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The neuronal basis and ontogeny of empathy and mind reading: review of literature and implications for future research.

Social neuro-science has recently started to investigate the neuronal mechanisms underlying our ability to understand the mental and emotional states of others. In this review, imaging research conducted on theory of mind (ToM or mentalizing) and empathy is selectively reviewed. It is proposed that even though these abilities are often used as synonyms in the literature these capacities represent different abilities that rely on different neuronal circuitry. ToM refers to our ability to understand mental states such as intentions, goals and beliefs, and relies on structures of the temporal lobe and the pre-frontal cortex. In contrast, empathy refers to our ability to share the feelings (emotions and sensations) of others and relies on sensorimotor cortices as well as limbic and para-limbic structures. It is further argued that the concept of empathy as used in lay terms refers to a multi-level construct extending from simple forms of emotion contagion to complex forms of cognitive perspective taking. Future research should investigate the relative contribution of empathizing and mentalizing abilities in the understanding of other people's states. Finally, it is suggested that the abilities to understand other people's thoughts and to share their affects display different ontogenetic trajectories reflecting the different developmental paths of their underlying neural structures. In particular, empathy develops much earlier than mentalizing abilities, because the former relys on limbic structures which develop early in ontogeny, whereas the latter rely on lateral temporal lobe and pre-frontal structures which are among the last to fully mature.

Brain↗

Neuronal correlates of theory of mind and empathy: a functional magnetic resonance imaging study in a nonverbal task.

Theory of Mind (ToM), the ability to attribute mental states to others, and empathy, the ability to infer emotional experiences, are important processes in social cognition. Brain imaging studies in healthy subjects have described a brain system involving medial prefrontal cortex, superior temporal sulcus and temporal pole in ToM processing. Studies investigating networks associated with empathic responding also suggest involvement of temporal and frontal lobe regions. In this fMRI study, we used a cartoon task derived from Sarfati et al. (1997) [Sarfati, Y., Hardy-Bayle, M.C., Besche, C., Widlocher, D. 1997. Attribution of intentions to others in people with schizophrenia: a non-verbal exploration with comic strips. Schizophrenia Research 25, 199-209.]with both ToM and empathy stimuli in order to allow comparison of brain activations in these two processes. Results of 13 right-handed, healthy, male volunteers were included. Functional images were acquired using a 1.5 T Phillips Gyroscan. Our results confirmed that ToM and empathy stimuli are associated with overlapping but distinct neuronal networks. Common areas of activation included the medial prefrontal cortex, temporoparietal junction and temporal poles. Compared to the empathy condition, ToM stimuli revealed increased activations in lateral orbitofrontal cortex, middle frontal gyrus, cuneus and superior temporal gyrus. Empathy, on the other hand, was associated with enhanced activations of paracingulate, anterior and posterior cingulate and amygdala. We therefore suggest that ToM and empathy both rely on networks associated with making inferences about mental states of others. However, empathic responding requires the additional recruitment of networks involved in emotional processing. These results have implications for our understanding of disorders characterized by impairments of social cognition, such as autism and psychopathy.

Adult↗

A visual joke fMRI investigation into Theory of Mind and enhanced risk of schizophrenia.

Theory of Mind (ToM) or mentalizing is the ability of individuals to determine the intentions and behavior of others. This ability is known to be compromised in schizophrenia and has been shown to fluctuate with symptom severity. Neuropsychological investigations into relatives of individuals with schizophrenia have shown that some relatives also show a deficit in this area of social cognition. In order to address this state and trait issue, we investigated the performance of high-risk relatives of individuals with schizophrenia to those of a matched control group (n = 13) on a blocked design visual joke fMRI paradigm. The task involved looking at two sets of cartoon jokes, one set which required mentalizing abilities to understand the jokes and another set that did not require such abilities. Relatives were divided into two groups based on the presence (HR+, n = 12) or absence (HR-, n = 12) of positive symptoms. The task provided robust activations across the groups in areas previously associated with mentalizing abilities, such as the PFC, precuneus, and temporal lobes. Significant between-group activations were observed in the PFC (primarily BA6, 8, and 9) with the HR- activating significantly greater than the HR+ in these regions. Both a secondary state-specific analysis and a third post hoc analysis further investigating state effects showed significant PFC between-group differences. This study is the first time relatives of individuals with schizophrenia have been imaged using a ToM paradigm, and the results provide evidence of both a state and state-mediated trait effect.

Adult↗

Children's and adults' neural bases of verbal and nonverbal 'theory of mind'.

Theory of mind (ToM) - our ability to predict behaviors of others in terms of their underlying intentions - has been examined through verbal and nonverbal false-belief (FB) tasks. Previous brain imaging studies of ToM in adults have implicated medial prefrontal cortex (mPFC) and temporo-parietal junction (TPJ) for adults' ToM ability. To examine age and modality related differences and similarities in neural correlates of ToM, we tested 16 adults (18-40 years old) and 12 children (8-12 years old) with verbal (story) and nonverbal (cartoon) FB tasks, using functional magnetic resonance imaging (fMRI). Both age groups showed significant activity in the TPJ bilaterally and right inferior parietal lobule (IPL) in a modality-independent manner, indicating that these areas are important for ToM during both adulthood and childhood, regardless of modality. We also found significant age-related differences in the ToM condition-specific activity for the story and cartoon tasks in the left inferior frontal gyrus (IFG) and left TPJ. These results suggest that depending on the modality adults may utilize different brain regions from children in understanding ToM.

Adult↗

A neuropsychological investigation into 'Theory of Mind' and enhanced risk of schizophrenia.

Theory of Mind (ToM) is the ability to correctly determine the intentions and behaviours of others. It is known that this capability is compromised in individuals with schizophrenia. It is has not been fully elucidated whether this observed phenomenon is of a state or trait nature. This study investigated whether ToM impairments could be linked to schizophrenia liability. A battery of ToM tests (the Hinting Task, a Self-Monitoring drawing task and cartoon picture stories) were used to compare healthy controls (n=13) with relatives of individuals with schizophrenia who had experienced psychotic symptoms (HR+, n=12) and those relatives who had not (HR-, n=13). All participants belonged to the Edinburgh High Risk Study. Significant group differences were seen on the Self-Monitoring and cartoon tasks for the HR+ group, particularly those who had experienced symptoms at or around the time of testing. The observed ToM deficits measured by this battery of ToM tasks appeared to be related to state effects rather than enhanced risk of schizophrenia.

Adult↗

In two minds: dual-process accounts of reasoning.

Researchers in thinking and reasoning have proposed recently that there are two distinct cognitive systems underlying reasoning. System 1 is old in evolutionary terms and shared with other animals: it comprises a set of autonomous subsystems that include both innate input modules and domain-specific knowledge acquired by a domain-general learning mechanism. System 2 is evolutionarily recent and distinctively human: it permits abstract reasoning and hypothetical thinking, but is constrained by working memory capacity and correlated with measures of general intelligence. These theories essentially posit two minds in one brain with a range of experimental psychological evidence showing that the two systems compete for control of our inferences and actions.

Journal Article↗

Imaging a science of mind.

I believe that the study of neuroimaging has supported localization of mental operations within the human brain. Most studies have shown a small number of widely distributed brain areas that must be orchestrated to carry out a cognitive task. Although, as in all sciences, there are disagreements, the convergence of results in areas of attention and language in particular seem impressive. Moreover, the anatomical data has helped us to specify the computations that are used by the brain to carry out cognitive tasks. Building upon localization of cognitive operations, imaging methods are being applied to studies of the circuitry, plasticity and individual development of neural networks. Working together with cellular and genetic methods, there is movement towards a more unified view of the role of the human brain in supporting the mind.

Journal Article↗

Becoming symbol-minded.

No facet of human development is more crucial than becoming symbol-minded. To participate fully in any society, children have to master the symbol systems that are important in that society. Children today must learn to use more varieties of symbolic media than ever before, so it is even more important to understand the processes involved in symbolic development. Recent research has greatly expanded what we know about early symbol use. We have learned, for example, that infants initially accept a wide range of entities as potential symbols and that young children are often confused about the nature of symbol-referent relations. During the first few years of life, however, children make rapid progress towards becoming competent symbol users.

Child↗

Developmental parallels in understanding minds and bodies.

A recent article by Onishi and Baillargeon presents evidence that 15-month-old infants attribute false beliefs (FBs) to other people. If correct, it lends dramatic new support to the idea that mental state concepts ("theory of mind") emerge from a specialized neurocognitive mechanism that matures during the second year of life. But it also raises new puzzles concerning the FB task--puzzles that have intriguing parallels in results from infants' reasoning about solid bodies.

Brain↗

Domain-specificity and theory of mind: evaluating neuropsychological evidence.

Humans' unique aptitude for reasoning about mental states, known as Theory of Mind (ToM), can help explain the unique character of human communication and social interaction. ToM has been studied extensively in children, but there is no clear account of the cognitive basis of ToM in adults. Evidence from functional imaging and neuropsychology is beginning to address this surprising gap in our understanding, and this evidence is often thought to favour a domain-specific or modular architecture for ToM. We present a systematic approach to this issue for the paradigmatic case of belief reasoning, and argue that neuropsychological data provide no clear evidence for domain-specificity or modularity. Progress in understanding ToM requires new tasks that isolate potentially distinct components of this complex ability.

Adult↗

Joint action: bodies and minds moving together.

The ability to coordinate our actions with those of others is crucial for our success as individuals and as a species. Progress in understanding the cognitive and neural processes involved in joint action has been slow and sparse, because cognitive neuroscientists have predominantly studied individual minds and brains in isolation. However, in recent years, major advances have been made by investigating perception and action in social context. In this article we outline how studies on joint attention, action observation, task sharing, action coordination and agency contribute to the understanding of the cognitive and neural processes supporting joint action. Several mechanisms are proposed that allow individuals to share representations, to predict actions, and to integrate predicted effects of own and others' actions.

Attention↗

Beyond mind-reading: multi-voxel pattern analysis of fMRI data.

A key challenge for cognitive neuroscience is determining how mental representations map onto patterns of neural activity. Recently, researchers have started to address this question by applying sophisticated pattern-classification algorithms to distributed (multi-voxel) patterns of functional MRI data, with the goal of decoding the information that is represented in the subject's brain at a particular point in time. This multi-voxel pattern analysis (MVPA) approach has led to several impressive feats of mind reading. More importantly, MVPA methods constitute a useful new tool for advancing our understanding of neural information processing. We review how researchers are using MVPA methods to characterize neural coding and information processing in domains ranging from visual perception to memory search.

Algorithms↗

Transcription factor single-minded 2 (SIM2) is ubiquitinated by the RING-IBR-RING-type E3 ubiquitin ligases.

Human single-minded 2 (SIM2) is a member of the basic helix-loop-helix/Per-Arnt-Sim (bHLH/PAS) family of transcription factors and is associated with the etiology of Down syndrome phenotype. Here, we examined a possibility of the post-translational modification of SIM2 protein by transfecting various expression constructs followed by the analysis with immunoprecipitation and Western blotting. In fact, transient expression of SIM2 cDNA in HEK293 cells revealed poly-ubiquitination of SIM2 protein. In the stable transfectants, a proteasome inhibitor MG132 protected the poly-ubiquitinated SIM2 protein from degradation. Furthermore, in the cells co-transfected with SIM2 and each of four different E3 ubiquitin ligases, SIM2 was immunoprecipitated with the RING-IBR-RING-type E3 ubiquitin ligases, Parkin and HHARI, but it was not immunoprecipitated with other E3 ligases, such as one RING-type Siah-1 and the PHD type AIRE. A series of deletion constructs revealed that Parkin actually binds to SIM2 with the IBR (294-377)-RING2 (378-465) domains and that the sites for poly-ubiquitination of SIM2 reside within the PAS1-PAS2 region (aa 141-289). We postulated that transcription factor SIM2 and E3 ubiquitin ligase Parkin may interact each other to play an important physiological role in the brain development which is controlled by ubiquitination.

Animals↗

Imaging the mind.

At the forefront of cognitive neuroscience research in normal humans are the new techniques of functional brain imaging: positron emission tomography (PET) and, more recently, magnetic resonance imaging (MRI). The signal used by PET is based on the fact that changes in the cellular activity of the brain of normal, awake humans and laboratory animals are accompanied almost invariably by changes in local blood flow. This robust, empirical relationship has fascinated scientists for well over a hundred years. PET provided a level of precision in the measurement of blood flow that opened up the modern era of functional human brain mapping. Further, the discovery with PET that these changes in blood flow are unaccompanied by quantitatively similar changes in oxygen consumption has paved the way for the explosive rise in the use of MRI in functional brain imaging. The remarkable success of this enterprise is a fitting tribute to men like Michel Ter-Pogossian. He pioneered the use of positron emitting radionuclides in biology and medicine when most had abandoned them in favor of more conventional nuclear medicine radionuclides. Importantly, also, he welcomed into his laboratory young scientists with a broad range of talents, many of whom subsequently became leaders in imaging the mind in research centers throughout the world.

Animals↗

Indexical and symbolic referencing: what role do they play in children's success on theory of mind tasks?

Numerous measures have been employed in the last 17 years to assess theory of mind (ToM). The literature reports marked variability in the age at which children succeed on these measures. To account for this variability, researchers have provided explanations ranging from cognitive shifts and voids to the inability to understand the language of the tasks or to social/pragmatic considerations, all of which tell us little if anything about the internal mechanism underlying ToM. The main purpose of this paper is to provide a comprehensive theoretical account of children's success and the discrepancies found across different ToM tasks. We test the hypothesis that children's understanding of ToM is sensitive to the basic elements of language, that is, to whether the language is indexical or symbolic. Support for this account was found in the analysis of selected test protocols in four published studies of ToM, and new data collected from 53 children (4--6 years) which showed that a higher percentage of children succeeded on tasks with a high ratio of indexical to symbolic references than on tasks with a high ratio of symbolic to indexical references. There was also a main effect of age with older children succeeding at higher rates on both tasks than younger children. Our findings suggest that indexical representation can afford ToM understanding in 4-year-olds, but is not sufficient for a more mature ToM. The latter requires symbolic representation that was demonstrated by the majority of 5--6-year-olds.

Child↗

Children's understanding that utterances emanate from minds: using speaker belief to aid interpretation.

Children interpreted an utterance made by a protagonist with a false belief, such as, 'I would like the car in the garage.' Calculating the speaker's belief in conjunction with the literal meaning of the utterance would lead to the correct interpretation that the intended referent is the car on the track, given that the car in the garage swapped places with the one on the track. In Experiments 1 and 2, many children aged around 4 and 5 years wrongly indicated the car in the garage. In contrast, many correctly indicated the car on the track when it was unnecessary to consider the speaker's belief because the utterance was, 'the car I put in the garage'. Six-year-olds found both kinds of utterance equally easy in Experiment 1, while 3-year-olds had equal difficulty with both. In Experiments 2 and 3, the speaker gave an ambiguous utterance and many children aged between 3 and 6 years successfully used information about the speaker's belief to identify which of several candidate referents was intended. We discuss the results in relation to characteristics of utterance comprehension and consider implications for developments in understanding the mind by children beyond 4 years.

Age Factors↗

Luria: a unitary view of human brain and mind.

Special questions the eminent Russian psychologist and neuropsychologist Aleksandr R. Luria (1902-1977) dealt with in his research regarded the relationship between animal and human brain, child and adult mind, normal and pathological, theory and rehabilitation, clinical and experimental investigation. These issues were integrated in a unitary theory of cerebral and psychological processes, under the influence of both different perspectives active in the first half of the Nineteenth century (psychoanalysis and historical-cultural school, first of all) and the growing contribution of neuropsychological research on brain-injured patients.

Aging↗

Xenopus single-minded (xSim) is a nuclear factor allowing nuclear translocation of its cytoplasmic partner xArnt.

Transcription factors belonging to the basic helix-loop-helix Per-Arnt-Sim (bHLH/PAS) family control a wide variety of biological processes in mammalian and/or Drosophila. We have previously isolated bHLH/PAS Xenopus amphibian homologs of Single-minded (xSim) and aryl receptor nuclear translocator (xArnt) and characterized their expression pattern during embryogenesis. We show in this paper that xSim protein is a functional homolog of Drosophila or mammalian Sim(s). Biochemical analysis indicates that xSim forms a heterodimer with xArnt. Subcellular localization analysis of bHLH/PAS chimeric fluorescent versions in Xenopus or mammalian cell lines shows that xSim is constitutively localized in the nuclear compartment. On the opposite, xArnt appears to be predominantly expressed in the cytoplasm. In addition, we demonstrate that xArnt nuclear localization depends on the presence of xSim. Thus xSim appears to be an essential factor in the nuclear translocation of the xSim/xArnt complex. In perfect agreement, we show that the C-terminal half of xSim contains the information for this nuclear localization.

Amino Acid Sequence↗