Interacting with autistic virtual characters: intrapersonal synchrony of nonverbal behavior affects participants' perception.

Temporal coordination of communicative behavior is not only located between but also within interaction partners (e.g., gaze and gestures). This intrapersonal synchrony (IaPS) is assumed to constitute interpersonal alignment. Studies show systematic variations in IaPS in individuals with autism, which may affect the degree of interpersonal temporal coordination. In the current study, we reversed the approach and mapped the measured nonverbal behavior of interactants with and without ASD from a previous study onto virtual characters to study the effects of the differential IaPS on observers (N = 68), both with and without ASD (crossed design). During a communication task with both characters, who indicated targets with gaze and delayed pointing gestures, we measured response times, gaze behavior, and post hoc impression formation. Results show that character behavior indicative of ASD resulted in overall enlarged decoding times in observers and this effect was even pronounced in observers with ASD. A classification of observer's gaze types indicated differentiated decoding strategies. Whereas non-autistic observers presented with a rather consistent eyes-focused strategy associated with efficient and fast responses, observers with ASD presented with highly variable decoding strategies. In contrast to communication efficiency, impression formation was not influenced by IaPS. The results underline the importance of timing differences in both production and perception processes during multimodal nonverbal communication in interactants with and without ASD. In essence, the current findings locate the manifestation of reduced reciprocity in autism not merely in the person, but in the interactional dynamics of dyads.

Differentiated, rather than shared, strategies for time-coordinated action in social and non-social domains in autistic individuals.

Autism spectrum disorder (ASD) is a neurodevelopmental condition with a highly heterogeneous adult phenotype that includes social and non-social behavioral characteristics. The link between the characteristics assignable to the different domains remains unresolved. One possibility is that social and non-social behaviors in autism are modulated by a common underlying deficit. However, here we report evidence supporting an alternative concept that is individual-centered rather than deficit-centered. Individuals are assumed to have a distinctive style in the strategies they adopt to perform social and non-social tasks with these styles presumably being structured differently between autistic individuals and typically-developed (TD) individuals. We tested this hypothesis for the execution of time-coordinated (synchronized) actions. Participants performed (i) a social task that required synchronized gaze and pointing actions to interact with another person, and (ii) a non-social task that required finger-tapping actions synchronized to periodic stimuli at different time-scales and sensory modalities. In both tasks, synchronization behavior differed between ASD and TD groups. However, a principal component analysis of individual behaviors across tasks revealed associations between social and non-social features for the TD persons but such cross-domain associations were strikingly absent for autistic individuals. The highly differentiated strategies between domains in ASD are inconsistent with a general synchronization deficit and instead highlight the individualized developmental heterogeneity in the acquisition of domain-specific behaviors. We propose a cognitive model to help disentangle individual-centered from deficit-centered effects in other domains. Our findings reinforce the importance to identify individually differentiated phenotypes to personalize autism therapies.

Intrapersonal synchrony analysis reveals a weaker temporal coherence between gaze and gestures in adults with autism spectrum disorder.

The temporal encoding of nonverbal signals within individuals, referred to as intrapersonal synchrony (IaPS), is an implicit process and essential feature of human communication. Based on existing evidence, IaPS is thought to be a marker of nonverbal behavior characteristics in autism spectrum disorders (ASD), but there is a lack of empirical evidence. The aim of this study was to quantify IaPS in adults during an experimentally controlled real-life interaction task. A sample of adults with a confirmed ASD diagnosis and a matched sample of typically-developed adults were tested (N = 48). Participants were required to indicate the appearance of a target invisible to their interaction partner nonverbally through gaze and pointing gestures. Special eye-tracking software allowed automated extraction of temporal delays between nonverbal signals and their intrapersonal variability with millisecond temporal resolution as indices for IaPS. Likelihood ratio tests of multilevel models showed enlarged delays between nonverbal signals in ASD. Larger delays were associated with greater intrapersonal variability in delays. The results provide a quantitative constraint on nonverbal temporality in typically-developed adults and suggest weaker temporal coherence between nonverbal signals in adults with ASD. The results provide a potential diagnostic marker and inspire predictive coding theories about the role of IaPS in interpersonal synchronization processes.

Distinct functional roles of the mirror neuron system and the mentalizing system.

Movements can inform us about what people are doing and also about how they feel. This phenomenologically evident distinction has been suggested to correspond functionally with differential neural correlates denoted as mirror neuron system (MNS) and mentalizing system (MENT). To separate out the roles of the underlying systems we presented identical stimuli under different task demands: character animations showing everyday activities (mopping, sweeping) performed in different moods (angry, happy). Thirty-two participants were undergoing functional magnetic resonance imaging (fMRI) while asked to identify either the performed movement or the displayed mood. Univariate GLM analysis revealed the expected activation of either in MNS or MENT depending on the task. A complementary multivariate pattern-learning analysis based on the "social brain atlas" confirmed the expected recruitment of both systems. In conclusion, both approaches converge onto clearly distinct functional roles of both social neural networks in a novel dynamic social perception paradigm.

Introducing ACASS: An Annotated Character Animation Stimulus Set for Controlled (e)Motion Perception Studies.

Others' movements inform us about their current activities as well as their intentions and emotions. Research on the distinct mechanisms underlying action recognition and emotion inferences has been limited due to a lack of suitable comparative stimulus material. Problematic confounds can derive from low-level physical features (e.g., luminance), as well as from higher-level psychological features (e.g., stimulus difficulty). Here we present a standardized stimulus dataset, which allows to address both action and emotion recognition with identical stimuli. The stimulus set consists of 792 computer animations with a neutral avatar based on full body motion capture protocols. Motion capture was performed on 22 human volunteers, instructed to perform six everyday activities (mopping, sweeping, painting with a roller, painting with a brush, wiping, sanding) in three different moods (angry, happy, sad). Five-second clips of each motion protocol were rendered into AVI-files using two virtual camera perspectives for each clip. In contrast to video stimuli, the computer animations allowed to standardize the physical appearance of the avatar and to control lighting and coloring conditions, thus reducing the stimulus variation to mere movement. To control for low level optical features of the stimuli, we developed and applied a set of MATLAB routines extracting basic physical features of the stimuli, including average background-foreground proportion and frame-by-frame pixel change dynamics. This information was used to identify outliers and to homogenize the stimuli across action and emotion categories. This led to a smaller stimulus subset (n = 83 animations within the 792 clip database) which only contained two different actions (mopping, sweeping) and two different moods (angry, happy). To further homogenize this stimulus subset with regard to psychological criteria we conducted an online observer study (N = 112 participants) to assess the recognition rates for actions and moods, which led to a final sub-selection of 32 clips (eight per category) within the database. The ACASS database and its subsets provide unique opportunities for research applications in social psychology, social neuroscience, and applied clinical studies on communication disorders. All 792 AVI-files, selected subsets, MATLAB code, annotations, and motion capture data (FBX-files) are available online.

Sex-Related Cognitive Profile in Autism Spectrum Disorders Diagnosed Late in Life: Implications for the Female Autistic Phenotype.

Females with high-functioning ASD are known to camouflage their autistic symptoms better than their male counterparts, making them prone to being under-ascertained and delayed in diagnostic assessment. Thus far the underlying cognitive processes that enable such successful socio-communicative adaptation are not well understood. The current results show sex-related differences in the cognitive profile of ASD individuals, which were diagnosed late in life exclusively. Higher verbal abilities were found in males (n = 69) as opposed to higher processing speed and better executive functions in females with ASD (n = 38). Since both sexes remained unidentified during childhood and adolescence, these results are suggestive for sex-distinctive cognitive strategies as an alternative to typically-developed reciprocal social behavior and social mimicry in high functioning ASD.

Perceiving nonverbal behavior: neural correlates of processing movement fluency and contingency in dyadic interactions.

Despite the fact that nonverbal dyadic social interactions are abundant in the environment, the neural mechanisms underlying their processing are not yet fully understood. Research in the field of social neuroscience has suggested that two neural networks appear to be involved in social understanding: (1) the action observation network (AON) and (2) the social neural network (SNN). The aim of this study was to determine the differential contributions of the AON and the SNN to the processing of nonverbal behavior as observed in dyadic social interactions. To this end, we used short computer animation sequences displaying dyadic social interactions between two virtual characters and systematically manipulated two key features of movement activity, which are known to influence the perception of meaning in nonverbal stimuli: (1) movement fluency and (2) contingency of movement patterns. A group of 21 male participants rated the "naturalness" of the observed scenes on a four-point scale while undergoing fMRI. Behavioral results showed that both fluency and contingency significantly influenced the "naturalness" experience of the presented animations. Neurally, the AON was preferentially engaged when processing contingent movement patterns, but did not discriminate between different degrees of movement fluency. In contrast, regions of the SNN were engaged more strongly when observing dyads with disturbed movement fluency. In conclusion, while the AON is involved in the general processing of contingent social actions, irrespective of their kinematic properties, the SNN is preferentially recruited when atypical kinematic properties prompt inferences about the agents' intentions.

Paralimbic cortical thickness in first-episode depression: evidence for trait-related differences in mood regulation.

OBJECTIVE: Impaired mood regulation is a key deficit of major depressive disorder that is primarily mediated by an interaction between the paralimbic cortex (i.e., orbitofrontal, cingulate, insular, parahippocampal, and temporopolar cortices) and limbic regions. The authors investigated whether depressed patients and healthy comparison subjects have differences in cortical thickness in the paralimbic cortex and whether potential differences are evident only during a depressive state or are trait related. METHOD: Forty patients with a first episode of major depressive disorder participated: 20 medication-naive currently depressed patients and 20 medication-free recovered patients. The patients and 31 matched healthy comparison subjects underwent structural magnetic resonance imaging. Group differences in mean cortical thickness of the paralimbic cortex were measured by using FreeSurfer software, with adjustment for age, sex, and intracranial volume, and subgroup analyses were performed to assess state and trait effects. RESULTS: The medial orbitofrontal cortex was thinner in the depressed patients than in the comparison subjects. Greater thickness was present in the temporal pole and the caudal anterior and posterior cingulate cortex. All changes were trait related. CONCLUSIONS: The data provide evidence that even early in the course of depression brain regions involved in mood regulation show trait-related differences in cortical thickness.

Morphometry of structural disconnectivity indicators in subjects at risk and in age-matched patients with schizophrenia.

Structural disconnectivity has been hypothesized as being accountable for the pathophysiology of schizophrenia. Morphometric variables suitable for the empirical study of disconnectivity were studied aiming at the research question whether empirical indicators for disconnectivity are already informative in subjects at risk (SAR) and in young matched patients diagnosed with schizophrenia (SZ). In MRI data of subjects of the two diagnostic groups SZ and SAR, the size of the corpus callosum (CC) as indicator for interhemispherical long distance connections and the gyrification index (GI) as indicator for cortico-cortical connections were analyzed compared to a healthy controls (HC). Each subgroup consists of 21 subjects matched for sex and age. Measurements of the CC and GI were estimated in manually performed tracing procedures. GI data revealed significant differences between the diagnostic groups of both SAR and SZ as compared to HC in the frontal and parietal cortices. Measurements of total CC yielded no significant differences between diagnostic groups. The results are suggestive for impaired cortico-cortical connections as indicated by gyrification changes in SZ and also in SAR, whereas interhemispherical connectivity at the same time appears to be unaffected.

Imaging derived cortical thickness reduction in high-functioning autism: key regions and temporal slope.

Cortical thickness (CT) changes possibly contribute to the complex symptomatology of autism. The aberrant developmental trajectories underlying such differences in certain brain regions and their continuation in adulthood are a matter of intense debate. We studied 28 adults with high-functioning autism (HFA) and 28 control subjects matched for age, gender, IQ and handedness. A surface-based whole brain analysis utilizing FreeSurfer was employed to detect CT differences between the two diagnostic groups and to investigate the time course of age-related changes. Direct comparison with control subjects revealed thinner cortex in HFA in the posterior superior temporal sulcus (pSTS) of the left hemisphere. Considering the time course of CT development we found clusters around the pSTS and cuneus in the left and the paracentral lobule in the right hemisphere to be thinner in HFA with comparable age-related slopes in patients and controls. Conversely, we found clusters around the supramarginal gyrus and inferior parietal lobule (IPL) in the left and the precentral and postcentral gyrus in the right hemisphere to be thinner in HFA, but with different age-related slopes in patients and controls. In the latter regions CT showed a steady decrease in controls but no analogous thinning in HFA. CT analyses contribute in characterizing neuroanatomical correlates of HFA. Reduced CT is present in brain regions involved in social cognition. Furthermore, our results demonstrate that aberrant brain development leading to such differences is proceeding throughout adulthood. Discrepancies in prior morphometric studies may be induced by the complex time course of cortical changes.

Prefrontal cortex gyrification index in twins: an MRI study.

Cortical development and folding seems to be under environmental as well as genetic control. The aim of our study was to estimate the genetic influence on gyrification and cortical volumes, comparing prefrontal gyrification index (GI) in monozygotic (MZ) and dizygotic (DZ) twin pairs, and unrelated pairs. Twenty-four subjects (6 pairs of MZ and 6 pairs of DZ twins) were included in this study. Prefrontal cortical folding (gyrification) was measured by an automated and manual version of the gyrification index (A-GI, M-GI) according to previously published protocols. MR-imaging was performed and 3 representative slices were selected from coronar MR-imaging scans. The volumes of the total brain, temporal lobes, prefrontal lobes, and cerebellum were analyzed, too. To evaluate similarity in GI, absolute differences in GI, and brain volumes as well as intraclass correlations of twin pairs were compared with regard to twin status. Finally, a control group of unrelated pairs was assembled from the first two study groups and analyzed. Compared to unrelated pairs, twin pairs exhibited more similarity concerning different brain volumes and a trend to more similarity concerning A-GI. MZ twins did not present more similarity concerning GI (automatically and manually measured) and volume measurements compared to DZ twins. Different factors, like intrauterine factors, postnatal development conditions, and especially environmental factors might account for the differences between related and unrelated pairs. The nonexistence of a pronounced similarity in MZ twins compared to DZ twins concerning prefrontal GI raises questions about the extent of genetic influence on GI.

Corpus callosum size in adults with high-functioning autism and the relevance of gender.

The goal of the study was to investigate the size of the corpus callosum (CC) and its subsegments in relation to total brain volume (TBV) as an empirical indicator of impaired connectivity in autism with special respect to gender. In MRI data sets of 29 adults with high-functioning autism (HFA) and 29 age-, gender- and IQ-matched control subjects, the TBV was measured and the CC was analyzed as a whole and in subsegments employing two different manual segmentation procedures. With respect to diagnosis, there were no significant differences in the dependent variables (CC, CC subsegments, and TBV). With respect to gender, only TBV was significantly increased in males compared with females, resulting in a significantly decreased CC/TBV ratio in males. This finding, however, was independent from gender and can be fully attributed to brain size. Our findings do not support the following hypotheses: (1) a hypothesis of impaired CC in HFA adults as a subgroup of patients with autism spectrum disorders, and (2) the sexual dimorphism hypothesis of the CC.

Minds made for sharing: initiating joint attention recruits reward-related neurocircuitry.

The ability and motivation to share attention is a unique aspect of human cognition. Despite its significance, the neural basis remains elusive. To investigate the neural correlates of joint attention, we developed a novel, interactive research paradigm in which participants' gaze behavior--as measured by an eye tracking device--was used to contingently control the gaze of a computer-animated character. Instructed that the character on screen was controlled by a real person outside the scanner, 21 participants interacted with the virtual other while undergoing fMRI. Experimental variations focused on leading versus following the gaze of the character when fixating one of three objects also shown on the screen. In concordance with our hypotheses, results demonstrate, firstly, that following someone else's gaze to engage in joint attention resulted in activation of anterior portion of medial prefrontal cortex (MPFC) known to be involved in the supramodal coordination of perceptual and cognitive processes. Secondly, directing someone else's gaze toward an object activated the ventral striatum which--in light of ratings obtained from participants--appears to underlie the hedonic aspects of sharing attention. The data, therefore, support the idea that other-initiated joint attention relies upon recruitment of MPFC previously related to the "meeting of minds." In contrast, self-initiated joint attention leads to a differential increase of neural activity in reward-related brain areas, which might contribute to the uniquely human motivation to engage in the sharing of experiences.

Hippocampal surface analysis in subjective memory impairment, mild cognitive impairment and Alzheimer's dementia.

BACKGROUND/AIMS: Alzheimer's disease (AD) is preceded by prodromal states. To determine the neuroanatomical basis for the relationship among such states, we assessed surface conformations of the hippocampus in AD, mild cognitive impairment (MCI) and subjective memory impairment (SMI). METHODS: Hippocampal surfaces were reconstructed three-dimensionally via large-deformation high-dimensional MRI brain mapping in 14 SMI, 15 MCI, 12 AD and 13 controls. The surfaces were divided a priori into lateral, superior and inferior-medial zones, which approximated the CA1, combined CA2, CA3, CA4 subfields and the subiculum, respectively. RESULTS: Group differences reached statistical significance in the lateral zone (F = 3.2, d.f. = 3, p = 0.033) and inferior-medial zone (F = 2.8, d.f. = 3, p = 0.049) subfields. The groups differed in total hippocampal volume only at the trend level (F = 2.5, d.f. = 3, p = 0.071). Surface deformation maps revealed similar patterns in SMI, MCI and AD subjects, but quantitative differences were significant only when comparing MCI and AD with control subjects. CONCLUSIONS: Hippocampal surface deformation in the CA1 subfield was most pronounced in AD, less so in MCI and minor in SMI subjects. These results suggest that hippocampus degeneration develops gradually in AD, and may be observable long before dementia is apparent.

The hippocampus in families with schizophrenia in relation to obstetric complications.

BACKGROUND: Hippocampal volume reduction is a well replicated finding in schizophrenia. Evidence indicates a contribution of genetic and environmental factors, especially the influence of obstetric complications to this volume reduction. The aim of this study was to compare hippocampal volume of schizophrenic patients as well as and their relatives with control subjects and to quantify the additional contribution of obstetric complications. METHODS: T1 weighted MRI brain scans of 50 schizophrenic patients, 88 first-degree relatives and 53 healthy control subjects were used to perform volumetric measurements on the left and right hippocampus. A set of clinical measures including obstetric complications were recorded for all family members. RESULTS: Numerically our measurements revealed a hippocampal volume reduction in schizophrenic patients (left: -14%, right: -15%) and, although less pronounced, in their unaffected relatives (left: -6%, right: -10%). Noted differences in hippocampal volume between schizophrenic patients and controls were only significant for the left side. Hippocampal volumes of patients and their relatives with obstetric complications were reduced bilaterally. CONCLUSIONS: Hippocampal volume reduction is present in schizophrenic patients and their first-degree relatives, suggesting an influence of genetic factors. In addition, however, obstetric complications have also been shown to play a major role.

Automated gray level index measurements reveal only minor cytoarchitectonic changes of Brodmann area 9 in schizophrenia.

Using an automatized gray level index (GLI) method, we recently found cytoarchitectonic abnormalities in schizophrenia in Brodmann area 10 (BA10) [Vogeley, K., Tepest, R., Schneider-Axmann, T., Hutte, H., Zilles, K., Honer, W.G., Falkai, P., 2003. Automated image analysis of disturbed cytoarchitecture in Brodmann area 10 in schizophrenia, Schizophrenia Research 62, 133-140]. As another potential key region involved in the pathophysiology of schizophrenia, we have now investigated BA9 in the same sample consisting of 20 schizophrenic cases and 20 controls. The GLI value represents the area-percentage covered by perikarya in measuring fields of microscopic images. BA9 was analyzed with respect to the factors diagnosis and gender for six different compartments approximately corresponding to the neocortical layers. The main result in BA9 was a significant interaction of diagnosis and gender for GLI in layers IV and V on the left side. Subsequent analyses separately performed concerning gender revealed a significant GLI increase in layer V on the left side in male patients compared with controls. However, after an adjustment of error probabilities for multiple testing, differences did not reach significance. No GLI difference was observed in the sample between diagnostic groups for females and between the diagnostic groups in general. Comparisons with our BA10 results suggest that cytoarchitectural changes relevant to schizophrenia appear different in various Brodmann areas. Since increases in GLI were found only in selected layers (V and VI) of BA9, these findings do not support a generalized neuropil reduction across all cortical layers.

Reduction of the internal capsule in families affected with schizophrenia.

BACKGROUND: The anterior limb of the internal capsule (ALIC), connecting cortical and subcortical structures, is involved in functional important circuits. To detect volumetric changes in ALIC, including the influence of genetic factors, a magnetic resonance imaging (MRI) study of families affected with schizophrenia was performed. METHODS: The study sample comprised 22 family members with schizophrenia (FM-SZ), 34 family members without schizophrenia (FM-NSZ), and 43 control subjects. In addition to manual tracing of ALIC, subjects underwent proton magnetic resonance spectroscopy in the left prefrontal cortex, psychopathological rating, and neuropsychological assessment of frontal lobe function. RESULTS: Compared with controls, a significant reduction of right ALIC volume was seen in all family members (12%-16% reduction, p < .01) and a reduction of left ALIC volume in FM-NSZ (10% reduction, p = .028) was also observed. Both groups of family members showed a bilateral reduction in maximal cross sectional area of the ALIC. FM-SZ performed significantly worse on neurocognitive measures (Subject Ordered Pointing Task [SOPT] and Wisconsin Card Sorting Test), and performance correlated negatively with the ALIC volume (SOPT, r = -.6, p = .03). CONCLUSIONS: A reduced volume of ALIC in affected families supports the hypothesis of disturbed frontothalamic connectivity in schizophrenia and demonstrates functional relevance by an association with reduced neurocognitive performance.

Disturbed frontal gyrification within families affected with schizophrenia.

OBJECTIVE: Recently, in a post-mortem and a subsequent structural MR study, a significantly increased gyrification index (GI) was demonstrated in the frontal lobe in individuals with schizophrenia. To examine whether frontal lobe hypergyria is region-specific and whether this might be a suitable endophenotype in the search for the genetic basis of schizophrenia, the frontal as well as parieto-occipital GI were determined in MRI scans of families affected with schizophrenia. METHOD: In the MRI scans of 48 subjects suffering from schizophrenia, in 82 of their first-degree relatives and in 41 control subjects, the GI was determined in three sections anterior to the genu of the corpus callosum and three sections posterior to the splenium, thus allowing for a selective determination of this measure in the frontal as well as the parietal lobe. Outer and inner contours constituting the GI was determined in each section by manual tracing. Statistical analysis was performed using MANOVA with factors diagnostic group and intervening factors from preliminary analyses. RESULTS: The frontal, but not parieto-occipital GI was significantly higher in schizophrenic patients as well as unaffected relatives compared with control subjects (right: 7%, F=13.24, df=3, 155, p<0.0005, left: 6%, F=8.92, df=3, 155, p<0.0005). There was no overall difference between affected and unaffected family members. On the left side however, there was a significant interaction between diagnostic group and genetic loading (F=4.68, df=2, 101, p=0.01): significantly higher GI was found in affected compared with unaffected family members only in uniaffected and not multiaffected families. CONCLUSIONS: These results support our primary finding of hypergyria in the frontal lobe in schizophrenic patients. Compared to the parietal lobe, hypergyria seems to affect the frontal lobe selectively and serves as a suitable neurodevelopmental, possibly even an endophenotypic marker.

Proton magnetic resonance spectroscopy in subjects at risk for schizophrenia.

We used proton magnetic resonance spectroscopy (1H MRS) to examine biochemical characteristics of the brain tissue in subjects at risk for schizophrenia. Nineteen participants fulfilling research criteria for an early (n=10) or a late (n=9) at-risk syndrome, 21 patients with full disease according to DSM IV and 31 healthy control subjects were included in the study. Single-voxel 1H MRS was performed in the left frontal lobe, the anterior cingulate gyrus and the left superior temporal lobe. Subjects were followed longitudinally to detect conversion to schizophrenia. We observed a significant reduction of the metabolic ratios NAA/Cr and NAA/Cho in the left frontal lobe and of NAA/Cr in the anterior cingulate gyrus in both at-risk groups and in the schizophrenic patients compared with healthy controls. Those at-risk subjects, who converted to schizophrenia within the observation period, had a higher Cho/Cr and a lower NAA/Cho ratio in the anterior cingulate gyrus compared with non-converters. NAA/Cr did not differ between converters and non-converters. Six at-risk subjects were taking antidepressants, two were taking antipsychotics. There was no difference in any metabolic ratio in any region between at-risk subjects with and without medication. We conclude that the reduction of the neuronal marker NAA in the left prefrontal lobe and the anterior cingulate gyrus may represent a vulnerability indicator for schizophrenia in at-risk subjects, while elevated Cho in the anterior cingulate gyrus may be a predictor for conversion from the prodromal state to the full disease.