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1.  Counterfactual thinking in moral judgment: an experimental study 
Counterfactual thinking is thinking about a past that did not happen. This is often the case in “if only…” situations, where we wish something had or had not happened. To make a choice in a moral decision-making situation is particularly hard and, therefore, may be often associated with the imagination of a different outcome. The main aim of the present study is to investigate counterfactual thinking in the context of moral reasoning. We used a modified version of Greene's moral dilemmas test, studying both the time needed to provide a counterfactual in the first and third person and the type of given response (in context-out of context) in a sample of 90 healthy subjects. We found a longer response time for personal vs. impersonal moral dilemmas. This effect was enhanced in the first person perspective, while in the elderly there was an overall slowing of response time. Out of context/omissive responses were more frequent in the case of personal moral dilemmas presented in the first person version, with females showing a marked increase in this kind of response. These findings suggest that gender and perspective have a critical role in counterfactual thinking in the context of moral reasoning, and may have implications for the understanding of gender-related inclinations as well as differences in moral judgment.
doi:10.3389/fpsyg.2014.00451
PMCID: PMC4033199  PMID: 24904468
moral dilemma; decision making; gender; aging; utilitaristic reasoning
2.  Frontopolar cortex and decision-making efficiency: comparing brain activity of experts with different professional background during an exploration-exploitation task 
An optimal balance between efficient exploitation of available resources and creative exploration of alternatives is critical for adaptation and survival. Previous studies associated these behavioral drives with, respectively, the dopaminergic mesocorticolimbic system and frontopolar-intraparietal networks. We study the activation of these systems in two age and gender-matched groups of experienced decision-makers differing in prior professional background, with the aim to understand the neural bases of individual differences in decision-making efficiency (performance divided by response time). We compare brain activity of entrepreneurs (who currently manage the organization they founded based on their venture idea) and managers (who are constantly involved in making strategic decisions but have no venture experience) engaged in a gambling-task assessing exploitative vs. explorative decision-making. Compared with managers, entrepreneurs showed higher decision-making efficiency, and a stronger activation in regions of frontopolar cortex (FPC) previously associated with explorative choice. Moreover, activity across a network of regions previously linked to explore/exploit tradeoffs explained individual differences in choice efficiency. These results suggest new avenues for the study of individual differences in the neural antecedents of efficient decision-making.
doi:10.3389/fnhum.2013.00927
PMCID: PMC3897871  PMID: 24478664
decision-making; efficiency; exploration-exploitation; fMRI; frontopolar cortex
3.  Brain metabolic maps in Mild Cognitive Impairment predict heterogeneity of progression to dementia 
NeuroImage : Clinical  2014;7:187-194.
[18F]FDG-PET imaging has been recognized as a crucial diagnostic marker in Mild Cognitive Impairment (MCI), supporting the presence or the exclusion of Alzheimer's Disease (AD) pathology. A clinical heterogeneity, however, underlies MCI definition. In this study, we aimed to evaluate the predictive role of single-subject voxel-based maps of [18F]FDG distribution generated through statistical parametric mapping (SPM) in the progression to different dementia subtypes in a sample of 45 MCI. Their scans were compared to a large normal reference dataset developed and validated for comparison at single-subject level. Additionally, Aβ42 and Tau CSF values were available in 34 MCI subjects. Clinical follow-up (mean 28.5 ± 7.8 months) assessed subsequent progression to AD or non-AD dementias. The SPM analysis showed: 1) normal brain metabolism in 14 MCI cases, none of them progressing to dementia; 2) the typical temporo-parietal pattern suggestive for prodromal AD in 15 cases, 11 of them progressing to AD; 3) brain hypometabolism suggestive of frontotemporal lobar degeneration (FTLD) subtypes in 7 and dementia with Lewy bodies (DLB) in 2 subjects (all fulfilled FTLD or DLB clinical criteria at follow-up); and 4) 7 MCI cases showed a selective unilateral or bilateral temporo-medial hypometabolism without the typical AD pattern, and they all remained stable. In our sample, objective voxel-based analysis of [18F]FDG-PET scans showed high predictive prognostic value, by identifying either normal brain metabolism or hypometabolic patterns suggestive of different underlying pathologies, as confirmed by progression at follow-up. These data support the potential usefulness of this SPM [18F]FDG PET analysis in the early dementia diagnosis and for improving subject selection in clinical trials based on MCI definition.
Highlights
•We used an optimized voxel-based single-subject [18F]FDG-PET analysis•We showed different hypometabolic patterns (AD and non-AD) underlying MCI condition•Heterogeneous PET profiles predicted progression into specific dementia subtypes.•Statistical analyses showed high positive and negative post-test probability values.•CSF findings agreed with [18F]FDG-PET imaging in single cases.
doi:10.1016/j.nicl.2014.12.004
PMCID: PMC4300010  PMID: 25610780
Mild Cognitive Impairment; [18F]FDG; PET imaging; Dementia diagnosis; Alzheimer's disease
4.  Validation of an optimized SPM procedure for FDG-PET in dementia diagnosis in a clinical setting 
NeuroImage : Clinical  2014;6:445-454.
Diagnostic accuracy in FDG-PET imaging highly depends on the operating procedures. In this clinical study on dementia, we compared the diagnostic accuracy at a single-subject level of a) Clinical Scenarios, b) Standard FDG Images and c) Statistical Parametrical (SPM) Maps generated via a new optimized SPM procedure. We evaluated the added value of FDG-PET, either Standard FDG Images or SPM Maps, to Clinical Scenarios. In 88 patients with neurodegenerative diseases (Alzheimer's Disease—AD, Frontotemporal Lobar Degeneration—FTLD, Dementia with Lewy bodies—DLB and Mild Cognitive Impairment—MCI), 9 neuroimaging experts made a forced diagnostic decision on the basis of the evaluation of the three types of information. There was also the possibility of a decision of normality on the FDG-PET images. The clinical diagnosis confirmed at a long-term follow-up was used as the gold standard. SPM Maps showed higher sensitivity and specificity (96% and 84%), and better diagnostic positive (6.8) and negative (0.05) likelihood ratios compared to Clinical Scenarios and Standard FDG Images. SPM Maps increased diagnostic accuracy for differential diagnosis (AD vs. FTD; beta 1.414, p = 0.019). The AUC of the ROC curve was 0.67 for SPM Maps, 0.57 for Clinical Scenarios and 0.50 for Standard FDG Images. In the MCI group, SPM Maps showed the highest predictive prognostic value (mean LOC = 2.46), by identifying either normal brain metabolism (exclusionary role) or hypometabolic patterns typical of different neurodegenerative conditions.
Highlights
•Brain FDG-PET was evaluated with a new optimized SPM procedure in dementias.•We compared the diagnostic accuracy of clinical information, visual and SPM FDG-PET.•SPM had the best sensitivity (96%), specificity (84%) and positive and negative LR.•In an MCI subgroup, SPM had the highest predictive prognostic value.
doi:10.1016/j.nicl.2014.10.009
PMCID: PMC4225527  PMID: 25389519
FDG-PET imaging; Statistical Parametrical Mapping; Voxel-based analysis; Dementia diagnosis
5.  How to assess abstract conceptual knowledge: construction, standardization and validation of a new battery of semantic memory tests 
Functional Neurology  2014;29(1):47-55.
Summary
The neuropsychological investigation of semantic memory has mainly focused on concrete concepts, while abstract concepts have been relatively neglected. We describe a new battery for assessing abstract concepts in brain-damaged patients. The battery includes three different tests: an association task, a multiple-choice naming-to-description task and a sentence completion task.
The three tasks are based on the same 40 stimuli belonging to different categories of abstract concepts and they are tightly controlled for variables that can account for quantitative differences between abstract concepts (i.e. concreteness, imageability, context availability, familiarity, age of acquisition, mode of acquisition, emotional valence and arousal). The three tasks showed high reliability. Normative data were collected from 108 healthy Italian adults. To assess its sensitivity, the battery was administered to 13 patients with probable Alzheimer's disease who performed worse than matched controls. Significant correlations were also found between the tests and other semantic memory tests, supporting the validity of the battery.
PMCID: PMC4172247  PMID: 25014049
abstract concepts; battery of tests; semantic memory; standardization; validity
6.  Observed Manipulation Enhances Left Fronto-Parietal Activations in the Processing of Unfamiliar Tools 
PLoS ONE  2014;9(6):e99401.
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 hand-tool spatial relationships.
doi:10.1371/journal.pone.0099401
PMCID: PMC4049811  PMID: 24911053
7.  Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia 
Brain  2011;134(9):2456-2477.
Based on the recent literature and collective experience, an international consortium developed revised guidelines for the diagnosis of behavioural variant frontotemporal dementia. The validation process retrospectively reviewed clinical records and compared the sensitivity of proposed and earlier criteria in a multi-site sample of patients with pathologically verified frontotemporal lobar degeneration. According to the revised criteria, ‘possible’ behavioural variant frontotemporal dementia requires three of six clinically discriminating features (disinhibition, apathy/inertia, loss of sympathy/empathy, perseverative/compulsive behaviours, hyperorality and dysexecutive neuropsychological profile). ‘Probable’ behavioural variant frontotemporal dementia adds functional disability and characteristic neuroimaging, while behavioural variant frontotemporal dementia ‘with definite frontotemporal lobar degeneration’ requires histopathological confirmation or a pathogenic mutation. Sixteen brain banks contributed cases meeting histopathological criteria for frontotemporal lobar degeneration and a clinical diagnosis of behavioural variant frontotemporal dementia, Alzheimer’s disease, dementia with Lewy bodies or vascular dementia at presentation. Cases with predominant primary progressive aphasia or extra-pyramidal syndromes were excluded. In these autopsy-confirmed cases, an experienced neurologist or psychiatrist ascertained clinical features necessary for making a diagnosis according to previous and proposed criteria at presentation. Of 137 cases where features were available for both proposed and previously established criteria, 118 (86%) met ‘possible’ criteria, and 104 (76%) met criteria for ‘probable’ behavioural variant frontotemporal dementia. In contrast, 72 cases (53%) met previously established criteria for the syndrome (P < 0.001 for comparison with ‘possible’ and ‘probable’ criteria). Patients who failed to meet revised criteria were significantly older and most had atypical presentations with marked memory impairment. In conclusion, the revised criteria for behavioural variant frontotemporal dementia improve diagnostic accuracy compared with previously established criteria in a sample with known frontotemporal lobar degeneration. Greater sensitivity of the proposed criteria may reflect the optimized diagnostic features, less restrictive exclusion features and a flexible structure that accommodates different initial clinical presentations. Future studies will be needed to establish the reliability and specificity of these revised diagnostic guidelines.
doi:10.1093/brain/awr179
PMCID: PMC3170532  PMID: 21810890
behavioural variant frontotemporal dementia; diagnostic criteria; frontotemporal lobar degeneration; FTD; pathology
8.  The Neural Bases of Social Intention Understanding: The Role of Interaction Goals 
PLoS ONE  2012;7(7):e42347.
Decoding others' intentions is a crucial aspect of social cognition. Neuroimaging studies suggest that inferring immediate goals engages the neural system for action understanding (i.e. mirror system), while the decoding of long-term intentions requires the system subserving the attribution of mental states (i.e. mentalizing). A controversial issue, stimulated by recent inconsistent results, concerns whether the two systems are concurrently vs. exclusively involved in intention understanding. This issue is particularly relevant in the case of social interactions, whose processing has been mostly, but not uncontroversially, associated with the mentalizing system. We tested the alternative hypothesis that the relative contribution of the two systems in intention understanding may also depend on the shared goal of interacting agents. To this purpose, 27 participants observed social interactions differing in their cooperative vs. affective shared goal during functional-Magnetic-Resonance-Imaging. The processing of both types of interactions activated the right temporo-parietal junction involved in mentalizing on action goals. Additionally, whole-brain and regions-of-interest analyses showed that the action understanding system (inferior prefrontal-parietal cortex) was more strongly activated by cooperative interactions, while the mentalizing-proper system (medial prefrontal cortex) was more strongly engaged by affective interactions. These differences were modulated by individual differences in empathizing. Both systems can thus be involved in understanding social intentions, with a relative weighting depending on the specific shared goal of the interaction.
doi:10.1371/journal.pone.0042347
PMCID: PMC3407127  PMID: 22848759
9.  Neural Coding of Cooperative vs. Affective Human Interactions: 150 ms to Code the Action's Purpose 
PLoS ONE  2011;6(7):e22026.
The timing and neural processing of the understanding of social interactions was investigated by presenting scenes in which 2 people performed cooperative or affective actions. While the role of the human mirror neuron system (MNS) in understanding actions and intentions is widely accepted, little is known about the time course within which these aspects of visual information are automatically extracted. Event-Related Potentials were recorded in 35 university students perceiving 260 pictures of cooperative (e.g., 2 people dragging a box) or affective (e.g., 2 people smiling and holding hands) interactions. The action's goal was automatically discriminated at about 150–170 ms, as reflected by occipito/temporal N170 response. The swLORETA inverse solution revealed the strongest sources in the right posterior cingulate cortex (CC) for affective actions and in the right pSTS for cooperative actions. It was found a right hemispheric asymmetry that involved the fusiform gyrus (BA37), the posterior CC, and the medial frontal gyrus (BA10/11) for the processing of affective interactions, particularly in the 155–175 ms time window. In a later time window (200–250 ms) the processing of cooperative interactions activated the left post-central gyrus (BA3), the left parahippocampal gyrus, the left superior frontal gyrus (BA10), as well as the right premotor cortex (BA6). Women showed a greater response discriminative of the action's goal compared to men at P300 and anterior negativity level (220–500 ms). These findings might be related to a greater responsiveness of the female vs. male MNS. In addition, the discriminative effect was bilateral in women and was smaller and left-sided in men. Evidence was provided that perceptually similar social interactions are discriminated on the basis of the agents' intentions quite early in neural processing, differentially activating regions devoted to face/body/action coding, the limbic system and the MNS.
doi:10.1371/journal.pone.0022026
PMCID: PMC3131384  PMID: 21760948
10.  Specificity of Esthetic Experience for Artworks: An fMRI Study 
In a previous functional magnetic resonance imaging (fMRI) study, where we investigated the neural correlates of esthetic experience, we found that observing canonical sculptures, relative to sculptures whose proportions had been modified, produced the activation of a network that included the lateral occipital gyrus, precuneus, prefrontal areas, and, most interestingly, the right anterior insula. We interpreted this latter activation as the neural signature underpinning hedonic response during esthetic experience. With the aim of exploring whether this specific hedonic response is also present during the observation of non-art biological stimuli, in the present fMRI study we compared the activations associated with viewing masterpieces of classical sculpture with those produced by the observation of pictures of young athletes. The two stimulus-categories were matched on various factors, including body postures, proportion, and expressed dynamism. The stimuli were presented in two conditions: observation and esthetic judgment. The two stimulus-categories produced a rather similar global activation pattern. Direct comparisons between sculpture and real-body images revealed, however, relevant differences, among which the activation of right antero-dorsal insula during sculptures viewing only. Along with our previous data, this finding suggests that the hedonic state associated with activation of right dorsal anterior insula underpins esthetic experience for artworks.
doi:10.3389/fnhum.2011.00139
PMCID: PMC3220187  PMID: 22121344
neuroesthetics; sculpture; human body; insula
11.  Understanding Others' Regret: A fMRI Study 
PLoS ONE  2009;4(10):e7402.
Previous studies showed that the understanding of others' basic emotional experiences is based on a “resonant” mechanism, i.e., on the reactivation, in the observer's brain, of the cerebral areas associated with those experiences. The present study aimed to investigate whether the same neural mechanism is activated both when experiencing and attending complex, cognitively-generated, emotions. A gambling task and functional-Magnetic-Resonance-Imaging (fMRI) were used to test this hypothesis using regret, the negative cognitively-based emotion resulting from an unfavorable counterfactual comparison between the outcomes of chosen and discarded options. Do the same brain structures that mediate the experience of regret become active in the observation of situations eliciting regret in another individual? Here we show that observing the regretful outcomes of someone else's choices activates the same regions that are activated during a first-person experience of regret, i.e. the ventromedial prefrontal cortex, anterior cingulate cortex and hippocampus. These results extend the possible role of a mirror-like mechanism beyond basic emotions.
doi:10.1371/journal.pone.0007402
PMCID: PMC2756584  PMID: 19826471

Results 1-11 (11)