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With Motor imagery (MI), movements are mentally rehearsed without overt actions; this procedure has been adopted in motor rehabilitation, primarily in brain-damaged patients. Here we rather tested the clinical potentials of MI in purely orthopaedic patients who, by definition, should maximally benefit of mental exercises because of their intact brain. To this end we studied the recovery of gait after total knee arthroplasty and evaluated whether MI combined with physiotherapy could speed up the recovery of gait and even limit the occurrence of future falls. We studied 48 patients at the beginning and by the end of the post-surgery residential rehabilitation program: half of them completed a specific MI training supported by computerized visual stimulation (experimental group); the other half performed a non-motoric cognitive training (control group). All patients also had standard physiotherapy. By the end of the rehabilitation, the experimental group showed a better recovery of gait and active knee flexion-extension movements, and less pain. The number of falls or near falls after surgery was significantly lower in the experimental group. These results show that MI can improve gait abilities and limit future falls in orthopaedic patients, without collateral risks and with limited costs.

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 Z .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.(c) 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

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.

There are few things as irrefutable as the evidence that our limbs belong to us. However, persons with body integrity dysphoria (BID) [1] deny the ownership of one of their fully functional limbs and seek its amputation [2]. We tapped into the brain mechanisms of BID, examining sixteen men desiring the removal of the left healthy leg. The primary sensorimotor area of the to-be-removed leg and the core area of the conscious representation of body size and shape (the right superior parietal lobule [rSPL]) [3, 4] were less functionally connected to the rest of the brain. Furthermore, the left premotor cortex, reportedly involved in the multisensory integration of limb information [5-7], and the rSPL were atrophic. The more atrophic the rSPL, the stronger the desire for amputation, and the more an individual pretended to be an amputee by using wheelchairs or crutches to solve the mismatch between the desired and actual body. Our findings illustrate the pivotal role of the connectivity of the primary sensorimotor limb area in the mediation of the feeling of body ownership. They also delineate the morphometric and functional alterations in areas of higher-order body representation possibly responsible for the dissatisfaction with a standard body configuration. The neural correlates of BID may foster the understanding of other neuropsychiatric disorders involving the bodily self. Ultimately, they may help us understand what most of us take for granted, i.e., the experience of body and self as a seamless unity.

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., Here we investigated whether the addition of visual cues could make motor imagery (MI) performance more comparable with explicit motor execution in gait tasks at the behavioural and neurofunctional level. The MI quality was lower when participants were allowed to visually explore the environment. 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. We conclude that both visually‐cued and internally‐cued MI are associated with the neurofunctional activation of a gait specific motor system; however, the lower MI quality while keeping eyes open may be attributed to the processing load implied in visual monitoring and scanning of the environment.

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.

Dyslexia can have different manifestations: this has motivated different theories on its nature, on its underlying brain bases and enduring controversies on how to best treat it. The relative weight of the different manifestations has never been evaluated using both behavioural and fMRI measures, a challenge taken here to assess the major systems called into play in dyslexia by different theories. We found that adult well-compensated dyslexics were systematically impaired only in reading and in visuo-phonological tasks, while deficits for other systems (e.g., motor/cerebellar, visual magnocellular/motion perception) were only very occasional. In line with these findings, fMRI showed a reliable hypoactivation only for the task of reading, in the left occipito-temporal cortex (l-OTC). The l-OTC, normally a crossroad between the reading system and other systems, did not show the same level of intersection in dyslexics; yet, it was not totally silent because it responded, in segregated parts, during auditory phonological and visual motion perception tasks. This minimal behavioural and functional anatomical comorbidity demonstrates that a specific deficit of reading is the best description for developmental dyslexia, at least for adult well-compensated cases, with clear implications for rehabilitation strategies. The reduced intersection of multiple systems in the l-OTC suggests that dyslexics suffer from a coarser connectivity, leading to disconnection between the multiple domains that normally interact during reading.

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.

Action observation triggers imitation, a powerful mechanism permitting interpersonal coordination. Coordination, however, also occurs when the partners’ actions are nonimitative and physically incongruent. One influential theory postulates that this is achieved via top-down modulation of imitation exerted by prefrontal regions. Here, we rather argue that coordination depends on sharing a goal with the interacting partner: this shapes action observation, overriding involuntary imitation, through the predictive activity of the left ventral premotor cortex (lvPMc). During functional magnetic resonance imaging (fMRI), participants played music in turn with a virtual partner in interactive and noninteractive conditions requiring 50% of imitative/nonimitative responses. In a full-factorial design, both perceptual features and low-level motor requirements were kept constant throughout the experiment. Behaviorally, the interactive context minimized visuomotor interference due to the involuntary imitation of physically incongruent movements. This was paralleled by modulation of neural activity in the lvPMc, which was specifically recruited during the interactive task independently of the imitative/nonimitative nature of the social exchange. This lvPMc activity reflected the predictive decoding of the partner’s actions, as revealed by multivariate pattern analysis. This demonstrates that, during interactions, we process our partners’ behavior to prospectively infer their contribution to the shared goal achievement, generating motor predictions for cooperation beyond low-level imitation.

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.

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

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., Highlights • Patients with chronic knee arthrosis show impairment in gait motor imagery • Impairment is selective for gait and paralleled by hypoactivation in premotor areas • Peripheral limitation of lower limb movements affects central gait motor control • Dynamic motor imagery favours the recruitment of a motor strategy during imagery • Mental motor training might help to restore gait control in orthopaedic patients

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.

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.

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.

We describe the clinical manifestations and the lesion patterns of five patients with somatoparaphrenia, the denial of ownership for a paralyzed limb, who showed the rare dissociation from anosognosia for hemiplegia. Similar cases have been only occasionally cited in the literature with scanty descriptions of their symptoms and no detailed anatomical assessment. All patients had extrapersonal and at least mild personal neglect. The lesions pattern was mainly subcortical, with a significant involvement of the right thalamus, the basal ganglia and the internal capsule. A formal comparison between the anatomical pattern previously associated with anosognosia in a study performed in 2005 by Berti and colleagues, and the lesion distribution of each patient clearly shows that our pure somatoparaphrenic patients had a sparing of most of the regions associated with anosognosia for hemiplegia. The behavioral dissociation between SP and anosognosia for hemiplegia, together with this new anatomical evidence, suggests that motor awareness is not sufficient to build up a sense of ownership and therefore these two cognitive abilities are at least in part functionally independent and qualitatively different.

According to recent theories, drug addicted patients suffer of an impaired response inhibition and salience attribution (I-RISA) together with a perturbed connectivity between the nuclei accumbens (NAcs) and the orbito-prefrontal (oPFC) and dorsal prefrontal (dPFC) cortices, brain regions associated with motivation and cognitive control. To empirically test these assumptions, we evaluated the (neuro)psychological trait and the functional organization of the resting state brain networks associated with the NAcs in 18 former cocaine abusers (FCAs), while being in drug abstinence since 5 months. The psychological data were grouped into three empirical variables related with emotion regulation, emotion awareness and strategic and controlled behaviour. Comparison of the resting state patterns between the entire sample of FCAs and 19 controls revealed a reduction of functional connectivity between the NAcs and the dPFC and enhanced connectivity between the NAcs and the dorsal-striatum. In the 8 FCAs who relapsed into cocaine use after 3 months, the level of functional connectivity between the NAcs and dPFC was lower than the functional connectivity estimated in the group of patients that did not relapsed. Finally, in the entire sample of FCAs, the higher the connectivity between the NAc and the oPFC the lower was the level of strategic and controlled behaviour. Taken together, these results are compatible with models of the interactions between the NAcs, the dorsal striatum and frontal cortices in the I-RISA syndrome, showing that such interactions are particularly perturbed in patients at greater risk of relapse into cocaine abuse.

Motor imagery (M.I.) is a cognitive process in which movements are mentally evoked without overt actions. Behavioral and fMRI studies show a decline of explicit M.I. ability (e.g., the mental rehearsal of finger oppositions) with normal ageing: this decline is accompanied by the recruitment of additional cortical networks. However, none of these studies investigated behavioral and the related fMRI ageing modifications in implicit M.I. tasks, like the hand laterality task (HLT). To address this issue, we performed a behavioral and fMRI study: 27 younger subjects (mean age: 31 years) and 29 older subjects (mean age: 61 years) underwent two event-related design fMRI experiments. In the HLT, participants were asked to decide whether a hand rotated at different angles was a left or right hand. To test the specificity of any age related difference in the HLT, we used a letter rotation task as a control experiment: here subjects had to decide whether rotated letters were presented in a standard or a mirror orientation. We did not find any group difference in either behavioral task; however, we found significant additional neural activation in the elderly group in occipito-temporal regions: these differences were stronger for the HLT rather than for the LRT with group by task interactions effects in right occipital cortices. We interpret these results as evidence of compensatory processes associated with ageing that permit a behavioral performance comparable to that of younger subjects. This process appears to be more marked when the task specifically involves motor representations, even when these are implicitly evoked. (C) 2016 Elsevier B.V. All rights reserved.

The ability to share feelings with those of someone in pain is affected by the racial difference between the target and the onlooker. A differential empathic activation for race (DEAR effect) in favor of in-group members has been documented in the brain pain matrix. However, we are also capable of unbiased responses that manifest politically correct behaviors toward people of a different race. To address the neurofunctional signatures underlying both the DEAR effect and the manifestation of politically correct behaviors, we scanned with fMRI Caucasian participants while watching African or Caucasian actors touched by either a rubber eraser or a needle. Participants were instructed to empathize with the actors during the video presentation (stimulus phase) and to explicitly judge the pain level experienced by the actors (response phase). During the stimulus phase, we found a typical DEAR effect within the pain-matrix. This effect correlated with the level of implicit racial bias as measured by the IAT. On the other hand, during the response phase a significant out-group specific DEAR effect emerged in the prefrontal cortices. This latter effect was coupled with a revealing behavioral pattern: while the magnitude of the painful experience attributed to Caucasians and Africans was the same, our participants were significantly slower when judging the pain experience of the African actors. We propose a model that logically integrates these two contrasting forces at the neurobiological and behavioral level.

Two experiments investigated whether dealing with a homogeneous subset of syllogisms with time-constrained responses encouraged participants to develop and use heuristics for abstract (Experiment 1) and thematic (Experiment 2) syllogisms. An atmosphere-based heuristic accounted for most responses with both abstract and thematic syllogisms. With thematic syllogisms, a weaker effect of a belief heuristic was also observed, mainly where the correct response was inconsistent with the atmosphere of the premises. Analytic processes appear to have played little role in the time-constrained condition, whereas their involvement increased in a self-paced, unconstrained condition. From a dual-process perspective, the results further specify how task demands affect the recruitment of heuristic and analytic systems of reasoning. Because the syllogisms and experimental procedure were the same as those used in a previous neuroimaging study by Goel, Buchel, Frith, and Dolan (2000), the result also deepen our understanding of the cognitive processes investigated by that study.

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. We used fMRI to investigate the neural correlates of voluntary motor control in adult GTS patients, with two different finger opposition tasks, one explicit and one imagined. We found task-dependent cortical hyperactivations in GTS, broader for motor imagery, proportional to the severity of the disease. The presence of an explicit motor outflow in GTS mitigated the manifestation of tics and the need for compensatory brain activity in the brain regions showing task dependent hyperactivations.

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.

We assessed the effects of age of acquisition and language exposure on the cerebral correlates of lexical retrieval in high‐proficient, early‐acquisition bilinguals. Functional MRI was used to study Spanish–Catalan bilinguals who acquired either Spanish or Catalan as a first language in the first years of life. Subjects were exposed to the second language at 3 years of age, and have used both languages in daily life since then. Subjects had a comparable level of proficiency in the comprehension of both languages. Lexical retrieval with the verbal fluency task resulted in the well‐established pattern of left hemispheric activation centered on the inferior frontal region. The effect of age of acquisition was assessed by dividing the subjects into two groups, on the basis of the language acquired first (Catalan‐born or Spanish‐born bilinguals). Functional comparisons indicated that less extensive brain activation was associated with lexical retrieval in the language acquired earlier in life. The two groups were also different in language usage/exposure, as assessed with a specific questionnaire; in particular, the exposure to the second language (Spanish) was less intensive in the case of Catalans. This was reflected in a significant interaction, indicating a more extensive activation in Catalans during production in Spanish. Overall, these results indicate that, during a production task, both age of acquisition and language exposure affect the pattern of brain activation in bilinguals, even if both languages are acquired early and with a comparable level of proficiency. Hum. Brain Mapping 19:170–182, 2003. © 2003 Wiley‐Liss, Inc.

The aim of this study was to assess, by positron emission tomography (PET), the effect on cerebral functional activity of a new lorazepam-γ-aminobutyric acid (GABA) conjugate [3-(4-acetamido)-butyrril lorazepam (DDS2700)]. Ten healthy volunteers were studied by PET and [ 18 F]fluoro-deoxy-D-glucose ([ 18 F]FDG) under baseline conditions and following the administration of DDS2700. Regional cerebral blood flow (rCBF) was measured by PET and 15 O-water in three additional participants while they performed attentive tasks, before and after drug administration. DDS2700 induced a decrease in the regional cerebral metabolic rate of glucose (rCMRglu) in the thalamus (-17%), cerebellum (-11%) and caudate nucleus (-8%). The observed effects on glucose metabolism were probably related to the subjective sedation and tiredness reported by the participants. During the attentive tasks, rCBF increased in frontal and temporal regions associated with attentional processing of auditory material. These circuits were no longer active after DDS2700 administration, while rCBF increased in cingulate cortex, occipitoparietal regions, pons and cerebellum. These drug-induced activations might be directly related to intervening sleepiness and to the consequent effort in keeping attention focused on the tasks. The effects of DDS2700 on glucose metabolism at rest, and on rCBF during activation conditions, indicate a drug action on cerebral networks involved in alertness, vigilance and attention maintenance. PET assessment by [ 18 F]FDG and water may provide complementary information in pharmacodynamic studies.

The [18F]fluorodeoxyglucose ([18F]FDG) method for measuring brain metabolism has not the wide clinical application that one might expect, partly because of its high cost and the complexity of the quantification procedure, but also because of reporting techniques based on region of interest (ROI) analysis, which are time-consuming and not fully objective. In this paper we report a clinical validation of statistical parametric mapping (SPM) using rCMRglc (quantitative) and radioactivity distribution (nonquantitative) [18F]FDG PET data. We show that a 10-min noninteractive voxel-based SPM analysis on a standard workstation enables objective assessment, including localization in stereotactic space, of regional glucose consumption abnormalities, whose reliability can be assessed on statistical and clinical grounds. Clinical validity was established using a small series of patients with degenerative or developmental disorders, including probable Alzheimer's disease, progressive aphasia, multiple sclerosis, developmental specific language impairment, and epilepsy. Analysis of quantitative and nonquantitative data showed the same pattern of results, suggesting that, for clinical purposes, quantitation and invasive arterial cannulation can be avoided. This should facilitate a wider application of the technique and the extension of SPM clinical analysis to H215O PET or high resolution SPECT perfusion studies.

Neglect patients' performance during cancellation tasks is characterized by left sided omissions and, in many cases, by the production of inappropriate material of various kinds in the ipsilesional space, e.g. additional marks over already cancelled targets, marks drawn away from targets, scribbles, irrelevant drawings. It is unclear whether these behaviours, which have collectively been called perseverative, are functionally and anatomically connected and whether they correlate with the severity of neglect. Here we report a retrospective study on 33 right brain damaged patients with neglect after right hemisphere lesions in whom we measured the intensity of perseveration of the three following kinds: (1) 'additional marks' (AM) perseveration where patients cancelled a target with two or more well separated marks; (2) 'scribble' perseveration, where patients, instead of cancelling the target with a single pen stroke as required by the task, performed multiple pen strokes without breaking the pen-to-paper contact, with the final product being a scribble; (3) 'flying marks' (FM) perseveration where patients produced cancellation marks well away from the targets. We found that AM and FM perseveration correlated with neglect severity, while 'scribble' perseveration did not. The lesion-symptom mapping showed three separate anatomical areas in the right hemisphere: 'scribble' perseveration was associated with lesions of the orbitofrontal cortex and caudate nucleus; AM perseveration was associated with damage to the rolandic operculum, superior temporal gyrus and inferior frontal gyrus; FM perseveration was associated with damage to the dorsal premotor cortex and the temporal pole. Neglect severity followed damage to a region which grossly corresponds to the sum of the regions associated with AM and FM perseveration respectively. This complex behavioural and anatomical pattern is interpreted in terms of a three-factor model, in which AM perseveration is caused by a deficit of disengagement of attention from the right side (also causing omissions), FM perseveration is caused by directional hypokinesia (also causing left-side omissions), and 'scribble' perseveration is the consequence of a failure to inhibit an initiated motor act, which is completely separate (both anatomically and functionally) from the disorder inducing omissions. © 2013 Elsevier Ltd.

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 45A degrees 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 180A degrees; for the palm view, the longest RTs were at 90A degrees 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.

In a small proportion of the normal population, stimulation in one modality can lead to perceptual experience in another, a phenomenon known as synaesthesia. In the most common form of synaesthesia, hearing a word can result in the experience of colour. We have used the technique of PET, which detects brain activity as changes of regional cerebral blood flow (rCBF), to study the physiology of colour-word synaesthesia in a group of six synaesthete women. During rCBF measurements synaesthetes and six controls were blindfolded and were presented with spoken words or pure tones. Auditory word, but not tone, stimulation triggered synaesthesia in synaesthetes. In both groups word stimulation compared with tone stimulation activated the classical language areas of the perisylvian regions. In synaesthetes, a number of additional visual associative areas, including the posterior inferior temporal cortex and the parieto-occipital junctions, were activated. The former has been implicated in the integration of colour with shape and in verbal tasks which require attention to visual features of objects to which words refer. Synaesthetes also showed activations in the right prefrontal cortex, insula and superior temporal gyrus. By contrast, no significant activity was detected in relatively lower visual areas, including areas V1, V2 and V4. These results suggest that colour-word synaesthesia may result from the activity of brain areas concerned with language and visual feature integration. In the case of colour-word synaesthesia, conscious visual experience appears to occur without activation of the primary visual cortex.

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, theBAD-respondersshowed 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 theBAD-respondershad 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.

Motor imagery (M.I.) is a mental state in which real movements are evoked without overt actions. There is some behavioural evidence that M.I. declines with ageing. The neurofunctional correlates of these changes have been investigated only in two studies, but none of the these studies has measured explicit correlations between behavioural variables and the brain response, nor the correlation of M.I. and motor execution (M.E.) of the same acts in ageing. In this paper, we report a behavioural and functional magnetic resonance imaging (fMRI) experiment that aimed to address this issue. Twenty-four young subjects (27 ± 5.6 years) and twenty-four elderly subjects (60 ± 4.6 years) performed two block-design fMRI tasks requiring actual movement (M.E.) or the mental rehearsal (M.I.) of finger movements. Participants also underwent a behavioural mental chronometry test in which the temporal correlations between M.I. and M.E. were measured. We found significant neurofunctional and behavioural differences between the elderly subjects and the young subjects during the M.E. and the M.I. tasks: for the M.E. task, the elderly subjects showed increased activation in frontal and prefrontal (pre-SMA) cortices as if M.E. had become more cognitively demanding; during the M.I. task, the elderly over-recruited occipito-temporo-parietal areas, suggesting that they may also use a visual imagery strategy. We also found between-group behavioural differences in the mental chronometry task: M.I. and M.E. were highly correlated in the young participants but not in the elderly participants. The temporal discrepancy between M.I. and M.E. in the elderly subjects correlated with the brain regions that showed increased activation in the occipital lobe in the fMRI. The same index was correlated with the premotor regions in the younger subjects. These observations show that healthy elderly individuals have decreased or qualitatively different M.I. compared to younger subjects.

Deduction is the ability to draw necessary conclusions from previous knowledge. Here we propose a novel approach to understanding the neural basis of deduction, which exploits fine-grained inter-participant variability in such tasks. Participants solved deductive problems and were grouped by the behavioral strategies employed, i.e., whether they were sensitive to the logical form of syllogistic premises, whether the problems were solved correctly, and whether heuristic strategies were employed. Differential profiles of neural activity can predict membership of the first two of these groups. The predictive power of activity profiles is distributed non-uniformly across the brain areas activated by deduction. Activation in left ventro-lateral frontal (BA47) and lateral occipital (BA19) cortices predicts whether logically valid solutions are sought. Activation of left inferior lateral frontal (BA44/45) and superior medial frontal (BA6/8) cortices predicts sensitivity to the logical structure of problems. No specific pattern of activation was associated with the use of a non-logical heuristic strategy. Not only do these findings corroborate the hypothesis that left BA47, BA44/45 and BA6/8 are critical for making syllogistic deductions, but they also imply that they have different functional roles as components of a dedicated network. We propose that BA44/45 and BA6/8 are involved in the extraction and representation of the formal structure of a problem, while BA47 is involved in the selection and application of relevant inferential rules. Finally, our findings suggest that deductive reasoning can be best described as a cascade of cognitive processes requiring the concerted operation of several, functionally distinct, brain areas.

Two cases of aphasia after right hemispheric stroke in right handed patients are described. The first patient had a severe mixed transcortical aphasia, apraxia and neglect after a lesion involving the right lenticular nucleus and periventricular white matter; aphasia was still present after three months. The second patient had a mild, transient fluent aphasia after a small right hemispheric periventricular lesion. Studies with [18F]FDG and positron emission tomography (PET) showed functional depression extending to the structurally unaffected left hemisphere in both patients in the acute stage. After three months, in the patient with persistent aphasia, metabolism was still reduced in the right hemisphere, with some recovery of hypometabolism on the left, while metabolic values had returned to normal in the patient with full language recovery. A close parallelism between glucose metabolism and clinical course in crossed aphasia is shown, as well as the presence of a functional involvement of the structurally unaffected left hemisphere in the acute stage.

A 2-[18F]-Fluoro-2-Deoxy- D -Glucose ([18F]FDG) and positron emission tomography (PET) study was performed in the acute and chronic phase of stroke in one patient with unilateral neglect due to a right hemispheric lesion. In the acute phase, severe neglect, as well as hypometabolism in both the right and in the left unaffected cerebral hemisphere, was demonstrated. At follow-up evaluation the patient showed an almost complete recovery fromunilateral neglect. This was associated with a return of left hemisphere metabolism to normal values and partial metabolic recovery in the right hemisphere, where frontal and parietal areas remained functionally impaired. Another patient with an extensive right cerebral ischaemic lesion on CT and severe unilateral neglect was studied by PET in chronic phase. A severe metabolic depression in the left unaffected hemisphere and in the right cerebral areas spared by the lesion, was found. These data suggest that the remission of unilateral neglect might be associated to a functional metabolic recovery in both the undamaged left hemisphere and the unaffected regions of the right hemisphere.

Amnestic mild cognitive impairment (a-MCI) is associated with the highest annual incidence of conversion to Alzheimer's disease (AD) (10-15%). a-MCI patients may have only a memory deficit (single domain: sd-a-MCI) or additional dysfunctions affecting other cognitive domains (multiple domain: md-a-MCI). Using functional magnetic resonance imaging (fMRI), we investigated brain activation in 16 sd-a-MCI patients and 14 controls during four different tasks assessing language, memory, attention and empathy functions. We found greater activation in sd-a-MCI compared with controls in the left inferior temporal gyrus (language), the right superior temporal gyrus (memory) and the right dorsal precentral gyrus (attention). Moreover, patients' activation correlated significantly with neuropsychological scores obtained at tests exploring the corresponding function. These findings indicate that fMRI is sensitive to detect early changes occurring in AD pathology and that individuals with sd-a-MCI show increased activation in multiple task-related brain regions. We suggest that these functional changes relate to the development of early compensatory mechanisms that reduce cognitive deficits associated with the progressive accumulation of brain damage.

Many hypotheses have been proposed about the brain underpinnings of developmental dyslexia, but none of them accommodates the variable deficits observed. To address the issue of anatomical deficits in dyslexia; total and partial volumes, lateralization indices (LI), and local gray matter volumes (LGMV) were measured. Analyses were performed in large samples of control and dyslexic subjects, and in correlation with their performance on phonological, reading, and spelling tests. Results indicate an absence of net differences in terms of volumes but significant continuities and discontinuities between groups in their correlations between LI, LGMV, and performances. Structural connectivity also highlighted correlations between areas showing (dis)continuities between control and dyslexic subjects. Overall, our data put forward the idea of a multifocal brain abnormalities in dyslexia with a major implication of the left superior temporal gyrus, occipital‐temporal cortices, and lateral/medial cerebellum, which could account for the diverse deficits predicted by the different theories. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.

Vocabulary acquisition is such a major aspect of language learning in children, but also in adults when learning a foreign language, that a dedicated vocabulary learning device may exist within the language organ. To identify the relevant brain systems, we performed regional cerebral blood flow measurements in normal subjects while they were learning a list of neologisms or a list of word–nonword pairs. Structures implicated in phonological short-term memory (Broca's area, left temporo-parietal junction) were steadily activated during nonwords learning, while the left temporal lobe neocortical and paralimbic structures (parahippocampal region), associated with long-term memory, contributed to learning in a time-dependent manner, with maximal activation at the beginning of the process. The neural system specifically activated when learning new vocabulary was strongly lateralized to the left hemisphere. This evidence refines current models of memory function and supports theories which emphasise the importance of phonological competence in hemispheric dominance for language.

The wide variety of techniques and tasks used to study the neural correlates of noun and verb processing has resulted in a body of inconsistent evidence. We performed a functional magnetic resonance imaging (fMRI) experiment to detect grammatical class effects that generalize across tasks. A total of 12 participants undertook a grammatical-class switching task (GCST), in which they were presented with a noun (or a verb) and were asked to retrieve the corresponding verb (or noun), and a classical picture naming task (PNT) widely used in the previous aphasiological and imaging literature. The GCST was explicitly designed to ensure control over confounding variables, such as stimulus complexity or imageability. Conjunction analyses of the haemodynamic responses measured in the two tasks indicated a shared verb-related activation of a dorsal premotor and posterior parietal network, pointing to a strong relationship between verb representation and action-oriented (visuo-)spatial knowledge. On the other hand, no brain area was consistently associated with nouns in both tasks. Moreover, there were task-dependent differences between noun and verb retrieval both at behavioural and at physiological level; the grammatical class that elicited the longest reaction times in both tasks (i.e., verbs in the PNT and nouns in the GCST) triggered a greater activation of the left inferior frontal gyrus. Therefore, we suggest that this area reflects a general increase in task demand rather than verb processing per se.

Background: Left caloric vestibular stimulation (CVS) transiently reduces impairments of right-brain-damaged patients with left unilateral neglect, including left hemianesthesia, contralateral to the side of the lesion (contralesional). Conversely, no effect on right contralesional hemianesthesia in left-brain-damaged patients is seen with right CVS. This discrepancy is unexplained. Methods: The authors explored the effect of CVS on right- and left-brain-damaged patients with hemianesthesia. One left-brain-damaged patient had an fMRI study during tactile stimulation before and after left CVS. The same fMRI touch study, without CVS, was performed in neurologically unimpaired subjects. Results: A transient remission of right hemianesthesia associated with left brain damage was observed, provided that cold CVS was administered to the left ear. In the left-brain-damaged patient studied with fMRI, left CVS modulated the neural response to right hand tactile stimuli of a portion of the secondary somatosensory area (SII) of the right hemisphere. In neurologically unimpaired subjects, fMRI scans showed that the same part of area SII in the right hemisphere was activated by ipsilateral right-sided touches and to a larger extent than area SII in the left hemisphere by left-sided touches. Conclusions: Left caloric vestibular stimulation is effective on both left and right hemianesthesia because it modulates the hemisphere that has a more complete representation of, or is capable to attend to, the whole somatosensory surface of the body. These results suggest a hardwired hemispheric asymmetry in hand representation, starting from a somatotopically organized brain region such as area SII.

In everyday life, the successful monitoring of behavior requires continuous updating of the effectiveness of motor acts; one crucial step is becoming aware of the movements one is performing. We studied the anatomical distribution of lesions in right-brain–damaged hemiplegic patients, who obstinately denied their motor impairment, claiming that they could move their paralyzed limbs. Denial was associated with lesions in areas related to the programming of motor acts, particularly Brodmann's premotor areas 6 and 44, motor area 4, and the somatosensory cortex. This association suggests that monitoring systems may be implemented within the same cortical network that is responsible for the primary function that has to be monitored.

A positron emission tomography (PET) study was conducted to investigate the neurofunctional correlate of auditory within-modality and auditory-to-visual cross-modality stem completion priming. Compared to the auditory-to-auditory priming condition, cross-modality priming was associated with a significantly larger regional cerebral blood flow (rCBF) decrease at the boundary between left inferior temporal and fusiform gyri, brain regions previously associated with modality independent lexical retrieval and reading. Instead, within-modality auditory priming was associated with a bilateral pattern of prefrontal rCBF increase. This was likely the expression of more efficient access to output lexical representations and involuntary retrieval of the recent episode during which the just generated word had been encountered.

Regional cerebral blood flow (rCBF) PET scans were used to study the physiological bases of lipreading, a natural skill of extracting language from mouth movements, which contributes to speech perception in everyday life. Viewing connected mouth movements that could not be lexically identified and that evoke perception of isolated speech sounds (nonlexical lipreading) was associated with bilateral activation of the auditory association cortex around Wernicke's area, of left dorsal premotor cortex, and left opercular-premotor division of the left inferior frontal gyrus (Broca's area). The supplementary motor area was active as well. These areas have all been implicated in phonological processing, speech and mouth motor planning, and execution. In addition, nonlexical lipreading also differentially activated visual motion areas. Lexical access through lipreading was associated with a similar pattern of activation and with additional foci in ventral- and dorsolateral prefrontal cortex bilaterally and in left inferior parietal cortex. Linear regression analysis of cerebral blood flow and proficiency for lexical lipreading further clarified the role of these areas in gaining access to language through lipreading. The results suggest cortical activation circuits for lipreading from action representations that may differentiate lexical access from nonlexical processes.

Objective: To investigate the central neural contribution to chest pain perception in cardiac syndrome X (angina-like pain, ECG changes during stress, angiographically normal coronary arteriogram). Subjects: Eight syndrome X patients and eight healthy volunteers. Methods: Dobutamine stress using echocardiography to assess myocardial function, and positron emission tomography to measure changes in regional cerebral blood flow, as an index of neuronal activity. Results: During similar doses of dobutamine, syndrome X patients and controls showed comparable regional cerebral blood flow changes in the hypothalamus, thalami, right orbito-frontal cortex, and anterior temporal poles, associated with the sensation of a fast or powerful heart beat. In patients, but not controls, the stress also generated severe chest pain associated with increased activity in the right anterior insula/frontal operculum junction. There were ischaemia-like ECG changes in the syndrome X patients, but no left ventricular dysfunction on echocardiography. Activation of the right insula during chest pain clearly distinguished the syndrome X patients from a group of patients with known coronary disease. Conclusions: Chest pain and ECG changes were not accompanied by demonstrable myocardial dysfunction in syndrome X patients, but altered central neural handling of afferent signals may contribute to the abnormal pain perception in these patients.

Acupuncture is largely used for pain control in several pathological conditions. Its effects on the central nervous system are not well defined. We investigated the effect of the application of acupuncture to 13 normal subjects (males, 21-32 years). (H2O)-O-15 bolus PET scans were read before the application of the needles (Rest, R) and after 25 min of needle insertion. Data were acquired by scanning in 3-D mode. The acupuncture application, true acupuncture (TA), was alternated to a placebo needle application (PA) in two:different sequences (seven and six subjects, respectively), either R,PA,R, TA or R,TA,R,PA, a period of 15 min being left after every first TA or PA to allow for the recovery of basal conditions. Here we show that classic acupuncture activates the left Anterior Cingulus, the Insulae bilaterally, the Cerebellum bilaterally, the left Superior Frontal Gyrus, and the right Medial and Inferior Frontal Gyri. Most of the activated areas are shared with areas activated in acute and chronic pain states as described in the literature. Thus acupuncture appears to act by activating areas also involved in pain. This indicates that acupuncture could relief pain by unbalancing the equilibrium of distributed pain-related central networks

The recognition of dyslexia as a neurodevelopmental disorder has been hampered by the belief that it is not a specific diagnostic entity because it has variable and culture-specific manifestations. In line with this belief, we found that Italian dyslexics, using a shallow orthography which facilitates reading, performed better on reading tasks than did English and French dyslexics. However, all dyslexics were equally impaired relative to their controls on reading and phonological tasks. Positron emission tomography scans during explicit and implicit reading showed the same reduced activity in a region of the left hemisphere in dyslexics from all three countries, with the maximum peak in the middle temporal gyrus and additional peaks in the inferior and superior temporal gyri and middle occipital gyrus. We conclude that there is a universal neurocognitive basis for dyslexia and that differences in reading performance among dyslexics of different countries are due to different orthographies.

Functional imaging of the presynaptic dopaminergic activity using single-photon emission tomography (SPET) and iodine-123 labelled 2-beta-carboxymethoxy-3-beta-(4-iodophenyl)tropane ([123I]beta-CIT) is important for the assessment of disease severity and progression in patients with Parkinson's disease (PD). However, its capability to discriminate between different extrapyramidal disorders has not yet been assessed. The aim of this study was to evaluate the possibility of differentiating patients with PD and with progressive supranuclear palsy (PSP) by means of this method. The distribution of [123I]beta-CIT in the basal ganglia was assessed in six normal subjects, 13 petients with PD and five patients with PSP in whom the disease was mild. SPET images were obtained 24+/-2 h after i.v. injection of the tracer using a brain-dedicated system (CERASPECT). MR and SPET images were co-registered in four normal subjects and used to define a standard set of 16 circular regions of interest (ROIs) on the slice showing the highest striatal activity. The basal ganglia ROIs corresponded to (1) the head of caudate, (2) a region of transition between the head of caudate and the anterior putamen, (3) the anterior putamen and (4) the posterior putamen. A ratio of specific to non-displaceable striatal uptake was calculated normalising the activity of the basal ganglia ROIs to that of the occipital cortex (V3"). ANOVA revealed a global reduction of V3" in all ROIs of PD and PSP patients compared with normal controls (P

Background The neural correlates of recovery of unilateral neglect (ULN), as well as of other consequences of focal brain damage, are largely unknown. Functional neuroimaging methods (in particular, positron emission tomography [PET]) can be applied to the in vivo study of recovery mechanisms in neurologic patients. Objective To evaluate the functional cerebral correlates of recovery from ULN in patients with right-sided lesions, with the use of a PET activation paradigm. Methods Study of 3 patients with cerebrovascular lesions that involved corticosubcortical (patient 1) or subcortical (patients 2 and 3) areas of the right hemisphere. Unilateral neglect was tested twice, before and after completion of a 2-month rehabilitation program, after which all 3 patients showed considerable improvement. Similarly, 2 PET examinations were performed, before and after recovery, during the performance of a visuospatial task requiring the patients to detect and respond to visual targets moving on a computer screen from the right to the left visual hemifield (experimental condition). The cerebral activation was compared with a baseline task in which subjects responded to a black dot flashing in a fixed position of the right hemifield. Results The brain areas activated by the performance of the visuospatial task before and after recovery were compared. In all 3 patients, the regions notably more active after recovery were almost exclusively found in right-sided cortical areas and largely overlapped with those observed in a group of 4 normal subjects performing the same task. Other areas, which have been shown to be involved in attentional and oculomotor tasks in other PET studies, were also activated in patients with ULN. Conclusions The behavioral recovery of ULN in these patients with predominantly subcortical lesions is mainly associated with cerebral activations in cortical regions similar to those observed in normal subjects. There is some evidence of functional reorganization in individual subjects, which involves other areas related to space representation and exploration.

Functional imaging methods show differences in the pattern of cerebral activation associated with the subject's native language (L1) compared with a second language (L2). In a recent PET investigation on bilingualism we showed that auditory processing of stories in L1 (Italian) engages the temporal lobes and temporoparietal cortex more extensively than L2 (English). However, in that study the Italian subjects learned L2 late and attained a fair, but not an excellent command of this language (low proficiency, late acquisition bilinguals). Thus, the different patterns of activation could be ascribed either to age of acquisition or to proficiency level. In the current study we use a similar paradigm to evaluate the effect of early and late acquisition of L2 in highly proficient bilinguals. We studied a group of Italian-English bilinguals who acquired L2 after the age of 10 years (high proficiency, late acquisition bilinguals) and a group of Spanish-Catalan bilinguals who acquired L2 before the age of 4 years (high proficiency, early acquisition bilinguals). The differing cortical responses we had observed when low proficiency volunteers listened to stories in L1 and L2 were not found in either of the high proficiency groups in this study. Several brain areas, similar to those observed for L1 in low proficiency bilinguals, were activated by L2. These findings suggest that, at least for pairs of L1 and L2 languages that are fairly close, attained proficiency is more important than age of acquisition as a determinant of the cortical representation of L2.

International audience; Functional magnetic resonance imaging was used to assess inter-subject variability in the cortical representation of language comprehension processes. Moderately fluent French-English bilinguals were scanned while they listened to stories in their first language (L1 = French) or in a second language (L2 = English) acquired at school after the age of seven. In all subjects, listening to L1 always activated a similar set of areas in the left temporal lobe, clustered along the left superior temporal sulcus. Listening to L2, however, activated a highly variable network of left and right temporal and frontal areas, sometimes restricted only to right-hemispheric regions. These results support the hypothesis that first language acquisition relies on a dedicated left-hemispheric cerebral network, while late second language acquisition is not necessarily associated with a reproducible biological substrate. The postulated contribution of the right hemisphere to L2 comprehension is found to hold only on average, individual subjects varying from complete right lateralization to standard left lateralization for L2.

Summary A rhyming and a short-term memory task with visually presented letters were used to study brain activity in five compensated adult developmental dyslexics. Their only cognitive difficulty was in phonological processing, manifest in a wide range of tasks including spoonerisms, phonemic fluency and digit naming speed. PET scans showed that for the dyslexics, a subset only of the brain regions normally involved in phonological processing was activated: Broca 's area during the rhyming task, temporo-parietal cortex during the short-term memory task. In contrast to normal controls these areas were not activated in concert. Furthermore the left insula was never activated. We propose that the defective phonological system of these dyslexics is due to weak connectivity between anterior and posterior language areas. This could be due to a dysfunctional left insula which may normally act as an anatomical bridge between Broca's area, superior temporal and inferior parietal cortex. The independent activation of the posterior and anterior speech areas in dyslexics supports the notion that representations of unsegmented and segmented phonology are functionally and anatomically separate.

Positron emission tomography (PET) was used to localize brain regions that are active during the observation of grasping movements. Normal, right-handed subjects were tested under three conditions. In the first, they observed grasping movements of common objects performed by the experimenter. In the second, they reached and grasped the same objects. These two conditions were compared with a third condition consisting of object observation. On the basis of monkey data, it was hypothesized that during grasping observation, activations should be present in the region of the superior temporal sulcus (STS) and in inferior area 6. The findings in humans demonstrated that grasp observation significantly activates the cortex of the middle temporal gyrus including that of the adjacent superior temporal sulcus (Brodmann's area 21) and the caudal part of the left inferior frontal gyrus (Brodmann's area 45). The possible functional homologies between these areas and the monkey STS region and frontal area F5 are discussed.