An fMRI paradigm based on Williams inhibition test to study the neural substrates of attention and inhibitory control.

The purpose of this study is to present an fMRI paradigm, based on the Williams inhibition test (WIT), to study attentional and inhibitory control and their neuroanatomical substrates. We present an index of the validity of the proposed paradigm and test whether the experimental task discriminates the behavioral performances of healthy participants from those of individuals with acquired brain injury. Stroop and Simon tests present similarities with WIT, but this latter is more demanding. We analyze the BOLD signal in 10 healthy participants performing the WIT. The dorsolateral prefrontal cortex, the inferior prefrontal cortex, the anterior cingulate cortex, and the posterior cingulate cortex were defined for specified region of interest analysis. We additionally compare behavioral data (hits, errors, reaction times) of the healthy participants with those of eight acquired brain injury patients. Data were analyzed with GLM-based random effects and Mann-Whitney tests. Results show the involvement of the defined regions and indicate that the WIT is sensitive to brain lesions. This WIT-based block design paradigm can be used as a research methodology for behavioral and neuroimaging studies of the attentional and inhibitory components of executive functions.

Understanding task- and expertise-specific motor acquisition and motor memory formation and consolidation.

This study aimed to assess how the capacity to acquire, form and consolidate motor memories might vary across different tasks and different groups (with and without motor expertise). 20 athletes and 21 non-athletes were tested on five motor tasks: a motor sequence task, a reaction time task, two visuo-manual tasks, and a balance task. Performance was measured before training (T0), immediately after training (T1), and 24 hours after training (T2), to assess motor acquisition and motor memory formation and consolidation. T2 performance was higher in both groups, without additional training, on the motor sequence task, reaction time task and one of the visuo-manual tasks (Pouring Task). Athletes had better baseline performance at TO than non-athletes on these tasks. Findings suggest that differential formation and consolidation processes underlie different motor tasks. Although athletes did not outperform non-athletes on motor memory consolidation, they were more efficient in acquiring novel tasks, perhaps because the required motor schemas might have been based on previously acquired ones.

Physiotherapy case reports on three people with progressive supranuclear palsy.

Introduction: Progressive supranuclear palsy (PSP) is a neurodegenerative brain disease that affects patient's functionality and quality of life. Physiotherapy should be recommended at the time of diagnosis to slow the progression of disability and enhance the quality of life of these patients. Clinical presentation: Here, we describe three cases of patients with PSP, outlining their motor and non-motor symptoms and examining their clinical progression with physiotherapy intervention. During the initial intervention years, a reduction in the number of falls was achieved, along with improvements in gait and balance. Conclusion: Exercise and physiotherapy appear to be beneficial for patients with PSP by enhancing their functionality and quality of life. Controlling or reducing the number of falls should be the primary goal of any intervention for patients with PSP.

Looking for the Brain Inside the Initial Teacher Training and Outreach Books in Portugal.

The fascination with brain research is widespread, and school teachers are no exception. This growing interest, usually noticed by the increased supply of short-term training or books on how to turn the brain more efficient, leads us to think about their basic training and outreach resources available. Little is known about what the official Initial Teacher Training (ITT) offers concerning the brain literature and if it meets scientific standards. Also, what are the science communication materials that teachers can access to learn about the developing brain remain undiscussed. First, we examined the ITT courses taught in Portuguese Higher Education, both in public and private institutions, to identify the syllabus with updated neuroscientific knowledge. Second, we searched for the neuroscience-related books published in the last 6 years through the National Library of Portugal database. Thirty ITT courses and 35 outreach publications were reviewed through a rapid review methodology. Our results showed an absence of curricular units indicating in their programs that brain research, and its relationship with learning, would be taught in a representative and updated way. In contrast, the number of brain-related books for educators increased in Portugal, corroborating the demand for this field of study by these professionals. Based on the literature that shows how misunderstandings about the brain have increased in school contexts, our discussion recognizes that science outreach could be a way to increase the scientific literacy of school teachers with the research community working more in this direction, but, since a previous problem seems to be unsolved, there is an urgent need for specialized attention to the development of training curricula for future kindergarten and elementary school teachers.

At-distance neurocognitive rehabilitation during COVID-19 pandemic: A first glance of patients' perspectives about the process and an online platform.

Despite the use of digital communication technologies in neurocognitive rehabilitation has been widely used in face-to-face interventions, the difficulties of using ICT-based tools to provide rehabilitation services and the unfamiliarity of the neuropsychologists with internet interventions limited the use of these kinds of interventions in their clinical practices. The lockdown and mitigating measures associated with the COVID-19 pandemic, on the other hand, forced the use of at-distance and online interventions as a means to mitigate the impact of those measures on the mental health and rehabilitation processes of people with neurological disorders. Overall, little is known about the perspectives of patients with acquired neurological conditions about rehabilitation services delivered at distance. Therefore, the main goal of this study was to explore the perceptions that patients with neurological disorders have on at-distance online neurocognitive rehabilitation, namely during the COVID-19 pandemic. Sixteen patients with acquired neurological conditions attending an online neurocognitive rehabilitation program in a Portuguese rehabilitation center filled in an online questionnaire during the mandatory lockdown. The results of this study highlight the potential of delivering rehabilitation services at distance, presenting its advantages and limitations from patients' perspectives, as well as suggestions for improving both neurorehabilitation processes and the online rehabilitation platform used.

Disentangling Pantomime From Early Sign in a New Sign Language: Window Into Language Evolution Research.

In this study, we aim to disentangle pantomime from early signs in a newly-born sign language: Sao Tome and Principe Sign Language. Our results show that within 2 years of their first contact with one another, a community of 100 participants interacting everyday was able to build a shared language. The growth of linguistic systematicity, which included a decrease in use of pantomime, reduction of the amplitude of signs and an increase in articulation economy, showcases a learning, and social interaction process that constitutes a continuum and not a cut-off system. The human cognitive system is endowed with mechanisms for symbolization that allow the process of arbitrariness to unfold and the expansion of linguistic complexity. Our study helps to clarify the role of pantomime in a new sign language and how this role might be linked with language itself, showing implications for language evolution research.

Revisiting 'The influence of literacy in paraphasias of aphasic speakers'.

Literature suggests that illiterate subjects are unaware of the phonological structure of language. This fact may influence the characteristics of aphasic speech, namely the structure of paraphasias. A battery of tests was developed for this study to be used with aphasic subjects (literate and illiterate), in order to explore this topic in more detail. This article aims to present the experimental design and the results of this test battery composed of two sub-tests: (i) a naming test with words that belong to three distinct groups: high frequency simple words (HFSW), low frequency simple words (LFSW), and low frequency complex words (LFCW); and (ii) a word repetition test. The variables of literacy, frequency and word morphology, and their effect on the performance of aphasic groups, were correlated in this study. Morphology was the variable that exercised the greatest influence on the verbal production of the participants.

Neurological outcomes in children with and without amalgam-related mercury exposure: seven years of longitudinal observations in a randomized trial.

BACKGROUND: Although large-scale, randomized trials involving children have been completed and their results demonstrate an absence of neurobehavioral effects from clinical exposure to mercury amalgam, neurological findings from such studies have not been reported. METHODS: The authors conducted a randomized, prospective trial examining the safety of dental amalgam in which 507 children aged 8 through 12 years were assigned to treatment with either amalgam or resin-based composite. During seven years of follow-up, the authors performed annual clinical neurological examinations, including an evaluation of neurological hard signs (NHSs), presence of tremor and neurological soft signs (NSSs). RESULTS: The authors found no significant differences between treatment groups in any of the neurological measures. Groups did not differ with respect to the presence or absence of NHSs or tremor, nor the presence or absence or severity of NSSs at any point. As expected, NSS severity scores diminished with increasing age. CONCLUSIONS: Even at the levels of amalgam exposure in this study (a mean of 7.7-10.7 amalgam surfaces per subject across the seven years of follow-up), the authors conclude that exposure to mercury from dental amalgam does not adversely affect neurological status. CLINICAL IMPLICATIONS: The current evidence is that potential neurobehavioral or neurological effects from dental amalgam mercury exposure in children are inconsequential.

The temporal modulation structure of illiterate versus literate adult speech.

The temporal modulation structure of speech plays a key role in neural encoding of the speech signal. Amplitude modulations (AMs, quasi-rhythmic changes in signal energy or intensity) in speech are encoded by neuronal oscillations (rhythmic variations in neural excitability in large cell networks) that oscillate at matching temporal rates. To date, however, all neural studies have investigated adult-directed speech (ADS) as produced and perceived by highly literate adults. Whether temporal features of ADS vary with the skills of the speaker, for example literacy skills, is currently unknown. Here we analyse the temporal structure of ADS spoken by illiterate, low literate (≤ 4 years of literacy) and highly literate (≥ 12 years of literacy) adults. We find that illiterates produce speech differently. Spontaneous conversational speech produced by illiterate adults showed significantly less synchronised coupling between AM bands (less phase synchronisation) than conversational speech produced by low literate and highly literate adults, and contained significantly fewer syllables per second. There was also a significant relationship between years of literacy and the amount of theta-band energy in conversational speech. When asked to produce rhythmic proverbs learned in childhood, all groups could produce speech with similar AM phase synchronisation, suggesting that the differences in spontaneous conversational speech were not caused by physiological constraints. The data suggest that the temporal modulation structure of spoken language changes with the acquisition of cultural skills like literacy that are usually a product of schooling. There is a cultural effect on the temporal modulation structure of spoken language.

Executive functioning of Portuguese preschoolers in the Shape School test: A cross cultural study.

The Shape School is a neuropsychological test of executive functions (EF) for preschool-aged children. The purposes of this study were: (a) to adapt the use of the Shape School for European Portuguese preschool children and (b) to examine the cultural sensitivity of this test comparing the performance of Portuguese sample and U.S. normative sample. The executive functioning of 233 typically developing children aged 3 to 5 years old (M = 57.52; SD = 10.25; in months) was analyzed and according to our results, the adapted version was appropriate to obtain the discrimination among age-groups. Portuguese and American preschoolers show similar EF profiles. It was possible, in both samples, to note the sensitivity of the measurement to age-related differences, with the older age groups outperforming the younger. Therefore, the Portuguese version of the Shape School was considered suitable for research and clinical purposes.

Unisensory and multisensory Self-referential stimulation of the lower limb: An exploratory fMRI study on healthy subjects.

BACKGROUND: The holistic view of the person is the essence of the physiotherapy. Knowledge of approaches that develop the whole person promotes better patient outcomes. Multisensory Self-referential stimulation, more than a unisensory one, seems to produce a holistic experience of the Self ("Core-Self"). OBJECTIVES: (1) To analyze the somatotopic brain activation during unisensory and multisensorial Self-referential stimulus; and (2) to understand if the areas activated by multisensorial Self-referential stimulation are the ones responsible for the "Core-Self." METHODS: An exploratory functional magnetic resonance imaging (fMRI) study was performed with 10 healthy subjects, under the stimulation of the lower limbs with three Self-referential stimuli: unisensory auditory-verbal, unisensory tactile-manual, and multisensory, applying the unisensory stimuli simultaneously. RESULTS: Unisensory stimulation elicits bilateral activations of the temporoparietal junction (TPJ), of the primary somatosensory cortex (S1), of the primary motor cortex (BA4), of the premotor cortex (BA6) and of BA44; multisensory stimulation also elicits activity in TPJ, BA4, and BA6, and when compared with unisensory stimuli, activations were found in: (1) Cortical and subcortical midline structures-BA7 (precuneus), BA9 (medial prefrontal cortex), BA30 (posterior cingulated), superior colliculum and posterior cerebellum; and (2) Posterior lateral cortex-TPJ, posterior BA13 (insula), BA19, and BA37. Bilateral TPJ is the one that showed the biggest activation volume. CONCLUSION: This specific multisensory stimulation produces a brain activation map in regions that are responsible for multisensory Self-processing and may represent the Core-Self. We recommend the use of this specific multisensory stimulation as a physiotherapy intervention strategy that might promote the Self-reorganization.

The association of dental caries with blood lead in children when adjusted for IQ and neurobehavioral performance.

UNLABELLED: Associations between childhood lead exposures and dental caries in children have been reported for over 30 years, with widely varying findings and conclusions, and using measures of lead exposure which ranged from food sources and water to tooth, hair or blood lead concentrations. OBJECTIVES: This study examined the relationship of lead exposure and dental caries in a population of normatively healthy children. METHODS: This cross-sectional study used a population of 507 children aged 8-12 who were participating in a clinical trial of dental materials to examine the relationship between lead and caries. Blood lead concentrations and dental caries were examined for association in both primary and permanent teeth. Because it is possible that neurobehavioral status could be associated with both lead exposure and dental caries prevalence, we also examined neurobehavioral status of the subjects. RESULTS: A gender-specific association (males only) between lead exposure and dental caries was found in primary teeth only. Neurobehavioral measures and IQ were not associated with caries status in this population. CONCLUSIONS: This study did not support neurobehavioral status as mediating any association between lead exposure and caries in a normatively healthy population. A gender-specific association between lead and caries not previously reported was found in primary teeth, and no biological explanation for this has been suggested. We conclude that this study provides only weak evidence, if any, for an association of low-level lead exposure with dental caries.

Searching for a neurologic injury's Wechsler Adult Intelligence Scale-Third Edition profile.

This study aimed to investigate the presence of a Wechsler Adult Intelligence Scale-Third Edition (WAIS-III) cognitive profile in a Portuguese neurologic injured sample. The Portuguese WAIS-III was administered to 81 mixed neurologic patients and 81 healthy matched controls selected from the Portuguese standardization sample. Although the mixed neurologic injury group performed significantly lower than the healthy controls for the majority of the WAIS-III scores (i.e., composite measures, discrepancies, and subtests), the mean scores were within the normal range and, therefore, at risk of being unobserved in a clinical evaluation. ROC curves analysis showed poor to acceptable diagnostic accuracy for the WAIS-III composite measures and subtests (Working Memory Index and Digit Span revealed the highest accuracy for discriminating between participants, respectively). Multiple regression analysis showed that both literacy and the presence of brain injury were significant predictors for all of the composite measures. In addition, multiple regression analysis also showed that literacy, age of injury onset, and years of survival predicted all seven composite measures for the mixed neurologic injured group. Despite the failure to find a WAIS-III cognitive profile for mixed neurologic patients, the results showed a significant influence of brain lesion and literacy in the performance of the WAIS-III.

Interpreting WAIS-III performance after primary brain tumor surgery.

The literature lacks information on the performance of patients with brain tumors on the Wechsler Intelligence Scales. This study aimed to explore the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III) performance profile of 23 consecutive patients with brain tumors and 23 matched controls selected from the Portuguese WAIS-III standardization sample, using the technical manual steps recommended for score interpretation. The control group was demographically matched to the tumor group regarding gender, age, education, profession, and geographic region. The technical manual steps recommended for score interpretation were applied. Patients with brain tumors had significantly lower performances on the Performance IQ, Full-Scale IQ, Perceptual Organization Index, Working Memory Index, Processing Speed Index, Arithmetic, Object Assembly, and Picture Arrangement, though all scaled scores were within the normal range according to the manual tables. Only Vocabulary and Comprehension scatter scores were statistically different between groups. No strengths or weaknesses were found for either group. The mean discrepancy scores do not appear to have clinical value for this population. In conclusion, the study results did not reveal a specific profile for patients with brain tumors on the WAIS-III.

Impaired Pain Modulation in Fibromyalgia Patients in Response to Social Distress Manipulation.

OBJECTIVES: Fibromyalgia (FM), a chronic pain condition, is associated with abnormalities in pain modulation. A growing body of evidence has shown that social distress modulates pain sensitivity. The current study aimed to assess the effects of social distress manipulation on pain in FM patients compared with positive (rheumatoid arthritis, RA) and negative (pain-free) controls. MATERIALS AND METHODS: FM, RA patients and pain-free controls (PFC) were recruited. Demographic, medical, and psychological data were collected. Each participant was exposed to 3 study conditions in a random order: the inclusion (positive social effects) and exclusion (negative social effects) conditions of Cyberball, a game that manipulates social distress, and a control condition. Pain sensitivity in response to nociceptive electrical and thermal (cold) stimuli was assessed before and during each study condition. RESULTS: In response to electrical stimuli, pain decreased in both the inclusion and exclusion conditions in PFC and RA groups, whereas inclusion conditions significantly increased pain in the FM group. Social manipulation (inclusion or exclusion) did not affect pain sensitivity as measured in response to thermal stimulation. DISCUSSION: These results are in line with previous studies demonstrating altered pain inhibition in FM patients, and suggest that unlike PFC or other non-"stress-related" chronic pain conditions, being socially included may increase pain perception in FM patients. Possible underlying mechanisms and clinical relevance are discussed.

Biologicals and biosimilars: safety issues in Europe.

INTRODUCTION: Medicinal products of a biological origin are approved by the EMA at a centralized level. However, there is no harmonization about their use in Europe. The current regulation referring to the safety of biological medicinal products and biosimilars in Europe has been identified. The safety associated with medicinal products of a biological origin is assured by the pharmacovigilance system, which has evolved, but doesn't yet incorporate all of the specific information from this market segment, namely that related to the identification of drugs, and its use - including the prescription and dispensing, given the possibility of interchangeability and substitution. The terminology, information systems and traceability systems aren't entirely appropriate to ensure the safety requirements for therapy with medicinal products of a biological origin. Areas covered: This article aims to identify the prescription and dispensing profiles of reference biological medicines and biosimilars in the EU, and the determinants that support their safe use. Expert opinion: The European pharmacovigilance system must evolve to ensure the safety along all of the biologicals' therapeutic cycle. It must consider the safety for each of the medicines in addition to their safety pattern related to the eventual switching procedure.

[Biologicals and Biosimilars: Gaps in the Pharmacovigilance System in Portugal]. / Medicamentos Biológicos e Biossimilares: Descontinuidades no Sistema de Farmacovigilância em Portugal.

INTRODUCTION: Biological and biosimilar medicinal products have specific characteristics that call for a closer monitoring of their safety profile. Since the current legal framework stems from both European and national regulations, some gaps in the operational field may be expected. The goal of this paper is to identify these gaps and propose changes to the current information systems and pharmacovigilance regulations. MATERIAL AND METHODS: A qualitative analysis of current pharmacovigilance regulatory framework and supporting information system was conducted. RESULTS: Current pharmacovigilance system does not seem to vouch for the safe use of biologicals and biosimilar drugs. The gaps found in reviewed materials may be attributable to their lack of specificity for biopharmaceuticals. DISCUSSION: Biologicals therapy presents specific determinants related with the drugs, prescription, and traceability, without replication in any other segment of the pharmaceutical market. They are able to shape their safety profile. CONCLUSION: The existing pharmacovigilance's regulatory framework should be adjusted in order to improve the safety related with biopharmaceutical therapy. Some intervention measures are proposed.

Introdução: A monitorização da segurança associada aos medicamentos biológicos e biossimilares exige um sistema de informação alinhado com o enquadramento regulamentar. Tendo em conta que podem ocorrer descontinuidades entre a regulamentação europeia, nacional e a respetiva tradução operacional, importa pesquisar e identificar essas lacunas. Material e Métodos: Foi desenvolvida uma análise qualitativa dos suportes legais vigentes em julho de 2016 ao nível europeu e nacional, com foco na farmacovigilância. Desta análise decorreu a caracterização operacional do sistema em Portugal. Resultados: Foram identificadas zonas de descontinuidade no âmbito do sistema de farmacovigilância em Portugal, pela ausência de especificidade para os medicamentos biológicos e biossimilares. Discussão: A segurança associada à terapêutica biológica apresenta determinantes específicos relacionados com os medicamentos, prescrição e traçabilidade, que não encontram replicação nos outros segmentos do mercado farmacêutico. Conclusão: Com base nas lacunas identificadas, são apresentadas propostas de intervenção com o objetivo de incrementar a segurança associada à utilização clínica de medicamentos biológicos e biossimilares.

Study of behavioural and neural bases of visuo-spatial working memory with an fMRI paradigm based on an n-back task.

The goal of this study was to propose a new functional magnetic resonance imaging (fMRI) paradigm using a language-free adaptation of a 2-back working memory task to avoid cultural and educational bias. We additionally provide an index of the validity of the proposed paradigm and test whether the experimental task discriminates the behavioural performances of healthy participants from those of individuals with working memory deficits. Ten healthy participants and nine patients presenting working memory (WM) deficits due to acquired brain injury (ABI) performed the developed task. To inspect whether the paradigm activates brain areas typically involved in visual working memory (VWM), brain activation of the healthy participants was assessed with fMRIs. To examine the task's capacity to discriminate behavioural data, performances of the healthy participants in the task were compared with those of ABI patients. Data were analysed with GLM-based random effects procedures and t-tests. We found an increase of the BOLD signal in the specialized areas of VWM. Concerning behavioural performances, healthy participants showed the predicted pattern of more hits, less omissions and a tendency for fewer false alarms, more self-corrected responses, and faster reaction times, when compared with subjects presenting WM impairments. The results suggest that this task activates brain areas involved in VWM and discriminates behavioural performances of clinical and non-clinical groups. It can thus be used as a research methodology for behavioural and neuroimaging studies of VWM in block-design paradigms.

Neurobehavioral effects of dental amalgam in children: a randomized clinical trial.

CONTEXT: Dental (silver) amalgam is a widely used restorative material containing 50% elemental mercury that emits small amounts of mercury vapor. No randomized clinical trials have determined whether there are significant health risks associated with this low-level mercury exposure. OBJECTIVE: To assess the safety of dental amalgam restorations in children. DESIGN: A randomized clinical trial in which children requiring dental restorative treatment were randomized to either amalgam for posterior restorations or resin composite instead of amalgam. Enrollment commenced February 1997, with annual follow-up for 7 years concluding in July 2005. SETTING AND PARTICIPANTS: A total of 507 children in Lisbon, Portugal, aged 8 to 10 years with at least 1 carious lesion on a permanent tooth, no previous exposure to amalgam, urinary mercury level <10 microg/L, blood lead level <15 microg/dL, Comprehensive Test of Nonverbal Intelligence IQ > or =67, and with no interfering health conditions. INTERVENTION: Routine, standard-of-care dental treatment, with one group receiving amalgam restorations for posterior lesions (n = 253) and the other group receiving resin composite restorations instead of amalgam (n = 254). MAIN OUTCOME MEASURES: Neurobehavioral assessments of memory, attention/concentration, and motor/visuomotor domains, as well as nerve conduction velocities. RESULTS: During the 7-year trial period, children had a mean of 18.7 tooth surfaces (median, 16) restored in the amalgam group and 21.3 (median, 18) restored in the composite group. Baseline mean creatinine-adjusted urinary mercury levels were 1.8 microg/g in the amalgam group and 1.9 microg/g in the composite group, but during follow-up were 1.0 to 1.5 microg/g higher in the amalgam group than in the composite group (P<.001). There were no statistically significant differences in measures of memory, attention, visuomotor function, or nerve conduction velocities (average z scores were very similar, near zero) for the amalgam and composite groups over all 7 years of follow-up, with no statistically significant differences observed at any time point (P values from .29 to .91). Starting at 5 years after initial treatment, the need for additional restorative treatment was approximately 50% higher in the composite group. CONCLUSIONS: In this study, children who received dental restorative treatment with amalgam did not, on average, have statistically significant differences in neurobehavioral assessments or in nerve conduction velocity when compared with children who received resin composite materials without amalgam. These findings, combined with the trend of higher treatment need later among those receiving composite, suggest that amalgam should remain a viable dental restorative option for children. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00066118.

Feeling Hurt: Pain Sensitivity is Correlated With and Modulated by Social Distress.

OBJECTIVES: Social distress, resulting from loss or threat to social relationships, shares similar psychological and neuronal processes with physical pain. Recent evidence demonstrated that social distress may have an impact on pain. The current study aimed to further assess the relationship between these 2 phenomena. MATERIALS AND METHODS: Sixty healthy participants were randomly assigned to inclusion, noninclusion, or exclusion conditions of Cyberball, a virtual ball tossing game used to induce social distress. Pain and unpleasantness in response to noxious electrical stimuli were assessed before and after Cyberball manipulation. Psychological characteristics were evaluated by the Experiences in Close Relationships Questionnaire and the neuroticism scale of Big Five Inventory. RESULTS: Significant correlations were found between social distress and pre-Cyberball unpleasantness thresholds: those who perceived the Cyberball task as more distressing demonstrated lower unpleasantness thresholds. Post-Cyberball manipulation pain intensity ratings, but not unpleasantness ratings, were lower in the inclusion condition. No associations were found between the psychological characteristic and the effects of Cyberball on pain or unpleasantness ratings. DISCUSSION: The current study results indicate that participants' pre-Cyberball unpleasantness threshold is related to their responsiveness to social distress and that physical pain may be modulated by social events. Further studies are needed to clarify the clinical relevance of these results.