Autism spectrum disorders and schizophrenia: meta-analysis of the neural correlates of social cognition

Context

Impaired social cognition is a cardinal feature of Autism Spectrum Disorders (ASD) and Schizophrenia (SZ). However, the functional neuroanatomy of social cognition in either disorder remains unclear due to variability in primary literature. Additionally, it is not known whether deficits in ASD and SZ arise from similar or disease-specific disruption of the social cognition network.

Objective

To identify regions most robustly implicated in social cognition processing in SZ and ASD.

Data Sources

Systematic review of English language articles using MEDLINE (1995–2010) and reference lists.

Study Selection

Studies were required to use fMRI to compare ASD or SZ subjects to a matched healthy control group, provide coordinates in standard stereotactic space, and employ standardized facial emotion recognition (FER) or theory of mind (TOM) paradigms.

Data Extraction

Activation foci from studies meeting inclusion criteria (n = 33) were subjected to a quantitative voxel-based meta-analysis using activation likelihood estimation, and encompassed 146 subjects with ASD, 336 SZ patients and 492 healthy controls.

Results

Both SZ and ASD showed medial prefrontal hypoactivation, which was more pronounced in ASD, while ventrolateral prefrontal dysfunction was associated mostly with SZ. Amygdala hypoactivation was observed in SZ patients during FER and in ASD during more complex ToM tasks. Both disorders were associated with hypoactivation within the Superior Temporal Sulcus (STS) during ToM tasks, but activation in these regions was increased in ASD during affect processing. Disease-specific differences were noted in somatosensory engagement, which was increased in SZ and decreased in ASD. Reduced thalamic activation was uniquely seen in SZ.

Conclusions

Reduced frontolimbic and STS engagement emerged as a shared feature of social cognition deficits in SZ and ASD. However, there were disease- and stimulus-specific differences. These findings may aid future studies on SZ and ASD and facilitate the formulation of new hypotheses regarding their pathophysiology.     

Recruitment of both the mirror and the mentalizing networks when observing social interactions depicted by point-lights: a neuroimaging study

Background

Understanding social interactions requires the ability to accurately interpret conspecifics'' actions, sometimes only on the basis of subtle body language analysis. Here we address an important issue that has not yet received much attention in social neuroscience, that of an interaction between two agents. We attempted to isolate brain responses to two individuals interacting compared to two individuals acting independently.

Methodology/Principal Findings

We used minimalistic point-light displays to depict the characters, as they provide the most straightforward way to isolate mechanisms used to extract information from motion per se without any interference with other visual information. Functional magnetic resonance imaging (fMRI) method was used to determine which brain regions were recruited during the observation of two interacting agents, mimicking everyday social scenes. While the mirror and mentalizing networks are rarely concurrently active, we found that both of them might be needed to catch the social intentions carried by whole-body motion.

Conclusions/Significance

These findings shed light on how motor cognition contributes to social cognition when social information is embedded in whole-body motion only. Finally, the approach described here provides a valuable and original tool for investigating the brain networks responsible for social understanding, in particular in psychiatric disorders.     

Hormonal correlates of human paternal interactions: a hospital-based investigation in urban Jamaica

To expand our understanding of the neuroendocrine mechanisms underlying human fatherhood, including its cross-cultural expression, we investigated the hormonal correlates of fatherhood in the greater Kingston, Jamaica area. We recruited 43 men, aged 18-38, to participate: 15 single men; 16 "coresidential" fathers (men who live with their adult female partner and youngest child); and 12 "visiting" fathers (men who live apart from their adult female partner and youngest child). The research protocol entailed biological sampling before and after a 20-min behavioral session during which single men sat alone and fathers interacted with their partner and youngest child. Hormone measures relied upon minimally invasive techniques (salivary testosterone and cortisol, finger prick blood spot prolactin, urinary oxytocin and vasopressin). Results revealed significant group differences in average male testosterone levels (p=0.006), with post hoc contrasts indicating that visiting fathers had significantly (p<0.05) lower testosterone levels than single men. Prolactin profiles also differed significantly across groups (p=0.010) whereby post hoc contrasts showed that prolactin levels of single men declined significantly compared with the flat levels of visiting fathers (p<0.05). No group differences in cortisol, oxytocin or vasopressin levels were observed. However, among fathers, vasopressin levels were significantly and negatively (r=-.431, p=0.022) correlated with the age of a man's youngest child. These results thus implicate lower testosterone levels as well as prolactin and vasopressin in human fatherhood. These findings also highlight the importance of sociocultural context in human fatherhood while exhibiting parallels with existing data on the non-human vertebrate hormonal bases of paternal care.     

Before and below 'theory of mind': embodied simulation and the neural correlates of social cognition

The automatic translation of folk psychology into newly formed brain modules specifically dedicated to mind-reading and other social cognitive abilities should be carefully scrutinized. Searching for the brain location of intentions, beliefs and desires-as such-might not be the best epistemic strategy to disclose what social cognition really is. The results of neurocognitive research suggest that in the brain of primates, mirror neurons, and more generally the premotor system, play a major role in several aspects of social cognition, from action and intention understanding to language processing. This evidence is presented and discussed within the theoretical frame of an embodied simulation account of social cognition. Embodied simulation and the mirror neuron system underpinning it provide the means to share communicative intentions, meaning and reference, thus granting the parity requirements of social communication.     

The neural correlates of desire

In an event-related fMRI study, we scanned eighteen normal human subjects while they viewed three categories of pictures (events, objects and persons) which they classified according to desirability (desirable, indifferent or undesirable). Each category produced activity in a distinct part of the visual brain, thus reflecting its functional specialization. We used conjunction analysis to learn whether there is a brain area which is always active when a desirable picture is viewed, regardless of the category to which it belongs. The conjunction analysis of the contrast desirable > undesirable revealed activity in the superior orbito-frontal cortex. This activity bore a positive linear relationship to the declared level of desirability. The conjunction analysis of desirable > indifferent revealed activity in the mid-cingulate cortex and in the anterior cingulate cortex. In the former, activity was greater for desirable and undesirable stimuli than for stimuli classed as indifferent. Other conjunction analyses produced no significant effects. These results show that categorizing any stimulus according to its desirability activates three different brain areas: the superior orbito-frontal, the mid-cingulate, and the anterior cingulate cortices.     

EEG correlates of social creativity

EEG correlates of social creativity defined as ability to originally and flexibly interpret social significant situations were studied. It was found that the alpha2 and gamma2 rhythms are specific bands which make it possible to tell the difference between social creativity and control task. Solving socially significant problems in experimental conditions is accompanied by an increase in the power of the delta and gamma2 bands and desynchronization in the alpha2 band less pronounced in divergent tasks than during the interpretation of convergent visual stimuli.     

Neurological correlates of social behavior

Experimental evidence obtained over the past decade in nonhuman primates suggests that there are neural structures necessary for the maintenance of social bonds and affiliative behavior. These include the amygdaloid nuclei, which is the critical brain area, and two anatomically closely related cortical structures—the temporal pole and posterior medial orbital cortex. Bilateral ablation of any of the areas results in a syndrome that varies from a quantitative decrease in affiliative behavior in confined colonies to total social isolation in naturally free-ranging groups. Lesions of these areas in adult females are also incompatible with the maintenance of the maternal-infant bond, but operated infants thrive and are well cared for. Species-typical behavior will determine the response of group members to lesioned conspecifics, and may vary from attempts to reintegrate the affected subject to attack and ostracism.The amygdaloid nuclei are hypothesized to be essential to placing an emotional bias on sensory information; thus this brain area is sensitive to, and its function dependent on, the social/environmental context of ongoing behavior. Brain impairment per se, does not necessarily result in ostracism and may be compatible with maintenance of social bondings depending upon the neural structures involved, subject's affective state, communication ability, and species typical behaviors. Observations of brain-impaired humans closely parallel studies in nonhuman primates.     

Isolating neural correlates of the pacemaker for food anticipation

Mice fed a single daily meal at intervals within the circadian range exhibit food anticipatory activity. Previous investigations strongly suggest that this behaviour is regulated by a circadian pacemaker entrained to the timing of fasting/refeeding. The neural correlate(s) of this pacemaker, the food entrainable oscillator (FEO), whether found in a neural network or a single locus, remain unknown. This study used a canonical property of circadian pacemakers, the ability to continue oscillating after removal of the entraining stimulus, to isolate activation within the neural correlates of food entrainable oscillator from all other mechanisms driving food anticipatory activity. It was hypothesized that continued anticipatory activation of central nuclei, after restricted feeding and a return to ad libitum feeding, would elucidate a neural representation of the signaling circuits responsible for the timekeeping component of the food entrainable oscillator. Animals were entrained to a temporally constrained meal then placed back on ad libitum feeding for several days until food anticipatory activity was abolished. Activation of nuclei throughout the brain was quantified using stereological analysis of c-FOS expressing cells and compared against both ad libitum fed and food entrained controls. Several hypothalamic and brainstem nuclei remained activated at the previous time of food anticipation, implicating them in the timekeeping mechanism necessary to track previous meal presentation. This study also provides a proof of concept for an experimental paradigm useful to further investigate the anatomical and molecular substrates of the FEO.     

From observing to controlling: Inducible control of organelle dynamics and interactions

The dynamics and interactions of cellular organelles underlie many aspects of cellular functioning. Until recently, assessment of organelle dynamics has been primarily observational or required whole-cell perturbations to assess the implications of altered organelle motility and positioning. However, thanks to recently developed and optimized intervention strategies, we now have the ability to control organelles in their unperturbed state, altering organelle positioning, membrane trafficking pathways, as well as organelle interactions. This can be performed both globally and locally, giving fine control over the range, reversibility, and extent of organelle dynamics. Here, we describe how these tools are currently used for controlling organelles and give insight into the exciting future of this emerging field.     

Laser-Raman investigation of lysozyme-phospholipid interactions

The interaction of lysozyme with mixed 1,2-dipalmitoyl-l-phosphatidic acid/1,2-dimyristoyl-l-phosphatidylcholine liposomes was investigated by laser Raman spectroscopy. Substantial changes were observed in the spectra of both the lipid and protein in the mixed liposomes over the range 10–62°C. At temperatures below 27°C, interaction with lipid appears to slightly increase the amount of helical structure in lysozyme at the expense of random conformation. At temperatures above 30°C, considerable β-sheet is irreversibly formed. Onset of β-formation appears to coincide with the formation of disordered lipid side-chains in the acidic component of the lipid.At all temperatures, the O-P-O diester stretching mode at 782 cm^?1 is much more intense in the lipid/protein mixture than in lipid alone. It is observed that the dimyristoyl phosphatidylcholine chain-disorder transition is lowered by 3°C, while that of the phosphatidic acid is lowered by 12°C, yet the post-transition conformation contains a significantly higher proportion of trans-segments in the presence of lysozyme.These results are interpreted in terms of: (1) a polar interaction between acidic phospholipid and lysozyme at temperatures below either chain-disorder transition, in which lysozyme is essentially excluded from the hydrophobic portion of the lipid and (2) an interaction at higher temperatures which involves the lipid side-chains of dipalmitoyl phosphatidic acid in the disordered state and is manifested by a substantial conformational change.     

Introspective minds: using ALE meta-analyses to study commonalities in the neural correlates of emotional processing, social & unconstrained cognition

Previous research suggests overlap between brain regions that show task-induced deactivations and those activated during the performance of social-cognitive tasks. Here, we present results of quantitative meta-analyses of neuroimaging studies, which confirm a statistical convergence in the neural correlates of social and resting state cognition. Based on the idea that both social and unconstrained cognition might be characterized by introspective processes, which are also thought to be highly relevant for emotional experiences, a third meta-analysis was performed investigating studies on emotional processing. By using conjunction analyses across all three sets of studies, we can demonstrate significant overlap of task-related signal change in dorso-medial prefrontal and medial parietal cortex, brain regions that have, indeed, recently been linked to introspective abilities. Our findings, therefore, provide evidence for the existence of a core neural network, which shows task-related signal change during socio-emotional tasks and during resting states.     

Density-dependent mortality and the evolution of social interactions

Existing models of kin selection implicitly assume that the intensity of density-dependent mortality depends on the size or density of the entire deme. If individuals compete for locally limited resources, then mortality may also depend on local population density. In this paper, I derive conditions for evolutionary equilibrium when the fitness of an individual depends on (1) the phenotypes of a local group of conspecifics with which it interacts and (2) the size of the local group. In general, altruistic behaviours which reduce the individual fitness of the actor but increase that of the recipient are favoured towards individuals whose coefficient of relationship exceeds a threshold value. ‘Harming’ behaviours which reduce the individual fitness of both the actor and the recipient are favoured towards individuals below this threshold value. The magnitude of this threshold depends on the nature of the processes that cause density-dependent mortality and the average coefficient of relationship in the group.     

Behavioral and neural correlates of communication via pointing

Communicative pointing is a human specific gesture which allows sharing information about a visual item with another person. It sets up a three-way relationship between a subject who points, an addressee and an object. Yet psychophysical and neuroimaging studies have focused on non-communicative pointing, which implies a two-way relationship between a subject and an object without the involvement of an addressee, and makes such gesture comparable to touching or grasping. Thus, experimental data on the communicating function of pointing remain scarce. Here, we examine whether the communicative value of pointing modifies both its behavioral and neural correlates by comparing pointing with or without communication. We found that when healthy participants pointed repeatedly at the same object, the communicative interaction with an addressee induced a spatial reshaping of both the pointing trajectories and the endpoint variability. Our finding supports the hypothesis that a change in reference frame occurs when pointing conveys a communicative intention. In addition, measurement of regional cerebral blood flow using H(2)O(15) PET-scan showed that pointing when communicating with an addressee activated the right posterior superior temporal sulcus and the right medial prefrontal cortex, in contrast to pointing without communication. Such a right hemisphere network suggests that the communicative value of pointing is related to processes involved in taking another person's perspective. This study brings to light the need for future studies on communicative pointing and its neural correlates by unraveling the three-way relationship between subject, object and an addressee.     

Cognitive training: neural correlates of expert skills

Expertise is a ubiquitous pre-requisite for modern life, but little is known about what neural mechanisms underpin the acquisition or employment of such skills. Recent evidence from functional magnetic imaging studies suggests that a network of frontal and parietal regions plays a crucial role.     

Perceptual load-dependent neural correlates of distractor interference inhibition

Background

The load theory of selective attention hypothesizes that distractor interference is suppressed after perceptual processing (i.e., in the later stage of central processing) at low perceptual load of the central task, but in the early stage of perceptual processing at high perceptual load. Consistently, studies on the neural correlates of attention have found a smaller distractor-related activation in the sensory cortex at high relative to low perceptual load. However, it is not clear whether the distractor-related activation in brain regions linked to later stages of central processing (e.g., in the frontostriatal circuits) is also smaller at high rather than low perceptual load, as might be predicted based on the load theory.

Methodology/Principal Findings

We studied 24 healthy participants using functional magnetic resonance imaging (fMRI) during a visual target identification task with two perceptual loads (low vs. high). Participants showed distractor-related increases in activation in the midbrain, striatum, occipital and medial and lateral prefrontal cortices at low load, but distractor-related decreases in activation in the midbrain ventral tegmental area and substantia nigra (VTA/SN), striatum, thalamus, and extensive sensory cortices at high load.

Conclusions

Multiple levels of central processing involving midbrain and frontostriatal circuits participate in suppressing distractor interference at either low or high perceptual load. For suppressing distractor interference, the processing of sensory inputs in both early and late stages of central processing are enhanced at low load but inhibited at high load.     

Decision making: neural correlates of response time

Recent studies have measured the time taken by neural processes to decide between alternative stimuli. Overt responses are produced only as soon as neural processes are completed. The brain throttles the mind.