A meta-analytical account of the functional lateralization of the reading network.

The observation that the neural correlates of reading are left-lateralized is ubiquitous in the cognitive neuroscience and neuropsychological literature. Still, reading is served by a constellation of neural units, and the extent to which these units are consistently left-lateralized is unclear. In this regard, the functional lateralization of the fusiform gyrus is of particular interest, by virtue of its hypothesized role as a "visual word form area". A quantitative Activation Likelihood Estimation meta-analysis was conducted on activation foci from 35 experiments investigating silent reading, and both a whole-brain and a bayesian ROI-based approach were used to assess the lateralization of the data submitted to meta-analysis. Perirolandic areas showed the highest level of left-lateralization, the fusiform cortex and the parietal cortex exhibited only a moderate pattern of left-lateralization, while in the occipital, insular cortices and in the cerebellum the lateralization turned out to be the lowest observed. The relatively limited functional lateralization of the fusiform gyrus was further explored in a regression analysis on the lateralization profile of each study. The functional lateralization of the fusiform gyrus during reading was positively associated with the lateralization of the precentral and inferior occipital gyri and negatively associated with the lateralization of the triangular portion of the inferior frontal gyrus and of the temporal pole. Overall, the present data highlight how lateralization patterns differ within the reading network. Furthermore, the present data highlight how the functional lateralization of the fusiform gyrus during reading is related to the degree of functional lateralization of other language brain areas.

Sense of agency in schizophrenia: A reconciliation of conflicting findings through a theory-driven literature review.

The sense of agency is the experience of being the author of self-generated actions and their outcomes. Both clinical manifestations and experimental evidence suggest that the agency experience and the mechanisms underlying agency attribution may be dysfunctional in schizophrenia. Yet, studies investigating the sense of agency in these patients show seemingly conflicting results: some indicated under-attribution of self-agency (coherently with certain positive symptoms), while others suggested over-attribution of self-agency. In this review, we assess whether recent theoretical frameworks can reconcile these divergent results. We examine whether the identification of agency abnormalities in schizophrenia might depend on the measure of self-agency considered (depending on the specific task requirements) and the available agency-related cues. We conclude that all these aspects are relevant to predict and characterize the type of agency misattribution that schizophrenia patients might show. We argue that one particular model, based on the predictive coding theory, can reconcile the interpretation of the multifarious phenomenology of agency manifestations in schizophrenia, paving the way for testing agency disorders in novel ways.

Mapping the emotional homunculus with fMRI.

Emotions are commonly associated with bodily sensations, e.g., boiling with anger when overwhelmed with rage. Studies have shown that emotions are related to specific body parts, suggesting that somatotopically organized cortical regions that commonly respond to somatosensory and motor experiences might be involved in the generation of emotions. We used functional magnetic resonance imaging to investigate whether the subjective feelings of emotion are accompanied by the activation of somatotopically defined sensorimotor brain regions, thus aiming to reconstruct an "emotional homunculus." By defining the convergence of the brain activation patterns evoked by self-generated emotions during scanning onto a sensorimotor map created on participants' tactile and motor brain activity, we showed that all the evoked emotions activated parts of this sensorimotor map, yet with considerable overlap among different emotions. Although we could not find a highly specific segmentation of discrete emotions over sensorimotor regions, our results support an embodied experience of emotions.

Trait food craving predicts functional connectivity between dopaminergic midbrain and the fusiform food area during eating imagery.

Neurofunctional coupling between the dopaminergic midbrain (i.e., ventral tegmental area, VTA) and higher-order visual regions may contribute to food craving, leading to the onset or maintenance of obesity. We recently showed that the VTA resting-state functional connectivity with the occipitotemporal cortex, at the level of the fusiform gyrus (FFG), was specifically associated with trait food craving and the implicit bias for food images, suggesting that VTA-FFG connectivity may reflect the association between the visual representations of food and its motivational properties. To further test this hypothesis, this time we studied task-based functional connectivity in twenty-eight healthy-weight participants while imagining eating their most liked high-calorie (HC) or least liked low-calorie food (LC) or drinking water (control condition). Trait food craving scores were used to predict changes in task-based functional connectivity of the VTA during imagery of HC compared to LC foods (relative to the control condition). Trait food craving was positively associated with the functional connectivity of the VTA with the left FFG: people with higher trait food craving scores show stronger VTA-FFG connectivity, specifically for the imagery of the liked HC foods. This association was not linked to the quality of imagery nor to state measures of craving, appetite, or thirst. These findings emphasize the contribution of the functional coupling between dopaminergic midbrain and higher-order visual regions to food craving, suggesting a neurofunctional mechanism by which the mental representations of the HC food we like can become much more salient if not irresistible.

The sense of agency in near and far space.

The sense of agency is the ability to recognize that we are the actors of our actions and their consequences. We explored whether and how spatial cues may modulate the agency experience by manipulating the ecological validity of the experimental setup (real-space or computer-based setup) and the distance of the action-outcome (near or far). We tested 58 healthy adults collecting explicit agency judgments and the perceived time interval between movements and outcomes (to quantify the intentional binding phenomenon, an implicit index of agency). Participants show greater implicit agency for voluntary actions when there is a temporal and spatial action-outcome contingency. Conversely, participants reported similar explicit agency for outcomes appearing in the near and far space. Notably, these effects were independent of the ecological validity of the setting. These results suggest that spatial proximity, realistic or illusory, is essential for feeling implicitly responsible for the consequences of our actions.

Sensory Attenuation Deficit and Auditory Hallucinations in Schizophrenia: A Causal Mechanism or a Risk Factor? Evidence From Meta-Analyses on the N1 Event-Related Potential Component.

BACKGROUND: Sensory attenuation (SA), the dampened perception of self-generated sensory information, is typically associated with reduced event-related potential signals, such as for the N1 component of auditory event-related potentials. SA, together with efficient monitoring of intentions and actions, should facilitate the distinction between self-generated and externally generated sensory events, thereby optimizing interaction with the world. According to many, SA is deficient in schizophrenia. The question arises whether altered SA reflects a sufficient mechanism to explain positive symptoms such as auditory hallucinations. A systematic association of reduced auditory SA in hallucinating patients would support this hypothesis. METHODS: We conducted a series of meta-analyses on 15 studies on auditory SA in which the N1 component of event-related potential-electroencephalogram signals was measured during talking (self-generated sensory signals condition) or when listening to prerecorded vocalizations (externally generated sensory signals condition). RESULTS: We found that individuals with schizophrenia did show some auditory SA because their N1 signal was significantly attenuated in talking conditions compared with listening conditions. However, the magnitude of such attenuation was reduced in individuals with schizophrenia compared to healthy control participants. This phenomenon generalizes independently from the stage of the disease, the severity of positive symptoms, and whether patients have auditory hallucinations or not. CONCLUSIONS: These findings suggest that reduced SA cannot be a sufficient mechanism for explaining positive symptoms such as auditory hallucinations in schizophrenia. Because reduced SA was also present in participants at risk of schizophrenia, reduced SA may represent a risk factor for the disorder. We discuss the implications of these results for clinical-cognitive models of schizophrenia.

Mapping Gilles de la Tourette syndrome through the distress and relief associated with tic-related behaviors: an fMRI study.

Personal distress associated with tic urges or inhibition and relief associated with tic production are defining features of the personal experience in Gilles de la Tourette syndrome (GTS). These affective phenomena have not been studied using fMRI, hindering our understanding of GTS pathophysiology and possible treatments. Here, we present a novel cross-sectional fMRI study designed to map tic-related phenomenology using distress and relief as predicting variables. We adopted a mental imagery approach and dissected the brain activity associated with different phases of tic behaviors, premonitory urges, and the ensuing tic execution or inhibition: these were compared with the mental simulation of "relaxed situations" and pre-determined stereotyped motor behaviors. We then explored whether the ensuing brain patterns correlated with the distress or relief perceived for the different phases of the tasks. Patients experienced a higher level of distress during the imagery of tic-triggering scenarios and no relief during tic inhibition. On the other hand, patients experienced significant relief during tic imagery. Distress during tic-triggering scenarios and relief during tic imagery were significantly correlated. The distress perceived during urges correlated with increased activation in cortical sensorimotor areas, suggesting a motor alarm. Conversely, relief during tic execution was positively associated with the activity of a subcortical network. The activity of the putamen was associated with both distress during urges and relief during tic execution. These findings highlight the importance of assessing the affective component of tic-related phenomenology. Subcortical structures may be causally involved in the affective component of tic pathophysiology, with the putamen playing a central role in both tic urge and generation. We believe that our results can be readily translated into clinical practice for the development of personalized treatment plans tailored to each patient's unique needs.

Neuromodulation of the Left Inferior Frontal Cortex Affects Social Monitoring during Motor Interactions.

Motor interactions require observing and monitoring a partner's performance as the interaction unfolds. Studies in monkeys suggest that this form of social monitoring might be mediated by the activity of the ventral premotor cortex (vPMc), a critical brain region in action observation and motor planning. Our previous fMRI studies in humans showed that the left vPMc is indeed recruited during social monitoring, but its causal role is unexplored. In three experiments, we applied online anodal or cathodal transcranial direct current stimulation over the left lateral frontal cortex during a music-like interactive task to test the hypothesis that neuromodulation of the left vPMc affects participants' performance when a partner violates the agent's expectations. Participants played short musical sequences together with a virtual partner by playing one note each in turn-taking. In 50% of the trials, the partner violated the participant's expectations by generating the correct note through an unexpected movement. During sham stimulation, the partner's unexpected behavior led to a slowdown in the participant's performance (observation-induced posterror slowing). A significant interaction with the stimulation type showed that cathodal and anodal transcranial direct current stimulation induced modulation of the observation-induced posterror slowing in opposite directions by reducing or enhancing it, respectively. Cathodal stimulation significantly reduced the effect compared to sham stimulation. No effect of neuromodulation was found when the partner behaved as expected or when the observed violation occurred within a context that was perceptually matched but noninteractive in nature. These results provide evidence for the critical causal role that the left vPMc might play in social monitoring during motor interactions, possibly through the interplay with other brain regions in the posterior medial frontal cortex.

How images of food become cravingly salient in obesity.

OBJECTIVE: This case-control study was aimed at testing two main hypotheses: (i) obesity is characterized by neurofunctional alterations within the mesocorticolimbic reward system, a brain network originating from the midbrain ventral tegmental area (VTA); and (ii) these alterations are associated with a bias for food-related stimuli and craving. METHODS: Normal-weight individuals and individuals with obesity underwent a resting-state functional magnetic resonance imaging scan and the assessment of impulsivity, food craving, appetite, and implicit bias for food and non-food stimuli. The VTA was used as a seed to map, for each participant, the strength of its functional connections with the rest of the brain. The between-group difference in functional connectivity was then computed, and brain-behavior correlations were performed. RESULTS: Individuals with obesity showed hyper-connectivity of the VTA with part of the ventral occipitotemporal cortex, recently found to be specialized for food images, and hypo-connectivity with the left inferior frontal gyrus, devoted to cognitive control. VTA-ventral occipitotemporal cortex connectivity was positively associated with food craving and food-related bias; the reverse correlation was observed for VTA-inferior frontal gyrus connectivity. CONCLUSIONS: These findings reveal that, in obesity, food-related visual stimuli become cravingly salient through an imbalanced connectivity of the reward system with sensory-specific regions and the frontal cortex involved in cognitive control.

Emergent and planned interpersonal synchronization are both sensitive to 'tempo aftereffect contagion'.

Interpersonal synchronization is fundamental for motor coordination during social interactions. Discerning emergent (entrainment) from planned synchronization represents a non-trivial issue in visually bonded individuals acting together, as well as assessing whether inter-individual differences, e.g., in autistic traits, modulate both types of synchronization. In a visuomotor finger-tapping task, two participants replicated a target tempo either synchronizing ('joint' condition) or not ('non-interactive' condition, 'non-int') with each other. One participant was exposed ('induced') to tempo aftereffect (a medium tempo seems faster or slower after exposure to slower or faster inducing tempi), but not the other participant ('not induced'); thus they had different timing perceptions of the same target. We assessed to what degree emergent and/or planned synchronization affected dyads by analyzing inter-tap-intervals, synchronization indexes, and cross-correlation coefficients. Results revealed a 'tempo aftereffect contagion': inter-tap-intervals of both induced and not-induced participants showed aftereffect in both the joint and non-int conditions. Moreover, aftereffects did not correlate across conditions suggesting they might be due to (at least in part) different processes, but the propensity for tempo aftereffect contagion correlated with individuals' autistic traits only in the non-int condition. Finally, participants co-adjusted their tapping more in the joint condition than in the non-int one, as confirmed by higher synchronization indexes and the mutual adaptation pattern of cross-correlation coefficients. Altogether, these results show the subtle interplay between emergent and planned interpersonal synchronization mechanisms that act on a millisecond timescale independently from synching or not with the partner.

Error observation as a window on performance monitoring in social contexts? A systematic review.

Living in a social world requires social monitoring, i.e., the ability to keep track of others' actions and mistakes. Here, we demonstrate the good reliability of the behavioral and neurophysiological indexes ascribed to social monitoring. We also show that no consensus exists on the cognitive bases of this phenomenology and discuss three alternative hypotheses: (i) the direct matching hypothesis, postulating that observed errors are processed through automatic simulation; (ii) the attentional hypothesis, considering errors as unexpected events that take resources away from task processing; and (iii) the goal representation hypothesis, which weighs social error monitoring depending on how relevant the other's task is to the observer's goals. To date, evidence on the role played by factors that could help to disentangle these hypotheses (e.g., the human vs. non-human nature of the actor, the error rate, and the reward context) is insufficient, although the goal representation hypothesis seems to receive more support. Theory-driven experimental designs are needed to enlighten this debate and clarify the role of error monitoring during interactive exchanges.

Lateralized reading in the healthy brain: A behavioral and computational study on the nature of the visual field effect.

Despite its widespread use to measure functional lateralization of language in healthy subjects, the neurocognitive bases of the visual field effect in lateralized reading are still debated. Crucially, the lack of knowledge on the nature of the visual field effect is accompanied by a lack of knowledge on the relative impact of psycholinguistic factors on its measurement, thus potentially casting doubts on its validity as a functional laterality measure. In this study, an eye-tracking-controlled tachistoscopic lateralized lexical decision task (Experiment 1) was administered to 60 right-handed and 60 left-handed volunteers and word length, orthographic neighborhood, word frequency, and imageability were manipulated. The magnitude of visual field effect was bigger in right-handed than in left-handed participants. Across the whole sample, a visual field-by-frequency interaction was observed, whereby a comparatively smaller effect of word frequency was detected in the left visual field/right hemisphere (LVF/RH) than in the right visual field/left hemisphere (RVF/LH). In a subsequent computational study (Experiment 2), efficient (LH) and inefficient (RH) activation of lexical orthographic nodes was modelled by means of the Naïve Discriminative Learning approach. Computational data simulated the effect of visual field and its interaction with frequency observed in the Experiment 1. Data suggest that the visual field effect can be biased by word frequency. Less distinctive connections between orthographic cues and lexical/semantic output units in the RH than in the LH can account for the emergence of the visual field effect and its interaction with word frequency.

When action prediction grows old: An fMRI study.

Predicting the unfolding of others' actions (action prediction) is crucial for successfully navigating the social world and interacting efficiently. Age-related changes in this domain have remained largely unexplored, especially for predictions regarding simple gestures and independent of contextual information or motor expertise. Here, we evaluated whether healthy aging impacts the neurophysiological processes recruited to anticipate, from the observation of implied-motion postures, the correct conclusion of simple grasping and pointing actions. A color-discrimination task served as a control condition to assess the specificity of the age-related effects. Older adults showed reduced efficiency in performance that was yet not specific to the action prediction task. Nevertheless, fMRI results revealed task-specific age-related differences: while both groups showed stronger recruitment of the lateral occipito-temporal cortex bilaterally during the action prediction than the control task, the younger participants additionally showed a higher bilateral engagement of parietal regions. Importantly, in both groups, the recruitment of visuo-motor processes in the right posterior parietal cortex was a predictor of good performance. These results support the hypothesis of decreased involvement of sensorimotor processes in cognitive tasks when processing action- and body-related stimuli in healthy aging. These results have implications for social interaction, which requires the fast reading of others' gestures.

Neural structural abnormalities behind altered brain activation in obesity: Evidence from meta-analyses of brain activation and morphometric data.

Obesity represents a risk factor for disability with a major bearing on life expectancy. Neuroimaging techniques are contributing to clarify its neurobiological underpinnings. Here, we explored whether structural brain abnormalities might accompany altered brain activations in obesity. We combined and compared data from brain activation studies for food stimuli and the data reported in structural voxel-based morphometry studies. We found that obese individuals have reduced grey matter density and functional activations in the thalamus and midbrain. A functional connectivity analysis based on these two clusters and its quantitative decoding showed that these regions are part of the reward system functional brain network. Moreover, we found specific grey matter hypo-densities in prefrontal cortex for the obese subjects, regions involved in controlled behaviour. These results support theories of obesity that point to reduced bottom-up reward processes (i.e., the Reward Deficit Theory), but also top-down theories postulating a deficit in cognitive control (i.e., the Inhibitory Control Deficit Theory). The same results also warrant a more systematic exploration of obesity whereby the reward of food and the intentional control over consummatory behaviour is manipulated.

Imaging the neural underpinnings of freezing of gait in Parkinson's disease.

Freezing of gait (FoG) is a paroxysmal and sporadic gait impairment that severely affects PD patients' quality of life. This review summarizes current neuroimaging investigations that characterize the neural underpinnings of FoG in PD. The review presents and discusses the latest advances across multiple methodological domains that shed light on structural correlates, connectivity changes, and activation patterns associated with the different pathophysiological models of FoG in PD. Resting-state fMRI studies mainly report cortico-striatal decoupling and disruptions in connectivity along the dorsal stream of visuomotor processing, thus supporting the 'interference' and the 'perceptual dysfunction' models of FoG. Task-based MRI studies employing virtual reality and motor imagery paradigms reveal a disruption in functional connectivity between cortical and subcortical regions and an increased recruitment of parieto-occipital regions, thus corroborating the 'interference' and 'perceptual dysfunction' models of FoG. The main findings of fNIRS studies of actual gait primarily reveal increased recruitment of frontal areas during gait, supporting the 'executive dysfunction' model of FoG. Finally, we discuss how identifying the neural substrates of FoG may open new avenues to develop efficient treatment strategies.

The unexplored link between aesthetic perception and creativity: A theory-driven meta-analysis of fMRI studies in the visual domain.

Creative production (related to art-making) and aesthetic appreciation (related to art-viewing) are inherently linked in visual arts, but their relationship has never been explored explicitly in cognitive neuroscience, nor the nature of such connection. The available literature suggests two cognitive processes as possible foundations of these two experiences: motor simulation or inhibitory control. In a meta-analysis of fMRI studies, we addressed this issue: we investigated whether there are shared neurofunctional underpinnings behind aesthetic and creative experiences in the visual domain; further, we examined whether any shared brain activation may reflect either motor simulation or inhibitory processes. A conjunction analysis revealed a common involvement of the pre-SMA in both classes of studies, a brain region, if anything, more concerned with top-down inhibitory motor and volitional cognitive control rather than bottom-up motor simulation. In the art-viewing domain, this finding was primarily driven by figurative rather than abstract art. The methodological limitations in the available literature are discussed together with possible new ways to expand the existing findings.

How shared goals shape action monitoring.

Cooperation triggers expectations on our partners' contributions to achieve a common goal. A partner, however, may sometimes violate such expectations, driving us to perform immediate adjustments. What neurophysiological mechanisms support these adaptations? We tested the hypothesis of an interaction-specific brain system that can decode a partner's error and promote adaptive responses when cooperating toward a shared goal. During functional magnetic resonance imaging, the participants played short melodies with a virtual partner by performing one note each in turn-taking. A colored cue indicated which melody they had to execute at each trial, thus generating expectations on what notes the partner would play. The participants also performed the task in a perceptually matched Non-Interactive context. The results showed that task interactivity modulates the brain responses to a partner's error in dorsal fronto-temporoparietal and medial cingulo-opercular networks. Multivariate pattern analysis revealed that these neural activations reflect deep decoding of the partner's mistake. Within these networks, the automatic tendency to correct the partner's errors, as indexed by specific reaction times adaptations, depended on the activity of a right-lateralized fronto-opercular system that may enable mutual support during real-life cooperation. Future studies may unveil the role of this putative "interaction monitoring" brain system in social dysfunctions and their motor foundations.

The sense of agency in joint actions: A theory-driven meta-analysis.

The sense of agency is the feeling of voluntarily controlling our actions and their effects. It represents a crucial component of self-awareness, and it is foundational to our perception of responsibility toward what we do as individuals acting in a social context. While the sense of agency has been widely investigated in individual contexts, much less is known about the agency experienced when subjects are involved in motor interactions, despite its relevance in the social domain. To fill this gap, here we review the literature on the sense of agency experienced during motor interactions. We aimed to test the reliability of this sense of joint agency across studies and define what features can modulate its explicit and implicit components. To this end, we performed a formal meta-analysis of studies investigating the implicit feeling of agency in joint actions and a systematic review of studies addressing explicit judgments of agency during motor interactions. Our review indicates that, during interactions, a sense of agency can also be experienced for the partner's actions, both at an implicit and explicit level, and that this possibility strongly depends on predictive sensorimotor mechanisms. Contextual cues play a crucial role too, but mainly on explicit agency judgments, while they do not affect the implicit feeling of agency. These results are discussed in light of current cognitive theories on motor awareness and motor interactions. We also propose a hierarchical model based on recursive predictive and comparative processes whereby the sense of joint agency is grounded on a weighted combination of sensorimotor and contextual cues. Finally, we discuss how this model may provide a framework for future research in the social and clinical domains.

Attention to body parts prompts thermoregulatory reactions in Body Integrity Dysphoria.

In healthy subjects, the transient perturbation of body part ownership is accompanied by regional skin temperature decrease. This observation leaves an open question about a possible body part-specific thermoregulatory response in pathological conditions, in which the sense of ownership over that body part is altered. For instance, Body Integrity Dysphoria (BID), a poorly understood neuropsychiatric disorder, is characterised by the non-acceptance of one or more of one's extremities. This unsettling feeling pervasively captures the individuals' attention towards the unwanted limb. Previous studies characterised BID in terms of absent ownership feeling with preserved ownership judgment. We explored for the first time whether this altered feeling is also associated with a specific thermoregulatory response. We recorded thermal image sequences of circumscribed regions of the limbs' skin in seven individuals with BID desiring to remove one leg while they were invited to focus their attention toward one particular limb (arm or leg). Their event-related thermoregulatory pattern was compared to a group of healthy matched controls. In individuals with BID but not in control persons, we found a bilateral decrease in leg temperature when focusing their attention on either the unwanted or accepted leg. The event-related thermoregulatory response for both upper limbs was similar between individuals with BID and healthy controls. Our results suggest that the alteration of the sense of body ownership in neuropsychiatric conditions such as BID may critically rest on specific event-related thermoregulatory patterns in response to modulation of attention to body parts.