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Summary: 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.

Abstract 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.

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.

Many aspects of neuronal control degrade with ageing, including motor control. Using a meta-analysis of functional MRI images, it is made apparent that the ageing brain relies more on visual strategies than sensory stimuli to maintain motor function.

Abstract What is the key to successful interaction? Is it sufficient to represent a common goal, or does the way our partner achieves that goal count as well? How do we react when our partner misbehaves? We used a turn-taking music-like task requiring participants to play sequences of notes together with a partner, and we investigated how people adapt to a partner’s error that violates their expectations. Errors consisted of either playing a wrong note of a sequence that the agents were playing together (thus preventing the achievement of the joint goal) or playing the expected note with an unexpected action. In both cases, we found post-error slowing and inaccuracy suggesting the participants’ implicit tendency to correct the partner’s error and produce the action that the partner should have done. We argue that these “joint” monitoring processes depend on the motor predictions made within a (dyadic) motor plan and may represent a basic mechanism for mutual support in motor interactions.

Abstract Since the recruitment process, Italian Mafias impose on their members a strict code of conduct. These rigid rules regulate their private and public behavior, implying a total adhesion to the group’s values. Such juridical and social aspects substantially distinguish organized crime (OC) from ordinary crime. It is still unknown whether these two categories of offenders also show distinctive cognitive traits. Here we investigated the frontal lobe cognitive functions of 50 OC prisoners from the Mafia and 50 non-OC prisoners based on the performance of 50 non-prisoner controls. We found that OC members were more likely to show pathological risk-propensity than non-OC prisoners. We interpret this finding as the result of the internal dynamics of Mafia groups. OC is a worldwide threat, and the identification of cognitive traits behind criminal behavior will help in devising focused prevention policies.

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.

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.

An accurate prognosis on the outcome of brain-injured patients with disorders of consciousness (DOC) remains a significant challenge, especially in the acute stage. In this study, we applied a multiple-technique approach to provide accurate predictions on functional outcome after 6 months in 15 acute DOC patients. Electrophysiological correlates of implicit cognitive processing of verbal stimuli and data-driven voxel-wise resting-state fMRI signals, such as the fractional amplitude of low-frequency fluctuations (fALFF), were employed. Event-related electrodermal activity, an index of autonomic activation, was recorded in response to emotional words and pseudo-words at baseline (T0). On the same day, patients also underwent a resting-state fMRI scan. Six months later (T1), patients were classified as outcome-negative and outcome-positive using a standard functional outcome scale. We then revisited the baseline measures to test their predictive power for the functional outcome measured at T1. We found that only outcome-positive patients had an earlier, higher autonomic response for words compared to pseudo-words, a pattern similar to that of healthy awake controls. Furthermore, DOC patients showed reduced fALFF in the posterior cingulate cortex (PCC), a brain region that contributes to autonomic regulation and awareness. The event-related electrodermal marker of residual cognitive functioning was found to have a significant correlation with residual local neuronal activity in the PCC. We propose that a residual autonomic response to cognitively salient stimuli, together with a preserved resting-state activity in the PCC, can provide a useful prognostic index in acute DOC.

It is widely believed that intensive music training can boost cognitive and visuo-motor skills. However, this evidence is primarily based on retrospective studies; this makes it difficult to determine whether a cognitive advantage is caused by the intensive music training, or it is instead a factor influencing the choice of starting a music curriculum. To address these issues in a highly ecological setting, we tested longitudinally 128 students of a Middle School in Milan, at the beginning of the first class and, 1 year later, at the beginning of the second class. 72 students belonged to a Music curriculum (30 with previous music experience and 42 without) and 56 belonged to a Standard curriculum (44 with prior music experience and 12 without). Using a Principal Component Analysis, all the cognitive measures were grouped in four high-order factors, reflecting (a) General Cognitive Abilities, (b) Speed of Linguistic Elaboration, (c) Accuracy in Reading and Memory tests, and (d) Visuospatial and numerical skills. The longitudinal comparison of the four groups of students revealed that students from the Music curriculum had better performance in tests tackling General Cognitive Abilities, Visuospatial skills, and Accuracy in Reading and Memory tests. However, there were no significant curriculum-by-time interactions. Finally, the decision to have a musical experience before entering middle school was more likely to occur when the cultural background of the families was a high one. We conclude that a combination of family-related variables, early music experience, and pre-existent cognitive make-up is a likely explanation for the decision to enter a music curriculum at middle school.

Abstract Introduction Patients affected by the behavioral variant frontotemporal dementia (bvFTD) frequently experience, at a delayed onset, abnormal eating behavior involving increased food intake. Although delusional food‐related symptoms have attracted much attention, the behavioral and neural features of food aversion manifestations in bvFTD remain poorly documented. Methods We describe the rare case of a patient with bvFTD presenting with lack of interoception for swallowing and digestion, coupled with a dramatic food aversion at onset. We also compared his MRI scan to 84 healthy individuals using a voxel‐based morphometry approach. Results We found gray matter density reductions involving the postcentral gyrus bilaterally, insulae, and right medial orbitofrontal cortex. Discussion Our results shed new light on the behavioral and neuroanatomical features of food aversion and interoception deficits in bvFTD, suggesting that besides orbitofrontal cortex, also a distributed system associated with interoception might play a role in such behavioral manifestation.

Studies on athletes or neurological patients with motor disorders have shown a close link between motor experience and motor imagery skills. Here we evaluated whether a functional limitation due to a musculoskeletal disorder has an impact on the ability to mentally rehearse the motor patterns of walking, an overlearned and highly automatic behaviour. We assessed the behavioural performance (measured through mental chronometry tasks) and the neural signatures of motor imagery of gait in patients with chronic knee arthrosis and in age-matched, healthy controls. During fMRI, participants observed (i) stationary or (ii) moving videos of a path in a park shown in the first-person perspective: they were asked to imagine themselves (i) standing on or (ii) walking along the path, as if the camera were “their own eyes” (gait imagery (GI) task). In half of the trials, participants performed a dynamic gait imagery (DGI) task by combining foot movements with GI. Behavioural tests revealed a lower degree of isochrony between imagined and performed walking in the patients, indicating impairment in the ability to mentally rehearse gait motor patterns. Moreover, fMRI showed widespread hypoactivation during GI in motor planning (premotor and parietal) brain regions, the brainstem, and the cerebellum. Crucially, the performance of DGI had a modulatory effect on the patients and enhanced activation of the posterior parietal, brainstem, and cerebellar regions that the healthy controls recruited during the GI task. These findings show that functional limitations of peripheral origin may impact on gait motor representations, providing a rationale for cognitive rehabilitation protocols in patients with gait disorders of orthopaedic nature. The DGI task may be a suitable tool in this respect. Keywords: Gait, Orthopaedic patients, Motor imagery, fMRI

Body integrity dysphoria (BID), a long-lasting desire for the amputation of physically healthy limbs, is associated with reduced fMRI resting-state functional connectivity of somatosensory cortices. Here, we used fMRI to evaluate whether these findings could be replicated and expanded using a task-based paradigm. We measured brain activations during somatosensory stimulation and motor tasks for each of the four limbs in ten individuals with a life-long desire for the amputation of the left leg and fourteen controls. For the left leg, BID individuals had reduced brain activation in the right superior parietal lobule for somatosensory stimulation and in the right paracentral lobule for the motor task, areas where we previously found reduced resting-state functional connectivity. In addition, for somatosensory stimulation only, we found a robust reduction in activation of somatosensory areas SII bilaterally, mostly regardless of the stimulated body part. Areas SII were regions of convergent activations for signals from all four limbs in controls to a significantly greater extent than in subjects with BID. We conclude that BID is associated with altered integration of somatosensory and, to a lesser extent, motor signals, involving limb-specific cortical maps and brain regions where the first integration of body-related signals is achieved through convergence.

English serves as today’s lingua franca, a role not eased by the inconsistency of its orthography. Indeed, monolingual readers of more consistent orthographies such as Italian or German learn to read more quickly than monolingual English readers. Here, we assessed whether long-lasting bilingualism would mitigate orthography-specific differences in reading speed and whether the order in which orthographies with a different regularity are learned matters. We studied high-proficiency Italian-English and English-Italian bilinguals, with at least 20 years of intensive daily exposure to the second language and its orthography and we simulated sequential learning of the two orthographies with the CDP++ connectionist model of reading. We found that group differences in reading speed were comparatively bigger with Italian stimuli than with English stimuli. Furthermore, only Italian bilinguals took advantage of a blocked presentation of Italian stimuli compared to when stimuli from both languages were presented in mixed order, suggesting a greater ability to keep language-specific orthographic representations segregated. These findings demonstrate orthographic constraints on bilingual reading, whereby the level of consistency of the first learned orthography affects later learning and performance on a second orthography. The computer simulations were consistent with these conclusions.

In this paper we describe and validate a new coordinate-based method for meta-analysis of neuroimaging data based on an optimized hierarchical clustering algorithm: CluB (Clustering the Brain). The CluB toolbox permits both to extract a set of spatially coherent clusters of activations from a database of stereotactic coordinates, and to explore each single cluster of activation for its composition according to the cognitive dimensions of interest. This last step, called “cluster composition analysis,” permits to explore neurocognitive effects by adopting a factorial-design logic and by testing the working hypotheses using either asymptotic tests, or exact tests either in a classic inference, or in a Bayesian-like context. To perform our validation study, we selected the fMRI data from 24 normal controls involved in a reading task. We run a standard random-effects second level group analysis to obtain a “Gold Standard” of reference. In a second step, the subject-specific reading effects (i.e., the linear t-contrast “reading > baseline”) were extracted to obtain a coordinates-based database that was used to run a meta-analysis using both CluB and the popular Activation Likelihood Estimation method implemented in the software GingerALE. The results of the two meta-analyses were compared against the “Gold Standard” to compute performance measures, i.e., sensitivity, specificity, and accuracy. The GingerALE method obtained a high level of accuracy (0.967) associated with a high sensitivity (0.728) and specificity (0.971). The CluB method obtained a similar level of accuracy (0.956) and specificity (0.969), notwithstanding a lower level of sensitivity (0.14) due to the lack of prior Gaussian transformation of the data. Finally, the two methods obtained a good-level of concordance (AC1 = 0.93). These results suggested that methods based on hierarchical clustering (and post-hoc statistics) and methods requiring prior Gaussian transformation of the data can be used as complementary tools, with the GingerALE method being optimal for neurofunctional mapping of pooled data according to simpler designs, and the CluB method being preferable to test more specific, and localized, neurocognitive hypotheses according to factorial designs.

Voluntary actions can be fractionated in different phenomena: from the emergence of intentions and the ensuing motor plans and actions, to the anticipation and monitoring of their outcomes, to the appreciation of their congruency with intentions and to the eventual emergence of a sense of agency. It follows that motor intention and the sense of agency should occur at different stages in the normal generation of willed actions. Both these processes have been associated with a fronto-parietal motor network, but no study has investigated to what extent the two experiences can be dissociated for the brain regions involved. To this end, we assessed the PET/fMRI literature on agency and intentionality using a meta-analytic technique based on a hierarchical clustering algorithm. Beside a shared brain network involving the meso-frontal and prefrontal regions, the middle insula and subcortical structures, we found that motor intention and the sense of agency are functionally underpinned by separable sets of brain regions: an “intentionality network,” involving the rostral area of the mesial frontal cortex (middle cingulum and pre-supplementary motor area), the anterior insula and the parietal lobules, and a “self-agency network,” which involves the posterior areas of the mesial frontal cortex (the SMA proper), the posterior insula, the occipital lobe and the cerebellum. We were then able to confirm this functional organization by a subsequent seed-based fMRI resting-state functional connectivity analysis, with seeds derived from the intentionality/sense of agency specific clusters of the medial wall of the frontal lobe. Our results suggest the existence of a rostro-caudal gradient within the mesial frontal cortex, with the more anterior regions linked to the concept of motor intentionality and the brain areas located more posteriorly associated with the direct monitoring between the action and its outcome. This suggestion is reinforced by the association between the sense of agency and the activation of the occipital lobes, to suggest a direct comparison between the movement and its external (e.g., visual) consequences. The shared network may be important for the integration of intentionality and agency in a coherent appreciation of self-generated actions.

Motor imagery (M.I.) training has been widely used to enhance motor behavior. To characterize the neural foundations of its rehabilitative effects in a pathological population we studied twenty-two patients with rhizarthrosis, a chronic degenerative articular disease in which thumb-to-fingers opposition becomes difficult due to increasing pain while the brain is typically intact. Before and after surgery, patients underwent behavioral tests to measure pain and motor performance and fMRI measurements of brain motor activity.After surgery, the affected hand was immobilized, and patients were enrolled in a M.I. training. The sample was split in those who had a high compliance with the program of scheduled exercises (T+, average compliance: 84%) and those with low compliance (T−, average compliance: 20%; cut-off point: 55%). We found that more intense M.I. training counteracts the adverse effects of immobilization reducing pain and expediting motor recovery. fMRI data from the post-surgery session showed that T+ patients had decreased brain activation in the premotor cortex and the supplementary motor area (SMA); meanwhile, for the same movements, the T− patients exhibited a reversed pattern. Furthermore, in the post-surgery fMRI session, pain intensity was correlated with activity in the ipsilateral precentral gyrus and, notably, in the insular cortex, a node of the pain matrix.These findings indicate that the motor simulations of M.I. have a facilitative effect on recovery by cortical plasticity mechanisms and optimization of motor control, thereby establishing the rationale for incorporating the systematic use of M.I. into standard rehabilitation for the management of post-immobilization syndromes characteristic of hand surgery. Keywords: Mental imagery training, Trapeziometacarpal joint osteoarthritis, Rhizarthrosis, Brain plasticity

Cognitive skills are the emergent property of distributed neural networks. The distributed nature of these networks does not necessarily imply a lack of specialization of the individual brain structures involved. However, it remains questionable whether discrete aspects of high-level behavior might be the result of localized brain activity of individual nodes within such networks. The phonological loop of working memory, with its simplicity, seems ideally suited for testing this possibility. Central to the development of the phonological loop model has been the description of patients with focal lesions and specific deficits. As much as the detailed description of their behavior has served to refine the phonological loop model, a classical anatomoclinical correlation approach with such cases falls short in telling whether the observed behavior is based on the functions of a neural system resembling that seen in normal subjects challenged with phonological loop tasks or whether different systems have taken over. This is a crucial issue for the cross correlation of normal cognition, normal physiology, and cognitive neuropsychology. Here we describe the functional anatomical patterns of JB, a historical patient originally described by Warrington et al. (1971), a patient with a left temporo-parietal lesion and selective short phonological store deficit. JB was studied with the H215O PET activation technique during a rhyming task, which primarily depends on the rehearsal system of the phonological loop. No residual function was observed in the left temporo-parietal junction, a region previously associated with the phonological buffer of working memory. However, Broca's area, the major counterpart of the rehearsal system, was the major site of activation during the rhyming task. Specific and autonomous activation of Broca's area in the absence of afferent inputs from the other major anatomical component of the phonological loop shows that a certain degree of functional independence or modularity exists in this distributed anatomical-cognitive system.

In their attempt to define discrete subcomponents of intentionality, Brass and Haggard (2008) proposed their What, When, and Whether model (www-model) which postulates that the content, the timing and the possibility of generating an action can be partially independent both at the cognitive level and at the level of their neural implementation. The original proposal was based on a limited number of studies, which were reviewed with a discursive approach. To assess whether the model stands in front of the more recently published data, we performed a systematic review of the literature with a meta-analytic method based on a hierarchical clustering (HC) algorithm. We identified 15 PET/fMRI studies well-suited for this quest. HC revealed the existence of a rostro-caudal gradient within the medial prefrontal cortex, with the more anterior regions (the anterior cingulum) involved in more abstract decisions of whether to execute an action and the more posterior ones (the middle cingulum or the SMA) recruited in specifying the content and the timing components of actions. However, in contrast with the original www-model, this dissociation involves also brain regions well outside the median wall of the frontal lobe, in a component specific manner: the supramarginal gyrus for the what component, the pallidum and the thalamus for the when component, the putamen and the insula for the whether component. We then calculated co-activation maps on the three component-specific www clusters of the medial wall of the frontal/limbic lobe: to this end, we used the activation likelihood approach that we applied on the imaging studies on action contained in the BrainMap.org database. This analysis confirmed the main findings of the HC analyses. However, the BrainMap.org data analyses also showed that the aforementioned segregations are generated by paradigms in which subjects act in response to conditional stimuli rather than while driven by their own intentions. We conclude that the available data confirm that the neural underpinnings of intentionality can be fractionated in discrete components that are partially independent. We also suggest that intentionality manifests itself in discrete components through the boosting of general purpose action-related regions specialized for different aspects of action selection and inhibition.

We explored the neuropsychological and neuromorphometrical differences between probable Alzheimer's disease patients showing a good or a bad response to nine months treatment with donepezil. Before treatment, the neuropsychological profile of the two patient groups was perfectly matched. By the ninth month after treatment, the BAD-responders showed a decline of the MMSE score together with a progressive impairment of executive functions. A voxel-based morphometry investigation (VBM), at the time of the second neuropsychological assessment, showed that the BAD-responders had larger grey and white matter atrophies involving the substantia innominata of Meynert bilaterally, the ventral part of caudate nuclei and the left uncinate fasciculus, brain areas belonging to the cholinergic pathways. A more widespread degeneration of the central cholinergic pathways may explain the lack of donepezil efficacy in those patients not responding to a treatment that operates on the grounds that some degree of endogeneous release of acetylcholine is still available.

Introduction: According to the dual-route model, a printed string of letters can be processed through either a grapheme-to-phoneme conversion route or a lexical-semantic route. While meta-analyses of the imaging literature (Cattinelli, Borghese, Gallucci, & Paulesu, 2013; Taylor, Rastle, & Davis, 2012) have supported distinct and interacting procedures, individual neuroimaging studies exploring such neural correlates by means of reading, phonological and semantic tasks yielded results that remain not conclusive. Aims: To investigate the neural correlates of the lexical and sublexical reading procedures, we used a frame-manipulation paradigm whereby subjects read disyllabic Italian words embedded in lists of either irregular words, inducing lexical processing of the target words, or pseudowords, inducing sublexical reading processing of the target words. Possible linguistic confounders as word frequency, phonological complexity, orthographic neighborhood size and imageability were thus perfectly controlled. Methods: Thirty-three university subjects participated in the behavioral study and 22 were included in the fMRI study. Two reading tasks were created: in a first task, disyllabic word targets were embedded in filler lists (frames) formed of either loanwords or pseudowords, while, in the second task, disyllabic word targets were embedded in filler lists made of either trisyllabic words or pseudowords with a consonant-vowel structure. Moreover, at behavioral level, all subjects read a list of disyllabic target words (block condition). From fMRI data, we extracted: a) the lexical effect, computed as the activation pattern in the loanword frame and in the trisyllabic-word frame, while excluding areas showing the weakest trend for activation in the sublexical condition; b) the sublexical effect, computed as the activation pattern in the pseudoword frame, once weakest trend for activation in the lexical frame was excluded. It is worth emphasizing that the BOLD signal analyzed was always for reading real disyllabic words dispersed (40%) in the two different frames. Results and discussion: A significant main effect of the list condition emerged from behavioral data: participants were faster when reading disyllabic words embedded in a lexical frame than when reading targets embedded in a sublexical frame. Moreover, participants were faster when reading targets in a block condition than in either the lexical or the sublexical frame. Anatomofunctional results (Figure 1) showed that the left occipital, the anterior and posterior temporal regions, and the left intraparietal sulcus were specifically activated when reading targets in a lexical frame. The left posterior inferior temporal and inferior parietal regions were activated in sublexical condition. Finally, reading along the two routes commonly activated the Visual Word Form Area, the premotor cortex, the left frontal areas and the left SMA, suggesting an involvement of these regions in early-input (early orthographic processing) and late-output processes (phonological output buffer and articulatory programming). Conclusions: These results represent a new fine-grained description of the neurofunctional correlates of the dual route model partially supporting the recent anatomical investigations in patients with specific forms of acquired dyslexia (Ripamonti, Aggujaro, Molteni, Zonca, Ghirardi, & Luzzatti, 2014).