Preliminary findings on long-term effects of fMRI neurofeedback training on functional networks involved in sustained attention.

INTRODUCTION: Neurofeedback based on functional magnetic resonance imaging allows for learning voluntary control over one's own brain activity, aiming to enhance cognition and clinical symptoms. We previously reported improved sustained attention temporarily by training healthy participants to up-regulate the differential activity of the sustained attention network minus the default mode network (DMN). However, the long-term brain and behavioral effects of this training have not yet been studied. In general, despite their relevance, long-term learning effects of neurofeedback training remain under-explored. METHODS: Here, we complement our previously reported results by evaluating the neurofeedback training effects on functional networks involved in sustained attention and by assessing behavioral and brain measures before, after, and 2 months after training. The behavioral measures include task as well as questionnaire scores, and the brain measures include activity and connectivity during self-regulation runs without feedback (i.e., transfer runs) and during resting-state runs from 15 healthy individuals. RESULTS: Neurally, we found that participants maintained their ability to control the differential activity during follow-up sessions. Further, exploratory analyses showed that the training increased the functional connectivity between the DMN and the occipital gyrus, which was maintained during follow-up transfer runs but not during follow-up resting-state runs. Behaviorally, we found that enhanced sustained attention right after training returned to baseline level during follow-up. CONCLUSION: The discrepancy between lasting regulation-related brain changes but transient behavioral and resting-state effects raises the question of how neural changes induced by neurofeedback training translate to potential behavioral improvements. Since neurofeedback directly targets brain measures to indirectly improve behavior in the long term, a better understanding of the brain-behavior associations during and after neurofeedback training is needed to develop its full potential as a promising scientific and clinical tool.

Modeling Electric Fields in Transcutaneous Spinal Direct Current Stimulation: A Clinical Perspective.

Clinical findings suggest that transcutaneous spinal direct current stimulation (tsDCS) can modulate ascending sensitive, descending corticospinal, and segmental pathways in the spinal cord (SC). However, several aspects of the stimulation have not been completely understood, and realistic computational models based on MRI are the gold standard to predict the interaction between tsDCS-induced electric fields and anatomy. Here, we review the electric fields distribution in the SC during tsDCS as predicted by MRI-based realistic models, compare such knowledge with clinical findings, and define the role of computational knowledge in optimizing tsDCS protocols. tsDCS-induced electric fields are predicted to be safe and induce both transient and neuroplastic changes. This could support the possibility to explore new clinical applications, such as spinal cord injury. For the most applied protocol (2-3 mA for 20-30 min, active electrode over T10-T12 and the reference on the right shoulder), similar electric field intensities are generated in both ventral and dorsal horns of the SC at the same height. This was confirmed by human studies, in which both motor and sensitive effects were found. Lastly, electric fields are strongly dependent on anatomy and electrodes' placement. Regardless of the montage, inter-individual hotspots of higher values of electric fields were predicted, which could change when the subjects move from a position to another (e.g., from the supine to the lateral position). These characteristics underlines the need for individualized and patient-tailored MRI-based computational models to optimize the stimulation protocol. A detailed modeling approach of the electric field distribution might contribute to optimizing stimulation protocols, tailoring electrodes' configuration, intensities, and duration to the clinical outcome.

Evaluation of the reliability and validity of computerized tests of attention.

Different aspects of attention can be assessed through psychological tests to identify stable individual or group differences as well as alterations after interventions. Aiming for a wide applicability of attentional assessments, Psychology Experiment Building Language (PEBL) is an open-source software system for designing and running computerized tasks that tax various attentional functions. Here, we evaluated the reliability and validity of computerized attention tasks as provided with the PEBL package: Continuous Performance Task (CPT), Switcher task, Psychomotor Vigilance Task (PVT), Mental Rotation task, and Attentional Network Test. For all tasks, we evaluated test-retest reliability using the intraclass correlation coefficient (ICC), as well as internal consistency through within-test correlations and split-half ICC. Across tasks, response time scores showed adequate reliability, whereas scores of performance accuracy, variability, and deterioration over time did not. Stability across application sites was observed for the CPT and Switcher task, but practice effects were observed for all tasks except the PVT. We substantiate convergent and discriminant validity for several task scores using between-task correlations and provide further evidence for construct validity via associations of task scores with attentional and motivational assessments. Taken together, our results provide necessary information to help design and interpret studies involving attention assessments.

Vision- and touch-dependent brain correlates of body-related mental processing.

In humans, the nature of sensory input influences body-related mental processing. For instance, behavioral differences (e.g., response time) can be found between mental spatial transformations (e.g., mental rotation) of viewed and touched body parts. It can thus be hypothesized that distinct brain activation patterns are associated with such sensory-dependent body-related mental processing. However, direct evidence that the neural correlates of body-related mental processing can be modulated by the nature of the sensory stimuli is still missing. We thus analyzed event-related functional magnetic resonance imaging (fMRI) data from thirty-one healthy participants performing mental rotation of visually- (images) and haptically-presented (plastic) hands. We also dissociated the neural activity related to rotation or task-related performance using models that either regressed out or included the variance associated with response time. Haptically-mediated mental rotation recruited mostly the sensorimotor brain network. Visually-mediated mental rotation led to parieto-occipital activations. In addition, faster mental rotation was associated with sensorimotor activity, while slower mental rotation was associated with parieto-occipital activations. The fMRI results indicated that changing the type of sensory inputs modulates the neural correlates of body-related mental processing. These findings suggest that distinct sensorimotor brain dynamics can be exploited to execute similar tasks depending on the available sensory input. The present study can contribute to a better evaluation of body-related mental processing in experimental and clinical settings.

Abrupt visibility modifications affect specific subjective (not objective) aspects of body ownership.

The sense of body ownership builds on proper multisensory integration mechanisms. The Rubber-Hand Illusion (RHI) paradigm exploits a visuo-tactile multisensory conflict to induce illusory body ownership toward a fake hand, assessed by multidimensional subjective ratings and univocal objective measurements. Considering the controversy as to whether viewing the rubber hand is necessary or not to induce the illusion, we investigated the effects of targeted manipulations of visibility on subjective and objective aspects of the RHI. To this aim, we collected questionnaire and proprioceptive drift data from thirty participants receiving visuo-tactile stimulation in a setup that allowed for increasing and decreasing the visibility (illumination) of the rubber hand. We found that specific subjective ratings (Movement and Loss of Ownership) were sensitive to the interaction between rubber hand's visibility and illusory ownership. The interaction was not significant for the Embodiment subjective component and for the objective one (proprioceptive drift). Since different degrees of visibility did not differentially affect the RHI, these findings highlight that relatively abrupt changes in the visibility of the rubber hand can differentially impact subjective versus objective components of body ownership. This understanding may be critical for neuroscientific theories on the relationship between multisensory integration and body consciousness.

Early response competition over the motor cortex underlies proactive control of error correction.

Response inhibition is a fundamental brain function that must be flexible enough to incorporate proactive goal-directed demands, along with reactive, automatic and well consolidated behaviors. However, whether proactive inhibitory processes can be explained by response competition, rather than by active top-down inhibitory control, remains still unclear. Using a modified version of the Eriksen flanker task, we examined the behavioral and electrophysiological correlates elicited by manipulating the degree of inhibitory control in a task that involved the fast amendment of errors. We observed that restraining or encouraging the correction of errors did not affect the behavioral and neural correlates associated to reactive inhibition. We rather found that an early, sustained and bilateral activation, of both the correct and the incorrect response, was required for an effective proactive inhibitory control. Selective unilateral patterns of response preparation were instead associated with defective response suppression. Our results provide behavioral and electrophysiological evidence of a simultaneous dual pre-activation of two motor commands, likely underlying a global operating mechanism suggesting competition or lateral inhibition to govern the amendment of errors. These findings are consistent with the response inhibitory processes already observed in speed-accuracy tradeoff studies, and hint at a decisive role of early response competition to determine the success of multiple-choice action selection.

Social Touch Somatotopically Affects Mental Body Representations.

In pre-Covid days, many daily actions such as hand shaking or cheek kissing implied physical contact between our body and that of other people. With respect to touching an inanimate object (objectual touch), touching a person (social touch) concerns not only touching a human body, but also that this body belongs to a living person. This fundamental difference also may affect the way we figure our own movements and perceptions or, in other words, how we mentally represent our own body. To test this hypothesis, we asked 30 neurotypical participants to perform mental rotation of images representing hands, full bodies, and feet (an active cognitive task able to activate body representations without need of moving) in two tactile conditions: holding (one in each hand) either the thumbs of another person (social touch) or two plastic cylinders (objectual touch) of about the same circumference and size. Results showed that only mental rotation of hand images was affected by varying the tactile conditions, in that participants were faster during social than objectual touch. This suggests that the nature of hand-related tactile input (social or objectual touch) influences local (hand) and not global (body) mental representations of the body, and in a very somatotopic manner (hands but not feet). We interpret these findings with reference to the differentiation between sensorimotor (body schema) and visuospatial (body image) dynamics in the mental representation of our body. The present study shows that external social factors can affect the internal mental representations of one's own body.

Illusory Body Ownership Affects the Cortical Response to Vicarious Somatosensation.

Fundamental human feelings such as body ownership ("this" body is "my" body) and vicariousness (first-person-like experience of events occurring to others) are based on multisensory integration. Behavioral links between body ownership and vicariousness have been shown, but the neural underpinnings remain largely unexplored. To fill this gap, we investigated the neural effects of altered body ownership on vicarious somatosensation. While recording functional brain imaging data, first, we altered participants' body ownership by robotically delivering tactile stimulations ("tactile" stroking) in synchrony or not with videos of a virtual hand being brushed ("visual" stroking). Then, we manipulated vicarious somatosensation by showing videos of the virtual hand being touched by a syringe's plunger (touch) or needle (pain). Only after the alteration of body ownership (synchronous visuo-tactile stroking) and specifically during late epochs of vicarious somatosensation, vicarious pain was associated with lower activation in premotor and anterior cingulate cortices with respect to vicarious touch. At the methodological level, the present study highlights the importance of the neural response's temporal evolution. At the theoretical level, it shows that the higher-level (cognitive) impact of a lower-level (sensory) body-related processing (visuo-tactile) is not limited to body ownership but also extends to other psychological body-related domains, such as vicarious somatosensation.

Cognitive Training Improves Disconnected Limbs' Mental Representation and Peripersonal Space after Spinal Cord Injury.

Paraplegia following spinal cord injury (SCI) affects the mental representation and peripersonal space of the paralysed body parts (i.e., lower limbs). Physical rehabilitation programs can improve these aspects, but the benefits are mostly partial and short-lasting. These limits could be due to the absence of trainings focused on SCI-induced cognitive deficits combined with traditional physical rehabilitation. To test this hypothesis, we assessed in 15 SCI-individuals the effects of adding cognitive recovery protocols (motor imagery-MI) to standard physical rehabilitation programs (Motor + MI training) on mental body representations and space representations, with respect to physical rehabilitation alone (control training). Each training comprised at least eight sessions administered over two weeks. The status of participants' mental body representation and peripersonal space was assessed at three time points: before the training (T0), after the training (T1), and in a follow-up assessment one month later (T2). The Motor + MI training induced short-term recovery of peripersonal space that however did not persist at T2. Body representation showed a slower neuroplastic recovery at T2, without differences between Motor and the Motor + MI. These results show that body and space representations are plastic after lesions, and open new rehabilitation perspectives.

Neuro-Behavioral Correlates of Executive Dysfunctions in Dyslexia Over Development From Childhood to Adulthood.

Dyslexia is a neurobiological learning disability in the reading domain that has symptoms in early childhood and persists throughout life. Individuals with dyslexia experience difficulties in academia and cognitive and emotional challenges that can affect wellbeing. Early intervention is critical to minimize the long-term difficulties of these individuals. However, the behavioral and neural correlates which predict dyslexia are challenging to depict before reading is acquired. One of the precursors for language and reading acquisition is executive functions (EF). The present review aims to highlight the current atypicality found in individuals with dyslexia in the domain of EF using behavioral measures, brain mapping, functional connectivity, and diffusion tensor imaging along development. Individuals with dyslexia show EF abnormalities in both behavioral and neurobiological domains, starting in early childhood that persist into adulthood. EF impairment precedes reading disability, therefore adding an EF assessment to the neuropsychological testing is recommended for early intervention. EF training should also be considered for the most comprehensive outcomes.

Anatomo-Functional Origins of the Cortical Silent Period: Spotlight on the Basal Ganglia.

The so-called cortical silent period (CSP) refers to the temporary interruption of electromyographic signal from a muscle following a motor-evoked potential (MEP) triggered by transcranial magnetic stimulation (TMS) over the primary motor cortex (M1). The neurophysiological origins of the CSP are debated. Previous evidence suggests that both spinal and cortical mechanisms may account for the duration of the CSP. However, contextual factors such as cortical fatigue, experimental procedures, attentional load, as well as neuropathology can also influence the CSP duration. The present paper summarizes the most relevant evidence on the mechanisms underlying the duration of the CSP, with a particular focus on the central role of the basal ganglia in the "direct" (excitatory), "indirect" (inhibitory), and "hyperdirect" cortico-subcortical pathways to manage cortical motor inhibition. We propose new methods of interpretation of the CSP related, at least partially, to the inhibitory hyperdirect and indirect pathways in the basal ganglia. This view may help to explain the respective shortening and lengthening of the CSP in various neurological disorders. Shedding light on the complexity of the CSP's origins, the present review aims at constituting a reference for future work in fundamental research, technological development, and clinical settings.

Visual Neuropsychology in Development: Anatomo-Functional Brain Mechanisms of Action/Perception Binding in Health and Disease.

Vision is the main entrance for environmental input to the human brain. Even if vision is our most used sensory modality, its importance is not limited to environmental exploration. Rather it has strong links to motor competences, further extending to cognitive and social aspects of human life. These multifaceted relationships are particularly important in developmental age and become dramatically evident in presence of complex deficits originating from visual aberrancies. The present review summarizes the available neuropsychological evidence on the development of visual competences, with a particular focus on the associated visuo-motor integration skills in health and disease. With the aim of supporting future research and interventional settings, the goal of the present review is to constitute a solid base to help the translation of neuropsychological hypotheses into straightforward empirical investigations and rehabilitation/training protocols. This approach will further increase the impact, ameliorate the acceptance, and ease the use and implementation of lab-derived intervention protocols in real-life situations.

The Influence of Personality, Resilience, and Alexithymia on Mental Health During COVID-19 Pandemic.

Following the COVID-19 pandemic, many countries worldwide have put lockdowns in place to prevent the virus from spreading. Evidence shows that lockdown measures can affect mental health; it is, therefore, important to identify the psychological characteristics making individuals more vulnerable. The present study aimed, first, to identify, through a cluster analysis, the psychological attributes that characterize individuals with similar psychological responses to the COVID-19 home confinement; second, to investigate whether different psychological characteristics, such as personality traits, alexithymia, and resilience, specifically influence anxiety, stress, and depression, depending on the scope of the confinement. We analyzed data from 393 participants who completed an online survey on their experiences during two different phases of the Italian lockdown, characterized by more or less strict measures of confinement. Two clusters were identified which included participants reporting a better (+ER) and worse (-ER) emotional response to the lockdown, respectively. Individuals in the -ER group showed lower emotional stability, resilience, and higher alexithymia. Moreover, even if lifting part of the restrictions decreased psychological distress among all participants, a reduction in perceived stress was observed only among individuals with high resilience. Finally, personality traits, alexithymia, and resilience differently affected depression, anxiety, and stress. Our results suggest that different psychological interventions should be planned depending on the context: mental health professionals should focus on enhancing the individuals' coping strategies to alleviate stress in emergencies, while long-term intervention aiming at alleviating anxiety and depressive symptoms should focus on alexithymic tendencies and personality constructs.

Increased emotional eating during COVID-19 associated with lockdown, psychological and social distress.

Due to the spread of COVID 2019, the Italian government imposed a lockdown on the national territory. Initially, citizens were required to stay at home and not to mix with others outside of their household (Phase 1); eventually, some of these restrictions were lifted (Phase 2). To investigate the impact of lockdown on emotional and binge eating, an online survey was conducted to compare measures of self-reported physical (BMI), psychological (Alexithymia), affective (anxiety, stress, and depression) and social (income, workload) state during Phase 1 and Phase 2. Data from 365 Italian residents showed that increased emotional eating was predicted by higher depression, anxiety, quality of personal relationships, and quality of life, while the increase of bingeing was predicted by higher stress. Moreover, we showed that higher alexithymia scores were associated by increased emotional eating and higher BMI scores were associated with both increased emotional eating and binge eating. Finally, we found that from Phase 1 to Phase 2 binge and emotional eating decreased. These data provide evidence of the negative effects of isolation and lockdown on emotional wellbeing, and, relatedly, on eating behaviour.

Visual similarity and psychological closeness are neurally dissociable in the brain response to vicarious pain.

Personal and vicarious experience of pain activate partially overlapping brain networks. This brain activity is further modulated by low- and high-order factors, e.g., the perceived intensity of the model's pain and the model's similarity with the onlooker, respectively. We investigated which specific aspect of similarity modulates such empathic reactivity, focusing on the potential differentiation between visual similarity and psychological closeness between the onlooker and different types of models. To this aim, we recorded fMRI data in neurotypical participants who observed painful and tactile stimuli delivered to an adult human hand, a baby human hand, a puppy dog paw, and an anthropomorphic robotic hand. The interaction between type of vicarious experience (pain, touch) and nature of model (adult, baby, dog, robot) showed that the right supramarginal gyrus (rSMG) was selectively active for visual similarity (more active during vicarious pain for the adult and baby models), while the anterior cingulate cortex (ACC) was more sensitive to psychological closeness (specifically linked to vicarious pain for the baby model). These findings indicate that visual similarity and psychological closeness between onlooker and model differentially affect the activity of brain regions specifically implied in encoding interindividual sharing of sensorimotor and affective aspects of vicarious pain, respectively.

Temporo-parietal contribution to the mental representations of self/other face.

Face recognition requires comparing the current visual input with stored mental representations of faces. Based on its role in visual recognition of faces and mental representation of the body, we hypothesized that the right temporo-parietal junction (rTPJ) could be implicated also in processing mental representation of faces. To test this hypothesis, we asked 30 neurotypical participants to perform mental rotation (laterality judgment of rotated pictures) of self- and other-face images, before and after the inhibition of rTPJ through repetitive transcranial magnetic stimulation. After inhibition of rTPJ the mental rotation of self-face was slower than other-face. In the control condition the mental rotation of self/other faces was not significantly different. This supports that the role of rTPJ extends to mental representation of faces, specifically for the self. Since the experimental task did not require to explicitly recognize identity, we propose that unconscious identity attribution affects also the mental representation of faces. The present study offers insights on the involvement rTPJ in mental representation of faces and proposes that the neural substrate dedicated to mental representation of faces goes beyond the traditional visual and memory areas.

Network-based fMRI-neurofeedback training of sustained attention.

The brain regions supporting sustained attention (sustained attention network; SAN) and mind-wandering (default-mode network; DMN) have been extensively studied. Nevertheless, this knowledge has not yet been translated into advanced brain-based attention training protocols. Here, we used network-based real-time functional magnetic resonance imaging (fMRI) to provide healthy individuals with information about current activity levels in SAN and DMN. Specifically, 15 participants trained to control the difference between SAN and DMN hemodynamic activity and completed behavioral attention tests before and after neurofeedback training. Through training, participants improved controlling the differential SAN-DMN feedback signal, which was accomplished mainly through deactivating DMN. After training, participants were able to apply learned self-regulation of the differential feedback signal even when feedback was no longer available (i.e., during transfer runs). The neurofeedback group improved in sustained attention after training, although this improvement was temporally limited and rarely exceeded mere practice effects that were controlled by a test-retest behavioral control group. The learned self-regulation and the behavioral outcomes suggest that neurofeedback training of differential SAN and DMN activity has the potential to become a non-invasive and non-pharmacological tool to enhance attention and mitigate specific attention deficits.

3-Dimensional magnetic resonance imaging of the freely moving human eye.

Eye motion is a major confound for magnetic resonance imaging (MRI) in neuroscience or ophthalmology. Currently, solutions toward eye stabilisation include participants fixating or administration of paralytics/anaesthetics. We developed a novel MRI protocol for acquiring 3-dimensional images while the eye freely moves. Eye motion serves as the basis for image reconstruction, rather than an impediment. We fully reconstruct videos of the moving eye and head. We quantitatively validate data quality with millimetre resolution in two ways for individual participants. First, eye position based on reconstructed images correlated with simultaneous eye-tracking. Second, the reconstructed images preserve anatomical properties; the eye's axial length measured from MRI images matched that obtained with ocular biometry. The technique operates on a standard clinical setup, without necessitating specialized hardware, facilitating wide deployment. In clinical practice, we anticipate that this may help reduce burdens on both patients and infrastructure, by integrating multiple varieties of assessments into a single comprehensive session. More generally, our protocol is a harbinger for removing the necessity of fixation, thereby opening new opportunities for ethologically-valid, naturalistic paradigms, the inclusion of populations typically unable to stably fixate, and increased translational research such as in awake animals whose eye movements constitute an accessible behavioural readout.

Visuo-motor and interoceptive influences on peripersonal space representation following spinal cord injury.

Peripersonal space (PPS) representation is modulated by information coming from the body. In paraplegic individuals, whose lower limb sensory-motor functions are impaired or completely lost, the representation of PPS around the feet is reduced. However, passive motion can have short-term restorative effects. What remains unclear is the mechanisms underlying this recovery, in particular with regard to the contribution of visual and motor feedback and of interoception. Using virtual reality technology, we dissociated the motor and visual feedback during passive motion in paraplegics with complete and incomplete lesions and in healthy controls. The results show that in the case of paraplegics, the presence of motor feedback was necessary for the recovery of PPS representation, both when the motor feedback was congruent and when it was incongruent with the visual feedback. In contrast, visuo-motor incongruence led to an inhibition of PPS representation in the control group. There were no differences in sympathetic responses between the three groups. Nevertheless, in individuals with incomplete lesions, greater interoceptive sensitivity was associated with a better representation of PPS around the feet in the visuo-motor incongruent conditions. These results shed new light on the modulation of PPS representation, and demonstrate the importance of residual motor feedback and its integration with other bodily information in maintaining space representation.