Changes in brain activity following the voluntary control of empathy.

In neuroscience, empathy is often conceived as relatively automatic. The voluntary control that people can exert on brain mechanisms that map the emotions of others onto our own emotions has received comparatively less attention. Here, we therefore measured brain activity while participants watched emotional Hollywood movies under two different instructions: to rate the main characters' emotions by empathizing with them, or to do so while keeping a detached perspective. We found that participants yielded highly consistent and similar ratings of emotions under both conditions. Using intersubject correlation-based analyses we found that, when encouraged to empathize, participants' brain activity in limbic (including cingulate and putamen) and somatomotor regions (including premotor, SI and SII) synchronized more during the movie than when encouraged to detach. Using intersubject functional connectivity we found that comparing the empathic and detached perspectives revealed widespread increases in functional connectivity between large scale networks. Our findings contribute to the increasing awareness that we have voluntary control over the neural mechanisms through which we process the emotions of others.

Where and how our brain represents the temporal structure of observed action.

Reacting faster to the behaviour of others provides evolutionary advantages. Reacting to unpredictable events takes hundreds of milliseconds. Understanding where and how the brain represents what actions are likely to follow one another is, therefore, important. Everyday actions occur in predictable sequences, yet neuroscientists focus on how brains respond to unexpected, individual motor acts. Using fMRI, we show the brain encodes sequence-related information in the motor system. Using EEG, we show visual responses are faster and smaller for predictable sequences. We hope this paradigm encourages the field to shift its focus from single acts to motor sequences. It sheds light on how we adapt to the actions of others and suggests that the motor system may implement perceptual predictive coding.

Corticolimbic hyper-response to emotion and glutamatergic function in people with high schizotypy: a multimodal fMRI-MRS study.

Animal models and human neuroimaging studies suggest that altered levels of glutamatergic metabolites within a corticolimbic circuit have a major role in the pathophysiology of schizophrenia. Rodent models propose that prefrontal glutamate dysfunction could lead to amygdala hyper-response to environmental stress and underlie hippocampal overdrive in schizophrenia. Here we determine whether changes in brain glutamate are present in individuals with high schizotypy (HS), which refers to the presence of schizophrenia-like characteristics in healthy individuals, and whether glutamate levels are related to altered corticolimbic response to emotion. Twenty-one healthy HS subjects and 22 healthy subjects with low schizotypy (LS) were selected based on their Oxford and Liverpool Inventory of Feelings and Experiences rating. Glutamate levels were measured in the anterior cingulate cortex (ACC) using proton magnetic resonance spectroscopy, followed by a functional magnetic resonance imaging (fMRI) scan to measure corticolimbic response during emotional processing. fMRI results and fMRI × glutamate interactions were considered significant after voxel-wise P<0.05 family-wise error correction. While viewing emotional pictures, HS individuals showed greater activation than did subjects with LS in the caudate, and marginally in the ACC, hippocampus, medial prefrontal cortex (MPFC) and putamen. Although no between-group differences were found in glutamate concentrations, within the HS group ACC glutamate was negatively correlated with striatal activation (left: z=4.30, P=0.004 and right: z=4.12 P=0.008 caudate; left putamen: z=3.89, P=0.018) and marginally with MPFC (z=3.55, P=0.052) and amygdala (left: z=2.88, P=0.062; right: z=2.79, P=0.079), correlations that were not present in LS subjects. These findings provide, to our knowledge, the first evidence that brain glutamate levels are associated with hyper-responsivity in brain regions thought to be critical in the pathophysiology of psychosis.

Neural pathways of embarrassment and their modulation by social anxiety.

While being in the center of attention and exposed to other's evaluations humans are prone to experience embarrassment. To characterize the neural underpinnings of such aversive moments, we induced genuine experiences of embarrassment during person-group interactions in a functional neuroimaging study. Using a mock-up scenario with three confederates, we examined how the presence of an audience affected physiological and neural responses and the reported emotional experiences of failures and achievements. The results indicated that publicity induced activations in mentalizing areas and failures led to activations in arousal processing systems. Mentalizing activity as well as attention towards the audience were increased in socially anxious participants. The converging integration of information from mentalizing areas and arousal processing systems within the ventral anterior insula and amygdala forms the neural pathways of embarrassment. Targeting these neural markers of embarrassment in the (para-)limbic system provides new perspectives for developing treatment strategies for social anxiety disorders.

The autism brain imaging data exchange: towards a large-scale evaluation of the intrinsic brain architecture in autism.

Autism spectrum disorders (ASDs) represent a formidable challenge for psychiatry and neuroscience because of their high prevalence, lifelong nature, complexity and substantial heterogeneity. Facing these obstacles requires large-scale multidisciplinary efforts. Although the field of genetics has pioneered data sharing for these reasons, neuroimaging had not kept pace. In response, we introduce the Autism Brain Imaging Data Exchange (ABIDE)-a grassroots consortium aggregating and openly sharing 1112 existing resting-state functional magnetic resonance imaging (R-fMRI) data sets with corresponding structural MRI and phenotypic information from 539 individuals with ASDs and 573 age-matched typical controls (TCs; 7-64 years) (http://fcon_1000.projects.nitrc.org/indi/abide/). Here, we present this resource and demonstrate its suitability for advancing knowledge of ASD neurobiology based on analyses of 360 male subjects with ASDs and 403 male age-matched TCs. We focused on whole-brain intrinsic functional connectivity and also survey a range of voxel-wise measures of intrinsic functional brain architecture. Whole-brain analyses reconciled seemingly disparate themes of both hypo- and hyperconnectivity in the ASD literature; both were detected, although hypoconnectivity dominated, particularly for corticocortical and interhemispheric functional connectivity. Exploratory analyses using an array of regional metrics of intrinsic brain function converged on common loci of dysfunction in ASDs (mid- and posterior insula and posterior cingulate cortex), and highlighted less commonly explored regions such as the thalamus. The survey of the ABIDE R-fMRI data sets provides unprecedented demonstrations of both replication and novel discovery. By pooling multiple international data sets, ABIDE is expected to accelerate the pace of discovery setting the stage for the next generation of ASD studies.

An advanced simulation model for membrane bioreactors: development, calibration and validation.

Membrane wastewater treatment plants (WWTPs) have several advantages compared with conventionally designed WWTPs with classical purification techniques. The filtration process is the key to their commercial success in Germany with respect to energy consumption and effectiveness, enabled by the optimization of filtration using a dynamic simulation model. This work is focused on the development of a robust, flexible and practically applicable membrane simulation model for submerged hollow-fibre and flat-sheet membrane modules. The model is based on standard parameters usually measured on membrane WWTPs. The performance of the model is demonstrated by successful calibration and validation for three different full-scale membrane WWTPs achieving good results. Furthermore, the model is combinable with Activated Sludge Models.

Human amygdala reactivity is diminished by the ß-noradrenergic antagonist propranolol.

BACKGROUND: Animal models of anxiety disorders emphasize the crucial role of locus ceruleus-noradrenergic (norepinephrine, NE) signaling, the basolateral amygdala (BLA) and their interactions in the expression of anxiety-like behavioral responses to stress. Despite clinical evidence for the efficacy of a ß-noradrenergic receptor blockade with propranolol in the alleviation of anxiety symptoms and the secondary prevention of post traumatic stress disorder, preclinical evidence for a ß-noradrenergic modulation of BLA activity in humans is missing. METHOD: We combined functional magnetic resonance imaging in healthy volunteers with probabilistic mapping of intra-amygdalar responses to fearful, neutral and happy facial expressions to test the hypothesis that a ß-noradrenergic receptor blockade with propranolol would inactivate the BLA. RESULTS: Consistent with our a priori hypothesis, propranolol diminished BLA responses to facial expressions, independent of their emotional valence. The absence of activity changes in probabilistically defined visual control regions underscores the specific action of propranolol in the BLA. CONCLUSIONS: Our findings provide the missing link between the anxiolytic potential of propranolol and the biological basis of ß-noradrenergic activation in the human BLA as a key target for the pharmacological inhibition of anxiety neurocircuitry. Moreover, our findings add to emerging evidence that NE modulates both the reactivity (sensitivity) and the operating characteristics (specificity) of the BLA via ß-noradrenergic receptors.

Evidence for mirror systems in emotions.

Why do we feel tears well up when we see a loved one cry? Why do we wince when we see other people hurt themselves? This review addresses these questions from the perspective of embodied simulation: observing the actions and tactile sensations of others activates premotor, posterior parietal and somatosensory regions in the brain of the observer which are also active when performing similar movements and feeling similar sensations. We will show that seeing the emotions of others also recruits regions involved in experiencing similar emotions, although there does not seem to be a reliable mapping of particular emotions onto particular brain regions. Instead, emotion simulation seems to involve a mosaic of affective, motor and somatosensory components. The relative contributions of these components to a particular emotion and their interrelationship are largely unknown, although recent experimental evidence suggests that motor simulation may be a trigger for the simulation of associated feeling states. This mosaic of simulations may be necessary for generating the compelling insights we have into the feelings of others. Through their integration with, and modulation by, higher cognitive functions, they could be at the core of important social functions, including empathy, mind reading and social learning.

The anthropomorphic brain: the mirror neuron system responds to human and robotic actions.

In humans and monkeys the mirror neuron system transforms seen actions into our inner representation of these actions. Here we asked if this system responds also if we see an industrial robot perform similar actions. We localised the motor areas involved in the execution of hand actions, presented the same subjects blocks of movies of humans or robots perform a variety of actions. The mirror system was activated strongly by the sight of both human and robotic actions, with no significant differences between these two agents. Finally we observed that seeing a robot perform a single action repeatedly within a block failed to activate the mirror system. This latter finding suggests that previous studies may have failed to find mirror activations to robotic actions because of the repetitiveness of the presented actions. Our findings suggest that the mirror neuron system could contribute to the understanding of a wider range of actions than previously assumed, and that the goal of an action might be more important for mirror activations than the way in which the action is performed.

Out of sight but not out of mind: the neurophysiology of iconic memory in the superior temporal sulcus.

Iconic memory, the short-lasting visual memory of a briefly flashed stimulus, is an important component of most models of visual perception. Here we investigate what physiological mechanisms underlie this capacity by showing rapid serial visual presentation (RSVP) sequences with and without interstimulus gaps to human observers and macaque monkeys. For gaps of up to 93 ms between consecutive images, human observers and neurones in the temporal cortex of macaque monkeys were found to continue processing a stimulus as if it was still present on the screen. The continued firing of neurones in temporal cortex may therefore underlie iconic memory. Based on these findings, a neurophysiological vision of iconic memory is presented.

Audiovisual mirror neurons and action recognition.

Many object-related actions can be recognized both by their sound and by their vision. Here we describe a population of neurons in the ventral premotor cortex of the monkey that discharge both when the animal performs a specific action and when it hears or sees the same action performed by another individual. These 'audiovisual mirror neurons' therefore represent actions independently of whether these actions are performed, heard or seen. The magnitude of auditory and visual responses did not differ significantly in half the neurons. A neurometric analysis revealed that based on the response of these neurons, two actions could be discriminated with 97% accuracy.

Neuronal representation of disappearing and hidden objects in temporal cortex of the macaque.

Neurons in the anterior regions of the banks of the superior temporal sulcus (STSa) of the macaque monkey respond to the sight of biologically significant stimuli such as faces, bodies and their motion. In this study the responses of STSa neurons were recorded during the gradual occlusion of the experimenter and other mobile objects behind screens at distances of 0.5-4 m from the monkeys. The experimenter or other object remained out of sight for 3-15 s before emerging back in to view. We describe a population of neurons (n=33) showing increased activity during the occlusion of objects that was maintained for up to 11 s following complete occlusion (when only the occluder itself was visible). This increase in activity was selective for the position of the occlusion within the testing room. Many neurons showed little or no change in activity prior to occlusion when the object or experimenter was completely in view. By coding for the presence and location of recently occluded objects, these responses may contribute to the perceptual capacity for object permanence.

I know what you are doing. a neurophysiological study.

In the ventral premotor cortex of the macaque monkey, there are neurons that discharge both during the execution of hand actions and during the observation of the same actions made by others (mirror neurons). In the present study, we show that a subset of mirror neurons becomes active during action presentation and also when the final part of the action, crucial in triggering the response in full vision, is hidden and can therefore only be inferred. This implies that the motor representation of an action performed by others can be internally generated in the observer's premotor cortex, even when a visual description of the action is lacking. The present findings support the hypothesis that mirror neuron activation could be at the basis of action recognition.

The speed of sight.

Macaque monkeys were presented with continuous rapid serial visual presentation (RSVP) sequences of unrelated naturalistic images at rates of 14--222 msec/image, while neurons that responded selectively to complex patterns (e.g., faces) were recorded in temporal cortex. Stimulus selectivity was preserved for 65% of these neurons even at surprisingly fast presentation rates (14 msec/image or 72 images/sec). Five human subjects were asked to detect or remember images under equivalent conditions. Their performance in both tasks was above chance at all rates (14--111 msec/image). The performance of single neurons was comparable to that of humans and responded in a similar way to changes in presentation rate. The implications for the role of temporal cortex cells in perception are discussed.

Evidence for physiological asymmetries in the intertectal connections of the pigeon (Columba livia) and their potential role in brain lateralisation.

In pigeons, visual object processing is lateralised with a dominance of the left tectofugal system. To test the hypothesis, that avian visual lateralisation may arise, at least in part, from asymmetric interhemispheric inhibition, the intertectal modulation was quantified in 19 pigeons. Field potentials were recorded from intratectal electrodes in response to a stroboscope flash to the contralateral eye. Electrical stimulation of the contralateral tectum changed these flash-evoked potentials. This change was taken as a measure of intertectal modulation. It was found that the left-to-right tectotectal modulation was more pronounced than vice versa, supporting the hypothesis of an asymmetric modulation between the tecta of both hemispheres. It is conceivable that this lateralised interhemispheric crosstalk could constitute an important component of asymmetric visual processing.

Pharmacology of sensory gating in the ascending auditory system of the pigeon (Columba livia).

RATIONALE: Whether the underlying neurochemical basis of sensori(motor) gating is exclusively the result of mammalian brain evolution is not known. OBJECTIVE: The effects of ketamine (KET), benztropine (BTP), apomorphine (APO), methylphenidatehydrochloride (AMP) and haloperidol (HAL) on sensorimotor gating of the acoustic startle and gating of auditory input into the telelencephalon was assessed in a within-subject design in pigeons (Columba livia) using the prepulse inhibition (PPI) paradigm. METHODS: The startle blink reflex was recorded using EMG electrodes which were chronically implanted into the adjoining Musculus palpepralis superior et inferior, Musculus elevator palpebralis superior, and Musculus nictitantis. Thalamic gating was recorded using electrodes which were chronically implanted into the nucleus ovoidalis thalami and the neostriatum caudale (field L), respectively. RESULTS: KET, APO and AMP disrupted dose-dependently sensorimotor gating. The effect of APO and AMP was blocked by HAL. PPI disruption following BTP did not reach statistical significance. KET disrupted thalamic gating and increased prepulse-induced inhibition in field L. By contrast, AMP increased thalamic and decreased field L inhibition of field potentials when preceded by a pre-stimulus. Both effects were antagonised by HAL thus providing preliminary evidence for a D2-mediated auditory gating mechanism in the thalamus. However, while the effect of APO at the thalamic level was similar to AMP, prepulse-induced inhibition of field L activity was enhanced. This may be explained by concurrent D1-mediated telencephalic inhibition. CONCLUSION: It is concluded that thalamic gating is modulated by a dopaminergic/glutamatergic mechanism. The findings also confirm the notion of an homologous neurochemical basis of sensorimotor gating in mammals and birds.