Social perception in autism spectrum disorders: impaired category selectivity for dynamic but not static images in ventral temporal cortex.

Studies of autism spectrum disorders (ASDs) reveal dysfunction in the neural systems mediating object processing (particularly faces) and social cognition, but few investigations have systematically assessed the specificity of the dysfunction. We compared cortical responses in typically developing adolescents and those with ASD to stimuli from distinct conceptual domains known to elicit category-related activity in separate neural systems. In Experiment 1, subjects made category decisions to photographs, videos, and point-light displays of people and tools. In Experiment 2, subjects interpreted displays of simple, geometric shapes in motion depicting social or mechanical interactions. In both experiments, we found a selective deficit in the ASD subjects for dynamic social stimuli (videos and point-light displays of people, moving geometric shapes), but not static images, in the functionally localized lateral region of the right fusiform gyrus, including the fusiform face area. In contrast, no group differences were found in response to either static images or dynamic stimuli in other brain regions associated with face and social processing (e.g. posterior superior temporal sulcus, amygdala), suggesting disordered connectivity between these regions and the fusiform gyrus in ASD. This possibility was confirmed by functional connectivity analysis.

Aberrant neural mediation of verbal fluency in autism spectrum disorders.

OBJECTIVE: Contrasts of verbal fluency and automatic speech provide an opportunity to evaluate the neural underpinnings of generativity and flexibility in autism spectrum disorders (ASD). METHOD: We used functional magnetic resonance imaging (fMRI) to contrast brain activity in high functioning ASD (n=17, mean verbal IQ=117) and neurotypical (NT; n=20, mean verbal IQ=112) adolescent and young adult males (12-23years). Participants responded to three word generation conditions: automatic speech (reciting months), category fluency, and letter fluency. RESULTS: Our paradigm closely mirrored behavioral fluency tasks by requiring overt, free recall word generation while controlling for differences in verbal output between the groups and systematically increasing the task demand. The ASD group showed reduced neural response compared to the NT participants during fluency tasks in multiple regions of left anterior and posterior cortices, and sub-cortical structures. Six of these regions fell in cortico-striatal circuits previously linked to repetitive behaviors (Langen, Durston, Kas, van Engeland, & Staal, 2011), and activity in two of them (putamen and thalamus) was negatively correlated with autism repetitive behavior symptoms in the ASD group. In addition, response in left inferior frontal gyrus was differentially modulated in the ASD, relative to the NT, group as a function of task demand. CONCLUSIONS: These data indicate a specific, atypical brain response in ASD to demanding generativity tasks that may have relevance to repetitive behavior symptoms in ASD as well as to difficulties generating original verbal responses.

Broad and narrow conceptual tuning in the human frontal lobes.

Previous work has implicated prefrontal cortices in selecting among and retrieving conceptual information stored elsewhere. However, recent neurophysiological work in monkeys suggests that prefrontal cortex may play a more direct role in representing conceptual information in a flexible context-specific manner. Here, we investigate the nature of visual object representations from perceptual to conceptual levels in an unbiased data-driven manner using a functional magnetic resonance imaging adaptation paradigm with pictures of animals. Throughout much of occipital cortex, activity was highly sensitive to changes in 2D stimulus form, consistent with tuning to form and position within retinotopic coordinates and matching an automated measure of shape similarity. Broad superordinate conceptual information was represented as early as extrastriate and posterior ventral temporal cortex. These regions were not completely invariant to form, suggesting that form similarity remains an important organizational constraint into the temporal cortex. Separate sites within prefrontal cortex represented broad and narrow conceptual tuning, with more anterior sites tuned narrowly to close conceptual associates in a manner that was invariant to stimulus form/position and that matched independent similarity ratings of the stimuli. The combination of broad and narrow conceptual tuning within prefrontal cortex may support flexible selection, retrieval, and classification of objects at different levels of categorical abstraction.

Distinct deficits of repetition priming following lateral versus anteromedial frontal cortex damage.

Object repetition commonly leads to long-lasting improvements in identification speed and accuracy, a behavioral facilitation referred to as "repetition priming". Neuroimaging and non-invasive electromagnetic stimulation studies have most often implicated the involvement of left lateral frontal cortex in repetition priming, although convergent evidence from neuropsychological studies is lacking. In the current study, we examine the impact of surgical resection for the treatment of epilepsy on the magnitude of repetition priming at relatively short-term (30-60 min delay) and long-term (3 months) delays in 41 patients with varying seizure foci and resection locations. Overall, patients exhibited significant repetition priming at both short-term and long-term delays. However, patients with frontal resections (largely anterior and medial frontal) differed significantly from those with right anterior temporal resections in showing fully intact short-term priming but absent long-term priming. In a comparison set of 10 recovered aphasic patients, patients with left lateral frontal damage exhibited impaired short-term priming relative to other frontal damage locations, suggesting the differential involvement of lateral and anteromedial frontal regions in mediating repetition priming at short-lag and long-lag timescales, respectively.

Action-related properties shape object representations in the ventral stream.

The principles driving the organization of the ventral object-processing stream remain unknown. Here, we show that stimulus-specific repetition suppression (RS) in one region of the ventral stream is biased according to motor-relevant properties of objects. Quantitative analysis confirmed that this result was not confounded with similarity in visual shape. A similar pattern of biases in RS according to motor-relevant properties of objects was observed in dorsal stream regions in the left hemisphere. These findings suggest that neural specificity for "tools" in the ventral stream is driven by similarity metrics computed over motor-relevant information represented in dorsal structures. Support for this view is provided by converging results from functional connectivity analyses of the fMRI data and a separate neuropsychological study. More generally, these data suggest that a basic organizing principle giving rise to "category specificity" in the ventral stream may involve similarity metrics computed over information represented elsewhere in the brain.

Enhanced inter-regional coupling of neural responses and repetition suppression provide separate contributions to long-term behavioral priming.

Stimulus identification commonly improves with repetition over long delays ("repetition priming"), whereas neural activity commonly decreases ("repetition suppression"). Multiple models have been proposed to explain this brain-behavior relationship, predicting alterations in functional and/or effective connectivity (Synchrony and Predictive Coding models), in the latency of neural responses (Facilitation model), and in the relative similarity of neural representations (Sharpening model). Here, we test these predictions with fMRI during overt and covert naming of repeated and novel objects. While we find partial support for predictions of the Facilitation and Sharpening models in the left fusiform gyrus and left frontal cortex, the data were most consistent with the Synchrony model, with increased coupling between right temporoparietal and anterior cingulate cortex for repeated objects that correlated with priming magnitude across participants. Increased coupling and repetition suppression varied independently, each explaining unique variance in priming and requiring modifications of all current models.

Sources of group differences in functional connectivity: an investigation applied to autism spectrum disorder.

An increasing number of fMRI studies are using the correlation of low-frequency fluctuations between brain regions, believed to reflect synchronized variations in neuronal activity, to infer "functional connectivity". In studies of autism spectrum disorder (ASD), decreases in this measure of connectivity have been found by focusing on the response to task modulation, by using only the rest periods, or by analyzing purely resting-state data. This difference in connectivity, however, could result from a number of different mechanisms--differences in noise, task-related fluctuations, task performance, or spontaneous neuronal activity. In this study, we investigate the difference in functional connectivity between adolescents with high-functioning ASD and typically developing control subjects by examining the residual fluctuations occurring on top of the fMRI response to an overt verbal fluency task. We find decreased correlations of these residuals (a decreased "connectivity") in ASD subjects. Furthermore, we find that this decrease was not due to task-related effects, block-to-block variations in task performance, or increased noise, and the difference was greatest when primarily rest periods are considered. These findings suggest that the estimate of disrupted functional connectivity in ASD is likely driven by differences in task-unrelated neuronal fluctuations.

Identifying task-general effects of stimulus familiarity in the parietal memory network.

Studies of human memory have implicated a "parietal memory network" in the recognition of familiar stimuli. However, the automatic vs. top-down nature of information processing within this network is not yet understood. If the network processes stimuli automatically, one can expect repetition-related changes both when familiarity is central to an ongoing task and when it is task-irrelevant. Here, we tested this prediction in a group of 40 human subjects using fMRI. Subjects initially named 100 objects aloud in the scanner. They then repeated the same task with novel and previously-named objects intermixed (where familiarity was not task-relevant) and separately were asked to make old/new recognition decisions in response to pictures of novel and previously-named objects (where familiarity was central to task completion). Accuracy was matched across conditions, and voice reaction times reflected typical behavioral priming effects. Repetition enhancement effects were restricted primarily to parietal cortex-and in particular, the parietal memory network-and were task-general in nature, whereas repetition suppression effects were task-dependent and occurred primarily in frontal and ventral temporal cortex. Task context effects were also present in the parietal memory network and impacted responses to both novel and familiar items. We conclude by discussing implications of these findings with respect to current hypotheses regarding parietal contributions to memory retrieval.

Object identification leads to a conceptual broadening of object representations in lateral prefrontal cortex.

Recent experience identifying objects leads to later improvements in both speed and accuracy ("repetition priming"), along with simultaneous reductions of neural activity ("repetition suppression"). A popular interpretation of these joint behavioral and neural phenomena is that object representations become perceptually "sharper" with stimulus repetition, eliminating cells that are poorly stimulus-selective and responsive and reducing support for competing representations downstream. Here, we test this hypothesis in an fMRI-adaptation experiment using pictures of objects. Prior to fMRI, participants repeatedly named a set of object pictures. During fMRI, participants viewed adaptation sequences composed of rapidly repeated objects (3-6 repetitions over several seconds) that were either named previously or that were new for the fMRI session, followed by single "deviant" object pictures used to measure recovery from adaptation and that shared a relationship to the adapted picture (a different exemplar of the same object, a conceptual associate, or an unrelated picture). Effects of adaptation and recovery were found throughout visually responsive brain regions. Occipitotemporal cortical regions displayed repetition suppression to previously named relative to new adapters but failed to exhibit pronounced changes in neural tuning. In contrast, changes in the slope of the recovery curves were found in the left lateral prefrontal cortex: Greater residual adaptation was observed to exemplar stimuli and conceptual associates following previously named adapting stimuli, consistent with greater rather than reduced neural overlap among representations of conceptually related objects. Furthermore, this change in neural tuning was directly related to the proportion of conceptual errors made by participants in the naming sessions pre- and post-fMRI, establishing that the experience-dependent conceptual broadening of object representations seen in fMRI is also manifest in behavior. In a follow-up behavioral experiment, we further show that recent naming experience leads to greater semantic priming when using the previously named pictures as briefly presented primes. Taken together, our results fail to support perceptual sharpening as the primary mediator between repetition suppression and behavioral priming at durations typically used to study priming and instead highlight an experience-dependent broadening of conceptual representations. We suggest that alternative mechanisms, such as increases in neural synchronization, are more promising in explaining priming in the face of repetition suppression.

Understanding animate agents: distinct roles for the social network and mirror system.

How people understand the actions of animate agents has been vigorously debated. This debate has centered on two hypotheses focused on anatomically distinct neural substrates: The mirror-system hypothesis proposes that the understanding of others is achieved via action simulation, and the social-network hypothesis proposes that such understanding is achieved via the integration of critical biological properties (e.g., faces, affect). In this study, we assessed the areas of the brain that were engaged when people interpreted and imagined moving shapes as animate or inanimate. Although observing and imagining the moving shapes engaged the mirror system, only activation of the social network was modulated by animacy.