Incidence and Prevalence of Dementia: A 2015-2020 Population-Based Study in the Campania Region of Italy.

OBJECTIVE: The aims of this study were to provide population-based estimates of prevalence and incidence of any dementia and Alzheimer's dementia (AD) in the Campania region (South Italy) and to validate towards a clinical registry. METHODS: This was a population-based study, using routinely collected healthcare data of individuals living in the Campania region (South Italy) from 2015 to 2020. We included individuals aged ≥65 years alive at the prevalence day (January 1, 2021) who had at least one administrative record for dementia and/or AD from 2015 to 2020. Age-and sex-standardised prevalence rates were calculated using direct standardisation method (European population in 2020 as the reference population). To estimate the incidence, we tested three possible algorithms, which differed for the duration of the time interval between study baseline (January 1, 2015) and index date (first record for dementia and/or AD in administrative databases). We employed a clinical database for the validation of our algorithms towards neuropsychological test results. RESULTS: Among individuals aged over 65 years, 80,392 had dementia, of which 35,748 had AD. The age- and sex-standardised prevalence rates per 1,000 individuals for any dementia and AD were 77.64 (95% confidence interval [CI] = 77.57; 77.68) and 34.05 (95% CI = 34.01; 34.09), respectively. There were 82.10 incident cases of any dementia per 100,000 per year (0.79 sensitivity and 0.62 specificity) and 59.89 incident cases of AD per 100,000 per year (0.80 sensitivity and 0.59 specificity). The capture-recapture method showed a very low number of undetected cases (1.7% for any dementia and 3.0% for AD). Our algorithms showed acceptable performance with the area under the curve ranging from 0.59 to 0.72 and a double likelihood ratio of correctly identifying individuals above and below mini-mental status examination (MMSE) standard cut-offs (24 and 26). CONCLUSIONS: Prevalence and incidence of any dementia and AD in the Campania region (South Italy) from 2015 to 2020 are in line with previous estimates from other countries. Our algorithm, integrating administrative and clinical data, holds potential for assessing dementia's epidemiological burden, identifying risk factors, planning healthcare access, and developing prevention strategies.

The relation between cognitive functioning and activities of daily living in normal aging, mild cognitive impairment, and dementia: a meta-analysis.

Literature suggests that dementia and, more generally, cognitive impairment affect the capacity to carry out activities of daily living (ADL) in aging. However, it is important to decipher the weight of specific cognitive domains and neurodegenerative profiles mainly related to ADL difficulties. A meta-analysis was conducted to investigate the nature and strength of the association between cognitive functioning and ADL in healthy older adults, mild cognitive impairment (MCI), and dementia. A comprehensive search of the PubMed, PsycINFO (PROQUEST), and Scopus databases for cross-sectional or longitudinal studies up until December 2022. Our meta-analytic results revealed that: overall, instrumental ADL (IADL) showed a significant association with executive functioning, in particular, abstraction ability/concept formation, set-shifting, and processing speed/complex attention/working memory, regardless of type of participants (i.e., healthy older adults, MCI, and dementia); whereas ADL (both basic ADL, BADL, and IADL) significantly correlated with global cognitive functioning and long-term verbal memory, with a moderator effect of clinical condition (e.g., increasing ES based on the level of cognitive impairment). Moreover, visuospatial and language abilities significantly correlated with ADL, mainly when performance-based tasks were used for ADL assessment. These findings emphasize the importance of neuropsychological assessment in aging to early identify people most at risk of functional decline and shed light on the need to consider specific cognitive abilities in rehabilitation programs.

Optimal MoCA cutoffs for detecting biologically-defined patients with MCI and early dementia.

OBJECTIVE: In this phase II psychometric study on the Montreal cognitive assessment (MoCA), we tested the clinicometric properties of Italian norms for patients with mild cognitive impairment (PwMCI) and early dementia (PwD) and provided optimal cutoffs for diagnostic purposes. METHODS: Retrospective data collection was performed for consecutive patients with clinically and biologically defined MCI and early dementia. Forty-five patients (24 PwMCI and 21 PwD) and 25 healthy controls were included. Raw MoCA scores were adjusted according to the conventional 1-point correction (Nasreddine) and Italian norms (Conti, Santangelo, Aiello). The diagnostic properties of the original cutoff (< 26) and normative cutoffs, namely, the upper limits (uLs) of equivalent scores (ES) 1, 2, and 3, were evaluated. ROC curve analysis was performed to obtain optimal cutoffs. RESULTS: The original cutoff demonstrated high sensitivity (0.93 [95% CI 0.84-0.98]) but low specificity (0.44 [0.32-0.56]) in discriminating between patients and controls. Nominal normative cutoffs (ES0 uLs) showed excellent specificity (SP range = 0.96-1.00 [0.88-1.00]) but poor sensitivity (SE range = 0.09-0.24 [0.04-0.36]). The optimal cutoff for Nasreddine's method was 23.50 (SE = 0.82 [0.71-0.90]; SP = 0.72 [0.60-0.82]). Optimal cutoffs were 20.97, 22.85, and 22.29 (SE range = 0.69-0.73 [0.57-0.83], SP range = 0.88-0.92 [0.77-0.97]) for Conti's, Santangelo's, and Aiello's methods, respectively. CONCLUSION: Using the 1-point correction, combined with a cutoff of 23.50, might be useful in ambulatory settings with a large turnout. Our optimal cutoffs can offset the poor sensitivity of Italian cutoffs.

The "Little Circles Test" (LCT): a dusted-off tool for assessing fine visuomotor function.

BACKGROUND: The fine visuomotor function is commonly impaired in several neurological conditions. However, there is a scarcity of reliable neuropsychological tools to assess such a critical domain. AIMS: The aim of this study is to explore the psychometric properties and provide normative data for the Visual-Motor Speed and Precision Test (VMSPT). RESULTS: Our normative sample included 220 participants (130 females) aged 18-86 years (mean education = 15.24 years, SD = 3.98). Results showed that raw VMSPT scores were affected by higher age and lower education. No effect of sex or handedness was shown. Age- and education-based norms were provided. VMSPT exhibited weak-to-strong correlations with well-known neuropsychological tests, encompassing a wide range of cognitive domains of clinical relevance. By gradually intensifying the cognitive demands, the test becomes an indirect, performance-oriented measure of executive functioning. Finally, VMSPT seems proficient in capturing the speed-accuracy trade-off typically observed in the aging population. CONCLUSIONS: This study proposes the initial standardization of a versatile, time-efficient, and cost-effective neuropsychological tool for assessing fine visuomotor coordination. We propose renaming the VMSPT as the more approachable "Little Circles Test" (LCT).

Validation of a short Italian version of the Barratt Impulsiveness Scale (BIS-15) in non-clinical subjects: psychometric properties and normative data.

INTRODUCTION: The Barratt Impulsiveness Scale (BIS) is a questionnaire employed to measure impulsivity, which is associated with risky behaviors and mental disorders. We aimed to assess the psychometric properties of the BIS in the Italian general population and provide normative data for clinical use. MATERIALS AND METHODS: A cross-sectional survey methodology was employed to collect data. Then, 534 participants of different ages and educational levels completed the BIS, PHQ-9, GAD-7, and S-UPPS-P. We designed an ad hoc data-driven outcome checklist to identify which items deserved to be retained. Furthermore, internal consistency, convergent and divergent validity, and factorial structure were evaluated. A regression-based procedure was used to explore the influence of demographic variables on the BIS score and to provide adjusting factors and a sensitive cutoff. RESULTS: Item analysis suggested removing 15 items. Consequently, we tested the psychometric properties of a shorter version of the BIS (BIS-15). IRT test information functions indicated an almost identical measurement precision of the BIS-15 as compared to the original BIS. The BIS-15 demonstrated reliable internal consistency and good convergent and divergent validity. The PCA revealed a four-factor solution: "pure impulsivity," "planning and thinking," "lack of attention and concentration," and "impulsive buying." A significant effect of sex and years of education was found. Norms for the adjustment of raw scores were provided (cutoff = 37.39). CONCLUSIONS: The BIS-15 showed almost identical psychometric properties as compared with the original scale, reducing the administration time. Our norms may allow identifying individuals with impulsivity of clinical interest.

The Frontal Assessment Battery 20 years later: normative data for a shortened version (FAB15).

OBJECTIVE: The Frontal Assessment Battery (FAB) is a neuropsychological tool largely used to assess executive functions. Prior studies found a marked ceiling effect for the prehension behavior subtest (PBT) in healthy and clinical populations. Aims of the present study were (i) to examine the psychometric properties of the FAB without the contribution of PBT and (ii) to provide normative data for a revised version of the FAB after exclusion of PBT (FAB15). METHODS: The normative sample included 1,187 healthy participants. PBT had near-zero variance, poor content validity, and no discrimination power. Internal consistency increased when PBT was excluded. We assessed the FAB15 factorial structure, interrater, and test-retest reliabilities. Normative data  for the FAB15 were extracted through a regression-based procedure according to sex, age, and education. RESULTS: The principal component analysis revealed a single "executive factor" or alternatively a bifactorial solution reflecting the different degree of discriminative capability vs. difficulty of the subtests. The FAB15 demonstrated excellent interrater and test-retest reliabilities. Regression analysis showed that sex (lowly educated women < lowly educated men), higher age, and lower education affected FAB15 score. Accordingly, three grids for adjustment of raw scores (men, women, and both) were constructed. The cut-off was fixed at the non-parametric outer tolerance limit on the fifth centile (9.36, 95% CI). CONCLUSION: The observation of a ceiling effect in healthy subjects makes PBT not suitable for inclusion in a neuropsychological battery. The FAB15 may successfully replace the conventional FAB as a more severe and valid short screening tool to assess executive functioning.

Neuropsychology of posteromedial parietal cortex and conversion factors from Mild Cognitive Impairment to Alzheimer's disease: systematic search and state-of-the-art review.

In the present review, we discuss the rationale and the clinical implications of assessing visuospatial working memory (VSWM), awareness of memory deficits, and visuomotor control in patients with mild cognitive impairment (MCI). These three domains are related to neural activity in the posteromedial parietal cortex (PMC) whose hypoactivation seems to be a significant predictor of conversion from MCI to Alzheimer's disease (AD) as indicated by recent neuroimaging evidence. A systematic literature search was performed up to May 2021. Forty-eight studies were included: 42 studies provided analytical cross-sectional data and 6 studies longitudinal data on conversion rates. Overall, these studies showed that patients with MCI performed worse than healthy controls in tasks assessing VSWM, awareness of memory deficits, and visuomotor control; in some cases, MCI patients' performance was comparable to that of patients with overt dementia. Deficits in VSWM and metamemory appear to be significant predictors of conversion. No study explored the relationship between visuomotor control and conversion. Nevertheless, it has been speculated that the assessment of visuomotor abilities in subjects at high AD risk might be useful to discriminate patients who are likely to convert from those who are not. Being able to indirectly estimate PMC functioning through quick and easy neuropsychological tasks in outpatient settings may improve diagnostic and prognostic accuracy, and therefore, the quality of the MCI patient's management.

Hand movements in Mild Cognitive Impairment: clinical implications and insights for future research.

Decreased upper-extremity/visuomotor abilities are frequently encountered in healthy aging. However, few studies have assessed hand movements in the prodromal stage of dementia. The evaluation of visuomotor skills in patients with Mild Cognitive Impairment (PwMCI) may have non-negligible clinical relevance both in diagnostic and prognostic terms, given the strong relationships with executive functioning and functional autonomies. In the present review paper, these issues will be disclosed by describing general pathophysiological and neuropsychological mechanisms responsible for visuomotor deficits, and by reporting the available experimental results on differences in visuomotor functioning between PwMCI, healthy controls and/or patients with dementia. Moreover, the relationships binding visuomotor and executive domains to functional autonomies will be then addressed. Finally, we will propose insights for future research.

Italian version of the Starkstein Apathy Scale (SAS-I) and a shortened version (SAS-6) to assess "pure apathy" symptoms: normative study on 392 individuals.

OBJECTIVES: The present normative study aimed to (1) develop the Italian version of the Starkstein Apathy Scale (SAS-I) and (2) construct a shortened version including only the most sensitive items to "pure apathy" experiences. METHODS: The normative sample included 392 healthy subjects. A regression-based procedure was used to explore the effects of sex, age, and education on the raw SAS-I score. A correction grid was designed for adjusting raw scores by adding or subtracting the contribution of any significant variable and net of sociodemographic interindividual differences. Cutoff scores were also calculated and fixed at the external tolerance limit on the ninety-fifth centile. To obtain the shortened version, each SAS-I item was correlated with the Beck's Depression Inventory (BDI) score. The only items showing no correlation with BDI were implemented to bypass the well-known overlap between apathetic and depressive symptoms. RESULTS: The mean raw SAS-I score was 11.27 (SD = 4.42). A significant education effect was observed, with highly educated subjects obtaining lower scores than lowly educated ones. The proposed general cutoff score was 20.68. The SAS-I had fair internal consistency and discriminant validity. Internal consistency increased by removing item 3. The new SAS-6 included items 1, 2, 4, 10, 11, and 13 of the original scale. CONCLUSION: The SAS-I is a reliable assessment tool to support the diagnosis of apathy. The SAS-6, instead, is a brief questionnaire useful for quickly screening apathetic symptoms in outpatient practice, addressing or not the clinician to further investigations.

Psychometric properties of the STAI-Y scales and normative data in an Italian elderly population.

BACKGROUND: Early detection of anxiety symptoms in older people is capital as it may be linked to increased physical/functional disabilities, onset and progression of neurodegenerative disorders, and poor cognitive functioning. Nonetheless, there is a paucity of psychometrically validated anxiety measures in the elderly. AIMS: This study aimed at assessing the psychometric properties of the State-Trait Anxiety Inventory-Form Y (STAI-Y) and providing the first normative data for the Italian elderly population. METHODS: The sample included 361 individuals aged 65-94. All subjects underwent the Mini-Mental State Examination (MMSE), the Geriatric Depression Scale (GDS), and the state (S-Anxiety) and trait anxiety (T-anxiety) scales of the STAI-Y. RESULTS: The S-Anxiety and T-Anxiety scales showed reliable internal consistency and, overall, good item characteristics. Divergent validity was "apparently" threatened, with S-Anxiety scale correlating with MMSE and GDS, and T-Anxiety scale only with GDS. The principal component analysis revealed a three-factor solution for both scales, i.e., presence and absence of state (or trait) anxiety, and performance anxiety. Since no effect of sociodemographic variables was found, unadjusted cutoffs were provided. CONCLUSIONS: Although some questions on the psychometric properties of the STAI-Y remain unanswered, this normative study can help clinicians and researchers to monitor anxiety levels in the Italian elderly population.

Daily exposure to digital displays may affect the clock-drawing test: from psychometrics to serendipity.

BACKGROUND: The clock-drawing test (CDT) is a neuropsychological screening tool largely used to explore cognitive functioning. It requires participants to draw an analog clock face. Many studies have reported a good correlation between the CDT and the Mini-Mental State Examination (MMSE). The CDT has also showed a variable specificity. There are, however, some inconsistencies concerning the effect of sociodemographic variables (sex, age, education) on clock-drawing abilities. The present study aimed at examining these issues in a sample of middle-aged/young-old healthy adults. METHOD: Participants (n = 97) performed the MMSE and CDT. Clock drawings were assessed by five formal scoring systems (Wolf-Klein, Watson, Freedman, Manos, Shulman). In addition, three naïve raters provided a dichotomous judgment (normal vs. abnormal) for each clock. RESULTS: Sociodemographic variables did not affect CDT performance. Unlike earlier studies, CDT scores did not correlate with MMSE. Moreover, test specificity was appropriate only for Freedman's, Shulman's, and Wolf-Klein's methods. Interestingly, some participants drew clocks with numbers as they appear in digital clocks. By re-running the statistical analyses after removing these atypical clocks, four out of the five formal scores showed a significant correlation with MMSE; furthermore, CDT specificity slightly increased for all scoring systems including naïve ratings. CONCLUSIONS: CDT is not affected by sociodemographic variables. The finding of some clocks with digitally represented numbers suggests the need to align neuropsychological assessments with demands from an increasing digitalized environment. Moreover, the occurrence of high false-positives and possible digital contaminations suggest great caution in interpreting the clinical significance of CDT.

The fear of COVID-19 contagion: an exploratory EEG-fMRI study.

Pandemics have the potential to change how people behave and feel. The COVID-19 pandemic is no exception; thus, it may serve as a "challenging context" for understanding how pandemics affect people's minds. In this study, we used high-density electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) to examine the neural correlates of fear of contagion during the most critical moments of COVID-19 in Italy (i.e., October 2020-May 2021). To do that, we stimulated participants (N = 17; nine females) with artificial-intelligence-generated faces of people presented as healthy, recovered from COVID-19, or infected by SARS-CoV-2. The fMRI results documented a modulation of large bilateral fronto-temporo-parietal functional brain networks. Critically, we found selective recruitment of cortical (e.g., frontal lobes) and subcortical fear-related structures (e.g., amygdala and putamen) of the so-called social brain network when participants observed COVID-19-related faces. Consistently, EEG results showed distinct patterns of brain activity selectively associated with infected and recovered faces (e.g., delta and gamma rhythm). Together, these results highlight how pandemic contexts may reverberate in the human brain, thus influencing most basic social and cognitive functioning. This may explain the emergence of a cluster of psychopathologies during and after the COVID-19 pandemic. Therefore, this study underscores the need for prompt interventions to address pandemics' short- and long-term consequences on mental health.

The Relationship between Executive Functions and Body Weight: Sex as a Moderating Variable.

This study explores the interplay between executive functions and body weight, examining both the influence of biological factors, specifically sex, and methodological issues, such as the choice between Body Mass Index (BMI) and waist circumference (WC) as the primary anthropometric measure. A total of 386 participants (222 females, mean age = 45.98 years, SD = 17.70) were enrolled, from whom sociodemographic (sex, age, years of formal education) and anthropometric (BMI and WC) data were collected. Executive functions were evaluated using the Frontal Assessment Battery-15 (FAB15). The results showed the increased effectiveness of WC over BMI in examining the relationships between executive functions, sex differences, and body weight. In particular, this study revealed that there was a significant moderating effect of sex at comparable levels of executive functioning. Specifically, women with higher executive performance had lower WCs than their male counterparts, suggesting that executive function has a greater impact on WC in women than in men. Our findings highlight the importance of conducting more in-depth investigations of the complex relationship between cognitive deficits and weight gain, considering confounding variables of behavioral, psychobiological, and neurophysiological origin.

Influence of hand starting position on radial line bisection.

When normal individuals are asked to localize and mark the midpoint of a radial line, they tend to bisect it farther than the true center. It has been suggested that radial misbisection depends on the presence of a visual attentional bias directed toward the far space. The aim of the present study was to investigate whether the localization of the center of radial lines was affected by the starting position of the hand. There were two starting positions: one between the body and the radial line ("near"), the other beyond the radial line ("far"). Thirty-four subjects participated in the experiment. The results showed that (i) participants bisected radial lines farther than the true center, measured with reference to their body, in both near and far condition, and (ii) bisection errors in the near condition were greater than those in the far condition. We suggest that hand starting position and direction of ongoing movement influenced radial line misbisection by modulating visual attentional bias directed to far space.

What makes us more susceptible to false memories in the era of COVID-19? A focus on vaccines and Green Pass.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic was accompanied by an overabundance of fake news increasing the risk of developing false memories (FMs). Previous studies have shown that the relationship between fake news and FMs could be mediated by some individual variables, including attitudinal biases. We explored the role of these variables in true memories (TMs) and FMs formation, with special emphasis on vaccine- and Green Pass (GP)-related topics. METHOD: We set up a large online survey exploring several constructs including media usage, attitude toward vaccines and GP, perceived (PK) and objective knowledge (OK) about COVID-19-related information, fear of the disease, depression and anxiety symptoms, coping mechanisms, and reasoning skills. Then, we asked participants whether they remembered certain news (true or fake), providing confidence ratings. RESULTS: Data from 289 respondents (198 females) from the general population were analyzed. Participants with positive attitude reported a greater fear that their loved ones contracted the COVID-19, a more frequent use of traditional media, and a higher PK when compared with respondents with negative attitude. On the whole sample, participants reported higher confidence levels when required to judge their memory of true than fake news; however, participants with positive attitude reported a higher confidence for both true and fake news. The relationship between attitude and TM confidence was mediated by the PK, whereas the relationship between attitude and FM confidence was probably affected by OK. CONCLUSION: Attitude can modulate individual behaviors in the context of health issues. The PK and OK may interact with attitude in the memory formation.

Simultaneous real-time EEG-fMRI neurofeedback: A systematic review.

Neurofeedback (NF) is a biofeedback technique that teaches individuals self-control of brain functions by measuring brain activations and providing an online feedback signal to modify emotional, cognitive, and behavioral functions. NF approaches typically rely on a single modality, such as electroencephalography (EEG-NF) or a brain imaging technique, such as functional magnetic resonance imaging (fMRI-NF). The introduction of simultaneous EEG-fMRI tools has opened up the possibility of combining the high temporal resolution of EEG with the high spatial resolution of fMRI, thereby increasing the accuracy of NF. However, only a few studies have actively combined both techniques. In this study, we conducted a systematic review of EEG-fMRI-NF studies (N = 17) to identify the potential and effectiveness of this non-invasive treatment for neurological conditions. The systematic review revealed a lack of homogeneity among the studies, including sample sizes, acquisition methods in terms of simultaneity of the two procedures (unimodal EEG-NF and fMRI-NF), therapeutic targets field, and the number of sessions. Indeed, because most studies are based on a single session of NF, it is difficult to draw any conclusions regarding the therapeutic efficacy of NF. Therefore, further research is needed to fully understand non-clinical and clinical potential of EEG-fMRI-NF.

Mechanisms of Transmission and Processing of Pain: A Narrative Review.

Knowledge about the mechanisms of transmission and the processing of nociceptive information, both in healthy and pathological states, has greatly expanded in recent years. This rapid progress is due to a multidisciplinary approach involving the simultaneous use of different branches of study, such as systems neurobiology, behavioral analysis, genetics, and cell and molecular techniques. This narrative review aims to clarify the mechanisms of transmission and the processing of pain while also taking into account the characteristics and properties of nociceptors and how the immune system influences pain perception. Moreover, several important aspects of this crucial theme of human life will be discussed. Nociceptor neurons and the immune system play a key role in pain and inflammation. The interactions between the immune system and nociceptors occur within peripheral sites of injury and the central nervous system. The modulation of nociceptor activity or chemical mediators may provide promising novel approaches to the treatment of pain and chronic inflammatory disease. The sensory nervous system is fundamental in the modulation of the host's protective response, and understanding its interactions is pivotal in the process of revealing new strategies for the treatment of pain.

The assessment of executive functions to test the integrity of the nigrostriatal network: A pilot study.

Background: Parkinson's disease (PD) is a chronic neurodegenerative disorder characterized by motor and non-motor symptoms. The latter mainly include affective, sleep, and cognitive deficits. Non-demented PD patients often demonstrate impairments in several executive domains following neuropsychological evaluation. The current pilot study aims at assessing the discriminatory power of the Frontal Assessment Battery-15 (FAB15) in differentiating (i) non-demented PD patients and healthy controls and (ii) PD patients with more and less pronounced motor symptoms. Methods: Thirty-nine non-demented early-stage PD patients in the "on" dopamine state (26 females, mean age = 64.51 years, SD = 6.47, mean disease duration = 5.49 years, SD = 2.28) and 39 healthy participants (24 females, mean age = 62.60 years, SD = 5.51) were included in the study. All participants completed the FAB15. Motor symptoms of PD patients were quantified via the Unified Parkinson's Disease Rating Scale-Part III (UPDRS-Part III) and Hoehn and Yahr staging scale (H&Y). Results: The FAB15 score, adjusted according to normative data for sex, age, and education, proved to be sufficiently able to discriminate PD patients from healthy controls (AUC = 0.69 [95% CI 0.60-0.75], SE = 0.06, p = 0.04, optimal cutoff = 11.29). Conversely, the battery lacked sufficient discriminative capability to differentiate PD patients based on the severity of motor symptoms. Conclusion: The FAB15 may be a valid tool for distinguishing PD patients from healthy controls. However, it might be less sensitive in identifying clinical phenotypes characterized by visuospatial impairments resulting from posteroparietal and/or temporal dysfunctions. In line with previous evidence, the battery demonstrated to be not expendable in the clinical practice for monitoring the severity of PD-related motor symptoms.

On the functional brain networks involved in tool-related action understanding.

Tool-use skills represent a significant cognitive leap in human evolution, playing a crucial role in the emergence of complex technologies. Yet, the neural mechanisms underlying such capabilities are still debated. Here we explore with fMRI the functional brain networks involved in tool-related action understanding. Participants viewed images depicting action-consistent (e.g., nail-hammer) and action-inconsistent (e.g., scarf-hammer) object-tool pairs, under three conditions: semantic (recognizing the tools previously seen in the pairs), mechanical (assessing the usability of the pairs), and control (looking at the pairs without explicit tasks). During the observation of the pairs, task-based left-brain functional connectivity differed within conditions. Compared to the control, both the semantic and mechanical conditions exhibited co-activations in dorsal (precuneus) and ventro-dorsal (inferior frontal gyrus) regions. However, the semantic condition recruited medial and posterior temporal areas, whereas the mechanical condition engaged inferior parietal and posterior temporal regions. Also, when distinguishing action-consistent from action-inconsistent pairs, an extensive frontotemporal neural circuit was activated. These findings support recent accounts that view tool-related action understanding as the combined product of semantic and mechanical knowledge. Furthermore, they emphasize how the left inferior parietal and anterior temporal lobes might be considered as hubs for the cross-modal integration of physical and conceptual knowledge, respectively.