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Introduction: Standardized cognitive assessment would enhance diagnostic reliability across memory clinics. An expert consensus adapted the Uniform Dataset (UDS)-3 for European centers, the clinician's UDS (cUDS). This study assessed its implementation acceptability and feasibility. Methods: We developed a survey investigating barriers, facilitators, and willingness to implement the cUDS. With a mixed-methods design, we analyzed data from academic memory clinics. Results: Seventy-eight percent of responding clinicians were experienced neuropsychologists/psychologists and 22% were medical specialists coming from 18 European countries. Sixty-five percent clinicians were willing to implement cUDS. General barriers related to implementation (43%) and clinical-methodological domains (21%). Favorable clinicians reported finances (15%) and digitalization (9%) as facilitating, but unavailability of local norms (23%) as hindering. Unfavorable clinicians reported logistical (23%) and time issues (18%). Discussion: Despite challenges, data showed moderate clinicians' acceptability and requirements to improve feasibility. Nonetheless, these results come from academic clinicians. The next steps will require feasibility evaluation in non-academic contexts.

Item does not contain fulltext, As research and services in the Mediterranean region continue to increase, so do opportunities for global collaboration. To support such collaborations, the Alzheimer's Association was due to hold its seventh Alzheimer's Association International Conference Satellite Symposium in Athens, Greece in 2021. Due to the COVID-19 pandemic, the meeting was held virtually, which enabled attendees from around the world to hear about research efforts in Greece and the surrounding Mediterranean countries. Research updates spanned understanding the biology of, treatments for, and care of people with Alzheimer's disease (AD_ and other dementias. Researchers in the Mediterranean region have outlined the local epidemiology of AD and dementia, and have identified regional populations that may expedite genetic studies. Development of biomarkers is expected to aid early and accurate diagnosis. Numerous efforts have been made to develop culturally specific interventions to both reduce risk of dementia, and to improve quality of life for people living with dementia.

Background and ObjectiveThis was a multicenter study aimed at investigating the characteristics of cognitive decline, neuropsychiatric symptoms, and brain imaging in individuals with subjective cognitive decline (SCD) and subtle cognitive decline (pre-mild cognitive impairment [pre-MCI]).MethodsData were obtained from the Network-AD project (NET-2011-02346784). The included participants underwent baseline cognitive and neurobehavioral evaluation, FDG-PET, and amyloid PET. We used principal component analysis (PCA) to identify independent neuropsychological and neuropsychiatric dimensions and their association with brain metabolism.ResultsA total of 105 participants (SCD = 49, pre-MCI = 56) were included. FDG-PET was normal in 45% of participants and revealed brain hypometabolism in 55%, with a frontal-like pattern as the most frequent finding (28%). Neuropsychiatric symptoms emerging from the Neuropsychiatric Inventory and the Starkstein Apathy Scale were highly prevalent in the whole sample (78%). An abnormal amyloid load was detected in the 18% of the participants who underwent amyloid PET (n = 60). PCA resulted in 3 neuropsychological factors: (1) executive/visuomotor, correlating with hypometabolism in frontal and occipital cortices and basal ganglia; (2) memory, correlating with hypometabolism in temporoparietal regions; and (3) visuospatial/constructional, correlating with hypometabolism in frontoparietal cortices. Two factors emerged from the neuropsychiatric PCA: (1) affective, correlating with hypometabolism in orbitofrontal and cingulate cortex and insula; (2) hyperactive/psychotic, correlating with hypometabolism in frontal, temporal, and parietal regions.DiscussionFDG-PET evidence suggests either normal brain function or different patterns of brain hypometabolism in SCD and pre-MCI. These results indicate that SCD and pre-MCI represent heterogeneous populations. Different neuropsychological and neuropsychiatric profiles emerged, which correlated with neu

Noninvasive brain stimulation techniques (NiBS) have gathered substantial interest in the study of dementia, considered their possible role in help defining diagnostic biomarkers of altered neural activity for early disease detection and monitoring of its pathophysiological course, as well as for their therapeutic potential of boosting residual cognitive functions. Nevertheless, current approaches suffer from some limitations. In this study, we review and discuss experimental NiBS applications that might help improve the efficacy of future NiBS uses in Alzheimer's Disease (AD), including perturbation-based biomarkers for early diagnosis and disease tracking, solutions to enhance synchronization of oscillatory electroencephalographic activity across brain networks, enhancement of sleep-related memory consolidation, image-guided stimulation for connectome control, protocols targeting interneuron pathology and protein clearance, and finally hybrid-brain models for in-silico modeling of AD pathology and personalized target selection. The present work aims to stress the importance of multidisciplinary, translational, model-driven interventions for precision medicine approaches in AD.

OBJECTIVE: To investigate the types of errors produced in a picture naming task by patients with neurodegenerative dementia due to different etiologies and their neural correlates. METHODS: The same standardized picture naming test was administered to a consecutive sample of patients (n = 148) who had been studied with [18F] FDG-PET. The errors were analyzed in 3 categories (visual, semantic, and phonologic). The PET data were analyzed using an optimized single-subject procedure, and the statistical parametric mapping multiple regression design was used to explore the correlation between each type of error and brain hypometabolism in the whole group. Metabolic connectivity analyses were run at the group level on 7 left hemisphere cortical areas corresponding to an a priori defined naming network. RESULTS: Semantic errors were predominant in most patients, independent of clinical diagnosis. In the whole group analysis, visual errors correlated with hypometabolism in the right inferior occipital lobe and in the left middle occipital lobe. Semantic errors correlated with hypometabolism in the left fusiform gyrus, the inferior and middle temporal gyri, and the temporal pole. Phonologic errors were associated with hypometabolism in the left superior and middle temporal gyri. Both positive (occipital-posterior fusiform) and negative (anterior fusiform gyrus and the superior anterior temporal lobe) connectivity changes were associated with semantic errors. CONCLUSIONS: Naming errors reflect the dysfunction of separate stages of the naming process and are specific markers for different patterns of brain involvement. These correlations are not limited to primary progressive aphasia but extend to other neurodegenerative dementias.

The observation of neurological patients showing selective impairments for specific conceptual categories contributed in the development of semantic memory theories. Here, we studied two patients (P01, P02), affected, respectively, by the semantic variant of Primary Progressive Aphasia (sv-PPA) and Cortico-Basal Syndrome (CBS). An implicit lexical decision task, including concrete (animals, tools) and abstract (emotions, social, quantity) concepts, was administered to patients and healthy controls.P01 and P02 showed an abolished priming effect for social and quantity-related concepts, respectively. This double dissociation suggests a role of different brain areas in representing specific abstract categories, giving insights for current semantic memory theories.

Alzheimer's disease (AD) is the most common neurodegenerative disease among the elderly with a progressive decline in cognitive function significantly affecting quality of life. Both the prevalence and emotional and financial burdens of AD on patients, their families, and society are predicted to grow significantly in the near future, due to a prolongation of the lifespan. Several lines of evidence suggest that modifications of risk-enhancing life styles and initiation of pharmacological and non-pharmacological treatments in the early stage of disease, although not able to modify its course, helps to maintain personal autonomy in daily activities and significantly reduces the total costs of disease management. Moreover, many clinical trials with potentially disease-modifying drugs are devoted to prodromal stages of AD. Thus, the identification of markers of conversion from prodromal form to clinically AD may be crucial for developing strategies of early interventions. The current available markers, including volumetric magnetic resonance imaging (MRI), positron emission tomography (PET), and cerebral spinal fluid (CSF) analysis are expensive, poorly available in community health facilities, and relatively invasive. Taking into account its low cost, widespread availability and non-invasiveness, electroencephalography (EEG) would represent a candidate for tracking the prodromal phases of cognitive decline in routine clinical settings eventually in combination with other markers. In this scenario, the present paper provides an overview of epidemiology, genetic risk factors, neuropsychological, fluid and neuroimaging biomarkers in AD and describes the potential role of EEG in AD investigation, trying in particular to point out whether advanced analysis of EEG rhythms exploring brain function has sufficient specificity/sensitivity/accuracy for the early diagnosis of AD.

Background: In recent years, the potential usefulness of cognitive training procedures in normal aging and mild cognitive impairment (MCI) have received increased attention. Objective: The main aim of this study was to evaluate the efficacy of the face-to-face cognitive virtual reality rehabilitation system (VRRS) and to compare it to that of face-to-face cognitive treatment as usual for individuals with MCI. Moreover, we assessed the possibility of prolonging the effects of treatment with a telerehabilitation system. Methods: A total of 49 subjects with MCI were assigned to 1 of 3 study groups in a randomized controlled trial design: (a) those who received face-to-face cognitive VRRS (12 sessions of individualized cognitive rehabilitation over 4 weeks) followed by telerehabilitation (36 sessions of home-based cognitive VRRS training, three sessions for week); (b) those who received face-to-face cognitive VRRS followed by at-home unstructured cognitive stimulation (36 sessions of home-based unstructured cognitive stimulation, three sessions for week); and (c) those who received face-to-face cognitive treatment as usual (12 sessions of face-to-face cognitive treatment as usual). Results: An improvement in memory, language and visuo-constructional abilities was observed after the end of face-to-face VRRS treatment compared to face-to-face treatment as usual. The application of home-based cognitive VRRS telerehabilitation seems to induce more maintenance of the obtained gains than home-based unstructured stimulation. Discussion: The present study provides preliminary evidence in support of individualized VRRS treatment and telerehabilitation delivery for cognitive rehabilitation and should pave the way for future studies aiming at identifying optimal cognitive treatment protocols in subjects with MCI. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03486704.

An Intention Processing Network (IPN), involving the medial prefrontal cortex, precuneus, bilateral posterior superior temporal sulcus, and temporoparietal junctions, plays a fundamental role in comprehending intentions underlying action goals. In a previous fMRI study, we showed that, depending on the linguistic or extralinguistic (gestural) modality used to convey the intention, the IPN is complemented by activation of additional brain areas, reflecting distinct modality-specific input gateways to the IPN. These areas involve, for the linguistic modality, the left inferior frontal gyrus (LIFG), and for the extralinguistic modality, the right inferior frontal gyrus (RIFG). Here, we tested the modality-specific gateway hypothesis, by using DCM to measure inter-regional functional integration dynamics between the IPN and LIFG/RIFG gateways. We found strong evidence of a well-defined effective connectivity architecture mediating the functional integration between the IPN and the inferior frontal cortices. The connectivity dynamics indicate a modality-specific propagation of stimulus information from LIFG to IPN for the linguistic modality, and from RIFG to IPN for the extralinguistic modality. Thus, we suggest a functional model in which the modality-specific gateways mediate the structural and semantic decoding of the stimuli, and allow for the modality-specific communicative information to be integrated in Theory of Mind inferences elaborated through the IPN.

Frontotemporal Dementia (FTD) is preceded by a long period of subtle brain changes, occurring in the absence of overt cognitive symptoms, that need to be still fully characterized. Dynamic network analysis based on restingstate magnetic resonance imaging (rs-fMRI) is a potentially powerful tool for the study of preclinical FTD. In the present study, we employed a "chronnectome" approach (recurring, time-varying patterns of connectivity) to evaluate measures of dynamic connectivity in 472 at-risk FTD subjects from the Genetic Frontotemporal dementia research Initiative (GENFI) cohort. We considered 249 subjects with FTD-related pathogenetic mutations and 223 mutation non-carriers (HC). Dynamic connectivity was evaluated using independent component analysis and sliding-time window correlation to rs-fMRI data, and meta-state measures of global brain flexibility were extracted. Results show that presymptomatic FTD exhibits diminished dynamic fluidity, visiting less meta-states, shifting less often across them, and travelling through a narrowed meta-state distance, as compared to HC. Dynamic connectivity changes characterize preclinical FTD, arguing for the desynchronization of the inner fluctuations of the brain. These changes antedate clinical symptoms, and might represent an early signature of FTD to be used as a biomarker in clinical trials.

Background: There is little evidence about the prevalence of cognitive disorders and their effect on in-hospital mortality in large multicenter studies. The objectives of the 2016th edition of the “Italian Delirium Day,” a large multicenter study on in-hospital older patients, were to assess (i) the point prevalence of cognitive impairment/no dementia, dementia, delirium, and delirium superimposed on dementia and (ii) the effect of these conditions on in-hospital mortality. Methods: This multicenter study and included 2,037 older patients (aged ≥65 years) admitted to acute medical and surgical wards across 205 acute hospitals. The four cognitive disorders groups were defined with a structured approach including the four AT and the presence of a documented diagnosis of dementia. The outcome measure was in-hospital mortality, as reported by the researchers involved in the study in each center. Results: The mean age was 81.17 ± 7.7 years. Overall, 893 patients (43.8%) had neither delirium nor dementia nor cognitive impairment, 483 (23.7%) had cognitive impairment/no dementia, 230 (11.3%) dementia alone, 187 (9.2%) delirium alone, and 244 (12.0%) delirium superimposed on dementia. Overall, 99 (4.8%) patients died. Participants with delirium alone (odds ratio 2.56; 95% confidence interval: 1.29–5.09) and those with delirium superimposed on dementia (odds ratio 2.60; 95% confidence interval: 1.39–4.85) had higher mortality risk compared with the reference group of patients with “no cognitive impairment.” Conclusions: Delirium and delirium superimposed on dementia were highly prevalent among older hospitalized patients and significantly increased in-hospital mortality. Clinicians should systematically assess these conditions and recognize them as markers of critical conditions and predictors of imminent death.

BACKGROUND: Mild cognitive impairment (MCI) among an aging global population is a growing challenge for healthcare providers and payers. In many cases, MCI is an ominous portent for dementia. Early and accurate diagnosis of MCI provides a window of opportunity to improve the outcomes using a personalized care plan including lifestyle modifications to reduce the impact of modifiable risk factors (for example, blood pressure control and increased physical activity), cognitive training, dietary advice, and nutritional support. Souvenaid is a once-daily drink containing a mixture of precursors and cofactors (long-chain omega-3 fatty acids, uridine, choline, B vitamins, vitamin C, vitamin E, and selenium), which was developed to support the formation and function of neuronal membranes and synapses. Healthcare providers, patients, and carers require expert advice about the use of Souvenaid. METHODS: An international panel of experts was convened to review the evidence and to make recommendations about the diagnosis and management of MCI, identification of candidates for Souvenaid, and use of Souvenaid in real-world practice. This article provides a summary of the expert opinions and makes recommendations for clinical practice and future research. Early diagnosis of MCI requires the use of suitable neuropsychological tests combined with a careful clinical history. A multimodal approach is recommended; dietary and nutritional interventions should be considered alongside individualized lifestyle modifications. Although single-agent nutritional supplements have failed to produce cognitive benefits for patients with MCI, a broader nutritional approach warrants consideration. Evidence from randomized controlled trials suggests that Souvenaid should be considered as an option for some patients with early Alzheimer's disease (AD), including those with MCI due to AD (prodromal AD). CONCLUSION: Early and accurate diagnosis of MCI provides a window of opportunity to improve the outc

Objective: This study aimed to evaluate the association between polypharmacy and delirium, the association of specific drug categories with delirium, and the differences in drug-delirium association between medical and surgical units and according to dementia diagnosis. Methods: Data were collected during 2 waves of Delirium Day, a multicenter delirium prevalence study including patients (aged 65 years or older) admitted to acute and long-term care wards in Italy (2015-2016); in this study, only patients enrolled in acute hospital wards were selected (n = 4,133). Delirium was assessed according to score on the 4 "A's" Test. Prescriptions were classified by main drug categories; polypharmacy was defined as a prescription of drugs from 5 or more classes. Results: Of 4,133 participants, 969 (23.4%) had delirium. The general prevalence of polypharmacy was higher in patients with delirium (67.6% vs 63.0%, P =.009) but varied according to clinical settings. After adjustment for confounders, polypharmacy was associated with delirium only in patients admitted to surgical units (OR = 2.9; 95% CI, 1.4-6.1). Insulin, antibiotics, antiepileptics, antipsychotics, and atypical antidepressants were associated with delirium, whereas statins and angiotensin receptor blockers exhibited an inverse association. A stronger association was seen between typical and atypical antipsychotics and delirium in subjects free from dementia compared to individuals with dementia (typical: OR = 4.31; 95% CI, 2.94-6.31 without dementia vs OR = 1.64; 95% CI, 1.19-2.26 with dementia; atypical: OR = 5.32; 95% CI, 3.44-8.22 without dementia vs OR = 1.74; 95% CI, 1.26-2.40 with dementia). The absence of antipsychotics among the prescribed drugs was inversely associated with delirium in the whole sample and in both of the hospital settings, but only in patients without dementia. Conclusions: Polypharmacy is significantly associated with delirium only in surgical units, raising the issue of the relevance of

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In the prospect of improved disease management and future clinical trials in Frontotemporal Dementia, it is desirable to share common diagnostic procedures. To this aim, the Italian FTD Network, under the aegis of the Italian Neurological Society for Dementia, has been established. Currently, 85 Italian Centers involved in dementia care are part of the network. Each Center completed a questionnaire on the local clinical procedures, focused on (1) clinical assessment, (2) use of neuroimaging and genetics; (3) support for patients and caregivers; (4) an opinion about the prevalence of FTD. The analyses of the results documented a comprehensive clinical and instrumental approach to FTD patients and their caregivers in Italy, with about 1,000 newly diagnosed cases per year and 2,500 patients currently followed by the participating Centers. In analogy to other European FTD consortia, future aims will be devoted to collect data on epidemiology of FTD and its subtypes and to provide harmonization of procedures among Centers.

In this paper, performance of different indicators for the profiling of Ultra Wide Band (UWB) wireless propagation channel are analyzed. In particular, the γ-indicator and the kurtosis index k are compared in terms of the standard error. In order to improve the accuracy in the kurtosis case, results of the bootstrap error procedure are also accomplished. Further, an evaluation on the computational time needed for error estimation, is also provided. The comparison is made according to a real set of data derived from UWB measurement campaign accomplished within a modern laboratory/office building in which the two above mentioned indicators have been evaluated.

Neuroeconomics is providing insights into the neural bases of decision-making in normal and pathological conditions. In the neuropsychiatric domain, this discipline investigates how abnormal functioning of neural systems associated with reward processing and cognitive control promotes different disorders, and whether such evidence may inform treatments. This endeavor is crucial when studying different types of addiction, which share a core promoting mechanism in the imbalance between impulsive subcortical neural signals associated with immediate pleasurable outcomes and inhibitory signals mediated by a prefrontal reflective system. The resulting impairment in behavioral control represents a hallmark of alcohol use disorders (AUDs), a chronic relapsing disorder characterized by excessive alcohol consumption despite devastating consequences. This review aims to summarize available magnetic resonance imaging (MRI) evidence on reward-related decision-making alterations in AUDs, and to envision possible future research directions. We review functional MRI (fMRI) studies using tasks involving monetary rewards, as well as MRI studies relating decision-making parameters to neurostructural gray- or white-matter metrics. The available data suggest that excessive alcohol exposure affects neural signaling within brain networks underlying adaptive behavioral learning via the implementation of prediction errors. Namely, weaker ventromedial prefrontal cortex activity and altered connectivity between ventral striatum and dorsolateral prefrontal cortex likely underpin a shift from goal-directed to habitual actions which, in turn, might underpin compulsive alcohol consumption and relapsing episodes despite adverse consequences. Overall, these data highlight abnormal fronto-striatal connectivity as a candidate neurobiological marker of impaired choice in AUDs. Further studies are needed, however, to unveil its implications in the multiple facets of decision-making.

Decoding the meaning of others’ actions, a crucial step for social cognition, involves different neural mechanisms. While the “mirror” and “mentalizing” systems have been associated with, respectively, the processing of biological actions versus more abstract information, their respective contribution to intention understanding is debated. Processing social interactions seems to recruit both neural systems, with a different weight depending on cues emphasizing either shared action goals or shared mental states. We have previously shown that observing cooperative and affective social interactions elicits stronger activity in key nodes of, respectively, the mirror (left posterior superior temporal sulcus (pSTS), superior parietal cortex (SPL), and ventral/dorsal premotor cortex (vPMC/dPMC)) and mentalizing (ventromedial prefrontal cortex (vmPFC)) systems. To unveil their causal organization, we investigated the effective connectivity underlying the observation of human social interactions expressing increasing cooperativity (involving left pSTS, SPL, and vPMC) versus affectivity (vmPFC) via dynamic causal modeling in 36 healthy human subjects. We found strong evidence for a model including the pSTS and vPMC as input nodes for the observed interactions. The extrinsic connectivity of this model undergoes oppositely valenced modulations, with cooperativity promoting positive modulations of connectivity between pSTS and both SPL (forward) and vPMC (mainly backward), and affectivity promoting reciprocal positive modulations of connectivity between pSTS and vmPFC (mainly backward). Alongside fMRI data, such divergent effective connectivity suggests that different dimensions underlying the processing of social interactions recruit distinct, although strongly interconnected, neural pathways associated with, respectively, the bottom–up visuomotor processing of motor intentions, and the top–down attribution of affective/mental states.

Tools represent a special class of objects, as functional details of tools can afford certain actions. In addition, information gained via prior experience with tools can be accessed on a semantic level, providing a basis for meaningful object interactions. Conceptual representations of tools also encompass knowledge about tool manipulation which can be acquired via direct (active manipulation) or indirect (observation of others manipulating objects) motor experience. The present study aimed to explore the impact of observation of manipulation on the neural processing of previously unfamiliar, manipulable objects. Brain activity was assessed by means of functional magnetic resonance imaging while participants accomplished a visual matching task involving pictures of the novel objects before and after they received object-related training. Three training session in which subjects observed an experimenter manipulating one set of objects and visually explored another set of objects were used to make subjects familiar with the tools and to allow the formation of new tool representations. A control object set was not part of the training. Training-related brain activation increases were found for observed manipulation objects compared to not trained objects in a left-hemispheric network consisting of inferior frontal gyrus (iFG) pars opercularis and triangularis and supramarginal/angular gyrus. This illustrates that direct manipulation experience is not required to elicit tool-associated activation changes in the action system. While the iFG activation might indicate a close relationship between the areas involved in tool representation and those involved in observational knowledge acquisition, the parietal activation is discussed in terms of non-semantic effects of object affordances and handtool spatial relationships.

Sensory/functional accounts of semantic memory organization emphasize that object representations in the brain reflect the modalities involved in object knowledge acquisition. The present study aimed to elucidate the impact of different types of object-related sensorimotor experience on the neural representations of novel objects. Sixteen subjects engaged in an object matching task while their brain activity was assessed with functional magnetic resonance imaging (fMRI), before and after they acquired knowledge about previously unfamiliar objects. In three training sessions subjects learned about object function, actively manipulating only one set of objects (manipulation training objects, MTO), and visually exploring a second set (visual training objects, VTO). A third object set served as control condition and was not part of the training (no training objects, NTO). While training-related activation increases were observed in the fronto-parietal cortex for both VTO and MTO, post training activity in the left inferior/middle frontal gyrus and the left posterior inferior parietal lobule was higher for MTO than VTO and NTO. As revealed by Dynamic Causal Modeling of effective connectivity between the regions with enhanced post training activity, these effects were likely caused, respectively, by a down-regulation of a fronto-parietal tool use network in response to VTO, and by an increased connectivity for MTO. This pattern of findings indicates that the modalities involved in sensorimotor experience influence the formation of neural representations of objects in semantic memory, with manipulation experience specifically yielding higher activity in regions of the fronto-parietal cortex.

Decision making under risk entails the anticipation of prospective outcomes, typically leading to the greater sensitivity to losses than gains known as loss aversion. Previous studies on the neural bases of choice-outcome anticipation and loss aversion provided inconsistent results, showing either bidirectional mesolimbic responses of activation for gains and deactivation for losses, or a specific amygdala involvement in processing losses. Here we focused on loss aversion with the aim to address interindividual differences in the neural bases of choice-outcome anticipation. Fifty-six healthy human participants accepted or rejected 104 mixed gambles offering equal (50%) chances of gaining or losing different amounts of money while their brain activity was measured with functional magnetic resonance imaging (fMRI). We report both bidirectional and gain/loss-specific responses while evaluating risky gambles, with amygdala and posterior insula specifically tracking the magnitude of potential losses. At the individual level, loss aversion was reflected both in limbic fMRI responses and in gray matter volume in a structural amygdala-thalamus-striatum network, in which the volume of the "output" centromedial amygdala nuclei mediating avoidance behavior was negatively correlated with monetary performance. We conclude that outcome anticipation and ensuing loss aversion involve multiple neural systems, showing functional and structural individual variability directly related to the actual financial outcomes of choices. By supporting the simultaneous involvement of both appetitive and aversive processing in economic decision making, these results contribute to the interpretation of existing inconsistencies on the neural bases of anticipating choice outcomes.

Our study evaluated motor cortex involvement during silent reading of sentences referring to hand actions. We aimed at defining whether sentential polarity (affirmative vs. negative) would modulate motor cortex activation using the event-related desynchronization (ERD) analysis of the mu rhythm. Eleven healthy volunteers performed a reading task involving 160 sentences (80 affirmative: 40 hand-related, 40 abstract; 80 negative: 40 hand-related, 40 abstract). After reading each sentence, subjects had to decide whether the verb was high or low frequency in Italian. Electroencephalographic (EEG) activity was recorded with 32 surface electrodes and mu ERD analyses were performed for each subject. Hand-action related sentences induced a greater mu ERD over the left premotor and motor hand areas compared to abstract sentences. Mu ERD was greater and temporally delayed when the hand-related verbs were presented in the negative versus affirmative form. As predicted by the embodied semantic theory of language understanding, motor areas were activated during sentences referring to hand actions. In addition, motor cortex activation was larger for negative than affirmative motor sentences, a finding compatible with the hypothesis that comprehension is more demanding in the specific case of motor content negation.

There is evidence that the human prefrontal cortex is asymmetrically involved in long-term episodic memory processing. Moreover, abstract and concrete words processing has been reported to differentially involve prefrontal and parietal areas. We implemented a two-stages functional magnetic resonance imaging (fMRI)-repetitive transcranial magnetic stimulation (rTMS) paradigm to investigate the role of the dorsolateral prefrontal cortices (DLPFCs) and parietal cortices (PARCs) in encoding and retrieval of abstract and concrete words. Using this paradigm we could select areas to be stimulated on the basis of single-subject (SS) anatomical and functional data, investigating the usefulness of this integration approach. With respect to fMRI, abstract and concrete words differed only for a greater left fusiform gyrus activation for concrete words. In turn, significant rTMS effects were found, but only for the retrieval of abstract words. Consistent with previous findings, repetitive stimulation of the right DLPFC had a specific impact on episodic retrieval. Memory retrieval performance was also disrupted when rTMS was applied to the left PARC. Finally, we found a significant positive correlation between the effect sizes of SS right PARC activations for abstract word retrieval and the consequent rTMS interference effects. Taken together these data provide for the first time evidence that also the PARC has a necessary role in episodic retrieval of abstract words. Importantly, from a methodological perspective, our data demonstrate that fMRI-guided rTMS with a SS approach provides a powerful tool to investigate the neural underpinnings of cognitive functions.

Two hundred and fifty one Italian patients with sporadic frontotemporal lobar degeneration (FTLD) and 259 age-matched controls were tested for association with the tagging single nucleotide polymorphisms (SNPs) rs741810 and rs1052352 in the fused in sarcoma/translated in liposarcoma gene (FUS/TLS). Only patients negative for GRN mutations were included. Considering each SNP alone, no differences in either allelic or genotypic frequencies between patients and controls were found (P > 0.05), even stratifying according to gender or the presence of concomitant motor neuron disease. Haplotype analysis failed to detect haplotypes associated with FTLD. According to these results, FUS/TLS is not a susceptibility factor for the development of sporadic FTLD. © 2010-IOS Press and the authors. All rights reserved.