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Transcranial Direct Current Stimulation (tDCS) has become an increasingly promising tool for understanding the relationship between brain and behavior. The purpose of this study was to investigate whether the magnitude of sex- and age-related tDCS effects previously found in the medial prefrontal cortex (mPFC) during a Theory of Mind (ToM) task correlates with social cognition performance; in particular, we explored whether different patterns of activity would be detected in high- and low-performing participants. For this, young and elderly, male and female participants were categorized as a low- or high-performer according to their score on the Reading the Mind in the Eyes task. Furthermore, we explored whether sex- and age-related effects associated with active tDCS on the mPFC were related to cognitive functioning. We observed the following results: (i) elderly participants experience a significant decline in ToM performance compared to young participants; (ii) low-performing elderly females report slowing of reaction time when anodal tDCS is applied over the mPFC during a ToM task; and (iii) low-performing elderly females are characterized by lower scores in executive control functions, verbal fluency and verbal short-term memory. The relationship between tDCS results and cognitive functioning is discussed in light of the neuroscientific literature on sex- and age-related differences.

Aging is accompanied by changes in cognitive abilities and a great interest is spreading among researchers about aging impact on social cognition skills, such as the Theory of Mind (ToM). Transcranial direct current stimulation (tDCS) has been used in social cognition studies founding evidence of sex-related different effects on cognitive ToM task in a young people sample. In this randomized, double-blind, sham-controlled study, we applied one active and one sham tDCS session on the medial prefrontal cortex (mPFC) during a cognitive ToM task, including both social (i.e., communicative) and nonsocial (i.e., private) intention attribution conditions, in sixty healthy aging individuals (30 males and 30 females). In half of the participants the anode was positioned over the mPFC, whereas in the other half the cathode was positioned over the mPFC. The results showed that: (i) anodal tDCS over the mPFC led to significant slower reaction times (vs. sham) for social intention attribution task only in female participants; (ii) No effects were found in both females and males during cathodal stimulation. We show for the first time sex-related differences in cognitive ToM abilities in healthy aging, extending previous findings concerning young participants.

Background: Parkinson's Disease (PD) with mild cognitive impairment (MCI) (PD-MCI) represents one of the most dreaded complications for patients with PD and is associated with a higher risk of developing dementia. Although transcranial direct current stimulation (tDCS) has been demonstrated to improve motor and non-motor symptoms in PD, to date, no study has investigated the effects of tDCS on Theory of Mind (ToM), i.e., the ability to understand and predict other people's behaviours, in PD-MCI., Methods: In this randomized, double-blind, sham-controlled study, we applied active tDCS over the medial frontal cortex (MFC) to modulate ToM performance in twenty patients with PD-MCI. Twenty matched healthy controls (HC) were also enrolled and were asked to perform the ToM task without receiving tDCS., Results: In the patients with PD-MCI, i) ToM performance was worse than that in the HC, ii) ToM abilities were poorer in those with fronto-executive difficulties, and iii) tDCS over the MFC led to significant shortening of latency for ToM tasks., Conclusions: We show for the first time that active tDCS over the MFC enhances ToM in patients with PD-MCI, and suggest that non-invasive brain stimulation could be used to ameliorate ToM deficits observed in these patients., Competing Interests: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee. Informed consent was obtained from all individual participants included in the study. Ethics approval was obtained from the local Ethical Committee (IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy).Not applicableThe authors declare that they have no competing interests.

Behavioural variant frontotemporal dementia (bvFTD) is a form of frontotemporal degeneration characterized by early changes in personality, emotional blunting, and/or loss of empathy. Recent research has highlighted that these features may be at least partially explained by impairments in the theory of mind (ToM; i.e., the ability to understand and predict other people's behaviour by attributing independent mental states to them). The aim of this randomized, double-blind, placebo-controlled study was to test the hypothesis that transcranial direct current stimulation (tDCS) over the medial frontal cortex (MFC) selectively enhances communicative intention processing, a specific ToM ability. Using a single-session online design, we administered a ToM task that measures the ability to represent other people's private and communicative intentions during active or sham tDCS to 16 bvFTD patients. To assess the impact of dementia on performance on the ToM task, we included 16 age-matched healthy volunteers who were asked to perform the entire experimental ToM task. BvFTD is characterized by an impairment in the comprehension of both communicative and private intentions relative to a healthy control group and by a disproportional impairment in communicative intention compared with private intention processing. Significant and selective accuracy improvement in the comprehension of communicative intentions after active stimulation was observed in patients with bvFTD. This is the first study that analyses ToM ability in patients with bvFTD using tDCS stimulation. Our findings could potentially contribute to the development of an effective, noninvasive brain stimulation treatment of ToM impairments in patients with bvFTD.

Background: Fibromyalgia (FM) is a syndrome characterized by chronic, widespread musculoskeletal pain, occurring predominantly in women. Previous studies have shown that patients with FM display a pattern of selective processing or cognitive bias which fosters the encoding of pain-related information. The present study tested the hypothesis of an increased attribution of pain to facial expressions of emotions (FEE), in patients with FM. As previous studies have shown that alexithymia influences the processing of facial expressions, independent of specific clinical conditions, we also investigated whether alexithymia, rather than FM per se, influenced attribution of pain to FEE., Methods: One hundred and twenty-three women (41 with FM, 82 healthy controls, HC) were enrolled in this cross-sectional case-control study. We adopted two pain-attribution tasks, the Emotional Pain Estimation and the Emotional Pain Ascription, both using a modified version of the Ekman 60 Faces Test. Psychological distress was assessed using the Hospital Anxiety and Depression Scale, and alexithymia was assessed using the Toronto Alexithymia Scale., Results: Patients with FM did not report increased attribution of pain to FEE. Alexithymic individuals demonstrated no specific problem in the recognition of basic emotions, but attributed significantly more pain to angry facial expression., Limitations: Our study involved a relatively small sample size. The use of self-reported instruments might have led to underestimation of the presence of frank alexithymia in individuals having borderline cut-off scores., Conclusions: Alexithymia, rather than FM per se, plays a key role in explaining the observed differences in pain attribution to anger-related facial expressions., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a treatment option for patients with advanced idiopathic PD successful at alleviating disabling motor symptoms. Nevertheless, the effects of STN-DBS on cognitive functions remain controversial and few studies have investigated modification of social cognitive abilities in patients with PD treated with STN-DBS. Here we expanded the typically-investigated spectrum of these abilities by simultaneously examining emotion recognition, and both affective and cognitive Theory of Mind (ToM). By means of a cross-sectional study, 20 patients with PD under dopaminergic replacement therapy, 18 patients with PD treated with STN-DBS, and 20 healthy controls performed the Ekman 60-Faces test, the full version of the Reading the Mind in the Eyes test, and the Protocol for the Attribution of Communicative Intentions. There were no differences between the PD groups (treated and not treated with STN-DBS) on any of the social cognitive tests. Our results suggest that patients with PD who are treated with STN-DBS do not experience detrimental effects on their social cognitive abilities. The present study, the first one examining a wide spectrum of social cognitive abilities after DBS of the STN, suggests that this surgical procedure can be considered safe from this standpoint.

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., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Gender differences in social cognition are a long discussed issue, in particular those concerning Theory of Mind (ToM), i.e., the ability to explain and predict other people's mental states. The aim of this randomized, double-blind, placebo-controlled study was to test the hypothesis that anodal tDCS over the medial prefrontal cortex (mPFC) selectively enhances cognitive ToM performance in females. In the first experiment we administered to sixteen females and sixteen males a cognitive ToM task during anodal or placebo tDCS over the mPFC. In the second experiment further sixteen females completed the task receiving anodal or placebo tDCS over the vertex. The results showed that anodal tDCS over the mPFC enhances ToM in females but not in males, an effect indicated by enhanced ToM in females that received anodal tDCS over the mPFC compared with females that received tDCS over the vertex. These findings are relevant for three reasons. First, we found evidence of gender-related differences in cognitive ToM, extending previous findings concerning affective ToM. Second, these differences emerge with anodal stimulation of the mPFC, confirming the crucial role of this area in cognitive ToM. Third, we show that taking into account gender-related differences is mandatory for the investigation of ToM.

Background: Parkinson's disease (PD) is characterised by well-known motor symptoms, whereas the presence of cognitive non-motor symptoms, such as emotional disturbances, is still underestimated. One of the major problems in studying emotion deficits in PD is an atomising approach that does not take into account different levels of emotion elaboration. Our study addressed the question of whether people with PD exhibit difficulties in one or more specific dimensions of emotion processing, investigating three different levels of analyses, that is, recognition, representation, and regulation., Methodology: Thirty-two consecutive medicated patients with PD and 25 healthy controls were enrolled in the study. Participants performed a three-level analysis assessment of emotional processing using quantitative standardised emotional tasks: the Ekman 60-Faces for emotion recognition, the full 36-item version of the Reading the Mind in the Eyes (RME) for emotion representation, and the 20-item Toronto Alexithymia Scale (TAS-20) for emotion regulation., Principal Findings: Regarding emotion recognition, patients obtained significantly worse scores than controls in the total score of Ekman 60-Faces but not in any other basic emotions. For emotion representation, patients obtained significantly worse scores than controls in the RME experimental score but no in the RME gender control task. Finally, on emotion regulation, PD and controls did not perform differently at TAS-20 and no specific differences were found on TAS-20 subscales. The PD impairments on emotion recognition and representation do not correlate with dopamine therapy, disease severity, or with the duration of illness. These results are independent from other cognitive processes, such as global cognitive status and executive function, or from psychiatric status, such as depression, anxiety or apathy., Conclusions: These results may contribute to better understanding of the emotional problems that are often seen in patients with PD and the measures used to test these problems, in particular on the use of different versions of the RME task.

The paper reviews of all of the current evidence on Theory of Mind (ToM) abilities in patients with neurodegenerative diseases. ToM refers to the abilities to attribute mental states to others. Two neural systems are involved in processing other people's beliefs and intentions (cognitive component) and others' emotions and feelings (affective component). We hypothesize that patients with different neurodegenerative diseases may present different patterns of ToM deficits on the basis of how different neuropathological processes affect the neural bases of ToM components during the progression of a disease. The studies we reviewed provided evidence of a deficit of the cognitive ToM component in cortical (Alzheimer's disease and frontotemporal dementia) and frontal-subcortical (amyotrophic lateral sclerosis and basal ganglia disorders) neurodegenerative diseases. As regards the affective ToM component, it resulted markedly impaired in frontotemporal dementia; it also resulted that performances in tasks assessing this process are heterogeneous in Parkinson's disease and amyotrophic lateral sclerosis. The findings presented support the opportunity to introduce validated ToM tasks in the neuropsychological assessment of neurodegenerative diseases., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Human communicative competence is based on the ability to process a specific class of mental states, namely, communicative intention. The present fMRI study aims to analyze whether intention processing in communication is affected by the expressive means through which a communicative intention is conveyed, that is, the linguistic or extralinguistic gestural means. Combined factorial and conjunction analyses were used to test two sets of predictions: first, that a common brain network is recruited for the comprehension of communicative intentions independently of the modality through which they are conveyed; second, that additional brain areas are specifically recruited depending on the communicative modality used, reflecting distinct sensorimotor gateways. Our results clearly showed that a common neural network is engaged in communicative intention processing independently of the modality used. This network includes the precuneus, the left and right posterior STS and TPJ, and the medial pFC. Additional brain areas outside those involved in intention processing are specifically engaged by the particular communicative modality, that is, a peri-sylvian language network for the linguistic modality and a sensorimotor network for the extralinguistic modality. Thus, common representation of communicative intention may be accessed by modality-specific gateways, which are distinct for linguistic versus extralinguistic expressive means. Taken together, our results indicate that the information acquired by different communicative modalities is equivalent from a mental processing standpoint, in particular, at the point at which the actor's communicative intention has to be reconstructed.

The ability to infer other people's mental states (i.e. Theory of Mind, ToM) is a major topic of interest in various neurological and psychiatric disorders. However, it is only recently that there has been an assessment of cognitive and affective components of ToM ability in neurodegenerative disorders. In this review, we examine studies investigating the ToM ability in Parkinson's disease (PD). Taken together, these studies provide preliminary evidence that ToM difficulties may occur in PD patients. In particular, these difficulties principally involve the cognitive component of ToM in the early stages of the disease. The spatio-temporal progression of dopamine depletion supports the hypothesis that the affective component may only be affected in the advanced stages of the disease. The relationships between executive functioning, dopaminergic therapies, and ToM in PD as well as the relationships between frontostriatal circuits and ToM processing are discussed., (Copyright © 2011 Elsevier B.V. All rights reserved.)

The present study aims at clarifying the nature of the Theory of Mind (ToM) deficits associated with Amyotrophic Lateral Sclerosis (ALS). ToM is the ability to attribute mental states such as intentions and beliefs to others in order to understand and predict their behaviour and to behave accordingly. Several neuroimaging studies reported the prefrontal cortices as the brain region underlying a key ToM ability, i.e. the comprehension of social intentions. Dysfunction of the prefrontal cortices in patients with ALS has been indicated by a range of neuroimaging studies. The frontal syndrome that appears to characterize up to 50% of ALS has been noted to be similar to the profile that characterizes patients with frontotemporal dementia (FTD), a neurodegenerative condition characterised by ToM deficits. In the present paper, we hypothesize that the performance of patients with ALS is significantly worse than healthy controls' performance on tasks requiring the comprehension of social contexts, whereas patients' performance is comparable to healthy controls' performance on tasks not requiring the comprehension of social contexts. To this end, we tested 15 patients with ALS with an experimental protocol that distinguishes between private (non-social) intentions and social intentions. The pattern of results followed the experimental hypothesis: the performance of patients with ALS and healthy controls significantly differed on the comprehension of social context only, with an impairment in patients with ALS. Single case analysis confirmed the findings at an individual level. The present study is the first which has examined and compared the understanding of social and non-social contexts in patients with ALS and shown a specific and selective deficit in the former only. The current findings further support the notion of a continuum of cognitive dysfunction ranging from ALS to FTD, with parallel cognitive profiles in both disorders.

The paper reviews convergent evidence on the ability to attribute mental states to one's self and to others (i.e., theory of mind, ToM) in patients affected by the behavioural variant of frontotemporal dementia (bv-FTD). This disease represents a particular challenge for researchers and clinicians, due to its insidious onset and ambiguous clinical features, which frequently render difficult a precise and timely diagnosis. The paper proposes a way to shed new light on the hypothesis that the neuropsychiatric profile of individuals with bv-FTD can be at least partially explained by a deficit in ToM ability. We examined both neuroimaging data on the neural correlates of ToM ability in healthy participants and studies investigating the progressive cerebral atrophy in patients with bv-FTD. Our findings suggest a link between the progressive degeneration of the anterior regions of medial frontal structures characterising the early stages of the bv-FTD and the ToM deficit these patients show. They also suggest the importance of using ToM tests during the diagnostic process of bv-FTD.

Neuroimaging studies have identified the anterior paracingulate cortex (PCC) as the key prefrontal region subserving theory of mind. We adopt an evolutionary perspective hypothesizing that, in response to the pressures of social complexity, a mechanism for manipulating information concerning social interaction has emerged in the anterior PCC. To date, neuroimaging studies have not properly distinguished between intentions of persons involved in social interactions and intentions of an isolated person. In two separate fMRI experiments, we demonstrated that the anterior PCC is not necessarily involved in the understanding of other people's intentions per se, but primarily in the understanding of the intentions of people involved in social interaction. Moreover, this brain region showed activation when a represented intention implies social interaction and therefore had not yet actually occurred. This result suggests that the anterior PCC is also involved in our ability to predict future intentional social interaction, based on an isolated agent's behavior. We conclude that distinct areas of the neural system underlying theory of mind are specialized in processing distinct classes of social stimuli.