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.

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.

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.

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.

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.

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.

[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.

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.

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.

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.

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.

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.

Reliability and Validity of the European Portuguese Version of the Social Touch Questionnaire.

Social touch is essential for physical and emotional well-being. However, different meanings can be attributed to physical contact during social interactions and may generate bonding or avoidant behaviors. This personal and unique experience is not usually taken into account in health and social care services. The aim of this study is to produce a valid and reliable European Portuguese version of the Social Touch Questionnaire (STQ, Wilhelm et al. in Biol Psychol 58:181-202, 2001. doi:10.1016/S0301-0511(01)00113-2). The STQ is a self-report questionnaire for adolescents and adults measuring behaviors and attitudes towards social touch. The original version was translated into European Portuguese using a forward-back translation process and its feasibility was examined. To evaluate the psychometric properties, a total of 242 Portuguese university students participated in the study (21.3 ± 3.8 years). The STQ was considered feasible, showed adequate internal consistency (Cronbach's α = .734), and the test-retest correlation with the STQ items demonstrated a high concordance between the tests over a two-week interval (ICC = .990; n = 50). Validity tests were performed, comparing the total score of the STQ with that of the anxiety and avoidance subscales of the Social Interaction and Performance Anxiety and Avoidance Scale (SIPAAS). A very significant conceptual convergence was confirmed between the STQ and with the SIPAAS-Anxiety (r = .64; p < .0001) and with the SIPAAS-Avoidance (r = .59; p < .0001). The exploratory factor analysis, with Promax rotation, revealed 3 factors: dislike of physical touch, liking of familiar physical touch and liking of public physical touch (Cronbach's alphas ranged from .68 to .75). Psychometric properties confirmed the adaptation of the STQ to the Portuguese culture. It is a reliable and valid self-report questionnaire and it appears to be a useful tool to assess behaviors and attitudes towards social touch.

Hand tactile discrimination, social touch and frailty criteria in elderly people: A cross sectional observational study.

Frailty is a common syndrome among elderly and sensory decline may exacerbate functional decline. The hand function, the manual dexterity, the performance of the daily living skills and the social interactions are determined, in a large degree, by sensory integrity. However, hand tactile sensory deterioration has been little explored in frailty. We performed a cross sectional observational study with 181 of institutionalized elders. From the initial sample we selected 50 subjects (68-99 years) who met the inclusion/exclusion criteria. Our goals were (1) to analyse the relationship between tactile discrimination (TD) of the hand, avoidance behaviours and attitudes towards social touch (BATST) and phenotype frailty criteria (unintentional weight loss, self-perception of exhaustion, decrease grip strength - GS, slow walking speed, low level of physical activity), (2) to explore whether other variables can contribute to explain the differences between pre-frail and frail elders. The results showed that increasing age is related to decline of TD of the hand (p=0.021) and to decrease in GS (p=0.025); women have significantly lower level of GS (p=0.001); TD decrease is correlated with higher avoidance BATST (p=0.000) and with lower GS (p=0.000); Lower GS corresponds to more avoidance BATST (p=0.003). Hand TD also can differentiate frail and pre-frail elderly subjects in this sample (p=0.037). Decreased TD of the hand may have implications on the functionality and on interpersonal relationships. TD of the hand also explains frailty levels in this sample. Hand TD should be used in assessment and intervention protocols in pre-frail and frail elders.

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.

Action verbal fluency in Parkinson's patients.

We compared the performance of 31 non-demented Parkinson's disease (PD) patients to 61 healthy controls in an action verbal fluency task. Semantic and phonemic fluencies, cognitive impairment and behavioural dysfunction were also assessed. The mean disease duration of PD was 9.8 years (standard deviation (SD) = 6.13). There were no age (U = 899.5, p = 0.616), gender(chi-square = 0.00, p = 1.00) or literacy (U = 956, p = 0.96) differences between the two groups. A significant difference was observed between the two groups in the action verbal fluency task (U = 406.5, p < 0.01) that was not found in the other fluency tasks. The education level was the only biographical variable that influenced the action (verb) fluency outcomes, irrespective of disease duration. Our findings suggest a correlation between the disease mechanisms in PD and a specific verb deficit, support the validity of the action (verb) fluency as an executive function measure and suggest that this task provides unique information not captured with traditional executive function tasks.

Action verbal fluency in Parkinson’s patients / Fluência verbal de ação em pacientes com doença de Parkinson

We compared the performance of 31 non-demented Parkinson´s disease (PD) patients to 61 healthy controls in an action verbal fluency task. Semantic and phonemic fluencies, cognitive impairment and behavioural dysfunction were also assessed. The mean disease duration of PD was 9.8 years (standard deviation (SD) = 6.13). There were no age (U = 899.5, p = 0.616), gender(chi-square = 0.00, p = 1.00) or literacy (U = 956, p = 0.96) differences between the two groups. A significant difference was observed between the two groups in the action verbal fluency task (U = 406.5, p < 0.01) that was not found in the other fluency tasks. The education level was the only biographical variable that influenced the action (verb) fluency outcomes, irrespective of disease duration. Our findings suggest a correlation between the disease mechanisms in PD and a specific verb deficit, support the validity of the action (verb) fluency as an executive function measure and suggest that this task provides unique information not captured with traditional executive function tasks.

Este estudo comparou o desempenho em provas de fluência verbal semântica, fonêmica e de ação, em 31 pacientes com doença de Parkinson (DP), sem demência, e 61 controlos saudáveis. As funções executivas e comportamentais foram igualmente avaliadas. O tempo de evolução foi de 9,8 anos (DP = 6,13). Não foram encontradas diferenças de idade (U = 899,5, p = 0,616), género (X2 = 0,00, p = 1,00) ou literacia (U = 956, p = 0,96) entre os dois grupos. Diferenças significativas foram encontradas na prova de fluência verbal de ação (U = 406,5, p < 0,01) que não se verificaram nas restantes provas. O nível educacional foi a única variável biográfica que influenciou o desempenho das tarefas, independentemente do tempo de evolução da doença. Os resultados sugerem uma correlação entre os mecanismos patológicos da DP e um déficit específico para a evocação de verbos e que a prova de fluência de ação providencia uma informação importante que não é detectada pelos restantes testes executivos.

Brain Activity during Lower-Limb Movement with Manual Facilitation: An fMRI Study.

Brain activity knowledge of healthy subjects is an important reference in the context of motor control and reeducation. While the normal brain behavior for upper-limb motor control has been widely explored, the same is not true for lower-limb control. Also the effects that different stimuli can evoke on movement and respective brain activity are important in the context of motor potentialization and reeducation. For a better understanding of these processes, a functional magnetic resonance imaging (fMRI) was used to collect data of 10 healthy subjects performing lower-limb multijoint functional movement under three stimuli: verbal stimulus, manual facilitation, and verbal + manual facilitation. Results showed that, with verbal stimulus, both lower limbs elicit bilateral cortical brain activation; with manual facilitation, only the left lower limb (LLL) elicits bilateral activation while the right lower limb (RLL) elicits contralateral activation; verbal + manual facilitation elicits bilateral activation for the LLL and contralateral activation for the RLL. Manual facilitation also elicits subcortical activation in white matter, the thalamus, pons, and cerebellum. Deactivations were also found for lower-limb movement. Manual facilitation is stimulus capable of generating brain activity in healthy subjects. Stimuli need to be specific for bilateral activation and regarding which brain areas we aim to activate.