Search

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.

Mental time travel (MTT) abilities could be particularly compromised in schizophrenic patients due to a deficit of the cognitive processes at the basis of remembering the past and imaging the future: constructive processes, theory of mind and self-awareness. Accordingly, we assumed that the neural circuits typically associated with MTT in healthy people might be partially compromised in chronic schizophrenic patients. To quantitatively and anatomically test our hypothesis, we run two meta-analyses using the Activation Likelihood Estimate method: (i) a neurofunctional meta-analysis on MTT in healthy subjects, (ii) a morphometrical meta-analysis on chronic schizophrenia. The results of the two meta-analyses were overlapped in order to identify the candidate regions involved in MTT deficit in schizophrenia. A significant overlap was found in the vmPFC, in the precuneus, in the hippocampus and in the insular cortex. We assume that MTT deficits in schizophrenic patients may be the results of a complex dysfunctional interaction between the system underlying the creation of self-representation, the constructive system and the salience attribution network.

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

In this study, we explored vagally-mediated heart rate variability (vmHRV) responses, a psychophysiological index of cognitive self-regulatory control, to map the dynamics associated with empathic responses for pain towards an out-group member. Accordingly, Caucasian participants were asked to judge the experience of African and Caucasian actors touched with either a neutral or a harmful stimulus. Results showed that (1) explicit judgment of pain intensity in African actors yielded higher rating score and (2) took longer time compared to Caucasian actors, (3) these behavioural outcomes were associated with a significant increment of RMSSD, Log-HF-HRV and HF-HRV n.u., (4) resting HF-HRV n.u. predicted the participants’ lag-time to judge painful stimulations delivered to African actors. Interestingly, these dynamics were associated with a measure of implicit racial attitudes and were, in part, abolished when participants performed a concurrent task during videos presentation. Taken together our results support the idea that a cognitive effort is needed to self-regulate our implicit attitude as predicted by the ‘Contrasting Forces Model’.

Question Neuroimaging studies suggest that brain aging can be characterized by a reduction of hemispheric lateralization while performing tasks that require the use of complex cognitive functions. Recently, some authors proposed that even young people show bilateral neural activation as task demand increased. In most studies, however, task’s difficulty had been parametrically increased in a static and pre-specified way, while individual response to task-demand was not systematically controlled. In the present study we investigate changes in neurofunctional lateralization due to increasing subjective cognitive load in young and older participants performing tasks involving different cognitive functions. Methods 24 young participants and 12 older adults performed a digit span backward (complex cognitive function) and a finger tapping task (basic motor function) at 3 levels of subjective task difficulty (“easy” 5/5 correct answers, “medium” 3/5, “difficult” 1/5) which were established before starting the experiment. Participants took part at three sessions in three different days: two real stimulation conditions and a sham condition. In the real conditions anodal tDCS (20 min, 1.5 mA) was delivered through a target electrode (5 × 5 cm) positioned to stimulate both the inferior frontal gyrus and the primary motor area, once over the left hemisphere and once over the right one. The cathode was placed over the contralateral supraorbital area. Results A 3 (left, right, sham) × 3 (easy, medium, difficult) mixed-model with random intercepts for subjects was run within each group. For the young group a significant interaction between difficulty and stimulation was found: right tDCS deteriorates the performance only during the hardest condition. The preliminary results obtained from the 12 elderlies suggest instead that tDCS influence performance only for the “easy” and “medium” conditions. Conclusions The results support the hypothesis that hemispheric lateralization is influenced by the subjective level of difficulty of the task. Our findings are also consistent with the hypothesis of a limited reserve of cognitive resources. Results will be presented and discussed in relation to recent neurocognitive models of aging.

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.

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.

According to the dual-route model, a printed string of letters can be processed by either a grapheme-to-phoneme conversion (GPC) route or a lexical-semantic route. Although meta-analyses of the imaging literature support the existence of distinct but interacting reading procedures, individual neuroimaging studies that explored neural correlates of reading yielded inconclusive results. We used a list-manipulation paradigm to provide a fresh empirical look at this issue and to isolate specific areas that underlie the two reading procedures. In a lexical condition, we embedded disyllabic Italian words (target stimuli) in lists of either loanwords or trisyllabic Italian words with unpredictable stress position. In a GPC condition, similar target stimuli were included within lists of pseudowords. The procedure was designed to induce participants to emphasize either the lexical-semantic or the GPC reading procedure, while controlling for possible linguistic confounds and keeping the reading task requirements stable across the two conditions. Thirty-three adults participated in the behavioral study, and 20 further adult participants were included in the fMRI study. At the behavioral level, we found sizeable effects of the framing manipulations that included slower voice onset times for stimuli in the pseudoword frames. At the functional anatomical level, the occipital and temporal regions, and the intraparietal sulcus were specifically activated when subjects were reading target words in a lexical frame. The inferior parietal and anterior fusiform cortex were specifically activated in the GPC condition. These patterns of activation represented a valid classifying model of fMRI images associated with target reading in both frames in the multi-voxel pattern analyses. Further activations were shared by the two procedures in the occipital and inferior parietal areas, in the premotor cortex, in the frontal regions and the left supplementary motor area. These regions are most likely involved in either early input or late output processes.

Introduction The ability to emphatically share feelings with those of someone in pain is affected by race difference between the target and the onlooker. A differential empathic activation for race (DEAR effect) in favour of the in-group members has been documented in the brain pain matrix (Azevedo et al., 2012; Xu, Zuo, Wang, & Han, 2009). However, we are also capable of unbiased responses to produce politically correct behaviours towards people of a different race. No brain signature for the politically correct responses has been described yet. Here we propose a neurocognitive model based on the interplay of two contrasting forces at the root of implicitly biased and explicitly unbiased empathic responses. Materials and Methods Twenty-four normal right-handed participants, 12 males (mean age=25.3 years, SD=4.81) were recruited among undergraduate university students. Before the fMRI scans, participants completed a Race (Black & White) Implicit Association Test (IAT) to assess the implicit race biases in favour of Black people or White people (Greenwald et al., 1998). During the fMRI scan participants watched 40 shorts videos in which the actor’s left hand was touched by the experimenter, alternatively with a rubber eraser (harmless stimulus) or with a needle (harmful stimulus), followed by a 4 seconds still image of the hand/tool interaction (stimulus phase); finally a question mark appeared on the centre of the computer screen for 3 seconds (pain assessment phase). At this time, participants judged how painful was the actor’s experience using a Likert scale from 0 (not painful at all) to 3 (highly painful) by pressing an appropriate key on a multi-key response pad. The stimuli involved 20 actors, five for each gender and race (Caucasian & African). A factorial design was computed for all the participants in order to isolate at the single-subject level the brain regions showing a race-by-stimulus interaction effect, our effect of interest that we called “DEAR”: Differential Empathic Activation for Race. In particular, the in-group DEAR effect was computed with the following contrast: [Caucasian (harmful stimulus - harmless stimulus)] - [African (harmful stimulus - harmless stimulus)]. The out-group DEAR effect was obtained by reversing (i.e., by multiplying by -1) the linear contrast for the in-group DEAR effect. These effects were entered in second level random effect analyses. Finally, the regional effects and the performance at the behavioural scales were entered in a bivariate correlation analysis to identify the candidate variables to build up a causal model that may connect behavioural variables and neurofunctional effects by means of a standard path-analysis approach. Results and Discussion Similar brain areas of the pain matrix (as defined by Peyron et al, 2000) were involved at the two time windows for the two complementary DEAR effects, suggesting that the embodied component (the more primitive component) is a necessary feature for the delivery of an empathic response. However, for the out-group DEAR effect recorded during the pain assessment phase there was also a PFC contribution coupled with a revealing behavioural pattern: while the participants judged the Caucasians and Africans’ videos as being equally painful, the expression of such unbiased response had a significant behavioural cost, with higher RTs to assess the pain experienced by the African actors. Taken together, these results suggest that out-group DEAR effect may represent the neurofunctional signature of the top-down controlled process necessary to manifest the typical politically correct response seen under these circumstances (for similar behavioural evidence, see, for example, Azevedo et al., 2012). Our interpretation is further supported by the results of a path analysis. The embodied physiological responses within the pain matrix were moderated by the level of the implicit racist bias as measured by the IAT: the higher the bias, the stronger the DEAR at the time of stimulus presentation for the in-group and the lower the DEAR in favour of the out-group at time of the pain assessment phase. Moreover, these biased physiological responses in the pain matrix predicted the manifestation of the out-group DEAR effect within the DLPFC during the pain assessment phase. We suggest that the out-group DEAR response of the DLPFC may serve to counterbalance the racist implicit bias; this in turn was causally linked with the VLPFC activity, which predicted the latency whereby the behavioural politically correct responses were given. References Azevedo, R. T., Macaluso, E., Avenanti, A., Santangelo, V., Cazzato, V., & Aglioti, S. M. (2012). Their pain is not our pain: Brain and autonomic correlates of empathic resonance with the pain of same and different race individuals. Hum Brain Mapp. doi: 10.1002/hbm.22133 Greenwald, A. G., McGhee, D. E., & Schwartz, J. L. (1998). Measuring individual differences in implicit cognition: the implicit association test. J Pers Soc Psychol, 74(6), 1464-1480. Peyron, R., Laurent, B., & García-Larrea, L. (2000). Functional imaging of brain responses to pain. A review and meta-analysis (2000). Neurophysiol Clin, 30(5), 263-288. Xu, X., Zuo, X., Wang, X., & Han, S. (2009). Do you feel my pain? Racial group membership modulates empathic neural responses. J Neurosci, 29(26), 8525-8529. doi: 10.1523/JNEUROSCI.2418-09.2009

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.

Developmental dyslexia has been the focus of much functional anatomical research. The main trust of this work is that typical developmental dyslexics have a dysfunction of the phonological and orthography to phonology conversion systems, in which the left occipito-temporal cortex has a crucial role. It remains to be seen whether there is a systematic co-occurrence of dysfunctional patterns of different functional systems perhaps converging on the same brain regions associated with the reading deficit. Such evidence would be relevant for theories like, for example, the magnocellular/attentional or the motor/cerebellar ones, which postulate a more basic and anatomically distributed disorder in dyslexia. We addressed this issue with a meta-analysis of all the imaging literature published until September 2013 using a combination of hierarchical clustering and activation likelihood estimation methods. The clustering analysis on 2360 peaks identified 193 clusters, 92 of which proved spatially significant. Following binomial tests on the clusters, we found left hemispheric network specific for normal controls (i.e., of reduced involvement in dyslexics) including the left inferior frontal, premotor, supramarginal cortices and the left infero-temporal and fusiform regions: these were preferentially associated with reading and the visual-to-phonology processes. There was also a more dorsal left fronto-parietal network: these clusters included peaks from tasks involving phonological manipulation, but also motoric or visuo-spatial perception/attention. No cluster was identified in area V5 for no task, nor cerebellar clusters showed a reduced association with dyslexics. We conclude that the examined literature demonstrates a specific lack of activation of the left occipito-temporal cortex in dyslexia particularly for reading and reading-like behaviors and for visuo-phonological tasks. Additional deficits of motor and attentional systems relevant for reading may be associated with altered functionality of dorsal left fronto-parietal cortex.

INTRODUZIONE Developmental dyslexia has been the focus of much functional anatomical research. The main trust of this work is that typical developmental dyslexics have a dysfunction of the phonological and orthography to phonology conversion systems, in which the left occipito-temporal cortex has a crucial role. It remains to be seen whether there is a systematic co-occurrence of dysfunctional patterns of different functional systems perhaps converging on the same brain regions associated with the reading deficit. Such evidence would be relevant for theories like, for example, the magnocellular/attentional or the motor/cerebellar ones, which postulate a more basic and anatomically distributed disorder in dyslexia. METODO We addressed this issue with a meta-analysis of all the imaging literature published until September 2013 using a combination of hierarchical clustering and activation likelihood estimates. RISULTATI The clustering analysis on 2360 peaks identified 193 clusters, 92 of which proved significant for spatial extent. Following binomial tests on the clusters, we found a normal-control specific (i.e. reduced involvement in dyslexics) left hemispheric network involving the left inferior frontal, premotor, supramarginal cortices and the left infero-temporal and fusiform region: these were specific for reading and the visual-to-phonology processes. There was also a more dorsal left fronto-parietal network: these clusters included peaks from tasks involving phonological manipulation, but also motoric or visuo-spatial perception/attention. No cluster was identified in area V5 for no task. No significant effects were found for cerebellar clusters either. CONCLUSIONI We conclude that the available literature demonstrates a specific lack of activation of the left occipitotemporal cortex in dyslexics that is specific for reading and reading-like behaviours and for visuo-phonological tasks. Additional deficits may be associated with dorsal fronto-parietal deficits.

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

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.

Although it is widely accepted that nouns and verbs are functionally independent linguistic entities, it is less clear whether their processing recruits different brain areas. This issue is particularly relevant for those theories of lexical semantics (and, more in general, of cognition) that suggest the embodiment of abstract concepts, i.e., based strongly on perceptual and motoric representations. This paper presents a formal meta-analysis of the neuroimaging evidence on noun and verb processing in order to address this dichotomy more effectively at the anatomical level. We used a hierarchical clustering algorithm that grouped fMRI/PET activation peaks solely on the basis of spatial proximity. Cluster specificity for grammatical class was then tested on the basis of the noun-verb distribution of the activation peaks included in each cluster. Thirty-two clusters were identified: three were associated with nouns across different tasks (in the right inferior temporal gyrus, the left angular gyrus, and the left inferior parietal gyrus); one with verbs across different tasks (in the posterior part of the right middle temporal gyrus); and three showed verb specificity in some tasks and noun specificity in others (in the left and right inferior frontal gyrus and the left insula). These results do not support the popular tenets that verb processing is predominantly based in the left frontal cortex and noun processing relies specifically on temporal regions; nor do they support the idea that verb lexical-semantic representations are heavily based on embodied motoric information. Our findings suggest instead that the cerebral circuits deputed to noun and verb processing lie in close spatial proximity in a wide network including frontal, parietal, and temporal regions. The data also indicate a predominant—but not exclusive—left lateralization of the network.

Over the last two decades, developmental dyslexia has been the focus of much research using functional neuroimaging. A wide range of paradigms, tackling different neurocognitive domains, has been used to assess its neural correlates. The main trust of this work is that typical developmental dyslexics have dysfunction of the phonological and orthography to phonology conversion systems, normally housed in the left occipitotemporal cortex. It remains to be seen whether, besides this well replicated finding, there is a systematic co-occurrence of dysfunctional patterns of different functional systems perhaps converging on the same brain regions associated with the reading deficit. Such evidence would be relevant for theories of dyslexia like, for example, the magnocellular one. To address this problem, we performed a meta-analysis based on an optimized hierarchical clustering algorithm (Cattinelli et al., 2012) which automatically grouped 1982 activation peaks, extracted from 48 neuroimaging studies (fMRI and PET), into clusters in which the activation peaks had minimized spatial variance. The data was based on the literature published up to December 2011 including experiments on reading but also on phonological awareness, motor control, visual motion perception and so forth. The clustering analysis identified 82 clusters. The functional role of the clusters was assessed on the basis of statistical criteria. In particular, the binomial test was used to identify which clusters showed a specific activation effect for dyslexics rather than for controls. The left inferior parietal lobule, the left middle temporal gyrus, the left fusiform gyrus and the left cerebellum showed a specific association with the normal control groups, not being active in the dyslexics; on the other hand early subdivisions of visual cortices, bilaterally, the left insula and the right opercular portion of the inferior frontal gyrus showed a specific association with the dyslexic subjects. A qualitative analysis of each cluster was also performed to evaluate the distribution of the activations peaks in relation to the experimental task (e.g. reading, phonological awareness, motor learning, visual motion discrimination, etc.). We found that the aforementioned difference in left fusiform gyrus was selectively due to a lack of commitment to reading in adult dyslexics while the same region showed occasional activation for more basic visual tasks. On the other hand, the specific activation of early visual cortices in dyslexics was associated with a variety of visual tasks with reading tasks playing a major role. We conclude that the available literature demonstrates a specific lack of activation of the left occipitotemporal cortex in dyslexics that is specific for reading and for visuo-phonological tasks. The larger early occipital activations in dyslexics may represent a compensatory effort for the visual analysis of printed words in the absence of a higher-level visual-word form neural expertise. References Cattinelli I., Borghese A.N., Gallucci M., Paulesu E. (In Press) Reading the reading brain: a new meta-analysis of functional imaging data of reading. J. Neurolinguistic.

The HAROLD (hemispheric asymmetry reduction in older adults) model, proposed by Cabeza in 2002, suggests that age-related neurofunctional changes are characterised by a significant reduction in the functional hemispheric lateralisation in the prefrontal cortex (PFC). The supporting evidence, however, has been derived from qualitative explorations of the data rather than from explicit statistical assessments of functional lateralisation. In contrast, the CRUNCH (compensation-related utilisation of neural circuits hypothesis) model posits that elderly subjects recruit additional brain regions that do not necessarily belong to the contralateral hemisphere as much as they rely on additional strategies to solve cognitive problems. To better assess the validity and generalisability of the HAROLD model, we analysed the fMRI patterns of twenty-four young subjects (age range: 18–30 years) and twenty-four healthy elderly subjects (age range: 50–80 years) collected during the performance of two linguistic/semantic tasks (a picture-naming task and a sentence judgment task) and two episodic long-term memory (eLTM) recognition tasks for the same materials. The functional hemispheric lateralisation in each group and the ensuing between-group differences were quantitatively assessed using statistical lateralisation maps (SLMs). The number of clusters showing a genuine HAROLD effect was proportional to the level of task demand. In addition, when quantitatively significant, these effects were not restricted to the PFC. We conclude that, in its original version, the HAROLD model captures only some of the age-related brain patterns observed in graceful ageing. The results observed in our study are compatible with the more general CRUNCH model, suggesting that the former patterns can be considered a special manifestation of age-related compensatory processes.

We studied the linguistic profile and neurolinguistic organization of a 14-year-old adolescent (EB) who underwent a left hemispherectomy at the age of 2.5 years. After initial aphasia, his language skills recovered within 2 years, with the exception of some word finding problems. Over the years, the neuropsychological assessments showed that EB's language was near-to-normal, with the exception of lexical competence, which lagged slightly behind for both auditory and written language. Moreover, EB's accuracy and speed in both reading and writing words and non-words were within the normal range, whereas difficulties emerged in reading loan words and in tasks with homophones. EB's functional magnetic resonance imaging (fMRI) patterns for several linguistic and metalinguistic tasks were similar to those observed in the dominant hemisphere of controls, suggesting that his language network conforms to a left-like linguistic neural blueprint. However, a stronger frontal recruitment suggests that linguistic tasks are more demanding for him. Finally, no specific reading activation was found in EB's occipitotemporal region, a finding consistent with the surface dyslexia-like behavioral pattern of the patient. While a lone right hemisphere may not be sufficient to guarantee full blown linguistic competences after early hemispherectomy, EB's behavioral and fMRI patterns suggest that his lone right hemisphere followed a left-like blueprint of the linguistic network.

We used fMRI to explore the extent of the anatomical overlap of three neural systems that the literature on developmental dyslexia associates with reading: the auditory phonological, the visual magnocellular, and the motor/cerebellar systems. Twenty‐eight normal subjects performed four tasks during fMRI scans: word and pseudoword reading, auditory rhyming for letter names, visual motion perception, and a motor sequence learning task. We found that the left occipitotemporal cortex (OTC), which previous studies reported to be dysfunctional in dyslexia, can be fractionated into different functional areas: an anterior and lateral area that was activated by both reading and auditory rhyming tasks; a posterior area that was commonly activated by both the reading and the motion perception task and a medial/intermediate area, including the so‐called Visual Word Form Area, which was specifically activated by the reading task. These results show that the left OTC is an area of segregated convergence of different functional systems. We compared our results with the hypoactivation pattern reported for reading in a previous cross‐cultural PET study on 36 dyslexic subjects from three countries. The region of decreased activation in dyslexia overlapped with regions that are specific for reading and those activated during both the auditory rhyming task and the single word and pseudoword reading task described in the present fMRI study. No overlap was found with the activation patterns for the visual motion perception task or for the motor sequence learning task. These observations challenge current theories of dyslexia. Hum Brain Mapp 34:2669–2687, 2013. © 2012 Wiley Periodicals, Inc.

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.

It is generally held that noun processing is specifically sub-served by temporal areas, while the neural underpinnings of verb processing are located in the frontal lobe. However, this view is now challenged by a significant body of evidence accumulated over the years. Moreover, the results obtained so far on the neural implementation of noun and verb processing appear to be quite inconsistent. The present review briefly describes and critically re-considers the anatomo-correlative, neuroimaging, MEG, TMS and cortical stimulation studies on nouns and verbs with the aim of assessing the consistency of their results, particularly within techniques. The paper also addresses the question as to whether the inconsistency of the data could be due to the variety of the tasks used. However, it emerged that neither the different investigation techniques used nor the different cognitive tasks employed fully explain the variability of the data. In the final section we thus suggest that the main reason for the emergence of inconsistent data in this field is that the cerebral circuits underlying noun and verb processing are not spatially segregated, at least for the spatial resolution currently used in most neuroimaging studies.

In the last decade, graceful aging has often been associated with frontal hyperactivations in working- and episodic long-term memory tasks, a compensatory process, according to some, that allows the best normal olders to perform these tasks at a juvenile level, in spite of the natural cortical impoverishment. It remains to be established, however, whether the frontal hyperactivation is the only possible neurofunctional manifestation of compensatory processes in halthy aging. In this thesis I present a systematic investigation of this issue and related issues on pathological aging seen in MCI. I first re-assessed the results of 23 recent neuroimaging papers on normal aging using a quantitative meta-analytic approach that allowed us to distinguish between task-dependent and task-independent age-related hyperactivations in healthy olders (Chapter 2). In particular, task-independent hyperactivations emerged in the prefrontal cortex (PFC) in line with the results commonly described in international litterature, while task-dependent hyperactivations emerged in brain regions beyond the prefrontal areas. Further, we investigated more directly the existence of task-specific neurofunctional manifestations of compensatory processes in a new fMRI / VBM study (Chapter 3). In this study, 24 young and 24 healthy elderly participants were compared. Graceful aging was explored by investigating domains where most healthy olders perform like youngers (e.g. lexical-semantic knowledge) and tasks that are typically more challenging, like episodic long-term recognition memory tasks. With voxel-based morphometry we also studied to what extent changes of fMRI activation were consistent with the pattern of brain atrophy. We found that hyperactivations in the group of healthy olders were not restricted to the frontal lobes, rather they presented with task-dependent patterns. Moreover, only hypoactivations did systematically overlap with regional atrophy. On the basis of these results we suggest that compensatory processes associated with graceful aging are not necessarily a sign of early saturation of executive resources, if this saturation was to be represented by a systematic frontal hyperactivation. The role of the PFC over-recruitment and age-related neurofunctional changes in healthy olders was further investigated in Chapter 4. In particular in this study we reviewed the neurofunctional data collected in the third Chapter in the light of the HAROLD model (Hemispheric Asymmetry Reduction in Olders). Again, the data clearly suggested that the manifestation of age-related neurofunctional changes of functional lateralization in healthy olders is not exclusively restricted to the frontal areas, rather these are distributed across the entire brain volume in a task-related manner. Finally, in order to better address neurofunctional and neuroanatomical changes in pathological aging and to create a link with theoretical frameworks that describe graceful aging, we compared behavioural, neurofunctional and neuroanatomical data of 24 healthy olders and 9 aMCI patients, challenged with the same lexical-semantic and episodic long-term memory tasks used in Chapter 3. The between groups differences were analysed in the light of our previous findings on the neural pattern of compensatory processes in healthy aging (described in Chapter 3). A systematic pattern emerged: aMCI patients showed over-activations in parts of the task-specific neural networks that are dysfunctional in highly-performing healthy olders, while they under-recruited the task-specific compensatory neural networks typically over-activated by healthy older controls. Moreover, the over-recruitments of areas which became of no use in healthy aging showed a negative correlation with the gray matter density in the medial temporal lobe structures. These results are discussed in terms of lack of neural plasticity in pathological aging. I conclude my dissertation with chapter 6 where I propose a neurocognitive account of healthy and pathological aging in terms of compensatory processes and neural plasticity.

The ability to learn new words peaks in childhood, even though adults continue to learn new words in their native language, as well in foreign languages (1). Leaning new words through reading represents a particular cognitive challenge, as the acquisition of the orthographic form is simultaneous to the learning of the phonological form. The neural mechanisms supporting the acquisition of new entries in the mental orthographic lexicon has not been extensively explored in adults, an issue that we addressed in this fMRI experiment. We assessed the learning of the phonological form and of the orthographic form of neologisms in 22 subjects. The experiment included an encoding phase when subjects read or heard and incidentally learned new-words that were repeated six times over six consecutive blocks of stimuli. Continuously changing distractors were mixed with the experimental items. In the second phase, during fMRI scanning, subjects explicitly recognized from distractors the new-words already seen/heard in the previous blocks. The event-related analysis of the fMRI data showed a common area of enhanced response in the left middle temporal gyrus for the successful recognition of non-words learned in both “listening” and “reading” conditions. There was also a double-dissociated pattern: written new-word forms recognition was associated with a specific enhancement in the left inferior frontal gyrus, the left inferior temporal/fusiform gyrus and the cerebellum, while a second region of the middle temporal gyrus was activated only for the recognition of words learned in the “listening” condition (2). This pattern of partially overlapping and dissociable systems for non-words learning in the auditory modality and in the reading modality is compatible with previous neuropsychological and anatomical observations in patient PV (3) who was completely unable to learn new-words when presented auditorily while retaining a marginal ability to learn new words when presented visually. References (1) Gathercole S.E., Baddeley A.D. Working memory and language. Hove: Lawrence Erlbaum, 1993. (2) Paulesu E., Vallar G., Berlingeri M., Signorini M., Vitali P., Burani C., et al. Supercalifragilisticexpialidocious: how the brain learns words never heard before. Neuroimage 2009; 45: 1368-77. (3) Baddeley, A.D., Papagno, C., Vallar, G. When long-term learning depends on short-term storage. Journal of memory and language 1988; 27: 586-595.

Graceful aging has been associated with frontal hyperactivations in working- and episodic long-term memory tasks, a compensatory process, according to some, that allows the best normal elders to perform these tasks at a juvenile level, in spite of natural cortical impoverishment. In this study, 24 young and 24 healthy elderly participants were compared. Graceful aging was explored by investigating domains where most healthy elders perform like youngers (e.g. lexical-semantic knowledge) and tasks that are typically more challenging, like episodic long-term recognition memory tasks. With voxel-based morphometry, we also studied to what extent changes of fMRI activation were consistent with the pattern of brain atrophy. We found that hyperactivations and hypoactivations of the elders were not restricted to the frontal lobes, rather they presented with task-dependent patterns. Only hypoactivations and normal levels of activation systematically overlapped with regional atrophy. We conclude that compensatory processes associated with graceful aging may not necessarily be a sign of early saturation of executive resources, if this was to be represented by a systematic frontal hyperactivation, but rather they may represent the ability of recruiting new cognitive strategies. We discuss two possible approaches to further test this hypothesis.

Although the functional independence of noun and verb lexical retrieval has been reliably established, it is not clear whether the processing of these grammatical classes recruits separate neural circuits [1]. Contrasting results might have emerged because different studies used different experimental and baseline tasks. The meta‑analysis described in this study aims at identifying (i) brain regions that are consistently associated with a given grammatical class across different tasks, and (ii) brain areas whose grammatical‑class specificity is modulated by the task used. We considered 620 activation peaks reported in 27 neuroimaging studies on nouns and verbs. A hierarchical cluster algorithm was used in order to automatically segregate groups of coordinates into separate clusters. This procedure produced a set of 52 clusters, which were assessed with a binomial test for specificity for grammatical class and/or task, and with a Fisher test for task‑by‑grammatical class interaction. One cluster was associated with nouns across different tasks in the right superior temporal gyrus; verb‑specific clusters were instead observed in the middle temporal gyrus bilaterally, in the right precuneus and in the left lingual gyrus. Other four clusters – located in the left inferior frontal gyrus, in the left insula, and in the left middle occipital gyrus – showed a task‑by‑grammatical class interaction. The impact of these results on the current neuroanatomical theories of noun and verb processing [2] will be discussed. [1] Berlingeri, M. et al. (2008), Cognitive Neuropsychology, 25, 528‑558. [2] Cappa, S. & Perani, D. (2003), Journal of Neurolinguistics, 16, 183‑189.

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 functional independence of noun and verb lexical retrieval has been repeatedly demonstrated over the last decade (e.g., Rapp and Caramazza, 2002); however, the evidence produced so far on whether these processes recruit separate neural circuits is far less clear (e.g., Bedny & Thompson‑Schill, 2006; Berlingeri et al., 2008). This may be due to the lack of homogeneity in the tasks used in the various experiments. The meta‑analysis described in this study aims at disentangling the brain regions that are systematically associated with a given grammatical class from those whose grammatical‑class specificity is modulated by the task used. We collected 620 activation coordinates associated with either nouns or verbs in simple effect analyses from 22 neuroimaging studies published from 1996 to 2008. A hierarchical cluster algorithm was employed adopting the Ward (1963) criterion to automatically segregate groups of coordinates into separate clusters (mean standard deviation < 7.5 mm in the x, y, and z directions for each cluster; Jobard et al., 2003). This procedure produced a set of 49 clusters, which were assessed with a binomial test for specificity for grammatical class and/or task, and with a Fisher test for task‑by‑grammatical class interaction. Two clusters turned out to be associated with nouns across different tasks, while five were associated with verbs (Figure 1a); the locations of these clusters do not support spatially segregated neural circuits for nouns and verbs, as suggested in some previous work (e.g., Cappa & Perani, 2003). Five clusters showed instead a task‑by‑grammatical class interaction (Figure 1b), which was mainly driven by noun‑specific activation in derivational tasks and by verb‑specific activation in picture naming and fluency tasks. These results will be discussed in the light of the cognitive processes entailed by the individual experimental tasks.

To date the evidence which has emerged from both anatomo‑correlative and neuroimaging studies investigating the brain areas responsible for noun and verb processing [e.g. 1, 2, 3] is inconsistent; this may be due to the lack of homogeneity in the tasks used in the various experiments. The metanalysis described in this study aims at disentangling brain regions that are systematically associated with a given grammatical class from those whose grammatical‑class specificity is modulated by the task used. We collected 441 activation peak coordinates associated with either nouns or verbs in simple effect analyses from 27 neuroimaging studies published from 1996 to 2008, and employed a hierarchical cluster algorithm adopting the Ward criterion [4] to automatically segregate groups of activation coordinates into separate clusters with mean standard deviations of less than 7.5 mm [5] in the three directions (x, y, z). This procedure produced a set of 37 clusters, which were tested with a chi‑square analysis for specificity for grammatical class and/or task. Nine of these clusters showed a significant task-by-grammatical class interaction, which in derivational tasks was usually caused by noun‑specific activation and in picture naming and fluency tasks by verb‑specific activation. These results are discussed in the light of the cognitive processes underlying the individual experimental tasks. REFERENCES [1] Perani, D., Cappa, S.F., Schnur, T., Tettamanti, M., Collina, S., Rosa, M.M., Fazio, F. (1999). The neural correlates of verb and noun processing. A PET study. Brain, 122, 2337­‑2344. [2] Aggujaro, S., Crepaldi, D., Pistarini, C., Taricco, M., Luzzatti, C. (2006). Neuro-anatomical correlates of impaired retrieval of verbs and nouns: Interaction of grammatical class, imageability and actionality. Journal of Neurolinguistics, 19, 175-194. [3] Tyler, L.K., Russell, R., Fadili, J., Moss, H.E. (2001). The neural representation of nouns and verbs: PET studies. Brain, 124, 1619-1634. [4] Ward, J.H. (1963). Hierarchical grouping to optimize an objective function. Journal of the American Statistical Association, 158, 236-244. [5] Jobard, G., Crivello, F., and Tzourio-Mazoyer, N. (2003). Evaluation of the dual route theory of reading: a metanalysis of 35 neuroimaging studies. NeuroImage, 20, 693-712.

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.

Introduction Current data on the neural correlates of noun and verb processing are inconsistent as studies using different imaging techniques and/or different tasks have provided remarkably different results. This fMRIstudy was designed to clarify this issue by assessing task-independent and task-dependent grammatical-class-specific effects during lexical retrieval tasks. Materials and Methods - Subjects: 12 right-handed Italian students (F=6, M=6), aged 20-34, 15 years of schooling. Materials: subjects retrieved nouns and verbs during two different tasks: a picture naming task similar to the one adopted in previous experiments (PNT) and a retrieval task (NVRT ) were verbs or nouns were derived from the corresponding noun or verb (say “vincere” (to win) when reading “vittoria” (victory), or vicversa; NVRT, see Crepaldi et al., 2006). It should be noted that the typical picture naming task used to assess noun or verb retrieval is necessarily imbalanced for imageability and visual complexity, with pictures for verbs being more complex than pictures for objects. On the other hand, in NVRT task nouns and verbs had the same level of imageability. We also had a simple reading task for nouns or for verbs as a control experiment. Before fMRI scans, subject familiarized with the experimental stimuli so that strategic search of targets was minimized. Here we recorded VOTs for the different tasks. - fMRI data acquisition and analysis: 1.5 T Marconi-Philips Infinion Scanner, EPI gradient echo sequence TR: 3”; TE: 60 msec; Flip angle: 90°. Data were collected in alternating 30” blocks of baseline and experimental tasks. Condition-specific effects were estimated according to the general linear model (GLM) in SPM2. Statistical thresholds: p