Inflexibility in Autism Spectrum Disorder: Need for certainty and atypical emotion processing share the blame.

Although ASD (Autism Spectrum Disorder) diagnosis requires the co-occurrence of socio-emotional deficits and inflexible behaviors, the interaction between these two domains remains unexplored. We used an emotional Wisconsin Card Sorting Test adapted to fMRI to explore this question. ASD and control participants matched a central card (a face) with one of four surrounding cards according to one of three rules: frame color, facial identity or expression. Feedback informed participants on whether to change or maintain the current sorting rule. For each rule, we modeled feedback onsets to change, switch (confirming the newly found rule) and maintenance events. "Bias error", which measures participants' willingness to switch, was larger in ASD participants for the emotional sorting rule. Brain activity to change events showed no group differences. In response to switch events significantly larger activity was observed for ASD participants in bilateral Inferior Parietal Sulci. Inflexibility in ASD appears characterized by the unwillingness to switch toward processing socio-emotional information, rather than a major disruption in cognitive flexibility. However, a larger activity to switch events in ASD highlights the need for a higher level of certainty before setting into a stable processing stage, which may be particularly detrimental in the highly changeable socio-emotional environment.

Different neural networks are involved in audiovisual speech perception depending on the context.

How are we able to easily and accurately recognize speech sounds despite the lack of acoustic invariance? One proposed solution is the existence of a neural representation of speech syllable perception that transcends its sensory properties. In the present fMRI study, we used two different audiovisual speech contexts both intended to identify brain areas whose levels of activation would be conditioned by the speech percept independent from its sensory source information. We exploited McGurk audiovisual fusion to obtain short oddball sequences of syllables that were either (a) acoustically different but perceived as similar or (b) acoustically identical but perceived as different. We reasoned that, if there is a single network of brain areas representing abstract speech perception, this network would show a reduction of activity when presented with syllables that are acoustically different but perceived as similar and an increase in activity when presented with syllables that are acoustically similar but perceived as distinct. Consistent with the long-standing idea that speech production areas may be involved in speech perception, we found that frontal areas were part of the neural network that showed reduced activity for sequences of perceptually similar syllables. Another network was revealed, however, when focusing on areas that exhibited increased activity for perceptually different but acoustically identical syllables. This alternative network included auditory areas but no left frontal activations. In addition, our findings point to the importance of subcortical structures much less often considered when addressing issues pertaining to perceptual representations.

Modular structure of functional networks in olfactory memory.

Graph theory enables the study of systems by describing those systems as a set of nodes and edges. Graph theory has been widely applied to characterize the overall structure of data sets in the social, technological, and biological sciences, including neuroscience. Modular structure decomposition enables the definition of sub-networks whose components are gathered in the same module and work together closely, while working weakly with components from other modules. This processing is of interest for studying memory, a cognitive process that is widely distributed. We propose a new method to identify modular structure in task-related functional magnetic resonance imaging (fMRI) networks. The modular structure was obtained directly from correlation coefficients and thus retained information about both signs and weights. The method was applied to functional data acquired during a yes-no odor recognition memory task performed by young and elderly adults. Four response categories were explored: correct (Hit) and incorrect (False alarm, FA) recognition and correct and incorrect rejection. We extracted time series data for 36 areas as a function of response categories and age groups and calculated condition-based weighted correlation matrices. Overall, condition-based modular partitions were more homogeneous in young than elderly subjects. Using partition similarity-based statistics and a posteriori statistical analyses, we demonstrated that several areas, including the hippocampus, caudate nucleus, and anterior cingulate gyrus, belonged to the same module more frequently during Hit than during all other conditions. Modularity values were negatively correlated with memory scores in the Hit condition and positively correlated with bias scores (liberal/conservative attitude) in the Hit and FA conditions. We further demonstrated that the proportion of positive and negative links between areas of different modules (i.e., the proportion of correlated and anti-correlated areas) accounted for most of the observed differences in signed modularity. Taken together, our results provided some evidence that the neural networks involved in odor recognition memory are organized into modules and that these modular partitions are linked to behavioral performance and individual strategies.

Perfumers' expertise induces structural reorganization in olfactory brain regions.

The human brain's ability to adapt to environmental changes is obvious in specific sensory domains of experts, and olfaction is one of the least investigated senses. As we have previously demonstrated that olfactory expertise is related to functional brain modifications, we investigated here whether olfactory expertise is also coupled with structural changes. We used voxel-based morphometry to compare the gray-matter volume in student and professional perfumers, as well as untrained control subjects, and accounted for all methodological improvements that have been recently developed to limit possible errors associated with image processing. In all perfumers, we detected an increase in gray-matter volume in the bilateral gyrus rectus/medial orbital gyrus (GR/MOG), an orbitofrontal area that surrounds the olfactory sulcus. In addition, gray-matter volume in the anterior PC and left GR/MOG was positively correlated with experience in professional perfumers. We concluded that the acute olfactory knowledge acquired through extensive olfactory training leads to the structural reorganization of olfactory brain areas.

Listening in silence activates auditory areas: a functional magnetic resonance imaging study.

Directing attention to some acoustic features of a sound has been shown repeatedly to modulate the stimulus-induced neural responses. On the contrary, little is known about the neurophysiological impact of auditory attention when the auditory scene remains empty. We performed an experiment in which subjects had to detect a sound emerging from silence (the sound was detectable after different durations of silence). Two frontal activations (right dorsolateral prefrontal and inferior frontal) were found, regardless of the side where sound was searched for, consistent with the well established role of these regions in attentional control. The main result was that the superior temporal cortex showed activations contralateral to the side where sound was expected to be present. The area extended from the vicinity of Heschl's gyrus to the surrounding areas (planum temporale/anterior lateral areas). The effect consisted of both an increase in the response to a sound delivered after attention was directed to detect its emergence and a baseline shift during the silent period. Thus, in absence of any acoustic stimulus, the search for an auditory input was found to activate the auditory cortex.

Deciphering human motion to discriminate social interactions: a developmental neuroimaging study.

Non-verbal communication plays a major role in social interaction understanding. Using functional magnetic resonance imaging, we explored the development of the neural networks involved in social interaction recognition based on human motion in children (8-11), adolescents (13-17), and adults (20-41). Participants watched point-light videos depicting two actors interacting or moving independently and were asked whether these agents were interacting or not. All groups successfully performed the discrimination task, but children had a lower performance and longer response times than the older groups. In all three groups, the posterior parts of the superior temporal sulci and middle temporal gyri, the inferior frontal gyri and the anterior temporal lobes showed greater activation when observing social interactions. In addition, adolescents and adults recruited the caudate nucleus and some frontal regions that are part of the mirror system. Adults showed greater activations in parietal and frontal regions (part of them belonging to the social brain) than adolescents.An increased number of regions that are part of the mirror system network or the social brain, as well as the caudate nucleus, were recruited with age. In conclusion, a shared set of brain regions enabling the discrimination of social interactions from neutral movements through human motion is already present in 8-year-old children. Developmental processes such as refinements in the social brain and mirror system would help grasping subtle cues in non-verbal aspects of social interactions.

Perception and judgement of physical causality involve different brain structures.

One basic type of 'mechanical' causality is that which occurs between physical objects. Subjects were presented with mechanically causal events (ball collides with and causes movement of another ball) or two non-causal events (a ball either passes underneath another ball, or rolls across the screen and changes colour). We investigated which brain regions exhibit increased activity during the judgement of causality ('judged causality') as compared with judgement of movement direction ('perceived causality'). We show an increase of medial frontal cortex activity when subjects were explicitly instructed to search for causality. Moreover, this increase was specifically associated with the search for causality and not with the perception of causality because the signal increase occurs whatever the nature of the stimulus (causal or non causal). Our study provides evidence for brain regions involved in a conscious level of inference about the presence of causality.

True and false recognition memories of odors induce distinct neural signatures.

Neural bases of human olfactory memory are poorly understood. Very few studies have examined neural substrates associated with correct odor recognition, and none has tackled neural networks associated with incorrect odor recognition. We investigated the neural basis of task performance during a yes-no odor recognition memory paradigm in young and elderly subjects using event-related functional magnetic resonance imaging. We explored four response categories: correct (Hit) and incorrect false alarm (FA) recognition, as well as correct (CR) and incorrect (Miss) rejection, and we characterized corresponding brain responses using multivariate analysis and linear regression analysis. We hypothesized that areas of the medial temporal lobe were differentially involved depending on the accuracy of odor recognition. In young adults, we found that significant activity in the hippocampus and the parahippocampal gyrus was associated with correct (true) recognition of odors, whereas the perirhinal cortex was associated with FAs and Misses. These findings are consistent with literature regarding hypothetical functional organization for memory processing. We also found that for correct recognition and rejection responses, the involvement of the hippocampus decreased when memory performances improved. In contrast to young individuals, elderly subjects were more prone to false memories and exhibited less specific activation patterns for the four response categories. Activation in the hippocampus and the parahippocampal gyrus was positively correlated with response bias scores for true and false recognition, demonstrating that conservative subjects produced an additional search effort leading to more activation of these two medial temporal lobe regions. These findings demonstrate that correct and incorrect recognition and rejection induce distinct neural signatures.

Cortical dynamics of a self driven choice: a MEG study during a card sorting task.

OBJECTIVE: The aim of this study was to disclose the dynamics of the frontal processes involved in a task shifting between two attentional states. METHODS: Magnetoencephalographic activities were recorded during a Wisconsin Card Sorting Test where subjects had to match card stimuli according to one of three possible dimensions ("maintained condition"). The matching dimension was intermittently changed and subjects, after feedback presentation, had to identify the new correct dimension ("shifted condition"). RESULTS: Source activations following the feedback to the subject's response in these two attentional conditions did not differ before 350 ms post feedback. After 350 ms, in the shifted condition, a lateral/posterior frontal activation was maintained later, while a medial/anterior frontal activation appeared up to 450 ms. CONCLUSIONS: The dynamics of activities corresponding to the two conditions disclose a spread of activation from posterior lateral frontal in the "maintained condition" to anterior medial frontal in the "shifted condition". SIGNIFICANCE: These results are consistent with fMRI results concerning the major involvement of medial frontal cortex in tasks involving reasoning and choice making.

Abnormal cerebral effective connectivity during explicit emotional processing in adults with autism spectrum disorder.

Several recent studies suggest that autism may result from abnormal communication between brain regions. We directly assessed this hypothesis by testing the presence of abnormalities in a model of the functional cerebral network engaged during explicit emotion processing in adults with high functioning autism or Asperger syndrome. Comparison of structural equation models revealed abnormal patterns of effective connectivity, with the prefrontal cortex as a key site of dysfunction. These findings provide evidence that abnormal long-range connectivity between structures of the 'social brain' could explain the socio-emotional troubles that characterize the autistic pathology.

Relationship between task-related gamma oscillations and BOLD signal: new insights from combined fMRI and intracranial EEG.

Cognitive neuroscience relies on two sets of techniques to map the neural networks underlying cognition in humans: recordings of either regional metabolic changes (fMRI or PET) or fluctuations in the neural electromagnetic fields (EEG and MEG). Despite major advances in the last few years, an explicit linkage between the two is still missing and the neuroimaging community faces two complementary but unrelated sets of functional descriptions of the human brain. Such an explicit framework, linking the two approaches in potentially complex cognitive tasks and in a variety of brain regions would permit to combine them into fine spatio-temporally-grained human brain mapping procedures. We combined fMRI and intra-cranial EEG recordings of the same epileptic patients during a semantic decision task and found a close spatial correspondence between regions of fMRI activations and recording sites showing EEG energy modulations in the gamma range (>40 Hz). Our findings further support previous findings that gamma band modulations co-localize with BOLD variations and also indicate that fMRI may be used as a constraint to improve source reconstruction of gamma band EEG responses.

Effect of initial fMRI data modeling on the connectivity reported between brain areas.

Nearly all neuroimaging data analysis rests upon some form of variance partitioning. Conventional analyses, with a general linear model (GLM), partition the variance in the measured response variable into partitions described by a design matrix of explanatory variables. This approach can also be adopted in the initial modeling of the data in studies using data-led methods to summarize functional connectivity, such as principle component analysis, or studies of effective connectivity, using for example structural equation modeling. The point made in this technical note is that the partition of the original time series has to be precisely described to qualify the sources of variations that are taken into account. For conventional analyses using the GLM, the partition investigated corresponds to the subspaces of the design matrix that are tested. However, in the analyses of functional and effective connectivity, the particular subspaces considered are not always specified explicitly. Here we show that selecting different subspaces, or variance partitions, can have a profound effect, both qualitatively and quantitatively, on the sample covariances and the ensuing inferences about connectivity. We will illustrate this using simulated data that include condition and block-related effects and their interactions. We will use these three subspaces to show how the correlation between two voxels depends on which sub-partitions are examined. We will also show how the partition of the design matrix influences the resulting correlation matrix observed when studying correlations between error terms. We will finally demonstrate, quantitatively, the effect of the variance partitions considered on the correlations between two regions using a real fMRI study of biological motion.

Functional and effective connectivity in an fMRI study of an auditory-related task.

This study investigates the sets of brain areas that are functionally connected during an auditory goal-directed task. We used a paradigm including a resting state condition and an active condition, which consisted in active listening to the footsteps of walking humans. The regional brain activity was measured using fMRI and the adjusted values of activity in brain regions involved in the task were analysed using both principal component analysis and structural equation modelling. A first set of connected areas includes regions located in Heschl's gyrus, planum temporale, posterior superior temporal sulcus (in the so-called 'social cognition' area), and parietal lobe. This network could be responsible for the perceptual integration of the auditory signal. A second set encompassing frontal regions is related to attentional control. Dorsolateral- and medial-prefrontal cortex have mutual negative influences which are similar to those described during a visual goal-directed task [T. Chaminade & P. Fonlupt (2003) Eur. J. Neurosci., 18, 675-679.]. Moreover, the dorsolateral prefrontal cortex (DLPFC) exerts a positive influence on the auditory areas during the task, as well as a strong negative influence on the visual areas. These results show that: (i) the negative influence between the medial and lateral parts of the frontal cortex during a goal-directed task is not dependent on the input modality (visual or auditory), and (ii) the DLPFC activates the pathway of the relevant sensory modality and inhibits the nonrelevant sensory modality pathway.

Listening to a walking human activates the temporal biological motion area.

A vivid perception of a moving human can be evoked when viewing a few point-lights on the joints of an invisible walker. This special visual ability for biological motion perception has been found to involve the posterior superior temporal sulcus (STSp). However, in everyday life, human motion can also be recognized using acoustic cues. In the present study, we investigated the neural substrate of human motion perception when listening to footsteps, by means of a sparse sampling functional MRI design. We first showed an auditory attentional network that shares frontal and parietal areas previously found in visual attention paradigms. Second, an activation was observed in the auditory cortex (Heschl's gyrus and planum temporale), likely to be related to low-level sound processing. Most strikingly, another activation was evidenced in a STSp region overlapping the temporal biological motion area previously reported using visual input. We thus propose that a part of the STSp region might be a supramodal area involved in human motion recognition, irrespective of the sensory modality input.

Changes of effective connectivity between the lateral and medial parts of the prefrontal cortex during a visual task.

Structural equation modelling was used to study the change of connectivity during a visual task with continuous variation of the attention load. The model was based on areas defined by the haemodynamic responses described elsewhere [Mazoyer, P., Wicker, B. & Fonlupt, P. (2002) A neural network elicited by parametric manipulation of the attention load. Neuroreport, 13, 2331-2334], including occipitotemporal, parietal, temporal and prefrontal (lateral and medial areas) cortices. We have studied stationary- (which does not depend on the attentional load) and attention-related coupling between areas. This allowed the segregation of two subsystems. The first could reflect a system performing the integration step of the visual signal and the second a system participating in response selection. The major finding is the mutual negative influence between the lateral and medial parts of the prefrontal cortex. This negative influence between these two brain regions increased with the attention load. This is interpreted as a modification of the balance between integration and decision processes that are needed for the task to be efficiently completed.

A relation between rest and the self in the brain?

Neuroimaging techniques such as positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) are widely used to identify the cerebral correlates of cognitive tasks. The resting state presents the advantage to serve as a reference in all experiments but is also an ill-defined mental state because it may vary both from one subject to another and within the same subject. The most challenging question concerns the areas whose activity (revealed by PET or fMRI imaging) is greater in rest state than in an active condition. The present work reports the result of a meta-analysis including five previously published studies. The five different tasks involved are the following: attribution of intention, judgement of stimulus pleasantness, discrimination of spatial attributes, judgement of other peoples' belief and perception of gaze. For each study, the general linear model was used to assess statistical difference and a contrast resting state minus other conditions was calculated. The intersection of the five contrasts was used to search for the variation jointly observed across the different experiments. This lead to a reduced number of clusters: one cluster in the lower/anterior part of the cingulate gyrus and four clusters located in the medial/superior frontal gyrus, along the superior frontal sulcus. We discuss the location of these areas with respect to the location of activations induced by different tasks: externally focused attention, memory, general reasoning, theory of mind and self-referential tasks. We observed that medial prefrontal cortex exhibits a lower activity when the subject's attention is focused towards the external world than when the subject has to additionally refer to some internal states. By contrast, this activity is greater during resting state than during both externally directed and internally directed attention. Thus, we hypothesize that during rest, the subject is in a state where he refers only to his own self.