Neural basis of interindividual variability in social perception in typically developing children and adolescents using diffusion tensor imaging.

Humans show great interindividual variability in the degree they engage in social relationship. The neural basis of this variability is still poorly understood, particularly in children. In this study, we aimed to investigate the neural basis of interindividual variability in the first step of social behavior, that is social perception, in typically developing children. For that purpose, we first used eye-tracking to objectively measure eye-gaze processing during passive visualization of social movie clips in 24 children and adolescents (10.5 ± 2.9 y). Secondly, we correlated eye-tracking data with measures of fractional anisotropy, an index of white matter microstructure, obtained using diffusion tensor imaging MRI. The results showed a large interindividual variability in the number of fixations to the eyes of characters during visualization of social scenes. In addition, whole-brain analysis showed a significant positive correlation between FA and number of fixations to the eyes,mainly in the temporal part of the superior longitudinal fasciculi bilaterally, adjacent to the posterior superior temporal cortex. Our results indicate the existence of a neural signature associated with the interindividual variability in social perception in children, contributing for better understanding the neural basis of typical and atypical development of a broader social expertise.

Neuroimaging evidence of brain abnormalities in mastocytosis.

Mastocytosis is a rare disease in which chronic symptoms are related to mast cell accumulation and activation. Patients can display depression-anxiety-like symptoms and cognitive impairment. The pathophysiology of these symptoms may be associated with tissular mast cell infiltration, mast cell mediator release or both. The objective of this study is to perform morphological or functional brain analyses in mastocytosis to identify brain changes associated with this mast cell disorder. We performed a prospective and monocentric comparative study to evaluate the link between subjective psycho-cognitive complaints, psychiatric evaluation and objective medical data using magnetic resonance imaging with morphological and perfusion sequences (arterial spin-labeled perfusion) in 39 patients with mastocytosis compared with 33 healthy controls. In the test cohort of 39 mastocytosis patients with psycho-cognitive complaints, we found that 49% of them had morphological brain abnormalities, mainly abnormal punctuated white matter abnormalities (WMA). WMA were equally frequent in cutaneous mastocytosis patients and indolent forms of systemic mastocytosis patients (42% and 41% of patients with WMA, respectively). Patients with WMA showed increased perfusion in the putamen compared with patients without WMA and with healthy controls. Putamen perfusion was also negatively correlated with depression subscores. This study demonstrates, for we believe the first time, a high prevalence of morphological and functional abnormalities in the brains of mastocytosis patients with neuropsychiatric complaints. Further studies are required to determine the mechanism underpinning this association and to ascertain its specificity.

Social cognition and the superior temporal sulcus: implications in autism.

The most common clinical sign of autism spectrum disorders (ASD) is social interaction impairment, which is associated with communication deficits and stereotyped behaviors. Based on brain-imaging results, our hypothesis is that abnormalities in the superior temporal sulcus (STS) are highly implicated in ASD. These abnormalities are characterized by decreased grey matter concentration, rest hypoperfusion and abnormal activation during social tasks. STS anatomofunctional anomalies occurring early across brain development could constitute the first step in the cascade of neural dysfunctions underlying autism. It is known that STS is highly implicated on social perception processing, from perception of biological movements, such as body movements or eye gaze, to more complex social cognition processes. Among the impairments that can be described in social perception processing, eye gaze perception is particularly relevant in autism. Gaze abnormalities can now be objectively measured using eye-tracking methodology. In the present work, we will review recent data on STS contributions to normal social cognition and its implication in autism, with particular focus on eye gaze perception.

[Brain imaging of infantile autism]. / Imagerie cérébrale dans l'autisme infantile.

Understanding of brain structural anomalies seen in children with autism has considerably progressed since the apparition of MRI and functional imaging. All the results are converging toward the description of anatomical and functional anomalies in the regions of the so-called "social brain". Statistical analyses show diminution of gray matter in the region of the superior temporal sulcus (STS). Functional studies with PET shows a diminution of brain blood flow at rest in the same region. Brain activation studies show absence of activation of the specialized region in processing human voice and hypoactivation of "social brain" regions in complex tasks of social cognition. At last, abnormal connectivity between the frontal and temporal regions has been showed. Those regions are implicated in processing sensorial inputs necessary for normal social life. All those anomalies could be responsible of the abnormal social behaviour pattern of children with autism.

Hearing loss severity: impaired processing of formant transition duration.

Normal hearing listeners exploit the formant transition (FT) detection to identify place of articulation for stop consonants. Neuro-imaging studies revealed that short FT induced less cortical activation than long FT. To determine the ability of hearing impaired listeners to distinguish short and long formant transitions (FT) from vowels of the same duration, 84 mild to severe hearing impaired listeners and 5 normal hearing listeners were asked to detect 10 synthesized stimuli with long (200 ms) or short (40 ms) FT among 30 stimuli of the same duration without FT. Hearing impaired listeners were tested with and without hearing aids. The effect of the difficulty of the task (short/long FT) was analysed as a function of the hearing loss with and without hearing aids. Normal hearing listeners were able to detect every FT (short and long). For hearing impaired listeners, the detection of long FT was better than that of short ones irrespective of their degree of hearing loss. The use of hearing aids improved detection of both kinds of FT; however, the detection of long FT remained much better than the detection of the short ones. The length of FT modified the ability of hearing impaired patients to detect FT. Short FT had access to less cortical processing than long FT and cochlea damages enhanced this specific deficit in short FT brain processing. These findings help to understand the limit of deafness rehabilitation in the time domain and should be taken into account in future devices development.

Posterior fossa imaging in 158 children with ataxia.

OBJECTIFS: To propose a MRI cerebellar algorithm that may be applied to guide genetic/malformative or biochemical investigations for patients with cerebellar ataxia. PATIENTS AND METHODS: Cerebral MRI of 158 patients with cerebellar ataxia and no supratentorial abnormality were examined according to a new categorization system based on posterior fossa imaging. The clinical and radiological findings were confronted to biochemical and/or genetic results using the MR cerebellar algorithm. Seven groups of cerebellar MRI pattern were described: vermian dysgenesis (n=27), cerebellar hypoplasia (n=15), hemispheric cerebellar dysgenesis (n=6), unilateral hemispheric atrophy (n=5), global cerebellar atrophy (n=84), signal abnormalities (n=11) and normal MRI (n=10). Cerebellar hypoplasia, vermian dysgenesis and hemispheric cerebellar dysgenesis groups were classified as malformative disorders. Global atrophy and signal abnormality groups were classified as metabolic disorders. RESULTS: In the vermian dysgenesis group, a specific genetic diagnosis was obtained in eight children (8/27) and all of the mutated genes (AHI1 (JBS3), CEP290 (JBS5), TMEM67 (JBS6), and RPGRIP1L (JBS7)) are involved in primary cilia function. In the group of pontocerebellar hypoplasia specific genetic diagnosis was obtained in one patient (PCH2) (1/15). Thus, nine of 42 children classified as malformative disorder had a molecular diagnosis. Global atrophy and signal abnormality groups were classified as metabolic disorders, specific biochemical was obtained in 46/95 children. In global atrophy group, respiratory chain deficiency was diagnosed in 18 children (18/84). In 21 children a congenital disorders of glycosylation type 1a (CDG Ia) was diagnosed (21/84) and infantile neuroaxonale dystrophy (INAD) was diagnosed in one child. In signal abnormalities group, specific biochemical diagnosis was obtained in six out of 11 children, five children with respiratory chain deficiency and one child with sulphite oxidase deficiency. In hemispheric cerebellar dysgenesis and normal MRI groups, no biological diagnosis was found for any of the patients. In the group of unilateral hemispheric atrophy, we hypothesized a clastic prenatal injury. CONCLUSION: The proposed MR cerebellar algorithm was useful to guide genetic/malformative or biochemical investigations, allowing an etiological diagnosis in 55 children.

Parieto-occipital grey matter abnormalities in children with Williams syndrome.

Williams syndrome (WS) is a neurodevelopmental disorder resulting from a hemizygous deletion of chromosome 7q11.23. The phenotype of WS consists of typical dysmorphic features, supravalvular aortic stenosis, infantile hypercalcemia and growth retardation. While language and facial recognition seem to be relatively spared, visuospatial constructive disabilities are a hallmark of the neurobehavioral profile of WS. In order to search for actual structural abnormalities underlying this precisely defined neurodevelopmental disorder, we performed anatomical magnetic resonance imaging (MRI) in 9 WS children (11.6 +/- 3.1 years; age range: 5.5-15 years) and 11 normal age-matched control children (11.8 +/- 2.2 years; age range: 8-15 years) using voxel-based morphometry (VBM). VBM is a fully automated whole-brain technique that delivers a voxel-wise assessment of regional grey and white matter concentration. A significant decrease in grey matter concentration was detected in the left parieto-occipital region of WS children (P < 0.05 corrected height threshold). The location of this abnormality in WS children coincides with the location of the structural abnormality previously described using the same method in 13 WS adults. These parieto-occipital abnormalities are consistent with the cognitive profile of WS which includes severe visuospatial construction and numerical cognition deficits. The demonstration of identical structural abnormalities in both adults and children argues for their early origin. Additionally, our study provides support for the use of advanced structural imaging techniques in children, in order to improve our understanding of neurobehavioral phenotypes associated with well-defined genetic disorders.

Superior temporal sulcus anatomical abnormalities in childhood autism: a voxel-based morphometry MRI study.

The underlying neurobiology of autism, a severe pervasive developmental disorder, remains unknown. Few neocortical brain MRI abnormalities have been reported. Using rest functional brain imaging, two independent studies have described localized bilateral temporal hypoperfusion in children with primary autism. In order to search for convergent evidence of anatomical abnormalities in autistic children, we performed an anatomical MRI study using optimized whole-brain voxel-based morphometry (VBM). High-resolution 3-D T1-weighted MRI data sets were acquired in 21 children with primary autism (mean age 9.3 +/- 2.2 years) and 12 healthy control children (mean age 10.8 +/- 2.7 years). By comparing autistic children to normal children, we found bilaterally significant decreases of grey matter concentration located in superior temporal sulcus (STS) (P < 0.05 corrected, after small volume correction; SVC). Children with autism were also found to have a decrease of white matter concentration located in the right temporal pole and in cerebellum (P < 0.05, corrected) compared to normal children. These results suggest that autism is associated with bilateral anatomical abnormalities localized in the STS and are remarkably consistent with functional hypoperfusion previously reported in children with autism. The multimodal STS areas are involved in highest level of cortical integration of both sensory and limbic information. Moreover, the STS is now recognized as a key cortical area of the "social brain" and is implicated in social perceptual skills that are characteristically impaired in autism. Therefore, the convergent anatomical and functional temporal abnormalities observed in autism may be important in the understanding of brain behavior relationships in this severe developmental disorder.

Anatomical and functional brain imaging evidence of lenticulo-insular anomalies in Smith Magenis syndrome.

Smith Magenis syndrome (SMS) is a clinically recognizable contiguous gene syndrome ascribed to an interstitial deletion of chromosome 17p11.2. The neurobehavioral phenotype of SMS includes mental retardation, speech delay, hyperactivity, attention deficit, decreased sensitivity to pain, self-injury, aggressive behavior and sleep disturbance. Therefore, we performed anatomical and functional brain imaging studies in five SMS boys. Anatomical magnetic resonance imaging (MRI) was analyzed using optimized voxel-based morphometry (VBM). This method can detect structural anomalies not apparent on visual inspection of the scans. Two comparison groups with similar mean age were studied: Group A with 12 healthy control children and Group B with 5 children with idiopathic mental retardation. In addition, positron emission tomography (PET) and water-labeled method were used to investigate a putative localized brain dysfunction in SMS. The control group was composed of mentally retarded children (Group B). A significant bilateral decrease of grey matter concentration was detected in the insula and lenticular nucleus in SMS children. In addition, a significant hypoperfusion was found in the same regions in SMS. These anatomo-functional evidences of bilateral insulo-lenticular anomalies in SMS are consistent with neurobehavioral symptoms of the disease. The identification of localized brain anomalies in SMS may help in understanding how this well-defined genetic entity can lead to a relatively specific severe neurobehavioral syndrome.

A primal sketch of the cortex mean curvature: a morphogenesis based approach to study the variability of the folding patterns.

In this paper, we propose a new representation of the cortical surface that may be used to study the cortex folding process and to recover some putative stable anatomical landmarks called sulcal roots usually buried in the depth of adult brains. This representation is a primal sketch derived from a scale space computed for the mean curvature of the cortical surface. This scale-space stems from a diffusion equation geodesic to the cortical surface. The primal sketch is made up of objects defined from mean curvature minima and saddle points. The resulting sketch aims first at highlighting significant elementary cortical folds, second at representing the fold merging process during brain growth. The relevance of the framework is illustrated by the study of central sulcus sulcal roots from antenatal to adult age. Some results are proposed for ten different brains. Some preliminary results are also provided for superior temporal sulcus.

[Bitemporal lobe dysfonction in infantile autism: positron emission tomography study]. / Dysfonctionnement bitemporal dans l'autisme infantile: étude en tomographie par émission de positons.

PURPOSE: Childhood autism is a severe developmental disorder that impairs the acquisition of some of the most important skills in human life. Progress in understanding the neural basis of childhood autism requires clear and reliable data indicating specific neuroanatomical or neurophysiological abnormalities. The purpose of the present study was to research localized brain dysfunction in autistic children using functional brain imaging. PATIENTS AND METHODS: Regional cerebral blood flow (rCBF) was measured with positron emission tomography (PET) in 21 primary autistic children and 10 age-matched non autistic children. RESULTS: A statistical parametric analysis of rCBF images revealed significant bilateral temporal hypoperfusion in the associative auditory cortex (superior temporal gyrus) and in the multimodal cortex (superior temporal sulcus) in the autistic group (p<0.001). In addition, temporal hypoperfusion was detected individually in 77% of autistic children. CONCLUSION: These findings provide robust evidence of well localized functional abnormalities in autistic children located in the superior temporal lobe. Such localized abnormalities were not detected with the low resolution PET camera,. This study suggests that high resolution PET camera combined with statistical parametric mapping is useful to understand developmental disorders.

[Auditory perception and language: functional imaging of speech sensitive auditory cortex]. / Perception auditive et langage: imagerie fonctionnelle du cortex auditif sensible au langage.

Since the description of cortical deafness, it has been known that the superior temporal cortex is bilaterally involved in the initial stages of language auditory perception but the precise anatomical limits and the function of this area remain debated. Here we reviewed more than 40 recent papers of positron emission tomography and functional magnetic resonance imaging related to language auditory perception, and we performed a meta-analysis of the localization of the peaks of activation in the Talairach's space. We found 8 studies reporting word versus non-word listening contrasts with 54 activation peaks in the temporal lobes. These peaks clustered in a bilateral and well-limited area of the temporal superior cortex, which is here operationally defined as the speech sensitive auditory cortex. This area is more than 4cm long, located in the superior temporal gyrus and the superior temporal sulcus, both anterior and posterior to Heschl's gyrus. It do not include the primary auditory cortex nor the ascending part of the planum temporale. The speech sensitive auditory cortex is not activated by pure tones, environmental sounds, or attention directed toward elementary components of a sound such as intensity, pitch, or duration, and thus has some specificity for speech signals. The specificity is not perfect, since we found a number of non-speech auditory stimuli activating the speech sensitive auditory cortex. Yet the latter studies always involve auditory perception mechanisms which are also relevant to speech perception either at the level of primitive auditory scene analysis processes, or at the level of specific schema-based recognition processes. The dorsal part of the speech sensitive auditory cortex may be involved in primitive scene analysis processes, whereas distributed activation of this area may contribute to the emergence of a broad class of "voice" schemas and of more specific "speech schemas/phonetic modules" related to different languages. In addition, this area is activated by language-related lip movement, suggesting that a multimodal integration of the auditory and the visual information relevant in speech perception occurs at this level. Finally, there is a task-related top-down modulation of the pattern of activation of the speech sensitive auditory cortex which may reflect the fact that the different parts of this structure are connected to different down-stream cortical regions involved in the neural processing of different types of tasks.

Striatal and pontocerebellar hypoperfusion in Hallervorden-Spatz syndrome.

Hallervorden-Spatz syndrome is a group of rare and severe disorders marked by extrapyramidal symptoms and iron accumulation in the globi pallidi, usually visible by magnetic resonance imaging. To assist in determining the functional correlates of these structural abnormalities, positron emission tomography was used to measure regional cerebral blood flows and dopaminergic function in a patient with Hallervorden-Spatz syndrome that manifested as progressive generalized dystonia, optic atrophy, and bilateral pallidal "eye of the tiger" sign. Voxel-by-voxel analysis of positron emission tomography images revealed no pallidal abnormalities but demonstrated significant hypoperfusion of the head of the right caudate nucleus, pons, and cerebellar vermis. Dopaminergic function of the basal ganglia, which was assessed based on visual- analysis of fixation of 18F-labeled fluoro-levodopa, was normal. These data suggest that Hallervorden-Spatz syndrome pathogenesis is not confined to the globi pallidi, and these data also may help to generate new pathogenic hypothesis.

Temporal lobe dysfunction in childhood autism: a PET study. Positron emission tomography.

OBJECTIVE: The nature of the underlying brain dysfunction of childhood autism, a life-long severe developmental disorder, is not well understood. Although researchers using functional brain imaging have attempted to contribute to this debate, previous studies have failed to report consistent localized neocortical brain dysfunction. The authors reasoned that early methods may have been insensitive to such dysfunction, which may now be detectable with improved technology. METHOD: To test this hypothesis, regional cerebral blood flow was measured with positron emission tomography (PET) in 21 children with primary autism and in 10 nonautistic children with idiopathic mental retardation. Autistic and comparison groups were similar in average age and developmental quotients. The authors first searched for focal brain dysfunction in the autistic group by using a voxel-based whole brain analysis and then assessed the sensitivity of the method to detect the abnormality in individual children. An extension study was then performed in an additional group of 12 autistic children. RESULTS: The first autistic group had a highly significant hypoperfusion in both temporal lobes centered in associative auditory and adjacent multimodal cortex, which was detected in 76% of autistic children. Virtually identical results were found in the second autistic group in the extension study. CONCLUSIONS: PET and voxel-based image analysis revealed a localized dysfunction of the temporal lobes in school-aged children with idiopathic autism. Further studies will clarify the relationships between these temporal abnormalities and the perceptive, cognitive, and emotional developmental abnormalities characteristic of this disorder.

A cortical region sensitive to auditory spectral motion.

The functional architecture of human auditory cortex is still poorly understood compared with that of visual cortex, yet anatomical and electrophysiological studies in non-human primates suggest that the auditory cortex also might be functionally specialized, in a model of parallel and hierarchical organization. In particular, spectral changes such as the formant transitions of speech, or spectral motion (SM) by analogy with visual motion, could be processed in specialized cortical regions. In this study, positron emission tomography (PET) was used to identify which auditory cortical region are involved in SM analysis. We found that a bilateral secondary auditory cortical region, located in the caudal-lateral belt of auditory cortex, was more sensitive to auditory stimuli containing spectral changes than to matched stimuli with a stationary spectral profile. This result suggests that analogies between sensory systems could prove useful in the research into the functional organization of the auditory cortex.

Structural group analysis of functional activation maps.

We present here a new method for cerebral activation detection over a group of subjects. This method is performed using individual activation maps of any sort. It aims at processing a group analysis while preserving individual information and at overcoming as far as possible limitations of the spatial normalization used to compare different subjects. We designed it such that it provides the individual occurrence of the activations detected at a group level. The localization can then be performed on the individual anatomy of each subject. The analysis starts with a hierarchical multiscale object-based description of each individual map. These descriptions are then compared, rather than comparing the images directly. The analysis is thus performed at an object level instead of voxel by voxel. It is made using a comparison graph, on which a labeling process is performed. The label field on the graph is modeled by a Markov random field, which allows us to introduce high-level rules of interrogation of the data. The process has been evaluated on simulated data and real data from a PET protocol.

Primary somatosensory cortex activation is not altered in patients with ventroposterior thalamic lesions: a PET study.

BACKGROUND AND PURPOSE: We know remarkably little about the mechanisms underlying cortical activation. Such mechanisms might be better understood by studying the effect of well-localized lesions on the cortical activations in simple paradigms. METHODS: We used H(2)(15)O and positron emission tomography to measure regional cerebral blood flow (rCBF) at rest and during hand vibration in 7 patients with unilateral thalamic lesion involving the ventroposterior (VP) somatosensory thalamic relay nuclei. We compared the results with those obtained in 6 patients with thalamic lesions sparing the VP nuclei and 6 healthy controls. RESULTS: The patients with VP lesions had a selective hypoperfusion at rest in the ipsilesional primary sensorimotor cortex (SM1). This hypoperfusion was significantly correlated with the degree of contralateral somatosensory deficit. This abnormality may reflect the deafferentation of SM1 from its somatosensory thalamic input. Despite this deafferentation, the ipsilesional SM1 was normally activated by the vibration of the hypoesthetic hand. CONCLUSIONS: The fact that a lesion of the somatosensory thalamic relay nuclei alters the rCBF at rest in SM1 but not its activation by hand vibration indicates that the mechanism of cortical activation is complex, even in the case of simple sensory stimulation. In addition, a dissociation may occur between obvious neurological deficits and apparently normal activation patterns, which suggests that activation studies should be interpreted cautiously in patients with focal brain lesions.

Ergonomics and work organization: the relationship between tayloristic design and workers' health in banks and credit cards companies.

The discussion developed in this paper is based on the results of an ergonomic work analysis carried out with attendants at call centers. Some critical issues and difficulties, like working pace, inadequate tools and workstations, and software inadequacies were detected in working situations. Operator-customer interactions are presented, attempting to put in evidence working constraints, working conditions, and their connection with health problems. The main conclusion is that serving clients, especially when the job is to provide information, is not a simple task, as information is not always available in the computerized system and is completely fragmented. The scope of workers' actions is very restricted and complicated and recurrent requests are redirected to others. Workers (individually or as groups) have limited possibilities to make adjustments to be able to give more adequate and personalized treatment to clients and, at the same time, to work in a less stressful environment. In periods of increased workload and work intensification, the situation is very much favorable to the incidence of health disorders, such as work related musculoskeletal disorders (WMSD) and others. Some suggestions to improve the work situation are discussed.

[Mechanisms of aphasia recovery and brain imaging]. / Mécanismes de la récupération de l'aphasie et imagerie cérébrale.

Aphasia recovery may depend on right hemisphere or non-lesioned left hemisphere structures, pre-morbid brain language organization, and de novo learning of language. Here we review the brain imaging evidence supporting these different hypotheses. CT-scan studies have investigated the prognosis value of size and site of left hemisphere lesions. The size of the lesion is a global but not an individual predictor of the initial severity and subsequent recovery of aphasia. Studies on the site of the lesion have given different results for verbal expression and comprehension. There is no consensus on a single critical site for recovery of verbal expression in non-fluent aphasia, which may depend on sub-cortical more than cortical extend of the lesion. Conversely the extend of the lesion in the superior temporal gyrus emerges as a critical negative factor for comprehension recovery. Rest measurements of brain metabolism have consistently shown that aphasia severity depends much more on the degree of dysfunction of language-related areas in the left hemisphere than on the site of the lesion it-self. This suggests that aphasia recovery may depend on metabolic dysfunction recovery in peri-lesional structures. More recently, activation studies have shown consistent right hemisphere activation during language tasks in aphasic subjects, but their role in recovery remains debated. It is likely limited, and may depend on atypical pre-morbid language lateralization. Left hemisphere activations are also found in aphasic patients. They are often relocalized in peri-lesional areas, and emerge in most studies as the main factor of aphasia recovery.