Social context and drug cues modulate inhibitory control in cocaine addiction: involvement of the STN evidenced through functional MRI.

Addictions often develop in a social context, although the influence of social factors did not receive much attention in the neuroscience of addiction. Recent animal studies suggest that peer presence can reduce cocaine intake, an influence potentially mediated, among others, by the subthalamic nucleus (STN). However, there is to date no neurobiological study investigating this mediation in humans. This study investigated the impact of social context and drug cues on brain correlates of inhibitory control in individuals with and without cocaine use disorder (CUD) using functional Magnetic Resonance Imaging (fMRI). Seventeen CUD participants and 17 healthy controls (HC) performed a novel fMRI "Social" Stop-Signal Task (SSST) in the presence or absence of an observer while being exposed to cocaine-related (vs. neutral) cues eliciting craving in drug users. The results showed that CUD participants, while slower at stopping with neutral cues, recovered control level stopping abilities with cocaine cues, while HC did not show any difference. During inhibition (Stop Correct vs Stop Incorrect), activity in the right STN, right inferior frontal gyrus (IFG), and bilateral orbitofrontal cortex (OFC) varied according to the type of cue. Notably, the presence of an observer reversed this effect in most areas for CUD participants. These findings highlight the impact of social context and drug cues on inhibitory control in CUD and the mediation of these effects by the right STN and bilateral OFC, emphasizing the importance of considering the social context in addiction research. They also comfort the STN as a potential addiction treatment target.

Auditory hemispheric asymmetry for actions and objects.

What is the function of auditory hemispheric asymmetry? We propose that the identification of sound sources relies on the asymmetric processing of two complementary and perceptually relevant acoustic invariants: actions and objects. In a large dataset of environmental sounds, we observed that temporal and spectral modulations display only weak covariation. We then synthesized auditory stimuli by simulating various actions (frictions) occurring on different objects (solid surfaces). Behaviorally, discrimination of actions relies on temporal modulations, while discrimination of objects relies on spectral modulations. Functional magnetic resonance imaging data showed that actions and objects are decoded in the left and right hemispheres, respectively, in bilateral superior temporal and left inferior frontal regions. This asymmetry reflects a generic differential processing-through differential neural sensitivity to temporal and spectral modulations present in environmental sounds-that supports the efficient categorization of actions and objects. These results support an ecologically valid framework of the functional role of auditory brain asymmetry.

Action Observation Network Activity Related to Object-Directed and Socially-Directed Actions in Adolescents.

The human action observation network (AON) encompasses brain areas consistently engaged when we observe other's actions. Although the core nodes of the AON are present from childhood, it is not known to what extent they are sensitive to different action features during development. Because social cognitive abilities continue to mature during adolescence, the AON response to socially-oriented actions, but not to object-related actions, may differ in adolescents and adults. To test this hypothesis, we scanned with functional magnetic resonance imaging (fMRI) male and female typically-developing teenagers (n = 28; 13 females) and adults (n = 25; 14 females) while they passively watched videos of manual actions varying along two dimensions: sociality (i.e., directed toward another person or not) and transitivity (i.e., involving an object or not). We found that action observation recruited the same fronto-parietal and occipito-temporal regions in adults and adolescents. The modulation of voxel-wise activity according to the social or transitive nature of the action was similar in both groups of participants. Multivariate pattern analysis, however, revealed that decoding accuracies in intraparietal sulcus (IPS)/superior parietal lobe (SPL) for both sociality and transitivity were lower for adolescents compared with adults. In addition, in the lateral occipital temporal cortex (LOTC), generalization of decoding across the orthogonal dimension was lower for sociality only in adolescents. These findings indicate that the representation of the content of others' actions, and in particular their social dimension, in the adolescent AON is still not as robust as in adults.SIGNIFICANCE STATEMENT The activity of the action observation network (AON) in the human brain is modulated according to the purpose of the observed action, in particular the extent to which it involves interaction with an object or with another person. How this conceptual representation of actions is implemented during development is largely unknown. Here, using multivoxel pattern analysis (MVPA) of functional magnetic resonance imaging (fMRI) data, we discovered that, while the action observation network is in place in adolescence, the fine-grain organization of its posterior regions is less robust than in adults to decode the abstract social dimensions of an action. This finding highlights the late maturation of social processing in the human brain.

Problem-solving training modifies cognitive functioning and related functional connectivity in healthy adults.

Cognitive functioning evolves throughout life. Regular practice of stimulating activities maintains or even strengthens cognitive skills. This study investigated the effects of a cognitive training programme based on complex closed-ended problem solving on innovative thinking. To this end, using partial least squares variance-based structural equation modeling, we first evaluated in 83 healthy adults how inhibition, cognitive flexibility, and reasoning were related to the distinct dimensions of innovative thinking. Second, we assessed how these interactions were modified after cognitive training based on problem solving in a subgroup of 16 subjects compared to leisure activity based on crossword solving in another subgroup of 15 subjects. Third, in a pilot fMRI study, we evaluated changes in brain connectivity at rest as a result of training in the problem solving group. Data on cognitive measures showed that innovative thinking was influenced by reasoning in control subjects, whereas it was influenced by cognitive flexibility following problem-solving training. These findings highlight that a cognitive intervention based on complex closed-ended problem solving promotes innovative thinking by changing the way subjects recruit and use relevant cognitive processes. Modifications in the resting-state connectivity of attention, default mode and visual networks were observed in the problem solving group.

Early Left-Planum Temporale Asymmetry in newborn monkeys (Papio anubis): A longitudinal structural MRI study at two stages of development.

The "language-ready" brain theory suggests that the infant brain is pre-wired for language acquisition prior to language exposure. As a potential brain marker of such a language readiness, a leftward structural brain asymmetry was found in human infants for the Planum Temporale (PT), which overlaps with Wernicke's area. In the present longitudinal in vivo MRI study conducted in 35 newborn monkeys (Papio anubis), we found a similar leftward PT surface asymmetry. Follow-up rescanning sessions on 29 juvenile baboons at 7-10 months showed that such an asymmetry increases across the two ages classes. These original findings in non-linguistic primate infants strongly question the idea that the early PT asymmetry constitutes a human infant-specific marker for language development. Such a shared early perisylvian organization provides additional support that PT asymmetry might be related to a lateralized system inherited from our last common ancestor with Old-World monkeys at least 25-35 million years ago.

The handwriting brain in middle childhood.

While the brain network supporting handwriting has previously been defined in adults, its organization in children has never been investigated. We compared the handwriting network of 23 adults and 42 children (8- to 11-year-old). Participants were instructed to write the alphabet, the days of the week, and to draw loops while being scanned. The handwriting network previously described in adults (five key regions: left dorsal premotor cortex, superior parietal lobule (SPL), fusiform and inferior frontal gyri, and right cerebellum) was also strongly activated in children. The right precentral gyrus and the right anterior cerebellum were more strongly activated in adults than in children, while the left fusiform gyrus (FuG) was more strongly activated in children than in adults. Finally, we found that, contrary to adults, children recruited prefrontal regions to complete the writing task. This constitutes the first comparative investigation of the neural correlates of writing in children and adults. Our results suggest that the network supporting handwriting is already established in middle childhood. They also highlight the major role of prefrontal regions in learning this complex skill and the importance of right precentral regions and cerebellum in the performance of automated handwriting.

Functional brain changes in the elderly for the perception of hand movements: A greater impairment occurs in proprioception than touch.

Unlike age-related brain changes linked to motor activity, neural alterations related to self-motion perception remain unknown. Using fMRI data, we investigated age-related changes in the central processing of somatosensory information by inducing illusions of right-hand rotations with specific proprioceptive and tactile stimulation. Functional connectivity during resting-state (rs-FC) was also compared between younger and older participants. Results showed common sensorimotor activations in younger and older adults during proprioceptive and tactile illusions, but less deactivation in various right frontal regions and the precuneus were found in the elderly. Older participants exhibited a less-lateralized pattern of activity across the primary sensorimotor cortices (SM1) in the proprioceptive condition only. This alteration of the interhemispheric balance correlated with declining individual performance in illusion velocity perception from a proprioceptive, but not a tactile, origin. By combining task-related data, rs-FC and behavioral performance, this study provided consistent results showing that hand movement perception was altered in the elderly, with a more pronounced deterioration of the proprioceptive system, likely due to the breakdown of inhibitory processes with aging. Nevertheless, older people could benefit from an increase in internetwork connectivity to overcome this kinesthetic decline.

Top-down activation of the visuo-orthographic system during spoken sentence processing.

The left ventral occipitotemporal cortex (vOT) is considered the key area of the visuo-orthographic system. However, some studies reported that the area is also involved in speech processing tasks, especially those that require activation of orthographic knowledge. These findings suggest the existence of a top-down activation mechanism allowing such cross-modal activation. Yet, little is known about the involvement of the vOT in more natural speech processing situations like spoken sentence processing. Here, we addressed this issue in a functional Magnetic Resonance Imaging (fMRI) study while manipulating the impacts of two factors, i.e., task demands (semantic vs. low-level perceptual task) and the quality of speech signals (sentences presented against clear vs. noisy background). Analyses were performed at the levels of whole brain and region-of-interest (ROI) focusing on the vOT voxels individually identified through a reading task. Whole brain analysis showed that processing spoken sentences induced activity in a large network including the regions typically involved in phonological, articulatory, semantic and orthographic processing. ROI analysis further specified that a significant part of the vOT voxels that responded to written words also responded to spoken sentences, thus, suggesting that the same area within the left occipitotemporal pathway contributes to both reading and speech processing. Interestingly, both analyses provided converging evidence that vOT responses to speech were sensitive to both task demands and quality of speech signals: Compared to the low-level perceptual task, activity of the area increased when efforts on comprehension were required. The impact of background noise depended on task demands. It led to a decrease of vOT activity in the semantic task but not in the low-level perceptual task. Our results provide new insights into the function of this key area of the reading network, notably by showing that its speech-induced top-down activation also generalizes to ecological speech processing situations.

Left Brain Asymmetry of the Planum Temporale in a Nonhominid Primate: Redefining the Origin of Brain Specialization for Language.

The planum temporale (PT) is a critical region of the language functional network in the human brain showing a striking size asymmetry toward the left hemisphere. Historically considered as a structural landmark of the left-brain specialization for language, a similar anatomical bias has been described in great apes but never in monkeys-indicating that this brain landmark might be unique to Hominidae evolution. In the present in vivo magnetic resonance imaging study, we show clearly for the first time in a nonhominid primate species, an Old World monkey, a left size predominance of the PT among 96 olive baboons (Papio anubis), using manual delineation of this region in each individual hemisphere. This asymmetric distribution was quasi-identical to that found originally in humans. Such a finding questions the relationship between PT asymmetry and the emergence of language, indicating that the origin of this cerebral specialization could be much older than previously thought, dating back, not to the Hominidae, but rather to the Catarrhini evolution at the common ancestor of humans, great apes and Old World monkeys, 30-40 million years ago.

Protracted Development of the Proprioceptive Brain Network During and Beyond Adolescence.

Proprioceptive processing is important for appropriate motor control, providing error-feedback and internal representation of movement for adjusting the motor command. Although proprioceptive functioning improves during childhood and adolescence, we still have few clues about how the proprioceptive brain network develops. Here, we investigated developmental changes in the functional organization of this network in early adolescents (n = 18, 12 ± 1 years), late adolescents (n = 18, 15 ± 1), and young adults (n = 18, 32 ± 4), by examining task-evoked univariate activity and patterns of functional connectivity (FC) associated with seeds placed in cortical (supramarginal gyrus) and subcortical (dorsal rostral putamen) regions. We found that although the network is already well established in early adolescence both in terms of topology and functioning principles (e.g., long-distance communication and economy in wiring cost), it is still undergoing refinement during adolescence, including a shift from diffuse to focal FC and a decreased FC strength. This developmental effect was particularly pronounced for fronto-striatal connections. Furthermore, changes in FC features continued beyond adolescence, although to a much lower extent. Altogether, these findings point to a protracted developmental time course for the proprioceptive network, which breaks with the relatively early functional maturation often associated with sensorimotor networks.

Taste at first (person) sight: Visual perspective modulates brain activity implicitly associated with viewing unhealthy but not healthy foods.

Every day, people are exposed to images of appetizing foods that can lead to high-calorie intake and contribute to overweight and obesity. Research has documented that manipulating the visual perspective from which eating is viewed helps resist temptation by altering the appraisal of unhealthy foods. However, the neural basis of this effect has not yet been examined using neuroimaging methods. Moreover, it is not known whether the benefits of this strategy can be observed when people, especially overweight, are not explicitly asked to imagine themselves eating. Last, it remains to be investigated if visual perspective could be used to promote healthy foods. The present work manipulated camera angles and tested whether visual perspective modulates activity in brain regions associated with taste and reward processing while participants watch videos featuring a hand grasping (unhealthy or healthy) foods from a plate during functional magnetic resonance imagining (fMRI). The plate was filmed from the perspective of the participant (first-person perspective; 1PP), or from a frontal view as if watching someone else eating (third-person perspective; 3PP). Our findings reveal that merely viewing unhealthy food cues from a 1PP (vs. 3PP) increases activity in brain regions that underlie representations of rewarding (appetitive) experiences (amygdala) and food intake (superior parietal gyrus). Additionally, our results show that ventral striatal activity is positively correlated with body mass index (BMI) during exposure to unhealthy foods from a 1PP (vs. 3PP). These findings suggest that unhealthy foods should be promoted through third-person (video) images to weaken the reward associated with their simulated consumption, especially amongst overweight people. It appears however that, as such, manipulating visual perspective fails to enhance the perception of healthy foods. Their promotion thus requires complementary solutions.

Automaticity of phonological and semantic processing during visual word recognition.

Reading involves activation of phonological and semantic knowledge. Yet, the automaticity of the activation of these representations remains subject to debate. The present study addressed this issue by examining how different brain areas involved in language processing responded to a manipulation of bottom-up (level of visibility) and top-down information (task demands) applied to written words. The analyses showed that the same brain areas were activated in response to written words whether the task was symbol detection, rime detection, or semantic judgment. This network included posterior, temporal and prefrontal regions, which clearly suggests the involvement of orthographic, semantic and phonological/articulatory processing in all tasks. However, we also found interactions between task and stimulus visibility, which reflected the fact that the strength of the neural responses to written words in several high-level language areas varied across tasks. Together, our findings suggest that the involvement of phonological and semantic processing in reading is supported by two complementary mechanisms. First, an automatic mechanism that results from a task-independent spread of activation throughout a network in which orthography is linked to phonology and semantics. Second, a mechanism that further fine-tunes the sensitivity of high-level language areas to the sensory input in a task-dependent manner.

Orthographic processing deficits in developmental dyslexia: Beyond the ventral visual stream.

Fast effortless reading has been associated with the Visual Word Form Area (VWFA), a region in the ventral visual stream that specializes in the recognition of letter strings. Several neuroimaging studies of dyslexia revealed an underactivation of this region. However, most of these studies used reading tasks and/or were carried out on adults. Given that fluent reading is severely impaired in dyslexics, any underactivation might simply reflect a well-established reading deficit in impaired readers and could be the consequence rather than the cause of dyslexia. Here, we designed a task that does not rely on reading per se but that tapped early visual orthographic processing that forms the basis of reading. Dyslexic children aged 8-12years and age-matched controls were asked to search for letters, digits, and symbols in 5-element strings (Experiment 1). This novel task was complemented by a classic task known to activate the VWFA, namely the passive viewing of pseudowords and falsefonts (Experiment 2). We found that in addition to significant group differences in the VWFA, dyslexic children showed a significant underactivation of the middle occipital gyrus (MOG) relative to the control group. Several areas in the MOG are known for their engagement in visuospatial processing, and it has been proposed that the MOG is necessary for ordering the symbols in unfamiliar strings. Our results suggest that the VWFA deficit might be secondary to an impairment of visuospatial processing in the MOG. We argue that efficient processing in MOG in the course of reading acquisition is critical for the development of effortless fast visual word recognition in the VWFA.

The average baboon brain: MRI templates and tissue probability maps from 89 individuals.

The baboon (Papio) brain is a remarkable model for investigating the brain. The current work aimed at creating a population-average baboon (Papio anubis) brain template and its left/right hemisphere symmetric version from a large sample of T1-weighted magnetic resonance images collected from 89 individuals. Averaging the prior probability maps output during the segmentation of each individual also produced the first baboon brain tissue probability maps for gray matter, white matter and cerebrospinal fluid. The templates and the tissue probability maps were created using state-of-the-art, freely available software tools and are being made freely and publicly available: http://www.nitrc.org/projects/haiko89/ or http://lpc.univ-amu.fr/spip.php?article589. It is hoped that these images will aid neuroimaging research of the baboon by, for example, providing a modern, high quality normalization target and accompanying standardized coordinate system as well as probabilistic priors that can be used during tissue segmentation.

Brain correlates of phonological recoding of visual symbols.

Learning to read involves setting up associations between meaningless visual inputs (V) and their phonological representations (P). Here, we recorded the brain signals (ERPs and fMRI) associated with phonological recoding (i.e., V-P conversion processes) in an artificial learning situation in which participants had to learn the associations between 24 unknown visual symbols (Japanese Katakana characters) and 24 arbitrary monosyllabic names. During the learning phase on Day 1, the strength of V-P associations was manipulated by varying the proportion of correct and erroneous associations displayed during a two-alternative forced choice task. Recording event related potentials (ERPs) during the learning phase allowed us to track changes in the processing of these visual symbols as a function of the strength of V-P associations. We found that, at the end of the learning phase, ERPs were linearly affected by the strength of V-P associations in a time-window starting around 200ms post-stimulus onset on right occipital sites and ending around 345ms on left occipital sites. On Day 2, participants had to perform a matching task during an fMRI session and the strength of these V-P associations was again used as a probe for identifying brain regions related to phonological recoding. Crucially, we found that the left fusiform gyrus was gradually affected by the strength of V-P associations suggesting that this region is involved in the brain network supporting phonological recoding processes.

Boosted activation of right inferior frontoparietal network: a basis for illusory movement awareness.

The feeling of illusory movement is considered important in the study of human behavior because it is deeply related to motor consciousness. However, the neural basis underlying the illusion of movement remains to be understood. Following optimal vibratory stimulation of muscle tendon, certain subjects experience illusory movements while others do not. In the present fMRI study, we sought to uncover the neural basis of illusory movement awareness by contrasting a posteriori these two types of subjects. Examining fMRI data using leave-one-subject-out general linear models and region of interest analyses, we found that a non-limb-specific associative network, including the opercular part of the right inferior frontal gyrus and the right inferior parietal lobule, was more active in subjects with illusions. On the other hand, levels of activation in other brain areas involved in kinaesthetic processing were rather similar between the two subsamples of subjects. These results suggest that activation of the right inferior frontoparietal areas, once passed a certain threshold, forms the basis of illusory movements. This is consistent with the global neuronal workspace hypothesis that associates conscious processing with surges of frontoparietal activity.

The dorsal medial frontal cortex mediates automatic motor inhibition in uncertain contexts: evidence from combined fMRI and EEG studies.

Response inhibition is commonly thought to rely on voluntary, reactive, selective, and relatively slow prefrontal mechanisms. In contrast, we suggest here that response inhibition is achieved automatically, nonselectively, within very short delays in uncertain environments. We modified a classical go/nogo protocol to probe context-dependent inhibitory mechanisms. Because no single neuroimaging method can definitely disentangle neural excitation and inhibition, we combined fMRI and EEG recordings in healthy humans. Any stimulus (go or nogo) presented in an uncertain context requiring action restraint was found to evoke activity changes in the supplementary motor complex (SMC) with respect to a control condition in which no response inhibition was required. These changes included: (1) An increase in event-related BOLD activity, (2) an attenuation of the early (170 ms) event related potential generated by a single, consistent source isolated by advanced blind source separation, and (3) an increase in the evoked-EEG Alpha power of this source. Considered together, these results suggest that the BOLD signal evoked by any stimulus in the SMC when the situation is unpredictable can be driven by automatic, nonselective, context-dependent inhibitory activities. This finding reveals the paradoxical mechanisms by which voluntary control of action may be achieved. The ability to provide controlled responses in unpredictable environments would require setting-up the automatic self-inhibitory circuitry within the SMC. Conversely, enabling automatic behavior when the environment becomes predictable would require top-down control to deactivate anticipatorily and temporarily the inhibitory set.

Functional specificity in the motor system: Evidence from coupled fMRI and kinematic recordings during letter and digit writing.

A few intriguing neuropsychologial studies report dissociations where agraphic patients are severely impaired for writing letters whereas they write digits nearly normally. Here, using functional magnetic resonance imaging (fMRI) together with graphic tablet recordings, we tested the hypothesis that the motor patterns for writing letters are coded in specific regions of the cortex. We found a set of three regions that were more strongly activated when participants wrote letters than when they wrote digits and whose response was not explained by low-level kinematic features of the graphic movements. Two of these regions (left dorsal premotor cortex and supplementary motor complex) are part of a motor control network. The left premotor activation belongs to what is considered in the literature a key area for handwriting. Another significant activation, likely related to phoneme-to-grapheme conversion, was found in the right anterior insula. This constitutes the first neuroimaging evidence of functional specificity derived from experience in the cortical motor system.

Planum temporale asymmetry in newborn monkeys predicts the future development of gestural communication's handedness.

The planum temporale (PT), a key language area, is specialized in the left hemisphere in prelinguistic infants and considered as a marker of the pre-wired language-ready brain. However, studies have reported a similar structural PT left-asymmetry not only in various adult non-human primates, but also in newborn baboons. Its shared functional links with language are not fully understood. Here we demonstrate using previously obtained MRI data that early detection of PT left-asymmetry among 27 newborn baboons (Papio anubis, age range of 4 days to 2 months) predicts the future development of right-hand preference for communicative gestures but not for non-communicative actions. Specifically, only newborns with a larger left-than-right PT were more likely to develop a right-handed communication once juvenile, a contralateral brain-gesture link which is maintained in a group of 70 mature baboons. This finding suggests that early PT asymmetry may be a common inherited prewiring of the primate brain for the ontogeny of ancient lateralised properties shared between monkey gesture and human language.

Writing letters in two graphic systems: Behavioral and neural correlates in Latin-Arabic biscripters.

Biscriptuality is the ability to read and write using two scripts. Despite the increasing number of biscripters, this phenomenon remains poorly understood. Here, we focused on investigating graphomotor processing in French-Arabic biscripters. We chose the French and Arabic alphabets because they have comparable visuospatial complexity and linguistic features, but differ dramatically in their graphomotor characteristics. In a first experiment we describe the graphomotor features of the two alphabets and showed that while Arabic and Latin letters are produced with the same velocity and fluency, Arabic letters require more pen lifts, contain more right-to-left strokes and clockwise curves, and take longer to write than Latin letters. These results suggest that Arabic and Latin letters are produced via different motor patterns. In a second experiment we used functional magnetic resonance imaging to ask whether writing the two scripts relies upon partially distinct or fully overlapping neural networks, and whether the elements of the previously described handwriting network are recruited to the same extent by the two scripts. We found that both scripts engaged the so-called "writing network", but that within the network, Arabic letters recruited the left superior parietal lobule (SPL) and the left primary motor cortex (M1) more strongly than Latin letters. Both regions have previously been identified as holding scale-invariant representations of letter trajectories. Arabic and Latin letters also activated distinct regions that do not belong to the writing network. Complementary analyses indicate that the differences observed between scripts at the neural level could be driven by the specific graphomotor features of each script. Overall, our results indicate that particular features of the practiced scripts can lead to different motor organization at both the behavioral and brain levels in biscripters.