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.

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.

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.

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.

Repetitive deep TMS for the reduction of body weight: Bimodal effect on the functional brain connectivity in "diabesity".

BACKGROUND AND AIMS: Deep repetitive Transcranial Magnetic Stimulation (deep rTMS) over the bilateral insula and prefrontal cortex (PFC) can promote weight-loss in obesity, preventing cardiometabolic complications as Type 2 Diabetes (T2D). To investigate the changes in the functional brain integration after dTMS, we conducted a resting-state functional connectivity (rsFC) study in obesity. METHODS AND RESULTS: This preliminary study was designed as a randomized, double-blind, sham-controlled study: 9 participants were treated with high-frequency stimulation (realTMS group), 8 were sham-treated (shamTMS group). Out of the 17 enrolled patients, 6 were affected by T2D. Resting-state fMRI scans were acquired at baseline (T0) and after the 5-week intervention (T1). Body weight was measured at three time points [T0, T1, 1-month follow-up visit (FU1)]. A mixed-model analysis showed a significant group-by-time interaction for body weight (p = .04), with a significant decrease (p < .001) in the realTMS group. The rsFC data revealed a significant increase of degree centrality for the realTMS group in the medial orbitofrontal cortex (mOFC) and a significant decrease in the occipital pole. CONCLUSION: An increase of whole-brain functional connections of the mOFC, together with the decrease of whole-brain functional connections with the occipital pole, may reflect a brain mechanism behind weight-loss through a diminished reactivity to bottom-up visual-sensory processes in favor of increased reliance on top-down decision-making processes. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT03009695.

Clinical Characterization of Atypical Primary Progressive Aphasia in a 3-Year Longitudinal Study: A Case Report.

The logopenic variant of primary progressive aphasia (lvPPA) is the most recent variant of primary progressive aphasia (PPA) to be identified; thus far, it has been poorly investigated. Despite being typically associated with Alzheimer disease (AD), lvPPA has recently been linked to frontotemporal lobe degeneration (FTLD), with distinctive cognitive and neural features that are worthy of further investigation. Here, we describe the neuropsychological and linguistic profile, as well as cerebral abnormalities, of an individual exhibiting PPA and carrying a pathogenetic variant in the GRN gene, from a 3-year longitudinal perspective. The individual's initial profile resembled lvPPA because it was characterized by word-finding difficulties and phonological errors in spontaneous speech in addition to sentence repetition and phonological short-term memory impairments. The individual's structural and metabolic imaging data demonstrated left temporal and bilateral frontal atrophy and hypometabolism, respectively. On follow-up, as the pathology progressed, dysprosody, stereotypical speech patterns, agrammatism, and orofacial apraxia appeared, suggesting an overlap with the nonfluent variant of PPA (nfvPPA). Severe sentence comprehension impairment also became evident. Our longitudinal and multidisciplinary diagnostic approach allowed us to better characterize the progression of a GRN-positive lvPPA profile, providing neuropsychological and imaging indicators that might be helpful to improve classification between different PPA variants and to address a nosological issue. Finally, we discuss the importance of early diagnosis of PPA given the possible overlap between different PPA variants during the progression of the pathology.

Dissecting the neurofunctional bases of intentional action.

Here we challenge and present evidence that expands the what, when, and whether anatomical model of intentional action, which states that internally driven decisions about the content and timing of our actions and about whether to act at all depend on separable neural systems, anatomically segregated along the medial wall of the frontal lobe. In our fMRI event-related paradigm, subjects acted following conditional cues or following their intentions. The content of the actions, their timing, or their very occurrence were the variables investigated, together with the modulating factor of intentionality. Besides a shared activation of the pre-supplementary motor area (pre-SMA) and anterior cingulate cortex (ACC) for all components and the SMA proper for the when component, we found specific activations beyond the mesial prefrontal wall involving the parietal cortex for the what component or subcortical gray structures for the when component. Moreover, we found behavioral, functional, anatomical, and brain connectivity evidence that the self-driven decisions on whether to act require a higher interhemispheric cooperation: This was indexed by a specific activation of the corpus callosum whereby the less the callosal activation, the greater was the decision cost at the time of the action in the whether trials. Furthermore, tractography confirmed that the fibers passing through the callosal focus of activation connect the two sides of the frontal lobes involved in intentional trials. This is evidence of non-unitary neural foundations for the processes involved in intentional actions with the pre-SMA/ACC operating as an intentional hub. These findings may guide the exploration of specific instances of disturbed intentionality.

Building the bodily self-awareness: Evidence for the convergence between interoceptive and exteroceptive information in a multilevel kernel density analysis study.

Exteroceptive and interoceptive signals shape and sustain the bodily self-awareness. The existence of a set of brain areas, supporting the integration of information coming from the inside and the outside of the body in building the sense of bodily self-awareness has been postulated, yet the evidence remains limited, a matter of discussion never assessed quantitatively. With the aim of unrevealing where in the brain interoceptive and exteroceptive signals may converge, we performed a meta-analysis on imaging studies of the sense of body ownership, modulated by external visuotactile stimulation, and studies on interoception, which involves the self-awareness for internal bodily sensations. Using a multilevel kernel density analysis, we found that processing of stimuli of the two domains converges primarily in the supramarginal gyrus bilaterally. Furthermore, we found a right-lateralized set of areas, including the precentral and postcentral, and superior temporal gyri. We discuss these results and propose this set of areas as ideal candidates to match multiple body-related signals contributing to the creation of a multidimensional representation of the bodily self.

Eyes wide shut: How visual cues affect brain patterns of simulated gait.

In the last 20 years, motor imagery (MI) has been extensively used to train motor abilities in sport and in rehabilitation. However, MI procedures are not all alike as much as their potential beneficiaries. Here we assessed whether the addition of visual cues could make MI performance more comparable with explicit motor performance in gait tasks. With fMRI we also explored the neural correlates of these experimental manipulations. We did this in elderly subjects who are known to rely less on kinesthetic information while favoring visual strategies during motor performance. Contrary to expectations, we found that the temporal coupling between execution and imagery times, an index of the quality of MI, was less precise when participants were allowed to visually explore the environment. While the brain activation patterns of the gait motor circuits were very similar in both an open-eyed and eye-shut virtual walking MI task, these differed for a vast temporo-occipito-parietal additional activation for open-eyed MI. Crucially, the higher was the activity in this posterior network, the less accurate was the MI performance with eyes open at a clinical test of gait. We conclude that both visually-cued and internally-cued MI are associated with the neurofunctional activation of a gait specific motor system. The less precise behavioral coupling between imagined and executed gait while keeping eyes open may be attributed to the processing load implied in visual monitoring and scanning of the environment. The implications of these observations for rehabilitation of gait with MI are discussed.

How aging affects the premotor control of lower limb movements in simulated gait.

Gait control becomes more demanding in healthy older adults, yet what cognitive or motor process leads to this age-related change is unknown. The present study aimed to investigate whether it might depend on specific decay in the quality of gait motor representation and/or a more general reduction in the efficiency of lower limb motor control. Younger and older healthy participants performed in fMRI a virtual walking paradigm that combines motor imagery (MI) of walking and standing on the spot with the presence (Dynamic Motor Imagery condition, DMI) or absence (pure MI condition) of overtly executed ankle dorsiflexion. Gait imagery was aided by the concomitant observation of moving videos simulating a stroll in the park from a first-person perspective. Behaviorally, older participants showed no sign of evident depletion in the quality of gait motor representations, and absence of between-group differences in the neural correlates of MI. However, while younger participants showed increased frontoparietal activity during DMI, older participants displayed stronger activation of premotor areas when controlling the pure execution of ankle dorsiflexion, regardless of the imagery task. These data suggest that reduced automaticity of lower limb motor control in healthy older subjects leads to the recruitment of additional premotor resources even in the absence of basic gait functional disabilities.

A Breakdown of Imagined Visuomotor Transformations and Its Neural Correlates in Young Elderly Subjects.

Several studies have shown age-related changes in motor imagery (MI) in older adults and the associated compensatory brain activation patterns; most of these studies have used explicit MI tasks or implicit MI tasks focused on mental rotation of body parts. Here, we address the effect of ageing on MI for the more complex visuomotor transformations entailed by mentally simulated hand-tool interactions triggered by a grip selection task (GST) for tools used in daily life. We studied 22 young and 22 elderly subjects performing the GST, in which they were asked to report whether they would grip a portrayed tool with an overhand or an underhand grip. We found a behavioral decline in the elderly group, accompanied by reduced activations of the left posterior parietal lobule, in a subregion associated specifically with reaching behavior by previous investigations. No differences were observed in the temporal cortices associated with object semantics. These results suggested a specific age-related vulnerability of the neural substrates, particularly for the imaginary reaching component of the task, rather than for the semantically driven grasping component. The combination of behavioral deficits and reduced activation of specific brain regions speaks in favor of a specific age-associated deficit for the complex imaginary movements required by the GST.

A tug of war: antagonistic effective connectivity patterns over the motor cortex and the severity of motor symptoms in Gilles de la Tourette syndrome.

We tested the hypothesis that Gilles de la Tourette syndrome (GTS) is characterized by perturbed connectivity within cortico-subcortical motor networks. To this end, we performed a dynamic causal modelling (DCM) analysis of fMRI data collected during a finger opposition task in 24 normal controls and 24 GTS patients. The DCM analysis allowed us to assess whether any GTS-specific patterns of brain activity were related to intrinsic and/or to task-dependent connectivity. While no abnormalities were found for task-dependent connectivity, intrinsic connectivity was abnormally increased in the premotor network, with stronger connections from the supplementary motor area (SMA), from the dorsolateral premotor cortex and from the putamen to the right superior frontal gyrus, an area where GTS showed over-activation in a previous univariate analysis. We also found a positive correlation between the connectivity strength from the right basal ganglia to the right primary motor cortex (M1) and disease severity measured by the Yale Global Tic Severity Scale (YGTSS). This pattern was mirrored by a negative correlation between the connection strength from the right SMA to the right area M1 and the YGTSS score. These two reverse correlation effects showed a specific relationship with individual disease severity: the greater the imbalance between subcortical and premotor connectivity towards area M1, the higher the YGTSS score. These results reveal the existence of perturbed intrinsic connectivity patterns in the motor networks of GTS patients with two competing forces operating in a tug of war-like mechanism: aberrant subcortical afferents to M1, compensated for by inputs from the premotor cortex.

Mental steps: Differential activation of internal pacemakers in motor imagery and in mental imitation of gait.

Gait imagery and gait observation can boost the recovery of locomotion dysfunctions; yet, a neurologically justified rationale for their clinical application is lacking as much as a direct comparison of their neural correlates. Using functional magnetic resonance imaging, we measured the neural correlates of explicit motor imagery of gait during observation of in-motion videos shot in a park with a steady cam (Virtual Walking task). In a 2 × 2 factorial design, we assessed the modulatory effect of gait observation and of foot movement execution on the neural correlates of the Virtual Walking task: in half of the trials, the participants were asked to mentally imitate a human model shown while walking along the same route (mental imitation condition); moreover, for half of all the trials, the participants also performed rhythmic ankle dorsiflexion as a proxy for stepping movements. We found that, beyond the areas associated with the execution of lower limb movements (the paracentral lobule, the supplementary motor area, and the cerebellum), gait imagery also recruited dorsal premotor and posterior parietal areas known to contribute to the adaptation of walking patterns to environmental cues. When compared with mental imitation, motor imagery recruited a more extensive network, including a brainstem area compatible with the human mesencephalic locomotor region (MLR). Reduced activation of the MLR in mental imitation indicates that this more visually guided task poses less demand on subcortical structures crucial for internally generated gait patterns. This finding may explain why patients with subcortical degeneration benefit from rehabilitation protocols based on gait observation. Hum Brain Mapp 38:5195-5216, 2017. © 2017 Wiley Periodicals, Inc.

Functional brain effects of hand disuse in patients with trapeziometacarpal joint osteoarthritis: executed and imagined movements.

The human trapeziometacarpal (TMC) joint has a crucial evolutionary importance as it permits rotation and opposition of the thumb to the other fingers. In chronic TMC joint osteoarthritis (i.e., rhizarthrosis), this motor ability, essential for pinching, grasping, and manipulating objects, may become difficult or impossible due to intolerable pain. Here, we assess whether patients with rhizarthrosis show signs of abnormal brain representation of hand movements. To this end, we studied 35 patients with rhizarthrosis, affecting predominantly one of the two hands, and 35 healthy subjects who underwent both behavioural and fMRI measures of brain activity during overtly executed or imagined thumb-to-finger-opposition movements. The patients with rhizarthrosis were slower than controls both in motor execution and imagination. In the patients, correlation between the motor execution and imagination times was preserved, even though such correlation was less strong than in normal controls. The fMRI measures showed reduced activation in the hand primary motor and dorsal premotor cortex for the patients only during explicit movements. This was true for both hands, yet more so for the most affected hand. No significant differences were seen for the motor imagery task. These results show that an orthopaedic disorder that reduces patients' motoric repertoire in the absence of any neurological impairment is sufficient to induce neurofunctional changes in the cortical representation of hand movements. The substantial preservation of motor imagery with its neural counterparts distinguishes the neurological patterns of rhizarthrosis from those of complete immobilization or amputation suggesting that motor imagery may be used to boost motor recovery in rhizarthrosis after surgical treatment.

A functional magnetic resonance imaging investigation of motor control in Gilles de la Tourette syndrome during imagined and executed movements.

The current study investigated the neural correlates of voluntary motor control in 24 adult Gilles de la Tourette (GTS) patients. We examined whether imagination and the execution of the same voluntary movement - finger oppositions with either hand - were associated with specific patterns of activation. We also explored whether these patterns correlated with the severity of the syndrome, as measured by the Yale Global Tic Severity Scale (YGTSS) for motor tics. The presence of brain morphometric abnormalities was also assessed using voxel-based morphometry. Crucial to our experiment was the manipulation of the presence of an explicit motor outflow in the tasks. We anticipated a reduction in the ticking manifestation during the explicit motor task and brain activation differences between GTS patients and 24 age/gender-matched normal controls. The anticipated differences were all evident in the form of hyperactivations in the GTS patients in the premotor and prefrontal areas for both motor tasks for both hands; however, the motor imagery hyperactivations also involved rostral pre-frontal and temporo-parietal regions of the right hemisphere. The blood oxygen level-dependent responses of the premotor cortices during the motor imagery task were significantly correlated with the YGTSS scores. In contrast, no significant brain morphometric differences were found. This study provides evidence of a different neurofunctional organisation of motor control between adult patients with GTS and healthy controls that is independent from the actual execution of motor acts. The presence of an explicit motor outflow in GTS mitigates the manifestation of tics and the need for compensatory brain activity in the brain regions showing task-dependent hyperactivations.

The anarchic brain in action: the contribution of task-based fMRI studies to the understanding of Gilles de la Tourette syndrome.

PURPOSE OF REVIEW: Gilles de la Tourette syndrome (GTS) is a frequent neurological disorder characterized by the production of tics, and frequently associated with obsessive-compulsive disorder or attention-deficit hyperactivity disorder. The aim of this article is to summarize the contribution of imaging activation techniques to the study of the syndrome. RECENT FINDINGS: GTS has been studied with a variety of functional MRI (fMRI)/PET activation paradigms to characterize the origin of tics or their suppression, and how they compare physiologically with voluntary actions or response inhibitions. Current studies indicate overactivations of prefrontal and premotor cortices, including the supplementary motor area, and subcortical structures. Resting state functional connectivity studies complement activation studies in showing perturbed connectivity of cortico-subcortical networks. Several such findings correlate with the severity of the disease. SUMMARY: fMRI activation techniques are contributing a system-level neurophysiological description of GTS and bridge the gap between animal models and clinical observations. fMRI clarifies brain networks involved in different aspects of GTS phenomenology with some good clinical face validity. A future generation of fMRI studies should have higher ambitions and contribute, for example, to treatment optimization including the identification of ideal targets for deep brain stimulation in drug-resistant cases; however, such goals will be achieved only through controlled large-scale cooperative studies.

Unrealistic representations of "the self": A cognitive neuroscience assessment of anosognosia for memory deficit.

Three cognitive components may play a crucial role in both memory awareness and in anosognosia for memory deficit (AMD): (1) a personal data base (PDB), i.e., a memory store that contains "semantic" representations about the self, (2) monitoring processes (MPs) and (3) an explicit evaluation system (EES), or comparator, that assesses and binds the representations stored in the PDB with information obtained from the environment. We compared both the behavior and the functional connectivity (as assessed by resting-state fMRI) of AMD patients with aware patients and healthy controls. We found that AMD is associated with an impoverished PDB, while MPs are necessary to successfully update the PDB. AMD was associated with reduced functional connectivity within both the default-mode network and in a network that includes the left lateral temporal cortex, the hippocampus and the insula. The reduced connectivity between the hippocampus and the insular cortex was correlated with AMD severity.

Like the back of the (right) hand? A new fMRI look on the hand laterality task.

There is a common saying for expressing familiarity with something. It refers to our hands, and strangely enough, in English, one says to know something like the back of the hand, whereas in other cultures, for example, Italy, Spain and France, the same expression is with the palm. Previous behavioural data have suggested that our ability to visually discriminate a right from a left hand is influenced by perspective. This behavioural finding has remained without neurophysiological counterparts. We used an implicit motor imagery task in which 30 right-handed subjects were asked to decide whether a picture portrayed a right rather than a left hand during an fMRI event-related experiment. Both views (back and palm) were used, and the hands were rotated by 45° in 8 possible angles. We replicated previous behavioural evidence by showing faster reaction times for the back-view and view-specific interaction effects with the angle of rotation: for the back view, the longest RTs were with the hand facing down at 180°; for the palm view, the longest RTs were at 90° with the hand pointing away from the midline. In addition, the RTs were particularly faster for back views of the right hand. fMRI measurements revealed a stronger BOLD signal increase in left premotor and parietal cortices for stimuli viewed from the palm, whereas back-view stimuli were associated with stronger occipital activations, suggesting a view-specific cognitive strategy: more visually oriented for the back of the hand; more in need of the support of a motoric imagery process for the palms. Right-hand back views were associated with comparatively smaller BOLD responses, attesting, together with the faster reaction times, to the lesser need for neural labour because of greater familiarity with that view of the hand. These differences suggest the existence of brain-encoded, view-dependent representations of body segments.

The physiology of motor delusions in anosognosia for hemiplegia: implications for current models of motor awareness.

Right brain damaged patients sometimes deny that their left arm is paralysed or even claim to have just moved it. This condition is known as anosognosia for hemiplegia (AHP). Here, we used fMRI to study patients with and without AHP during the execution of a motor task. We found that the delusional belief of having moved was preceded by brain activation of the cortical regions that are implicated in motor control in the left intact hemisphere and in the spared motor regions of the right hemisphere; patients without anosognosia did not present with the same degree of activation. We conclude that the false belief of movement is associated with a combination of strategically placed brain lesions and the preceding residual neural activity of the fronto-parietal motor network. These findings provide evidence that the activity of motor cortices contributes to our beliefs about the state of our motor system.

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.