GABAergic miR-34a regulates Dorsal Raphè inhibitory transmission in response to aversive, but not rewarding, stimuli.

The brain employs distinct circuitries to encode positive and negative valence stimuli, and dysfunctions of these neuronal circuits have a key role in the etiopathogenesis of many psychiatric disorders. The Dorsal Raphè Nucleus (DRN) is involved in various behaviors and drives the emotional response to rewarding and aversive experiences. Whether specific subpopulations of neurons within the DRN encode these behaviors with different valence is still unknown. Notably, microRNA expression in the mammalian brain is characterized by tissue and neuronal specificity, suggesting that it might play a role in cell and circuit functionality. However, this specificity has not been fully exploited. Here, we demonstrate that microRNA-34a (miR-34a) is selectively expressed in a subpopulation of GABAergic neurons of the ventrolateral DRN. Moreover, we report that acute exposure to both aversive (restraint stress) and rewarding (chocolate) stimuli reduces GABA release in the DRN, an effect prevented by the inactivation of DRN miR-34a or its genetic deletion in GABAergic neurons in aversive but not rewarding conditions. Finally, miR-34a inhibition selectively reduced passive coping with severe stressors. These data support a role of miR-34a in regulating GABAergic neurotransmitter activity and behavior in a context-dependent manner and suggest that microRNAs could represent a functional signature of specific neuronal subpopulations with valence-specific activity in the brain.

Theory of mind: A clue for the interpretation of functional movement disorders.

OBJECTIVES: Functional movement disorders (FMD) refer to a heterogeneous group of manifestations incongruent with known neurological diseases. Functional neuroimaging studies in FMD indicate the overlap between cerebral regions in which abnormal activation occurs and those considered crucial for theory of mind (ToM), the ability to attribute mental states. The aim of this study was to explore whether FMD might be related to ToM disorders to the extent that they reduce the ability to make inferences about the mental states underlying motor behaviour during social interaction. MATERIALS & METHODS: Eighteen subjects with FMD and 28 matched healthy controls (HC) were given a ToM battery. The severity of FMD was rated by the Simplified-FMD Rating Scale (S-FMDRS). Dissociative symptoms were evaluated by the Dissociative Experiences Scale (DES-II). RESULTS: FMD scored worse than the HC in most ToM tasks: second-order False Beliefs (p = .005), Faux-Pas Recognition Test (p < .001) and Reading the Mind in the Eyes Test (p = .020); control questions elicited normal scores. The DES-II indicated dissociative-borderline psychopathology and negatively correlated with accuracy on the second-order False Belief (Spearman's rho = -.444; p = .032); the positive correlation between DES-II and severity of motor symptoms (S-FMDRS) approached significance (Spearman's rho test = .392; p = .054). ToM disorders were not correlated with S-FMDRS, due to the typical variability in FMD over time with regard to the severity of symptoms and the district of body involved. CONCLUSIONS: Our results are consistent with the hypothesis that FMD are related to ToM deficits, and future studies are needed to define the specific nature of this relationship.

It is not always positive: emotional bias in young and older adults.

Healthy ageing has been associated with a bias toward positive information and greater psychological well-being. However, to what extent this positivity bias also applies to prioritizing positive information under emotional competition is unclear. Old and young adults performed a word-face interference task, in which they responded to the valence of positive and negative target-words while ignoring happy or angry distractor-faces that could be affectively congruent or incongruent. A control condition with scrambled neutral distractor-faces was also used. Findings showed small facilitation effects with faster responses when targets and distractors were affectively congruent and large interference effects with slower responses when targets and distractors were affectively incongruent compared to the control condition. Importantly, whereas for younger adults there was a similar pattern of interference from happy and angry distractor-faces, for older adults there was greater interference from angry distractor-faces. The present findings are discussed in the context of emotional bias literature.

Artificial Neural Network Detects Hip Muscle Forces as Determinant for Harmonic Walking in People after Stroke.

Many recent studies have highlighted that the harmony of physiological walking is based on a specific proportion between the durations of the phases of the gait cycle. When this proportion is close to the so-called golden ratio (about 1.618), the gait cycle assumes an autosimilar fractal structure. In stroke patients this harmony is altered, but it is unclear which factor is associated with the ratios between gait phases because these relationships are probably not linear. We used an artificial neural network to determine the weights associable to each factor for determining the ratio between gait phases and hence the harmony of walking. As expected, the gait ratio obtained as the ratio between stride duration and stance duration was found to be associated with walking speed and stride length, but also with hip muscle forces. These muscles could be important for exploiting the recovery of energy typical of the pendular mechanism of walking. Our study also highlighted that the results of an artificial neural network should be associated with a reliability analysis, being a non-deterministic approach. A good level of reliability was found for the findings of our study.

User-centered practices in the eyes of informal caregivers of in-patients with severe acquired brain injury: needs, caring experience, and satisfaction.

OBJECTIVE: This study examines the perceived needs, experience, and satisfaction of informal caregivers (ICGs) in in-hospital settings, related to their involvement in the design and delivery of services together with hospital staff, namely co-production. DESIGN: To obtain a picture of current ICG-staff relationship, a multicenter observational study was carried out. Participants were 75 ICGs recruited in five dedicated in-patient neurorehabilitation wards. Participants answered a self-report questionnaire tapping perceived information/communication needs, emotional/social needs, and their satisfaction; family-centered practices implemented by the staff (namely involving practices and cooperative communication); and ICGs' satisfaction with the service. RESULTS: Need satisfaction related positively to staff practices aimed at involving IGCs in treatment and training, but not in decision-making. Involving practices concerning treatment also related positively to ICGs' information/communication needs. In addition, the more the staff involved ICGs in decision-making and promoted cooperative communication regarding treatment, the more ICGs felt that their collaboration in the healthcare process was valuable. Finally, all involvement practices and cooperative communication were positively related to ICGs' overall satisfaction with the service. CONCLUSION: The results of the study help to identify gaps in meeting ICGs' needs and to promote strategies to implement family participation toward co-production in in-hospital settings.

Sensorized Assessment of Dynamic Locomotor Imagery in People with Stroke and Healthy Subjects.

Dynamic motor imagery (dMI) is a motor imagery task associated with movements partially mimicking those mentally represented. As well as conventional motor imagery, dMI has been typically assessed by mental chronometry tasks. In this paper, an instrumented approach was proposed for quantifying the correspondence between upper and lower limb oscillatory movements performed on the spot during the dMI of walking vs. during actual walking. Magneto-inertial measurement units were used to measure limb swinging in three different groups: young adults, older adults and stroke patients. Participants were tested in four experimental conditions: (i) simple limb swinging; (ii) limb swinging while imagining to walk (dMI-task); (iii) mental chronometry task, without any movement (pure MI); (iv) actual level walking at comfortable speed. Limb swinging was characterized in terms of the angular velocity, frequency of oscillations and sinusoidal waveform. The dMI was effective at reproducing upper limb oscillations more similar to those occurring during walking for all the three groups, but some exceptions occurred for lower limbs. This finding could be related to the sensory feedback, stretch reflexes and ground reaction forces occurring for lower limbs and not for upper limbs during walking. In conclusion, the instrumented approach through wearable motion devices adds significant information to the current dMI approach, further supporting their applications in neurorehabilitation for monitoring imagery training protocols in patients with stroke.

The Tower of London (ToL) in Italy: standardization of the ToL test in an Italian population.

Deficit in planning and problem-solving, affecting a wide range of neuropsychological patients, has been widely investigated using the Tower of London (ToL) test, as developed by Shallice (Philos Trans R Soc Lond Ser B Biol Sci 298:199-209, 1). The ToL taps on several executive functions (EF), such as planning, time for planning or rule breaks, which may be usefully indexed by different ToL measurements. However, in its original version, the different aspects involved in ToL are not evaluated in a specific way.Here, we report the standardization of the ToL, on 896 individuals aged 15-86 years, taking in account individual factors (i.e. gender, age, years of education) which may affect performances on ToL. We computed several indexes on the ToL including score, planning and execution times, perseverations, rule breaks and self-monitoring. We found that these indexes were affected by individual factors such as gender, age and education. Present results not only provide extensive normative data according to gender, as well as different age and education ranges, but also represent a very useful instrument for a more fine-grained diagnosis of EF deficits in a wide range of neuropsychological patients, including traumatic brain injury and brain-damaged patients, as well as Alzheimer's disease and Parkinson's disease patients.

The assessment of hemineglect syndrome with cancellation tasks: a comparison between the Bells test and the Apples test.

Unilateral spatial neglect (USN) is a frequent consequence of acquired brain injury, especially following right hemisphere damage. Traditionally, unilateral spatial neglect is assessed with cancellation tests such as the Bells test. Recently, a new cancellation test, the Apples test, has been proposed. The present study aims at comparing the accuracy of these two tests in detecting hemispatial neglect, on a sample of 56 right hemisphere stroke patients with a diagnosis of USN. In order to evaluate the agreement between the Apples and Bells tests, Cohen's kappa and McNemar's test were used to assess differences between the two methods of evaluation. Poor agreement and statistically significant differences emerged between the Apples and Bells tests. Overall, the Apples test was significantly more sensitive than the Bells test in detecting USN. Based on these results, the use of the Apples test for peripersonal neglect assessment is therefore highly recommended.

A biopsychosocial analysis of sexuality in adult males and their partners after severe traumatic brain injury.

PURPOSE: The primary aim of this study was to investigate changes in sexual function in males and their partners following severe TBI. Secondary aims of the study were to explore the relationship between selected sociodemographic, emotional/behavioural and sexual function variables. METHODS: Twenty males with a history of severe TBI and 20 healthy controls (HC) and their respective partners were recruited. Sexual life was assessed with the Sexuality Evaluation Schedule Assessment Monitoring (SESAMO). Study participant level of self-awareness was evaluated by the Awareness Questionnaire, whereas their neuropsychiatric and psychopathological statuses were assessed by the NPI, the HAM-D and STAI. RESULTS: A reduction in desire and frequency of sexual intercourse was found in all survivors and their partners. Moreover, higher levels of survivor depression correlated with lower partner harmony. Survivor feelings toward their partners gradually decreased over time, as did the ability to make decisions as a couple. The comparison with HC couples revealed that both survivors' and their partners' exaggerated the extent of disease. CONCLUSIONS: After male severe TBI, men appear to have a reduced quality of their sexual life, which may be more a result of relationship dysfunction than a sexual performance deficit related to their brain injury history.

Timing the events of directional cueing.

To explore the role of temporal context on voluntary orienting of attention, we submitted healthy participants to a spatial cueing task in which cue-target stimulus onset asynchronies (SOAs) were organized according to two-dimensional parameters: range and central value. Three ranges of SOAs organized around two central SOA values were presented to six groups of participants. Results showed a complex pattern of responses in terms of spatial validity (faster responses to correctly cued target) and preparatory effect (faster responses to longer SOAs). Responses to validly and neutrally cued targets were affected by the increase in SOA duration if the difference between longer and shorter SOA was large. On the contrary, responses to invalidly cued targets did not vary according to SOA manipulations. The observed pattern of cueing effects does not fit in the typical description of spatial attention working as a mandatory disengaging-shifting-engaging routine. In contrast, results rather suggest a mechanism based on the interaction between context sensitive top-down processes and bottom-up attentional processes.

Predicting Male Infertility Using Artificial Neural Networks: A Review of the Literature.

Male infertility is a relevant public health problem, but there is no systematic review of the different machine learning (ML) models and their accuracy so far. The present review aims to comprehensively investigate the use of ML algorithms in predicting male infertility, thus reporting the accuracy of the used models in the prediction of male infertility as a primary outcome. Particular attention will be paid to the use of artificial neural networks (ANNs). A comprehensive literature search was conducted in PubMed, Scopus, and Science Direct between 15 July and 23 October 2023, conducted under the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We performed a quality assessment of the included studies using the recommended tools suggested for the type of study design adopted. We also made a screening of the Risk of Bias (RoB) associated with the included studies. Thus, 43 relevant publications were included in this review, for a total of 40 different ML models detected. The studies included reported a good quality, even if RoB was not always good for all the types of studies. The included studies reported a median accuracy of 88% in predicting male infertility using ML models. We found only seven studies using ANN models for male infertility prediction, reporting a median accuracy of 84%.

Michelangelo Effect in Virtual Sculpturing: Prospective for Motor Neurorehabilitation in the Metaverse.

We investigated the Michelangelo effect, i.e. the facilitatory effect of a virtual art therapy in motor rehabilitation (Iosa et al. 2021), with a novel virtual reality paradigm in which users are engaged in motor exercises with 3D sculptures. In particular, thirty young adults were immersed in a virtual environment where they could sculpt, by using the real hands, some famous sculptures in the history of art, such as the David of Michelangelo, the Venus of Milo and the statue of Laocoon and His Sons, and their control stimuli, i.e. statues in very low resolution or cubes. We recorded the kinematics (length, the time to complete each trial, mean normalized jerk) and questionnaire answers (objective and subjective beauty, User Satisfaction Evaluation Questionnaire and Nasa Task Load Index). In general, we found that the perception of subjective and objective beauty was higher when sculpting the statues than control stimuli, the judgment of usability of the system was high. The perceived fatigue was not higher when sculpting the statues despite the longer time spent in completing the task that with respect to the control stimuli. Moreover, we found that the interaction with the experimental statues affected the fluidity and symmetry of hands movements. Finally, we discuss this evidence regarding the art therapy and neuroaesthetics principles for motor rehabilitation in the Metaverse with VR, including the possible role of virtual embodiment (illusory feeling to have a virtual body) for boosting the efficacy of the clinical applications.

Negative emotions enhance memory-guided attention in a visual search task by increasing frontoparietal, insular, and parahippocampal cortical activity.

Previous literature demonstrated that long-term memory representations guide spatial attention during visual search in real-world pictures. However, it is currently unknown whether memory-guided visual search is affected by the emotional content of the picture. During functional magnetic resonance imaging (fMRI), participants were asked to encode the position of high-contrast targets embedded in emotional (negative or positive) or neutral pictures. At retrieval, they performed a visual search for targets presented at the same location as during encoding, but at a much lower contrast. Behaviorally, participants detected more accurately targets presented in negative pictures compared to those in positive or neutral pictures. They were also faster in detecting targets presented at encoding in emotional (negative or positive) pictures than in neutral pictures, or targets not presented during encoding (i.e., memory-guided attention effect). At the neural level, we found increased activation in a large circuit of regions involving the dorsal and ventral frontoparietal cortex, insular and parahippocampal cortex, selectively during the detection of targets presented in negative pictures during encoding. We propose that these regions might form an integrated neural circuit recruited to select and process previously encoded target locations (i.e., memory-guided attention sustained by the frontoparietal cortex) embedded in emotional contexts (i.e., emotional contexts recollection supported by the parahippocampal cortex and emotional monitoring supported by the insular cortex). Ultimately, these findings reveal that negative emotions can enhance memory-guided visual search performance by increasing neural activity in a large-scale brain circuit, contributing to disentangle the complex relationship between emotion, attention, and memory.

Michelangelo Effect in Cognitive Rehabilitation: Using Art in a Digital Visuospatial Memory Task.

The Michelangelo effect is a phenomenon that shows a reduction in perceived effort and an improvement in performance among both healthy subjects and patients when completing a motor task related to artistic stimuli, compared to performing the same task with non-artistic stimuli. It could contribute to the efficacy of art therapy in neurorehabilitation. In this study, the possible occurrence of this effect was tested in a cognitive task by asking 15 healthy subjects and 17 patients with a history of stroke to solve a digital version of the classical memory card game. Three different types of images were used in a randomized order: French cards, artistic portraits, and photos of famous people (to compensate for the possible effects of face recognition). Healthy subjects were involved to test the usability and the load demand of the developed system, reporting no statistically significant differences among the three sessions (p > 0.05). Conversely, patients had a better performance in terms of time (p = 0.014) and the number of attempts (p = 0.007) needed to complete the task in the presence of artistic stimuli, accompanied by a reduction in the perceived effort (p = 0.033). Furthermore, artistic stimuli, with respect to the other two types of images, seemed more associated with visuospatial control than linguistic functions.

Are neuroaesthetic principles applied in art therapy protocols for neurorehabilitation? A systematic mini-review.

Art is an instrument created by humans as an alternative way of expression. For this reason, it has found its use in clinical contexts to improve mood, increase participation in therapy, or improve communication for patients with different pathologies. In this systematic mini-review, the Preferred Reporting Item for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were adopted. Internet-based bibliographic searches were conducted via major electronic databases (Web of Science and PubMed). We analyzed the quantitative studies in which art figures as a neurorehabilitation treatment to identify whether standard art therapy protocols exist and whether these are based on the principles of neuroaesthetics. Our review identified 8 quantitative and 18 qualitative studies. Although art therapy has been used for more than 20 years as a clinical tool, there are no standard protocols to refer to when planning interventions. Although the effectiveness of using arts as therapy has been reported in many qualitative or feasibility studies, there is still a lack of quantitative studies in which the outcomes of art therapy are directly based on the principles of neuroaesthetics.

Application of an Artificial Neural Network to Identify the Factors Influencing Neurorehabilitation Outcomes of Patients with Ischemic Stroke Treated with Thrombolysis.

The administration of thrombolysis usually reduces the risk of death and the consequences of stroke in the acute phase. However, having received thrombolysis administration is not a prognostic factor for neurorehabilitation outcome in the subacute phase of stroke. It is conceivably due to the complex intertwining of many clinical factors. An artificial neural network (ANN) analysis could be helpful in identifying the prognostic factors of neurorehabilitation outcomes and assigning a weight to each of the factors considered. This study hypothesizes that the prognostic factors could be different between patients who received and those who did not receive thrombolytic treatment, even if thrombolysis is not a prognostic factor per se. In a sample of 862 patients with ischemic stroke, the tested ANN identified some common factors (such as disability at admission, age, unilateral spatial neglect), some factors with higher weight in patients who received thrombolysis (hypertension, epilepsy, aphasia, obesity), and some other factors with higher weight in the other patients (dysphagia, malnutrition, total arterial circulatory infarction). Despite the fact that thrombolysis is not an independent prognostic factor for neurorehabilitation, it seems to modify the relative importance of other clinical factors in predicting which patients will better respond to neurorehabilitation.

Robot- and Technology-Boosting Neuroplasticity-Dependent Motor-Cognitive Functional Recovery: Looking towards the Future of Neurorehabilitation.

The sequelae of neurological disorders are the leading causes of disability in all industrialized countries [...].

Virtual Art Therapy: Application of Michelangelo Effect to Neurorehabilitation of Patients with Stroke.

In neurorehabilitation, some studies reported the effective use of art therapy for reducing psychological disorders and for enhancing physical functions and cognitive abilities. Neuroaesthetical studies showed that seeing an art masterpiece can spontaneously elicit a widespread brain arousal, also involving motor networks. To combine contemplative and performative benefits of art therapy protocols, we have developed an immersive virtual reality system, giving subjects the illusion that they are able to paint a copy of famous artistic paintings. We previously observed that during this virtual task, subjects perceived less fatigue and performed more accurate movements than when they were asked to color the virtual canvas. We named this upshot the Michelangelo effect. The aim of this study was to test the rehabilitative efficacy of our system. Ten patients with stroke in the subacute phase were enrolled and trained for one month with virtual art therapy (VAT) and physiotherapy. Their data were compared with those of ten patients matched for pathology, age and clinical parameters, trained only with conventional therapy for the same amount of time. The VAT group showed a significantly higher improvements in the Barthel Index score, a measure of independency in activities of daily living (66 ± 33% vs. 31 ± 28%, p = 0.021), and in pinching strength (66 ± 39% vs. 18 ± 33%, p = 0.008), with respect to the group treated with conventional rehabilitation.

Computer-assisted cognitive rehabilitation in neurological patients: state-of-art and future perspectives.

Background and aim: Advances in computing technology enabled researchers and clinicians to exploit technological devices for cognitive training and rehabilitation interventions. This expert review aims to describe the available software and device used for cognitive training or rehabilitation interventions of patients with neurological disorders. Methods: A scoping review was carried out to analyze commercial devices/software for computerized cognitive training (CCT) in terms of feasibility and efficacy in both clinical and home settings. Several cognitive domains responding to the different patients' needs are covered. Results: This review showed that cognitive training for patients with neurological diseases is largely covered by several devices that are widely used and validated in the hospital setting but with few translations to remote/home applications. It has been demonstrated that technology and software-based devices are potential and valuable tools to administer remotely cognitive rehabilitation with accessible costs. Conclusion: According to our results, CCT entails the possibility to continue cognitive training also in different settings, such as home, which is a significant breakthrough for the improvement of community care. Other possible areas of use should be the increase in the amount of cognitive therapy in the free time during the hospital stay.

The golden ratio as an ecological affordance leading to aesthetic attractiveness.

The golden ratio (GR) is an irrational number (close to 1.618) that repeatedly occurs in nature as well as in masterpieces of art. The GR has been considered a proportion perfectly representing beauty since ancient times, and it was investigated in several scientific fields, but with conflicting results. This study aims at investigating if this proportion is associated with a judgment of beauty independently of the type of the stimulus, and the factors that may affect this aesthetic preference. In Experiment 1, an online psychophysical questionnaire was administered to 256 volunteers asked to choose among three possible proportions between the parts of the same stimulus (GR, 1.5, and 1.8). In Experiment 2, we recorded eye movements in 15 participants who had to express an aesthetic judgment on the same stimuli of Experiment 1. The results revealed a slight overall preference for GR (53%, p < .001), with higher preferences for stimuli representing humans, anthropomorphic sculptures, and paintings, regardless of the cultural level. In Experiment 2, a shorter dwell time was significantly associated with a better aesthetic judgment (p = .005), suggesting the possibility that GR could be associated with easier visual processing, and it could be hence considered as a visual affordance.