Combined TMS-fMRI reveals behavior-dependent network effects of right temporoparietal junction neurostimulation in an attentional belief updating task.

Updating beliefs after unexpected events is fundamental for an optimal adaptation to the environment. Previous findings suggested a causal involvement of the right temporoparietal junction (rTPJ) in belief updating in an attention task. We combined offline continuous theta-burst stimulation (cTBS) over rTPJ with functional magnetic resonance imaging (fMRI) to investigate local and remote stimulation effects within the attention and salience networks. In a sham-controlled, within-subject crossover design, 25 participants performed an attentional cueing task during fMRI with true or false information about cue predictability. By estimating learning rates from response times, we characterized participants' belief updating. Model-derived cue predictability entered the fMRI analysis as a parametric regressor to identify the neural correlates of updating. rTPJ-cTBS effects showed high interindividual variability. The expected learning rate reduction with false cue predictability information by cTBS was only observed in participants showing higher updating in false than in true blocks after sham. cTBS modulated the neural signatures of belief updating, both in rTPJ and in nodes of the attention and salience networks. The interindividual variability of the behavioral cTBS effect was related to differential activity and rTPJ connectivity of the right anterior insula. These results demonstrate a crucial interaction between ventral attention and salience networks for belief updating.

Effect of body-part specificity and meaning in gesture imitation in left hemisphere stroke patients.

Previous studies showed that imitation of finger and hand/arm gestures could be differentially impaired after brain damage. However, so far, the interaction between gesture meaning and body part in imitation deficits has not been fully assessed. In the present study, we aimed at filling this gap by testing 36 unilateral left brain-damaged patients with and without apraxia (20 apraxics), and 29 healthy controls on an imitation task of either finger or hand/arm meaningful (MF) gestures and meaningless (ML) movements, using a large sample of stimuli and controlling for the composition of the experimental list. Left-brain damaged patients imitated ML finger worse than hand/arm movements, whereas they did not show the same difference in MF gesture imitation. In addition, apraxic patients imitated finger movements worse than hand/arm movements. Furthermore, apraxic patients' imitation performance was equally affected irrespective of the action meaning, whereas non-apraxic patients showed better imitation performance on MF gestures. Results suggest that MF gestures are processed as a whole, as imitation of these gestures relies on the stored motor programs in long-term memory, independently of the body part involved. In contrast, ML movements seem to be processed through direct visuo-motor transformations, with left-brain damage specifically disrupting imitation performance of the more cognitive demanding finger movements.

Late Frontal Negativity Discriminates Outcomes and Intentions in Trust-Repayment Behavior.

Altruism (a costly action that benefits others) and reciprocity (the repayment of acts in kind) differ in that the former expresses preferences about the outcome of a social interaction, whereas the latter requires, in addition, ascribing intentions to others. Interestingly, an individual's behavior and neurophysiological activity under outcome- versus intention-based interactions has not been compared directly using different endowments in the same subject and during the same session. Here, we used a mixed version of the Dictator and the Investment games, together with electroencephalography, to uncover a subject's behavior and brain activity when challenged with endowments of different sizes in contexts that call for an altruistic (outcome-based) versus a reciprocal (intention-based) response. We found that subjects displayed positive or negative reciprocity (reciprocal responses greater or smaller than that for altruism, respectively) depending on the amount of trust they received. Furthermore, a subject's late frontal negativity differed between conditions, predicting responses to trust in intentions-based trials. Finally, brain regions related with mentalizing and cognitive control were the cortical sources of this activity. Thus, our work disentangles the behavioral components present in the repayment of trust, and sheds light on the neural activity underlying the integration of outcomes and perceived intentions in human economic interactions.

Lateralization, functional specialization, and dysfunction of attentional networks.

The present review covers the latest findings on the lateralization of the dorsal and ventral attention systems, their functional specialization, and their clinical relevance for stroke-induced attentional dysfunction. First, the original assumption of a bilateral dorsal system for top-down attention and a right-lateralized ventral system for stimulus-driven attention is critically reviewed. The evidence for the involvement of the left parietal cortex in attentional functions is discussed and findings on putative pathways linking the dorsal and ventral network are presented. In the second part of the review, we focus on the different attentional subsystems and their lateralization, discussing the differences between spatial, feature- and object-based attention, and motor attention. We also review studies based on predictive coding frameworks of attentional functions. Finally, in the third section, we provide an overview of the consequences of specific disruption within the attention networks after stroke. The role of the interhemispheric (im)balance is discussed, and the results of new promising therapeutic approaches employing brain stimulation techniques such as transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS) are presented.

Resting-state Functional Connectivity of the Right Temporoparietal Junction Relates to Belief Updating and Reorienting during Spatial Attention.

Although multiple studies characterized the resting-state functional connectivity (rsFC) of the right temporoparietal junction (rTPJ), little is known about the link between rTPJ rsFC and cognitive functions. Given a putative involvement of rTPJ in both reorienting of attention and the updating of probabilistic beliefs, this study characterized the relationship between rsFC of rTPJ with dorsal and ventral attention systems and these two cognitive processes. Twenty-three healthy young participants performed a modified location-cueing paradigm with true and false prior information about the percentage of cue validity to assess belief updating and attentional reorienting. Resting-state fMRI was recorded before and after the task. Seed-based correlation analysis was employed, and correlations of each behavioral parameter with rsFC before the task, as well as with changes in rsFC after the task, were assessed in an ROI-based approach. Weaker rsFC between rTPJ and right intraparietal sulcus before the task was associated with relatively faster updating of the belief that the cue will be valid after false prior information. Moreover, relatively faster belief updating, as well as faster reorienting, were related to an increase in the interhemispheric rsFC between rTPJ and left TPJ after the task. These findings are in line with task-based connectivity studies on related attentional functions and extend results from stroke patients demonstrating the importance of interhemispheric parietal interactions for behavioral performance. The present results not only highlight the essential role of parietal rsFC for attentional functions but also suggest that cognitive processing during a task changes connectivity patterns in a performance-dependent manner.

Age-related changes in Bayesian belief updating during attentional deployment and motor intention.

Predicting upcoming events using past observations is a crucial component of an efficient allocation of attentional resources. Therefore, the deployment of attention is sensitive to different types of cues predicting upcoming events. Here we investigated probabilistic inference abilities in spatial and feature-based attentional, as well as in motor-intentional subsystems, focusing specifically on the age-related changes in these abilities. In two behavioral experiments, younger and older adults (20 younger and 20 older adults for each experiment) performed three versions of a cueing paradigm, where spatial, feature, or motor cues predicted the location, color, or motor response of a target stimulus. The percentage of cue validity (i.e., the probability of the cue being valid) changed over time, thereby creating a volatile environment. A Bayesian hierarchical model was used to estimate trial-wise beliefs concerning the cue validity from reaction times and to derive a subject-specific belief updating parameter ω in each task version. We also manipulated task difficulty: participants performed an easier version of the task in Experiment 1 and a more difficult version in Experiment 2. Results from Experiment 1 suggested a preserved ability of older adults to use the three different cues to generate predictions. However, the increased task demands of Experiment 2 uncovered a difference in belief updating between the two age groups, indicating moderate evidence for a reduction of the ability to update predictions with motor intention cues in older adults. These results point at a distinction of attentional and motor-intentional subsystems, with age-related differences tackling especially the motor-intentional subsystem.

Integrating modality-specific expectancies for the deployment of spatial attention.

The deployment of spatial attention is highly sensitive to stimulus predictability. Despite evidence for strong crossmodal links in spatial attentional systems, it remains to be elucidated how concurrent but divergent predictions for targets in different sensory modalities are integrated. In a series of behavioral studies, we investigated the processing of modality-specific expectancies using a multimodal cueing paradigm in which auditory cues predicted the location of visual or tactile targets with modality-specific cue predictability. The cue predictability for visual and tactile targets was manipulated independently. A Bayesian ideal observer model with a weighting factor was applied to trial-wise individual response speed to investigate how the two probabilistic contexts are integrated. Results showed that the degree of integration depended on the level of predictability and on the divergence of the modality-specific probabilistic contexts (Experiments 1-2). However, when the two probabilistic contexts were matched in their level of predictability and were highly divergent (Experiment 3), higher separate processing was favored, especially when visual targets were processed. These findings suggest that modality-specific predictions are flexibly integrated according to their reliability, supporting the hypothesis of separate modality-specific attentional systems that are however linked to guarantee an efficient deployment of spatial attention across the senses.

A neural signature of food semantics is associated with body-mass index.

Visual recognition of objects may rely on different features depending on the category to which they belong. Recognizing natural objects, such as fruits and plants, weighs more on their perceptual attributes, whereas recognizing man-made objects, such as tools or vehicles, weighs more upon the functions and actions they enable. Edible objects are perceptually rich but also prepared for specific functions, therefore it is unclear how perceptual and functional attributes affect their recognition. Two event-related potentials experiments investigated: (i) whether food categorization in the brain is differentially modulated by sensory and functional attributes, depending on whether the food is natural or transformed; (ii) whether these processes are modulated by participants' body mass index. In experiment 1, healthy normal-weight participants were presented with a sentence (prime) and a photograph of a food. Primes described either a sensory feature ('It tastes sweet') or a functional feature ('It is suitable for a wedding party') of the food, while photographs depicted either a natural (e.g., cherry) or a transformed food (e.g., pizza). Prime-feature pairs were either congruent or incongruent. This design aimed at modulating N400-like components elicited by semantic processing. In experiment 1, N400-like amplitude was significantly larger for transformed food than for natural food with sensory primes, and vice versa with functional primes. In experiment 2, underweight and obese women performed the same semantic task. We found that, while the N400-like component in obese participants was modulated by sensory-functional primes only for transformed food, the same modulation was found in underweight participants only for natural food. These findings suggest that the level of food transformation interacts with participants' body mass index in modulating food perception and the underlying brain processing.

Disruption of the Right Temporoparietal Junction Impairs Probabilistic Belief Updating.

Generating and updating probabilistic models of the environment is a fundamental modus operandi of the human brain. Although crucial for various cognitive functions, the neural mechanisms of these inference processes remain to be elucidated. Here, we show the causal involvement of the right temporoparietal junction (rTPJ) in updating probabilistic beliefs and we provide new insights into the chronometry of the process by combining online transcranial magnetic stimulation (TMS) with computational modeling of behavioral responses. Female and male participants performed a modified location-cueing paradigm, where false information about the percentage of cue validity (%CV) was provided in half of the experimental blocks to prompt updating of prior expectations. Online double-pulse TMS over rTPJ 300 ms (but not 50 ms) after target appearance selectively decreased participants' updating of false prior beliefs concerning %CV, reflected in a decreased learning rate of a Rescorla-Wagner model. Online TMS over rTPJ also impacted on participants' explicit beliefs, causing them to overestimate %CV. These results confirm the involvement of rTPJ in updating of probabilistic beliefs, thereby advancing our understanding of this area's function during cognitive processing.SIGNIFICANCE STATEMENT Contemporary views propose that the brain maintains probabilistic models of the world to minimize surprise about sensory inputs. Here, we provide evidence that the right temporoparietal junction (rTPJ) is causally involved in this process. Because neuroimaging has suggested that rTPJ is implicated in divergent cognitive domains, the demonstration of an involvement in updating internal models provides a novel unifying explanation for these findings. We used computational modeling to characterize how participants change their beliefs after new observations. By interfering with rTPJ activity through online transcranial magnetic stimulation, we showed that participants were less able to update prior beliefs with TMS delivered at 300 ms after target onset.

Spatial Attention, Motor Intention, and Bayesian Cue Predictability in the Human Brain.

Predictions about upcoming events influence how we perceive and respond to our environment. There is increasing evidence that predictions may be generated based upon previous observations following Bayesian principles, but little is known about the underlying cortical mechanisms and their specificity for different cognitive subsystems. The present study aimed at identifying common and distinct neural signatures of predictive processing in the spatial attentional and motor intentional system. Twenty-three female and male healthy human volunteers performed two probabilistic cueing tasks with either spatial or motor cues while lying in the fMRI scanner. In these tasks, the percentage of cue validity changed unpredictably over time. Trialwise estimates of cue predictability were derived from a Bayesian observer model of behavioral responses. These estimates were included as parametric regressors for analyzing the BOLD time series. Parametric effects of cue predictability in valid and invalid trials were considered to reflect belief updating by precision-weighted prediction errors. The brain areas exhibiting predictability-dependent effects dissociated between the spatial attention and motor intention task, with the right temporoparietal cortex being involved during spatial attention and the left angular gyrus and anterior cingulate cortex during motor intention. Connectivity analyses revealed that all three areas showed predictability-dependent coupling with the right hippocampus. These results suggest that precision-weighted prediction errors of stimulus locations and motor responses are encoded in distinct brain regions, but that crosstalk with the hippocampus may be necessary to integrate new trialwise outcomes in both cognitive systems.SIGNIFICANCE STATEMENT The brain is able to infer the environments' statistical structure and responds strongly to expectancy violations. In the spatial attentional domain, it has been shown that parts of the attentional networks are sensitive to the predictability of stimuli. It remains unknown, however, whether these effects are ubiquitous or if they are specific for different cognitive systems. The present study compared the influence of model-derived cue predictability on brain activity in the spatial attentional and motor intentional system. We identified areas with distinct predictability-dependent activation for spatial attention and motor intention, but also common connectivity changes of these regions with the hippocampus. These findings provide novel insights into the generality and specificity of predictive processing signatures in the human brain.

Dual-route imitation in preschool children.

Imitation can be realized via two different routes: a direct route that translates visual input into motor output when gestures are meaningless or unknown, and a semantic route for known/meaningful gestures. Young infants show imitative behaviours compatible with the direct route, but little is known about the development of the semantic route, studied here for the first time. The present study examined preschool children (3-5years of age) imitating gestures that could be transitive or intransitive, and meaningful or meaningless. Both routes for imitation were already present by three years of age, and children were more accurate at imitating meaningful-intransitive gestures than meaningless-intransitive ones; the reverse pattern was found for transitive gestures. Children preferred to use their dominant hand even if they had to anatomically imitate the model to do this, showing that a preference for specular imitation is not exclusive at these ages.

Functional mechanisms of probabilistic inference in feature- and space-based attentional systems.

Humans flexibly attend to features or locations and these processes are influenced by the probability of sensory events. We combined computational modeling of response times with fMRI to compare the functional correlates of (re-)orienting, and the modulation by probabilistic inference in spatial and feature-based attention systems. Twenty-four volunteers performed two task versions with spatial or color cues. Percentage of cue validity changed unpredictably. A hierarchical Bayesian model was used to derive trial-wise estimates of probability-dependent attention, entering the fMRI analysis as parametric regressors. Attentional orienting activated a dorsal frontoparietal network in both tasks, without significant parametric modulation. Spatially invalid trials activated a bilateral frontoparietal network and the precuneus, while invalid feature trials activated the left intraparietal sulcus (IPS). Probability-dependent attention modulated activity in the precuneus, left posterior IPS, middle occipital gyrus, and right temporoparietal junction for spatial attention, and in the left anterior IPS for feature-based and spatial attention. These findings provide novel insights into the generality and specificity of the functional basis of attentional control. They suggest that probabilistic inference can distinctively affect each attentional subsystem, but that there is an overlap in the left IPS, which responds to both spatial and feature-based expectancy violations.

Anatomical and spatial matching in imitation: Evidence from left and right brain-damaged patients.

Imitation is a sensorimotor process whereby the visual information present in the model's movement has to be coupled with the activation of the motor system in the observer. This also implies that greater the similarity between the seen and the produced movement, the easier it will be to execute the movement, a process also known as ideomotor compatibility. Two components can influence the degree of similarity between two movements: the anatomical and the spatial component. The anatomical component is present when the model and imitator move the same body part (e.g., the right hand) while the spatial component is present when the movement of the model and that of the imitator occur at the same spatial position. Imitation can be achieved by relying on both components, but typically the model's and imitator's movements are matched either anatomically or spatially. The aim of this study was to ascertain the contribution of the left and right hemisphere to the imitation accomplished either with anatomical or spatial matching (or with both). Patients with unilateral left and right brain damage performed an ideomotor task and a gesture imitation task. Lesions in the left and right hemispheres gave rise to different performance deficits. Patients with lesions in the left hemisphere showed impaired imitation when anatomical matching was required, and patients with lesions in the right hemisphere showed impaired imitation when spatial matching was required. Lesion analysis further revealed a differential involvement of left and right hemispheric regions, such as the parietal opercula, in supporting imitation in the ideomotor task. Similarly, gesture imitation seemed to rely on different regions in the left and right hemisphere, such as parietal regions in the left hemisphere and premotor, somatosensory and subcortical regions in the right hemisphere.

Selective imitation impairments differentially interact with language processing.

Whether motor and linguistic representations of actions share common neural structures has recently been the focus of an animated debate in cognitive neuroscience. Group studies with brain-damaged patients reported association patterns of praxic and linguistic deficits whereas single case studies documented double dissociations between the correct execution of gestures and their comprehension in verbal contexts. When the relationship between language and imitation was investigated, each ability was analysed as a unique process without distinguishing between possible subprocesses. However, recent cognitive models can be successfully used to account for these inconsistencies in the extant literature. In the present study, in 57 patients with left brain damage, we tested whether a deficit at imitating either meaningful or meaningless gestures differentially impinges on three distinct linguistic abilities (comprehension, naming and repetition). Based on the dual-pathway models, we predicted that praxic and linguistic performance would be associated when meaningful gestures are processed, and would dissociate for meaningless gestures. We used partial correlations to assess the association between patients' scores while accounting for potential confounding effects of aspecific factors such age, education and lesion size. We found that imitation of meaningful gestures significantly correlated with patients' performance on naming and repetition (but not on comprehension). This was not the case for the imitation of meaningless gestures. Moreover, voxel-based lesion-symptom mapping analysis revealed that damage to the angular gyrus specifically affected imitation of meaningless gestures, independent of patients' performance on linguistic tests. Instead, damage to the supramarginal gyrus affected not only imitation of meaningful gestures, but also patients' performance on naming and repetition. Our findings clarify the apparent conflict between associations and dissociations patterns previously observed in neuropsychological studies, and suggest that motor experience and language can interact when the two domains conceptually overlap.

Imitating others' actions: transcranial magnetic stimulation of the parietal opercula reveals the processes underlying automatic imitation.

The human tendency to imitate gestures performed by conspecifics is automatic in nature. However, whether this automatic imitation can be considered as a true imitative phenomenon or only as a special instance of spatial compatibility is still being debated. New evidence suggests that automatic imitation, otherwise known as 'imitative compatibility', shall be considered as a phenomenon that operates independently from spatial compatibility. So far there are only a few investigations directly aimed at identifying the neural structures dedicated to this process. In the present study, we applied double-pulse transcranial magnetic stimulation (TMS) over the parietal opercula to further investigate the role of these regions in coding imitative compatibility. We found that a temporary disruption of parietal opercula caused the reduction of the imitative compatibility relative to the sham condition. In particular, the TMS interference with the parietal opercula's activity modulated the imitative compatibility but not the spatial compatibility, suggesting that these two processes are likely to be independent.

Imitation components in the human brain: an fMRI study.

Human ability to imitate movements is instantiated in parietal, premotor and opercular structures, often referred to as the human homologue of the macaque mirror neuron system. As most studies employed imitation of specular models (participants imitated the seen movement as their mirror reflection), it is unclear whether the structures implicated code for the anatomical compatibility between the performer and the model or the spatial compatibility between the location at which both movements occur. We used fMRI to disentangle the neural mechanisms underlying anatomical and spatial components of imitation. Participants moved one finger which was either spatially or anatomically compatible with the finger moved in a video-display. In keeping with the existent behavioral literature, we found that during the spatial task, participants' responses were faster when the seen movement was also anatomically compatible, whereas in the anatomical task, responses were faster when the seen movement was also spatially compatible. Critically, the activity of the parietal opercula bilaterally was associated with the anatomical compatibility effect. Furthermore, increased activity of the left middle frontal gyrus and right superior temporal sulcus (extending to the temporo-parietal junction) was found in those trials in which the spatial mapping between the seen and executed movements was detrimental for the anatomical task. Our findings extend current understanding of the role played by spatial and anatomical components in imitation and provide new insights about the parietal opercula.

The effect of observed biological and non biological movements on action imitation: an fMRI study.

Past research has indicated that when individuals observe biological movements many areas in the observer's motor system become active. Nonetheless, recent behavioral evidence showed that observed movements can interfere with execution of incompatible movements, especially the biological ones. However, the hypothesis that the interference originates within a common neural network, encoding both movement observation and execution, and responding preferentially to biological movements, still awaits confirmation. To test this hypothesis, in the present fMRI study we compared patterns of activation obtained when participants executed finger-movements after having observed either a biological or a non biological model performing compatible (imitative) or incompatible (non imitative) movements. Moreover, we tested the possibility that imitative responses are influenced by the emotional facial expression (sad, neutral, angry) presented before the observed movement. Behaviorally, participants showed a marginally larger compatibility effect (compatible movements faster than incompatible movements) in the biological condition than in the non biological condition. In the imaging data, the interaction testing for areas more active when the observed model was biological (compared with non biological) and performed compatible movements (compared with incompatible movements), activated a network including the motor, premotor and parietal cortices. Notably, the interaction was significant for the neutral and sad facial expressions only. We showed that observing biological movements modulates the activation of motor-related regions, by facilitating the execution of compatible movements and/or interfering with the execution of incompatible movements.

Altered white matter integrity and development in children with autism: a combined voxel-based morphometry and diffusion imaging study.

BACKGROUND: A combined protocol of voxel-based morphometry (VBM) and diffusion-weighted imaging (DWI) was applied to investigate the neurodevelopment of gray and white matter in autism. METHODS: Twenty children with autism (mean age= 7 ± 2.75 years old; age range: 4-14; 2 girls) and 22 matched normally developing children (mean age = 7.68 ± 2.03 years old; age range: 4-11; 2 girls) underwent magnetic resonance imaging (MRI). VBM was employed by applying the Template-o-Matic toolbox (TOM), a new approach which constructs the age-matched customized template for tissue segmentation. Also, the apparent diffusion coefficients (ADC) of water molecules were obtained from the analysis of DWI. Regions of interests (ROIs), standardized at 5 pixels, were placed in cortical lobes and corpus callosum on the non-diffusion weighted echo-planar images (b = 0) and were then automatically transferred to the corresponding maps to obtain the ADC values. RESULTS: Compared to normal children, individuals with autism had significantly: (1) increased white matter volumes in the right inferior frontal gyrus, the right fusiform gyrus, the left precentral and supplementary motor area and the left hippocampus, (2) increased gray matter volumes in the inferior temporal gyri bilaterally, the right inferior parietal cortex, the right superior occipital lobe and the left superior parietal lobule, and (3) decreased gray matter volumes in the right inferior frontal gyrus and the left supplementary motor area. Abnormally increased ADC values in the bilateral frontal cortex and in the left side of the genu of the corpus callosum were also reported in autism. Finally, age correlated negatively with lobar and callosal ADC measurements in individuals with autism, but not in children with normal development. CONCLUSIONS: These findings suggest cerebral dysconnectivity in the early phases of autism coupled with an altered white matter maturation trajectory during childhood potentially taking place in the frontal and parietal lobes, which may represent a neurodevelopmental marker of the disorder, possibly accounting for the cognitive and social deficits.