Rehabilitation Modulates High-Order Interactions Among Large-Scale Brain Networks in Subacute Stroke.

The recovery of motor functions after stroke is fostered by the functional integration of large-scale brain networks, including the motor network (MN) and high-order cognitive controls networks, such as the default mode (DMN) and executive control (ECN) networks. In this paper, electroencephalography signals are used to investigate interactions among these three resting state networks (RSNs) in subacute stroke patients after motor rehabilitation. A novel metric, the O-information rate (OIR), is used to quantify the balance between redundancy and synergy in the complex high-order interactions among RSNs, as well as its causal decomposition to identify the direction of information flow. The paper also employs conditional spectral Granger causality to assess pairwise directed functional connectivity between RSNs. After rehabilitation, a synergy increase among these RSNs is found, especially driven by MN. From the pairwise description, a reduced directed functional connectivity towards MN is enhanced after treatment. Besides, inter-network connectivity changes are associated with motor recovery, for which the mediation role of ECN seems to play a relevant role, both from pairwise and high-order interactions perspective.

Relation between drug therapy-based comorbidity indices, Charlson's comorbidity index, polypharmacy and mortality in three samples of older adults.

BACKGROUND: Comorbidity indexes were designed in order to measure how the disease burden of a patient is related to different clinical outcomes such as mortality, especially in older and intensively treated people. Charlson's Comorbidity Index (CCI) is the most widely used rating system, based on diagnoses, but when this information is not available therapy-based comorbidity indices (TBCI) are an alternative: among them, Drug Derived Complexity Index (DDCI), Medicines Comorbidity Index (MCI), and Chronic Disease Score (CDS) are available. AIMS: This study assessed the predictive power for 1-year mortality of these comorbidity indices and polypharmacy. METHODS: Survival analysis and Receiver Operating Characteristic (ROC) analysis were conducted on three Italian cohorts: 2,389 nursing home residents (Korian), 4,765 and 633 older adults admitted acutely to geriatric or internal medicine wards (REPOSI and ELICADHE). RESULTS: Cox's regression indicated that the highest levels of the CCI are associated with an increment of 1-year mortality risk as compared to null score for all the three samples. DDCI and excessive polypharmacy gave similar results but MCI and CDS were not always statistically significant. The predictive power with the ROC curve of each comorbidity index was poor and similar in all settings. CONCLUSION: On the whole, comorbidity indices did not perform well in our three settings, although the highest level of each index was associated with higher mortality.

How the effects of actions become our own.

Every day, we do things that cause effects in the outside world with little doubt about who caused what. To some, this sense of agency derives from a post hoc reconstruction of a likely causal relationship between an event and our preceding movements; others propose that the sense of agency originates from prospective comparisons of motor programs and their effects. Using functional magnetic resonance imaging, we found that the sense of agency is associated with a brain network including the pre-supplementary motor area (SMA) and dorsal parietal cortex. Transcranial magnetic stimulation affected the sense of agency only when delivered over the pre-SMA and specifically when time-locked to action planning, rather than when the physical consequences of the actions appeared. These findings make a prospective theory of the sense of agency more likely.

Drug prescriptions in nursing home residents: an Italian multicenter observational study.

PURPOSE: Pharmacoepidemiological studies aimed to distinguish drug use in nursing home (NH) residents with and without dementia could be useful to target specific interventions to improve prescribing. This multicenter retrospective study aimed (i) to describe drug therapy in a large sample of NH residents according to the diagnosis of dementia, and (ii) to record the most frequent potentially severe drug-drug interactions. METHODS: This study was conducted in a sample of Italian long-term care NHs. Drug prescription information, diseases, and socio-demographic characteristics of NH residents were collected at three different times during 2018. RESULTS: The mean number of drugs was significantly higher in NH residents without dementia than in those with (p = 0.05). Antipsychotics, laxatives, benzodiazepines, antiplatelets, and proton pump inhibitors (PPIs) were most commonly prescribed in patients with dementia, and PPIs, benzodiazepines, and laxatives in those without. The prevalence of patients with potentially severe drug-drug interactions was higher among those without dementia, 1216 (64.7%) and 518 (74.2%, p < 0.0001). There were significant differences between the mean numbers of drugs prescribed in individual NH after adjusting the analysis for age, sex, and mean Charlson index, the estimated mean number of drugs prescribed (± standard error) ranging from 5.1 (± 0.3) to 9.3 (± 0.3) in patients with dementia (p < 0.0001) and from 6.0 (± 0.7) to 10.9 (± 0.50) in those without dementia (p < 0.0001). Chronic use of psychotropic drugs was common in NH residents with and without dementia. CONCLUSIONS: The wide variability between NHs in drug prescriptions and potentially inappropriate prescribing suggests the need to recommend a standardized approach to medication review of psychotropic drugs, antiulcer, laxatives, and antiplatelets in this complex and vulnerable population.

How Task Interactivity Shapes Action Observation.

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

Cardiovascular complications and drug prescriptions in subjects with and without diabetes in a Northern region of Italy, in 2002 and 2012.

BACKGROUND AND AIMS: In contrast to the well-documented global prevalence of diabetes, much less is known about the epidemiology of cardiovascular (CV) complications in recent years. We describe the incidence of major CV events, deaths and drug prescribing patterns from 2002 to 2012 in subjects with (DM) or without diabetes mellitus (No DM). METHODS AND RESULTS: Subjects and outcomes were identified using linkable health administrative databases of Lombardy, a region in Northern Italy. A logistic regression model was used to compare myocardial infarction (MI), stroke, major amputation and death between DM and No DM in 2002 and 2012 and between the two index years in each population. The interaction between years and diabetes was introduced in the model. From 2002 to 2012 the incidence of major CV complications and death fell in both groups with a larger reduction among DM only for CV events: OR (95% CI) for the interaction 0.86 (0.79-0.93) for MI, 0.89 (0.82-0.96) for stroke, 0.78 (0.57-1.06) for major amputations. CV prevention drugs rose considerably from 2002 to 2012 particularly in DM and a switch towards safer antihyperglycemic drugs was also observed. CONCLUSIONS: Major CV complications and death declined from 2002 to 2012 in both DM and No DM. This might be due to a larger increase in prescriptions of CV drugs in DM and a relevant change toward recommended antihyperglycemic drugs.

Prevalence and Risk Factors Associated with Use of QT-Prolonging Drugs in Hospitalized Older People.

AIMS: The objective of this study was to evaluate the prevalence of the prescription of QT-prolonging drugs at hospital admission and discharge and the risk factors associated with their use in older people (aged 65 years and older). METHODS: Data were obtained from the REPOSI (REgistro POliterapie SIMI [Società Italiana di Medicina Interna]) registry, which enrolled 4035 patients in 2008 (n = 1332), 2010 (n = 1380), and 2012 (n = 1323). Multivariable logistic regression was performed to determine the risk factors independently associated with QT-prolonging drug use. QT-prolonging drugs were classified by the risk of Torsades de Pointes (TdP) (definite, possible, or conditional) according to the Arizona Center for Education and Research on Therapeutics (AzCERT) classification. Specific drug combinations were also assessed. RESULTS: Among 3906 patients prescribed at least one drug at admission, 2156 (55.2%) were taking at least one QT-prolonging drug. Risk factors independently associated with the use of any QT-prolonging drugs were increasing age (odds ratio [OR] 1.02, 95% CI 1.01-1.03), multimorbidity (OR 2.69, 95% CI 2.33-3.10), hypokalemia (OR 2.79, 95% CI 1.32-5.89), atrial fibrillation (OR 1.66, 95% CI 1.40-1.98), and heart failure (OR 3.17, 95% CI 2.49-4.05). Furosemide, alone or in combination, was the most prescribed drug. Amiodarone was the most prescribed drug with a definite risk of TdP. Both the absolute number of QT-prolonging drugs (2890 vs. 3549) and the number of patients treated with them (2456 vs. 2156) increased at discharge. Among 1808 patients not prescribed QT-prolonging drugs at admission, 35.8% were prescribed them at discharge. CONCLUSIONS: Despite their risk, QT-prolonging drugs are widely prescribed to hospitalized older persons. The curriculum for both practicing physicians and medical students should be strengthened to provide more education on the appropriate use of drugs in order to improve the management of hospitalized older people.

Metabolic syndrome and drug discontinuation in schizophrenia: a randomized trial comparing aripiprazole olanzapine and haloperidol.

OBJECTIVE: To determine whether the prescription of aripiprazole, compared with olanzapine and haloperidol, was associated with a lower frequency of metabolic syndrome (MS) and treatment discontinuation at 1 year. METHOD: Patients were randomly assigned to be treated open-label and according to usual clinical practice with either aripiprazole, olanzapine, or haloperidol and followed up for 1 year. RESULTS: Three hundred out-patients with persistent schizophrenia were recruited in 35 mental health services. The intention-to-treat (ITT) analysis found no significant differences in the rate of MS between aripiprazole (37%), olanzapine (47%), and haloperidol (42%). Treatment discontinuation for any cause was higher for aripiprazole (52%) than for olanzapine (33%; OR, 0.41; P = 0.004), or haloperidol (37%; OR, 0.51; P = 0.030). No significant difference was found between olanzapine and haloperidol. Time to discontinuation for any cause was longer for olanzapine than for aripiprazole (HR, 0.55; P < 0.001). No significant differences were found between haloperidol and aripiprazole, or between olanzapine and haloperidol. CONCLUSION: The prescription of aripiprazole did not significantly reduce the rates of MS, but its treatment retention was worse. Aripiprazole cannot be considered the safest and most effective drug for maintenance treatment of schizophrenia in routine care, although it may have a place in antipsychotic therapy.

Under-detection of delirium and impact of neurocognitive deficits on in-hospital mortality among acute geriatric and medical wards.

BACKGROUND: Delirium is a neuropsychiatric disorder, triggered by medical precipitants causes. Study aims were to describe the prevalence and impact on in-hospital mortality of delirium identified through ICD-9 codes as well as evidence of neurocognitive deficits demonstrated in a population of older patients admitted to acute medical wards. METHODS: This was a prospective cohort multicenter study of 2521 older patients enrolled in the "Registro Politerapie SIMI (REPOSI)" during the years 2010 and 2012. The diagnosis of delirium was obtained by ICD-9 codes. Cognitive function was evaluated with the Short Blessed Test (SBT) and single SBT items were used as measures of deficits in attention, orientation and memory. Combination of deficits in SBT items was used as a proxy for delirium. Logistic regression was used to evaluate the association with in-hospital mortality of delirium and combined deficits in SBT items. RESULTS: Delirium was coded in 2.9%, while deficits in attention, orientation, and memory were found in 35.4%, 29.7% and 77.5% of patients. Inattention and either disorientation or memory deficits were found in 14.1%, while combination of the 3 deficits in 19.8%. Delirium, as per ICD-9 codes, was not a predictor of in-hospital mortality. In contrast, objective deficits of inattention, in combination with orientation and memory disorders, were stronger predictors after adjusting for covariates. CONCLUSIONS: The documentation of delirium is poor in medical wards of Italian acute hospitals. Neurocognitive deficits on objective testing (in a pattern suggestive of undiagnosed delirium) should be used to raise awareness of delirium, given their association with in-hospital mortality.

Erbium laser in gynecology.

The aim of this paper is to present a novel laser technology utilizing the erbium YAG laser for various minimally invasive, non-surgical procedures in gynecology. Non-ablative, thermal-only SMOOTH-mode erbium pulses are used to produce vaginal collagen hyperthermia, followed by collagen remodeling and the synthesis of new collagen fibers, resulting in improved vaginal tissue tightness and elasticity. This erbium laser technology is used for treatments of vaginal laxity, stress urinary incontinence, pelvic organ prolapse and vaginal atrophy. In the period from 2010 to 2014, several clinical studies covering all four indications were conducted with the aim to prove the efficacy and safety of this novel technology. An overview is presented of the results of these studies where several objective as well as subjective assessment tools were used. The results have shown that SMOOTH-mode erbium laser seems to be an effective and safe method for treating vaginal laxity, stress urinary incontinence, pelvic organ prolapses and vaginal atrophy.

Brain and kidney, victims of atrial microembolism in elderly hospitalized patients? Data from the REPOSI study.

BACKGROUND: It is well known that atrial fibrillation (AF) and chronic kidney disease (CKD) are associated with a higher risk of stroke, and new evidence links AF to cognitive impairment, independently from an overt stroke (CI). Our aim was to investigate, assuming an underlying role of atrial microembolism, the impact of CI and CKD in elderly hospitalized patients with AF. METHODS: We retrospectively analyzed the data collected on elderly patients in 66 Italian hospitals, in the frame of the REPOSI project. We analyzed the clinical characteristics of patients with AF and different degrees of CI. Multivariate logistic analysis was used to explore the relationship between variables and mortality. RESULTS: Among the 1384 patients enrolled, 321 had AF. Patients with AF were older, had worse CI and disability and higher rates of stroke, hypertension, heart failure, and CKD, and less than 50% were on anticoagulant therapy. Among patients with AF, those with worse CI and those with lower estimated glomerular filtration rate (eGFR) had a higher mortality risk (odds ratio 1.13, p=0.006). Higher disability levels, older age, higher systolic blood pressure, and higher eGFR were related to lower probability of oral anticoagulant prescription. Lower mortality rates were found in patients on oral anticoagulant therapy. CONCLUSIONS: Elderly hospitalized patients with AF are more likely affected by CI and CKD, two conditions that expose them to a higher mortality risk. Oral anticoagulant therapy, still underused and not optimally enforced, may afford protection from thromboembolic episodes that probably concur to the high mortality.

Inappropriate prescription of allopurinol and febuxostat and risk of adverse events in the elderly: results from the REPOSI registry.

PURPOSE: To investigate the prevalence of xanthine oxidase (XO) inhibitors prescription at admission and discharge in elderly hospital in-patients, to analyze the appropriateness of their use in relation to evidence-based indications, to evaluate the predictors of inappropriate prescription at discharge and the association with adverse events 3 months after hospital discharge. METHODS: This cross-sectional study, based upon a prospective registry, was held in 95 Italian internal medicine and geriatric hospital wards. The sample included 4035 patients aged 65 years or older at admission and 3502 at discharge. The prescription of XO inhibitors was considered appropriate in patients with diagnosis of gout, gout nephropathy, uric acid nephrolithiasis, tophi, and chemotherapy-induced hyperuricemia. In order to evaluate the predictors of inappropriate prescription of XO inhibitors, we compared the characteristics of patients considered inappropriately treated with those appropriately not treated. RESULTS: Among the 4035 patients eligible for the analysis, 467 (11.6 %) were treated with allopurinol or febuxostat at hospital admission and 461 (13.2 %) among 3502 patients discharged. At admission, 39 (8.6 %) of patients receiving XO inhibitors and 43 (9.4 %) at discharge were appropriately treated. Among those inappropriately treated, hyperuricemia, polytherapy, chronic renal failure, diabetes, obesity, ischemic cardiomyopathy, heart failure, and cardiac dysrhythmias were associated with greater prescription of XO inhibitors. Prescription of XO inhibitors was associated with a higher risk of adverse clinical events in univariate and multivariate analysis. CONCLUSIONS: Prevalence of inappropriate prescription of XO inhibitors remained almost the same at admission and discharge. Inappropriate use of these drugs is principally related to treatment of asymptomatic hyperuricemia and various cardiovascular diseases.

Gender-differences in disease distribution and outcome in hospitalized elderly: data from the REPOSI study.

BACKGROUND AND PURPOSE: Women live longer and outnumber men. On the other hand, older women develop more chronic diseases and conditions such as arthritis, osteoporosis and depression, leading to a greater number of years of living with disabilities. The aim of this study was to describe whether or not there are gender differences in the demographic profile, disease distribution and outcome in a population of hospitalized elderly people. METHODS: Retrospective observational study including all patients recruited for the REPOSI study in the year 2010. Analyses are referred to the whole group and gender categorization was applied. RESULTS: A total of 1380 hospitalized elderly subjects, 50.5% women and 49.5% men, were considered. Women were older than men, more often widow and living alone or in nursing homes. Disease distribution showed that malignancy, diabetes, coronary artery disease, chronic kidney disease and chronic obstructive pulmonary disease were more frequent in men, but hypertension, osteoarthritis, anemia and depression were more frequent in women. Severity and comorbidity indexes according to the Cumulative Illness Rating Scale (CIRS-s and CIRS-c) were higher in men, while cognitive impairment evaluated by the Short Blessed Test (SBT), mood disorders by the Geriatric Depression Scale (GDS) and disability in daily life measured by Barthel Index (BI) were worse in women. In-hospital and 3-month mortality rates were higher in men. CONCLUSIONS: Our study showed a gender dimorphism in the demographic and morbidity profiles of hospitalized elderly people, emphasizing once more the need for a personalized process of healthcare.

Prevalence of potentially inappropriate medications and risk of adverse clinical outcome in a cohort of hospitalized elderly patients: results from the REPOSI Study.

WHAT IS KNOWN AND OBJECTIVE: Inappropriate prescribing is highly prevalent for older people and has become a global healthcare concern because of its association with negative health outcomes including ADEs, hospitalization and resource utilization. Beers' criteria are widely utilized for evaluating the appropriateness of medications, and an up-to-date version has recently been published. To assess the prevalence of patients exposed to PIMs at hospital discharge according to the 2003 and 2012 versions of Beers' criteria and to evaluate the risk of adverse clinical events, re-hospitalization and all-cause mortality at 3-month follow-up. METHODS: This cross-sectional study was held in 66 Italian internal medicine and geriatric wards. The sample included 1380 inpatients aged 65 years or older. Prescriptions of PIM were analysed at hospital discharge. We considered all patients with complete 3-month follow-up. RESULTS AND DISCUSSION: The prevalence of patients receiving at least one PIM was 20·1% and 23·5% according to the 2003 and 2012 versions of the Beers' criteria, respectively. The 2012 Beers' criteria identified more patients with at least one PIM than the 2003 version, although a high percentage of those patients (72·2%) were also identified by the criteria updated in 2003. The main difference in the prevalence of patients receiving a PIM according to the two versions of Beers' criteria involved prescriptions of benzodiazepines for insomnia or agitation, chronic use of non-benzodiazepine hypnotics, prescription of antipsychotics in people with dementia and oral iron at dosage higher than 325 mg/day. Prescription of PIMs was not associated with a higher risk of adverse clinical events, re-hospitalization and all-cause mortality at 3-month follow-up in both univariate and multivariate analysis, after adjusting for age, sex and CIRS comorbidity index. WHAT IS NEW AND CONCLUSIONS: This study found no significant effect of inappropriate drug use according to Beers' criteria on health outcomes among older adults 3 month after discharge. Even though these criteria have been suggested as helpful in promoting appropriate prescribing, reducing drug-related adverse events and associated healthcare costs, to date there is no clear evidence that their application can achieve objective and quantifiable improvements in clinical outcomes. A possible explanation is that both versions of the Beers' criteria have several recognized limitations, one of the main ones being the restricted availability of some drugs in Europe or their limited prescription in everyday clinical practice.

Elevated risk of death and major cardiovascular events in subjects with newly diagnosed diabetes: findings from an administrative database.

AIMS: To investigate the incidence of major cardiovascular complications and mortality in the first years of follow-up in patients with newly diagnosed diabetes. METHODS AND RESULTS: We examined incidence rates of hospitalization for cardiovascular reasons and death among new patients with diabetes using the administrative health database of the nine million inhabitants of Lombardy followed from 2002 to 2007. Age and sex-adjusted rates were calculated and hazard ratios (HR) were estimated with a matched population without diabetes of the same sex, age (± 1 year) and general practitioner. There were 158,426 patients with newly diagnosed diabetes and 314,115 subjects without diabetes. Mean follow-up was 33.0 months (SD ± 17.5). 9.7% of patients with diabetes were hospitalized for cardiovascular events vs. 5.4% of subjects without diabetes; mortality rate was higher in patients with diabetes (7.7% vs. 4.4%). The estimated probability of hospitalization during the follow up was higher in patients with diabetes than in subjects without for coronary heart disease (HR 1.4, 95% CI 1.3-1.4), cerebrovascular disease (HR 1.3.95% CI 1.2-1.3), heart failure (HR 1.4, 95% CI 1.3-1.4) as was mortality (HR 1.4, 95% CI 1.4-1.4). Younger patients with diabetes had a risk of death or hospital admission for cardio-cerebrovascular events similar to subjects without diabetes ten years older. CONCLUSIONS: The elevated morbidity and mortality risks were clear since the onset of diabetes and rose over time. These data highlight the importance of prompt and comprehensive patients care in addition to anti-diabetic therapy in patients with newly diagnosed diabetes.

E-learning to improve the drug prescribing in the hospitalized elderly patients: the ELICADHE feasibility pilot study.

BACKGROUND: E-learning is an efficient and cost-effective educational method. AIMS: This study aimed at evaluating the feasibility of an educational e-learning intervention, focused on teaching geriatric pharmacology and notions of comprehensive geriatric assessment, to improve drug prescribing to hospitalized elderly patients. METHODS: Eight geriatric and internal medicine wards were randomized to intervention (e-learning educational program) or control. Clinicians of the two groups had to complete a specific per group e-learning program in 30 days. Then, ten patients (aged ≥75 years) had to be consecutively enrolled collecting clinical data at hospital admission, discharge, and 3 months later. The quality of prescription was evaluated comparing the prevalence of potentially inappropriate medications through Beer's criteria and of potential drug-drug interactions through a specific computerized database. RESULTS: The study feasibility was confirmed by the high percentage (90 %) of clinicians who completed the e-learning program, the recruitment, and follow-up of all planned patients. The intervention was well accepted by all participating clinicians who judged positively (a mean score of >3 points on a scale of 5 points: 0 = useless; 5 = most useful) the specific contents, the methodology applied, the clinical relevance and utility of e-learning contents and tools for the evaluation of the appropriateness of drug prescribing. CONCLUSIONS: The pilot study met all the requested goals. The main study is currently ongoing and is planned to finish on July 2015.

Comparison of disease clusters in two elderly populations hospitalized in 2008 and 2010.

BACKGROUND: As chronicity represents one of the major challenges in the healthcare of aging populations, the understanding of how chronic diseases distribute and co-occur in this part of the population is needed. OBJECTIVES: The aims of this study were to evaluate and compare patterns of diseases identified with cluster analysis in two samples of hospitalized elderly. METHODS: Data were obtained from the multicenter 'Registry Politerapie SIMI (REPOSI)' that included people aged 65 or older hospitalized in internal medicine and geriatric wards in Italy during 2008 and 2010. The study sample from the first wave included 1,411 subjects enrolled in 38 hospitals wards, whereas the second wave included 1,380 subjects in 66 wards located in different regions of Italy. To analyze patterns of multimorbidity, a cluster analysis was performed including the same diseases (19 chronic conditions with a prevalence >5%) collected at hospital discharge during the two waves of the registry. RESULTS: Eight clusters of diseases were identified in the first wave of the REPOSI registry and six in the second wave. Several diseases were included in similar clusters in the two waves, such as malignancy and liver cirrhosis; anemia, gastric and intestinal diseases; diabetes and coronary heart disease; chronic obstructive pulmonary disease and prostate hypertrophy. CONCLUSION: These findings strengthened the idea of an association other than by chance of diseases in the elderly population.

Frequency-based approach to the study of semantic brain networks connectivity.

The interactions among cerebral regions involved in semantic word generations are explored through connectivity analysis based on fMRI data through multivariate autoregressive model (MVAR). Connections among the pars triangularis of the left inferior frontal gyrus (L45), the lateral fusiform girus (LFG) and the left medial fusiform girus (MFG) were investigated. Ten healthy subjects were asked to covertly generate nouns belonging to two semantic categories (Animals and Tools). Time series for each voxel were derived from fMRI images, averaged within each area and concatenated over all subjects. The MVAR model allowed estimating spectral power, coherence and partial coherence between pairs of time series, and causality relations assessed through direct directed transfer function (dDTF). Spectral power is mostly concentrated in the frequency range of the imposed stimulus and the activation in the specific areas is modulated by conditions as well as coherence and partial coherence. dDTF values revealed stronger connections between L45 and LFG in "Tools" conditions, while a stronger causality was found between L45 and MFG in "Animals" conditions. In addition, comparing the same connections in the two conditions, a mirror reversal of the two weights was observed, with stronger causality L45-LFG in "Tools" vs "Animals" and stronger causality L45-MFG in "Animals" vs "Tools". The present study confirms and extends previous results obtained by structural equation modeling analysis, suggesting the suitability of a data-driven Granger causality approach in identifying condition-dependent effective connectivity from BOLD signals. The proposed methodology completes and integrates other analysis procedures providing new tools to explore brain functions.

Action-related semantic content and negation polarity modulate motor areas during sentence reading: an event-related desynchronization study.

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.