BIL&GIN: A neuroimaging, cognitive, behavioral, and genetic database for the study of human brain lateralization.

We report on a database, named BIL&GIN, designed for investigating the cognitive, behavioral, genetic, and brain morphological/functional correlates of hemispheric specialization. The database contains records from a sample of 453 adult participants enriched in left-handers (45%, N=205) as compared to the general population. For each subject, socio-demographic data, hand and eye laterality, family handedness, and cognitive abilities in the language, motor, visuo-spatial, and numerical domains have been recorded. T1-MRI and DTI data were also acquired, as well as resting-state functional MRI. Task-evoked functional MRI was performed in a sub-sample of 303 subjects (157 left-handers) using a customized functional battery of 16 cognitive tasks exploring the same three cognitive domains. Performances at the tasks executed in the magnet as well as post-acquisition debriefing were recorded. A saliva sample was obtained from the subjects of this sub-sample from which DNA was extracted. The BIL&GIN contains results of imaging data processing for each subject, namely maps of tissue (GM, WM, CSF) probability, cortical thickness, cortical surface, and diffusion parameters as well as regional values of these phenotypes for regions of both AAL and FreeSurfer parcellations. For the subjects who underwent FMRI, individual SPM contrast maps for each of the 8 runs were also calculated and included in the database, as well as corresponding BOLD variations in ROIs of the AAL and AICHA atlases, and Wilke's hemispheric functional lateralization index. The BIL&GIN data sharing is based on a collaborative model.

Relationships between hand laterality and verbal and spatial skills in 436 healthy adults balanced for handedness.

The relationship between manual laterality and cognitive skills remains highly controversial. Some studies have reported that strongly lateralised participants had higher cognitive performance in verbal and visuo-spatial domains compared to non-lateralised participants; however, others found the opposite. Moreover, some have suggested that familial sinistrality and sex might interact with individual laterality factors to alter cognitive skills. The present study addressed these issues in 237 right-handed and 199 left-handed individuals. Performance tests covered various aspects of verbal and spatial cognition. A principal component analysis yielded two verbal and one spatial factor scores. Participant laterality assessments included handedness, manual preference strength, asymmetry of motor performance, and familial sinistrality. Age, sex, education level, and brain volume were also considered. No effect of handedness was found, but the mean factor scores in verbal and spatial domains increased with right asymmetry in motor performance. Performance was reduced in participants with a familial history of left-handedness combined with a non-maximal preference strength in the dominant hand. These results elucidated some discrepancies among previous findings in laterality factors and cognitive skills. Laterality factors had small effects compared to the adverse effects of age for spatial cognition and verbal memory, the positive effects of education for all three domains, and the effect of sex for spatial cognition.

Assigning a social status from face adornments: an fMRI study.

For at least 150,000 years, the human body has been culturally modified by the wearing of personal ornaments and probably by painting with red pigment. The present study used functional magnetic resonance imaging to explore the brain networks involved in attributing social status from face decorations. Results showed the fusiform gyrus, orbitofrontal cortex, and salience network were involved in social encoding, categorization, and evaluation. The hippocampus and parahippocampus were activated due to the memory and associative skills required for the task, while the inferior frontal gyrus likely interpreted face ornaments as symbols. Resting-state functional connectivity analysis clarified the interaction between these regions. The study highlights the importance of these neural interactions in the symbolic interpretation of social markers on the human face, which were likely active in early Homo species and intensified with Homo sapiens populations as more complex technologies were developed to culturalize the human face.

Neuroimaging supports the representational nature of the earliest human engravings.

The earliest human graphic productions, consisting of abstract patterns engraved on a variety of media, date to the Lower and Middle Palaeolithic. They are associated with anatomically modern and archaic hominins. The nature and significance of these engravings are still under question. To address this issue, we used functional magnetic resonance imaging to compare brain activations triggered by the perception of engraved patterns dating between 540 000 and 30 000 years before the present with those elicited by the perception of scenes, objects, symbol-like characters and written words. The perception of the engravings bilaterally activated regions along the ventral route in a pattern similar to that activated by the perception of objects, suggesting that these graphic productions are processed as organized visual representations in the brain. Moreover, the perception of the engravings led to a leftward activation of the visual word form area. These results support the hypothesis that these engravings have the visual properties of meaningful representations in present-day humans, and could have served such purpose in early modern humans and archaic hominins.

A SENtence Supramodal Areas AtlaS (SENSAAS) based on multiple task-induced activation mapping and graph analysis of intrinsic connectivity in 144 healthy right-handers.

We herein propose an atlas of 32 sentence-related areas based on a 3-step method combining the analysis of activation and asymmetry during multiple language tasks with hierarchical clustering of resting-state connectivity and graph analyses. 144 healthy right-handers performed fMRI runs based on language production, reading and listening, both with sentences and lists of over-learned words. Sentence minus word-list BOLD contrast and left-minus-right BOLD asymmetry for each task were computed in pairs of homotopic regions of interest (hROIs) from the AICHA atlas. Thirty-two hROIs were identified that were conjointly activated and leftward asymmetrical in each of the three language contrasts. Analysis of resting-state temporal correlations of BOLD variations between these 32 hROIs allowed the segregation of a core network, SENT_CORE including 18 hROIs. Resting-state graph analysis applied to SENT_CORE hROIs revealed that the pars triangularis of the inferior frontal gyrus and the superior temporal sulcus were hubs based on their degree centrality (DC), betweenness, and participation values corresponding to epicentres of sentence processing. Positive correlations between DC and BOLD activation values for SENT_CORE hROIs were observed across individuals and across regions regardless of the task: the more a SENT_CORE area is connected at rest the stronger it is activated during sentence processing. DC measurements in SENT_CORE may thus be a valuable index for the evaluation of inter-individual variations in language areas functional activity in relation to anatomical or clinical patterns in large populations. SENSAAS (SENtence Supramodal Areas AtlaS), comprising the 32 supramodal sentence areas, including SENT_CORE network, can be downloaded at http://www.gin.cnrs.fr/en/tools/ .

Mental calculation in a prodigy is sustained by right prefrontal and medial temporal areas.

Calculating prodigies are individuals who are exceptional at quickly and accurately solving complex mental calculations. With positron emission tomography (PET), we investigated the neural bases of the cognitive abilities of an expert calculator and a group of non-experts, contrasting complex mental calculation to memory retrieval of arithmetic facts. We demonstrated that calculation expertise was not due to increased activity of processes that exist in non-experts; rather, the expert and the non-experts used different brain areas for calculation. We found that the expert could switch between short-term effort-requiring storage strategies and highly efficient episodic memory encoding and retrieval, a process that was sustained by right prefrontal and medial temporal areas.

Implicit identification of irrelevant local objects interacts with global/local processing of hierarchical stimuli.

This work aimed at studying interactions between automatic object identification and global/local perceptual processing. We designed a paradigm in which participants were presented with pairs of hierarchically organized items, composed of global forms made up of local forms. Both global and local forms could represent either objects or non-objects. Subjects were instructed to detect whether the two hierarchical items composing a pair were identical or different. In a dissimilar pair, items differed at one level (target level), the other level, made of similar forms on both sides, was irrelevant to perform the task. We hypothesized that the automatic identification of object could affect the global precedence principle defined by Navon. In agreement with our hypothesis, we found that when the irrelevant level was made of objects, the global precedence effect was reversed. In contrast, the irrelevant level had no effect when the target level included only objects, or when the irrelevant level was made of non-object, the global precedence principle was being preserved in these cases. This interaction is compatible with the existence of two distinct processes working in parallel, namely automatic identification and structural analysis, that could either interfere or act together for the detection of differences.

Neural impact of the semantic content of visual mental images and visual percepts.

The existence of hemispheric lateralization of visual mental imagery remains controversial. In light of the literature, we used fMRI to test whether processing of mental images of object drawings preferentially engages the left hemisphere to compared non-object drawings. An equivalent comparison was also made while participants actually perceived object and non-object drawings. Although these two conditions engaged both hemispheres, activation was significantly stronger in the left occipito-temporo-frontal network during mental inspection of object than of non-object drawings. This network was also activated when perception of object drawings was compared to that of non-object drawings. An interaction was nonetheless observed: this effect was stronger during imagery than during perception in the left inferior frontal and the left inferior temporal gyrus. Although the tasks subjects performed did not explicitly require semantic analysis, activation of this network probably reflected, at least in part, a semantic and possibly a verbal retrieval component when object drawings were processed. Mental imagery tasks elicited activation of early visual cortex at a lower level than perception tasks. In the context of the imagery debate, these findings indicate that, as previously suggested, figurative imagery could involve primary visual cortex and adjacent areas.

Between-hand difference in ipsilateral deactivation is associated with hand lateralization: fMRI mapping of 284 volunteers balanced for handedness.

In right-handers (RH), an increase in the pace of dominant hand movement results in increased ipsilateral deactivation of the primary motor cortex (M1). By contrast, an increase in non-dominant hand movement frequency is associated with reduced ipsilateral deactivation. This pattern suggests that inhibitory processes support right hand dominance in right-handers and raises the issues of whether this phenomenon also supports left hand preference in left-handers (LH), and/or whether it relates to asymmetry of manual ability in either group. Thanks to the BIL&GIN, a database dedicated to the investigation of hemispheric specialization (HS), we studied the variation in M1 activity during right and left finger tapping tasks (FTT) in a sample of 284 healthy participants balanced for handedness. An M1 fMRI localizer was defined for each participant as an 8 mm diameter sphere centered on the motor activation peak. RH exhibited significantly larger deactivation of the ipsilateral M1 when moving their dominant hand than their non-dominant hand. In contrast, LH exhibited comparable ipsilateral M1 deactivation during either hand movement, reflecting a bilateral cortical specialization. This pattern is likely related to left-handers' good performances with their right hand and consequent lower asymmetry in manual ability compared with RH. Finally, inter-individual analyses over the whole sample demonstrated that the larger the difference in manual skill across hands, the larger the difference in ipsilateral deactivation. Overall, we propose that difference in ipsilateral deactivation is a marker of difference in manual ability asymmetry reflecting differences in the strength of transcallosal inhibition when a given hand is moving.

Heschl's gyrification pattern is related to speech-listening hemispheric lateralization: FMRI investigation in 281 healthy volunteers.

This study investigates the structure-function relationships between the anatomy of Heschl's gyri (HG) and speech hemispheric lateralization in 281 healthy volunteers (135 left-handers). Hemispheric lateralization indices (HFLIs) were calculated with Wilke's method from the activations obtained via functional magnetic resonance imaging while listening to lists of words (LIST). The mean HFLI during LIST was rightward asymmetrical, and left-handers displayed a trend toward decreased rightward asymmetry. The correlations between LIST BOLD contrast maps and individual HFLIs demonstrated that among the cortical areas showing significant asymmetry during LIST, only phonological regions explained HFLI variability. Significant positive correlations were present among the left HG, supramarginal gyri, and the anterior insula. Significant negative correlations occurred in the mid-part of the right superior temporal sulcus. Left HG had the largest functional activity during LIST and explained 10% of the HFLI variance. There was a strong anatomo-functional link in the HG: duplication was associated with a decrease in both the surface area of the anterior HG and HG functional activity. Participants with a single left HG exhibited leftward anatomical and functional asymmetry of HG, but participants with a left duplication lost either anatomical and/or functional leftward asymmetries. Finally, manual preference was related to HG anatomy, but not to HG functional asymmetries measured during LIST. The anatomical characteristics of left-handers (lower occurrence of right HG duplication and a smaller surface area of the right first HG) thus appeared to be unrelated to variations in speech lateralization with handedness.

Descriptive anatomy of Heschl's gyri in 430 healthy volunteers, including 198 left-handers.

This study describes the gyrification patterns and surface areas of Heschl's gyrus (HG) in 430 healthy volunteers mapped with magnetic resonance imaging. Among the 232 right-handers, we found a large occurrence of duplication (64 %), especially on the right (49 vs. 37 % on the left). Partial duplication was twice more frequent on the left than complete duplication. On the opposite, in the right hemisphere, complete duplication was 10 % more frequent than partial duplication. The most frequent inter-hemispheric gyrification patterns were bilateral single HG (36 %) and left single-right duplication (27 %). The least common patterns were left duplication-right single (22 %) and bilateral duplication (15 %). Duplication was associated with decreased anterior HG surface area on the corresponding side, independently of the type of duplication, and increased total HG surface area (including the second gyrus). Inter-hemispheric gyrification patterns strongly influenced both anterior and total HG surface area asymmetries, leftward asymmetry of the anterior HG surface was observed in all patterns except double left HG, and total HG surface asymmetry favored the side of duplication. Compared to right-handers, the 198 left-handers exhibited lower occurrence of duplication, and larger right anterior HG surface and total HG surface areas. Left-handers' HG surface asymmetries were thus significantly different from those of right-handers, with a loss of leftward asymmetry of their anterior HG surface, and with significant rightward asymmetry of their total HG surface. In summary, gyrification patterns have a strong impact on HG surface and asymmetry. The observed reduced lateralization of HG duplications and anterior HG asymmetry in left-handers highlights HG inter-hemispheric gyrification patterns as a potential candidate marker of speech lateralization.

Cortical anatomy of mental imagery of concrete nouns based on their dictionary definition.

The functional anatomy of the interactions between spoken language and visual mental imagery was investigated with PET in eight normal volunteers during a series of three conditions: listening to concrete word definitions and generating their mental images (CONC), listening to abstract word definitions (ABST) and silent REST. The CONC task specifically elicited activations of the bilateral inferior temporal gyri, of the left premotor and left prefrontal regions, while activations in the bilateral superior temporal gyri were smaller than during the ABST task, during which an additional activation of the anterior part of the right middle temporal gyrus was observed. No activation of the occipital areas was observed during the CONC task when compared either to the REST or to the ABST task. The present study demonstrates that a network including part of the bilateral ventral stream and the frontal working memory areas is recruited when mental imagery of concrete words is performed on the basis of continuous spoken language.

Mental navigation along memorized routes activates the hippocampus, precuneus, and insula.

Positron emission tomography was used to investigate the functional anatomy of mental simulation of routes (MSR) in five normal volunteers. Normalized regional cerebral blood flow was measured while subjects mentally navigated between landmarks of a route which had been previously learned by actual navigation. This task was contrasted with both static visual imagery of landmarks (VIL) and silent Rest. MSR appears to be subserved by two distinct networks: a non-specific memory network including the posterior and middle parts of the hippocampal regions, the dorsolateral prefrontal cortex and the posterior cingulum, and a specific mental navigation network, comprising the left precuneus, insula and medial part of the hippocampal regions.

Picture naming without Broca's and Wernicke's area.

Lexical and semantic retrieval was investigated in normal volunteers with PET by comparing picture confrontation naming and verb generation related to the same pictures. Conjunction analysis of the naming and verb generation uncovered a common network including the occipito-temporal ventral pathway for object recognition, and the bilateral anterior insula, SMA and precentral gyrus for coordination, planning and overt word production. Naming and verb generation highlighted two different patterns: verb generation showed specific implication of Broca and Wernicke's areas, whereas naming specifically relied on the primary visual areas, the right fusiform and parahippocampal gyri and the left anterior temporal region. These results indicate that speech does not necessarily involve the Wernicke-Broca's language network and testify that naming relies on an early developmental language network.

Cortical networks for working memory and executive functions sustain the conscious resting state in man.

The cortical anatomy of the conscious resting state (REST) was investigated using a meta-analysis of nine positron emission tomography (PET) activation protocols that dealt with different cognitive tasks but shared REST as a common control state. During REST, subjects were in darkness and silence, and were instructed to relax, refrain from moving, and avoid systematic thoughts. Each protocol contrasted REST to a different cognitive task consisting either of language, mental imagery, mental calculation, reasoning, finger movement, or spatial working memory, using either auditory, visual or no stimulus delivery, and requiring either vocal, motor or no output. A total of 63 subjects and 370 spatially normalized PET scans were entered in the meta-analysis. Conjunction analysis revealed a network of brain areas jointly activated during conscious REST as compared to the nine cognitive tasks, including the bilateral angular gyrus, the left anterior precuneus and posterior cingulate cortex, the left medial frontal and anterior cingulate cortex, the left superior and medial frontal sulcus, and the left inferior frontal cortex. These results suggest that brain activity during conscious REST is sustained by a large scale network of heteromodal associative parietal and frontal cortical areas, that can be further hierarchically organized in an episodic working memory parieto-frontal network, driven in part by emotions, working under the supervision of an executive left prefrontal network.

Weak language lateralization affects both verbal and spatial skills: an fMRI study in 297 subjects.

The present study reappraised the relationship between hemispheric specialization strength and cognitive skills in a sample of 297 individuals including 153 left-handers. It additionally assessed the interaction with manual laterality factors, such as handedness, asymmetry of hand motor skills, and familial sinistrality. A Hemispheric Functional Lateralization Index (HFLI) for language was derived from fMRI. Through mixture Gaussian modeling, three types of language hemispheric lateralization were defined: typical (left hemisphere dominance with clear positive HFLI), ambilateral (no dominant hemisphere with HFLI values close to 0), and strongly-atypical (right-hemisphere dominance with clear negative HFLI values). Three cognitive scores were derived from 12 tests covering various aspects of verbal and spatial cognition. Compared to both typical and strongly-atypical participants, those ambilateral for language production had lower performances in verbal and non-verbal domains, indicating that hemispheric specialization and cognitive skills are related in adults. Furthermore, this relationship was independent from handedness and asymmetry for motor skills, as no interaction was observed between these factors. On the other hand, the relationship between familial sinistrality and cognitive skills tended to differ according to language lateralization type. In contrast to previous reports in children, in the present adult population, we found no linear correlation between HFLI and cognitive skills, regardless of lateralization type.

The neural correlates of highly iconic structures and topographic discourse in French Sign Language as observed in six hearing native signers.

"Highly iconic" structures in Sign Language enable a narrator to act, switch characters, describe objects, or report actions in four-dimensions. This group of linguistic structures has no real spoken-language equivalent. Topographical descriptions are also achieved in a sign-language specific manner via the use of signing-space and spatial-classifier signs. We used functional magnetic resonance imaging (fMRI) to compare the neural correlates of topographic discourse and highly iconic structures in French Sign Language (LSF) in six hearing native signers, children of deaf adults (CODAs), and six LSF-naïve monolinguals. LSF materials consisted of videos of a lecture excerpt signed without spatially organized discourse or highly iconic structures (Lect LSF), a tale signed using highly iconic structures (Tale LSF), and a topographical description using a diagrammatic format and spatial-classifier signs (Topo LSF). We also presented texts in spoken French (Lect French, Tale French, Topo French) to all participants. With both languages, the Topo texts activated several different regions that are involved in mental navigation and spatial working memory. No specific correlate of LSF spatial discourse was evidenced. The same regions were more activated during Tale LSF than Lect LSF in CODAs, but not in monolinguals, in line with the presence of signing-space structure in both conditions. Motion processing areas and parts of the fusiform gyrus and precuneus were more active during Tale LSF in CODAs; no such effect was observed with French or in LSF-naïve monolinguals. These effects may be associated with perspective-taking and acting during personal transfers.

Visual and mental exploration of visuo-spatial configurations: behavioral and neuroimaging approaches.

Do mental imagery and perception involve common processing mechanisms? Imagery researchers have devoted a great deal of effort to establishing the functional and structural similarities between images and perceptual events. Recent studies have focused on the comparison of images that are reconstructions of previous perceptual experience and images constructed from verbal descriptions. This article reports the findings of a research program based on the mental scanning paradigm; they reveal the similarities and differences between the two kinds of mental images. Neuroimaging studies have also provided evidence that the parieto-occipital cortex is involved in the processing of visual images, whether they are based on perceptual experience or constructed from linguistic inputs. However, the PET studies conducted by our research groups provide no evidence that the primary visual cortex is engaged in the generation of visual images. As there is contradictory evidence about this, further research is needed to clarify the role of the early visual areas in mental visual imagery.

A positron emission tomography study of visual and mental spatial exploration.

We measured normalized regional cerebral blood flow (NrCBF) using positron emission tomography (PET) and oxygen-15-labeled water in eight young right-handed healthy volunteers selected as high-imagers. during 2 runs of 3 different conditions: 1, rest in total darkness 2; visual exploration of a map 3; mental exploration of the same map in total darkness. NrCBF images were aligned with individual magnetic resonance images (MRI), and NrCBF variations between pairs of measurements (N = 15) were computed in regions of interest having anatomical boundaries that were defined using a three-dimensional (3-D) reconstruction of each subject MRI. During visual exploration, we found bilateral activations of primary visual areas, superior and inferior occipital gyri, fusiform and lingual gyri, cuneus and precuneus, bilateral superior parietal, and angular gyri. The right lateral premotor area was also activated during this task while superior temporal gyri and Broca's area were deactivated. By contrast, mental exploration activated the right superior occipital cortex, the supplementary motor area, and the cerebellar vermis. No activation was observed in the primary visual area. These results argue for a specific participation of the superior occipital cortex in the generation and maintenance of visual mental images.

Neural correlates of simple and complex mental calculation.

Some authors proposed that exact mental calculation is based on linguistic representations and relies on the perisylvian language cortices, while the understanding of proximity relations between numerical quantities implicates the parietal cortex. However, other authors opposed developmental arguments to suggest that number sense emerges from nonspecific visuospatial processing areas in the parietal cortex. Within this debate, the present study aimed at revealing the functional anatomy of the two basic resolution strategies involved in mental calculation, namely arithmetical fact retrieval and actual computation, questioning in particular the respective role of language and/or visuospatial cerebral areas. Regional cerebral blood flow was measured with positron emission tomography while subjects were at rest (Rest), read digits (Read), retrieved simple arithmetic facts from memory (i.e., 2 x 4, Retrieve), and performed mental complex calculation (i.e., 32 x 24, Compute). Compared to Read, Retrieve engaged a left parieto-premotor circuit representing a developmental trace of a finger-counting representation that mediates, by extension, the numerical knowledge in adult. Beside this basic network, Retrieve involved a naming network, including the left anterior insula and the right cerebellar cortex, while it did not engage the perisylvian language areas, which were deactivated as compared to Rest. In addition to this retrieval network, Compute specifically involved two functional networks: a left parieto-frontal network in charge of the holding of the multidigit numbers in visuospatial working memory and a bilateral inferior temporal gyri related to the visual mental imagery resolution strategy. Overall, these results provide strong evidence of the involvement of visuospatial representations in different levels of mental calculation.