaf population experiences in their daily life.

Early auditory deprivation leads to a reorganization of large-scale brain networks involving and extending beyond the auditory system. It has been documented that visuomotor transformation is impaired after early deafness, associated with a hyper-crosstalk between the task-critical frontoparietal network and the default-mode network. However, it remains unknown whether and how the reorganized large-scale brain networks involving the auditory cortex contribute to impaired visuomotor transformation after early deafness. Here, we asked deaf and early hard of hearing participants and normal hearing controls to judge the spatial location of a visual target. Compared with normal hearing controls, the superior temporal gyrus showed significantly increased functional connectivity with the frontoparietal network and the default-mode network in deaf and early hard of hearing participants, specifically during egocentric judgments. However, increased superior temporal gyrus-frontoparietal network and superior temporal gyrus-default-mode network coupling showed antagonistic effects on egocentric judgments. In deaf and early hard of hearing participants, increased superior temporal gyrus-frontoparietal network connectivity was associated with improved egocentric judgments, whereas increased superior temporal gyrus-default-mode network connectivity was associated with deteriorated performance in the egocentric task. Therefore, the data suggest that the auditory cortex exhibits compensatory neuroplasticity (i.e. increased functional connectivity with the task-critical frontoparietal network) to mitigate impaired visuomotor transformation after early auditory deprivation.

Cytoarchitectonic maps of human striate and extrastriate visual cortex based upon post-mortem brains can be correlated with functionally defined cortical areas using, for example, fMRI. We here assess the correspondence of anatomical maps of the visual cortex with functionally defined in vivo visual areas using retinotopic mapping. To this end, anatomical maximum probability maps (aMPM) derived from individual cytoarchitectonic maps of striate and extrastriate visual areas were compared with functional localisers for the early visual areas. Using fMRI, we delineated dorsal and ventral human retinotopic areas V1, V2, and V3, as well as a quarter-field visual field representation lateral to V3v, V4(v), in 24 healthy subjects. Based on these individual definitions, a functional maximum probability map (fMPM) was then computed in analogy to the aMPM. Functional and anatomical MPMs were highly correlated at group level: 78.5% of activated voxels in the fMPM were correctly assigned by the aMPM. The group aMPM was less effective in predicting functional retinotopic areas in the individual brain due to the large inter-individual variability in the location and extent of visual areas (mean overlap 32-69%). We conclude that cytoarchitectonic maps of striate and extrastriate visual areas may provide a valuable method for assigning functional group activations and thus add valuable a priori knowledge to the analysis of functional imaging data of the visual cortex.

The present study aimed at identifying dysfunctions in brain networks that may underlie disturbed empathic behavior in autism spectrum disorders (ASD). During functional magnetic resonance imaging, subjects were asked to identify the emotional state observed in a facial stimulus (other-task) or to evaluate their own emotional response (self-task). Behaviorally, ASD subjects performed equally to the control group during the other-task, but showed less emotionally congruent responses in the self-task. Activations in brain regions related to theory of mind were observed in both groups. Activations of the medial prefrontal cortex (MPFC) were located in dorsal subregions in ASD subjects and in ventral areas in control subjects. During the self-task, ASD subjects activated an additional network of frontal and inferior temporal areas. Frontal areas previously associated with the human mirror system were activated in both tasks in control subjects, while ASD subjects recruited these areas during the self-task only. Activations in the ventral MPFC may provide the basis for one's "emotional bond" with other persons' emotions. Such atypical patterns of activation may underlie disturbed empathy in individuals with ASD. Subjects with ASD may use an atypical cognitive strategy to gain access to their own emotional state in response to other people's emotions.

Healthy aging is accompanied by changes in brain activation patterns in the motor system. In older subjects, unilateral hand movements typically rely on increased recruitment of ipsilateral frontoparietal areas. While the two central concepts of aging-related brain activity changes, "Hemispheric Asymmetry Reduction in Older Adults" (HAROLD), and "Posterior to Anterior Shift in Aging" (PASA), have initially been suggested in the context of cognitive tasks and were attributed to compensation, current knowledge regarding the functional significance of increased motor system activity remains scarce. We, therefore, used online interference transcranial magnetic stimulation in young and older subjects to investigate the role of key regions of the ipsilateral frontoparietal cortex, that is, (a) primary motor cortex (M1), (b) dorsal premotor cortex (dPMC), and (c) anterior intraparietal sulcus (IPS) in the control of hand movements of different motor demands. Our data suggest a change of the functional roles of ipsilateral brain areas in healthy age with a reduced relevance of ipsilateral M1 and a shift of importance toward dPMC for repetitive high-frequency movements. These results support the notion that mechanisms conceptualized in the models of "PASA" and "HAROLD" also apply to the motor system.

Females frequently score higher on standard tests of empathy, social sensitivity, and emotion recognition than do males. It remains to be clarified, however, whether these gender differences are associated with gender specific neural mechanisms of emotional social cognition. We investigated gender differences in an emotion attribution task using functional magnetic resonance imaging. Subjects either focused on their own emotional response to emotion expressing faces (SELF-task) or evaluated the emotional state expressed by the faces (OTHER-task). Behaviorally, females rated SELF-related emotions significantly stronger than males. Across the sexes, SELF- and OTHER-related processing of facial expressions activated a network of medial and lateral prefrontal, temporal, and parietal brain regions involved in emotional perspective taking. During SELF-related processing, females recruited the right inferior frontal cortex and superior temporal sulcus stronger than males. In contrast, there was increased neural activity in the left temporoparietal junction in males (relative to females). When performing the OTHER-task, females showed increased activation of the right inferior frontal cortex while there were no differential activations in males. The data suggest that females recruit areas containing mirror neurons to a higher degree than males during both SELF- and OTHER-related processing in empathic face-to-face interactions. This may underlie facilitated emotional "contagion" in females. Together with the observation that males differentially rely on the left temporoparietal junction (an area mediating the distinction between the SELF and OTHERS) the data suggest that females and males rely on different strategies when assessing their own emotions in response to other people.

Activity changes in the ipsi- and contralesional parietal cortex and abnormal interhemispheric connectivity between these regions are commonly observed after stroke, however, their significance for motor recovery remains poorly understood. We here assessed the contribution of ipsilesional and contralesional anterior intraparietal cortex (aIPS) for hand motor function in 18 recovered chronic stroke patients and 18 healthy control subjects using a multimodal assessment consisting of resting-state functional MRI, motor task functional MRI, online-repetitive transcranial magnetic stimulation (rTMS) interference, and 3D movement kinematics. Effects were compared against two control stimulation sites, i.e. contralesional M1 and a sham stimulation condition. We found that patients with good motor outcome compared to patients with more substantial residual deficits featured increased resting-state connectivity between ipsilesional aIPS and contralesional aIPS as well as between ipsilesional aIPS and dorsal premotor cortex. Moreover, interhemispheric connectivity between ipsilesional M1 and contralesional M1 as well as ipsilesional aIPS and contralesional M1 correlated with better motor performance across tasks. TMS interference at individual aIPS and M1 coordinates led to differential effects depending on the motor task that was tested, i.e. index finger-tapping, rapid pointing movements, or a reach-grasp-lift task. Interfering with contralesional aIPS deteriorated the accuracy of grasping, especially in patients featuring higher connectivity between ipsi- and contralesional aIPS. In contrast, interference with the contralesional M1 led to impaired grasping speed in patients featuring higher connectivity between bilateral M1. These findings suggest differential roles of contralesional M1 and aIPS for distinct aspects of recovered hand motor function, depending on the reorganization of interhemispheric connectivity.

To characterize the neural correlates of being personally involved in social interaction as opposed to being a passive observer of social interaction between others we performed an fMRI study in which participants were gazed at by virtual characters (ME) or observed them looking at someone else (OTHER). In dynamic animations virtual characters then showed socially relevant facial expressions as they would appear in greeting and approach situations (SOC) or arbitrary facial movements (ARB). Differential neural activity associated with ME>OTHER was located in anterior medial prefrontal cortex in contrast to the precuneus for OTHER>ME. Perception of socially relevant facial expressions (SOC>ARB) led to differentially increased neural activity in ventral medial prefrontal cortex. Perception of arbitrary facial movements (ARB>SOC) differentially activated the middle temporal gyrus. The results, thus, show that activation of medial prefrontal cortex underlies both the perception of social communication indicated by facial expressions and the feeling of personal involvement indicated by eye gaze. Our data also demonstrate that distinct regions of medial prefrontal cortex contribute differentially to social cognition: whereas the ventral medial prefrontal cortex is recruited during the analysis of social content as accessible in interactionally relevant mimic gestures, differential activation of a more dorsal part of medial prefrontal cortex subserves the detection of self-relevance and may thus establish an intersubjective context in which communicative signals are evaluated.