The Body in Neurosciences: Representation, Perception and Space Processing.

The Special Issue "The Body in Neurosciences: Representation, Perception and Space Processing" deals with the understanding of body processing in terms of the multisensorial perception of bodily related information, interoception, and mental representation, as well as its relationship with the peripersonal, interpersonal, and extrapersonal spaces, integrating findings from normal and pathological functioning [...].

Towards precision medicine for phenylketonuria: The effect of restoring a strict metabolic control in adult patients with early-treated phenylketonuria.

BACKGROUND AND OBJECTIVE: Neonatal screening and early treatment have changed the natural history of PKU, preventing severe neurological and intellectual disability. Nevertheless, the outcome of the disease in early-treated adult patients (ETPKU) is less than optimal, the predictive value of metabolic biomarkers is feeble, and the recommended levels of blood phenylalanine (Phe) for adulthood are controversial. A crucial question whose answer will improve our understanding and treatment of PKU is whether cognitive outcomes can be modulated by levels of Phe even in early-treated adults. To address this question, we carried out an interventional study in seven ETPKU women planning a pregnancy. METHODS: They underwent an extensive neurocognitive assessment at baseline, and 3 and 6 months after having attained the blood Phe concentration recommended to prevent PKU fetopathy, but before pregnancy. RESULTS: After 3 and 6 months with a stable blood Phe level of about 240 µmol/L, all participants experienced significant improvements in almost all neurocognitive domains and tasks. IQ also increased of 11 to 21 points from the last assessment before enrolment. This pattern remained strong and consistent after correction for multiple comparisons. CONCLUSION: Our results indicate that a) strong cognitive improvement is possible even in adulthood and may be demonstrated by lowering Phe near normal levels; b) testing cognition under different metabolic conditions may unveil an individual vulnerability to Phe. These results pave the way for personalised treatment of the disease in adults with ETPKU.

Combining the Inner Self with the Map of the Body: Evidence for White Matter Contribution to the Relation Between Interoceptive Sensibility and Nonaction-oriented Body Representation.

Very recent studies on healthy individuals suggest that changes in the sensibility toward internal bodily sensations across the lifespan affect the ability to mentally represent one's body, in terms of action-oriented and nonaction-oriented body representation (BR). Little is known about the neural correlates of this relation. Here we fill this gap using the neuropsychological model provided by focal brain damage. Sixty-five patients with unilateral stroke (20 with left and 45 with right brain damage, LBD and RBD, respectively) participated in this study. Both action-oriented BR and nonaction-oriented BR were tested; interoceptive sensibility was assessed as well. First, we tested whether interoceptive sensibility predicted action-oriented BR and nonaction-oriented BR, in RBD and LBD separately. Then, a track-wise hodological lesion-deficit analysis was performed in a subsample of twenty-four patients to test the brain network supporting this relation. We found that interoceptive sensibility predicted the performances in the task tapping nonaction-oriented BR. The higher interoceptive sensibility was, the worse patients performed. This relation was associated with the disconnection probability of the corticospinal tract, the fronto-insular tract, and the pons. We expand over the previous findings on healthy individuals, supporting the idea that high levels of interoceptive sensibility negatively affect BR. Specific frontal projections and frontal u-shaped tracts may play a pivotal role in such an effect, likely affecting the development of a first-order representation of the self within the brainstem autoregulatory centers and posterior insula and of a second-order representation of the self within the anterior insula and higher-order prefrontal areas.

Neural substrates of interoceptive sensibility: An integrated study in normal and pathological functioning.

In early studies interoception strictly referred to the awareness of visceral sensations, but recent theories have expanded this concept to denote the ongoing status of the body, including somatosensory feelings. Here, we integrated data from normal and pathological functioning to disclose neural underpinnings of interoceptive sensibility, taking into account the crucial distinction between visceral and somatosensory feelings. Twenty-seven healthy young individuals underwent structural MRI (including T1w images and DTI). Voxel-wise analyses of the gyrification index (GI) and fractional anisotropy (FA) data were performed to assess the relation between interoceptive sensibility and surface morphometry and anatomical connectivity. Thirty-three unilateral brain-damaged patients took part in this study for Voxel-Based Lesion-Symptom Mapping (VLSM) and track-wise hodological lesion-deficit analysis (TWH). All participants completed the Self-Awareness Questionnaire (SAQ), a self-report tool assessing interoceptive sensibility of visceral (F1) and somatosensory feelings (F2). Tract-Based Spatial Statistics showed that F2 was positively associated with FA in the bilateral anterior thalamic radiation, corticospinal tract, cingulum, forceps, inferior longitudinal, fronto-occipital, superior longitudinal, and uncinate fasciculi; no significant association was detected for F1. However, F1 was positively associated with GI in the left anterior cingulate cortex. VLSM showed that F1 mainly relies on the right posterior insula, whereas F2 is related mostly to subcortical nuclei and surrounding white matter in the right hemisphere. Accordingly, patients with disconnection of the anterior thalamic projection, corticospinal tract, inferior fronto-occipital, inferior longitudinal, uncinate and superior longitudinal fasciculus III showed lower scores on F2. Overall, results support the dissociation between interoceptive sensibility of visceral and somatosensory feelings.

The bodily fundament of empathy: The role of action, nonaction-oriented, and interoceptive body representations.

Mental representations with bodily contents or in various bodily formats have been suggested to play a pivotal role in social cognition, including empathy. However, there is a lack of systematic studies investigating, in the same sample of participants and using an individual differences approach, whether and to what extent the sensorimotor, perceptual, and interoceptive representations of the body could fulfill an explanatory role in the empathic abilities.To address this goal, we carried out two studies in which healthy adults were given measures of interoceptive sensibility (IS), action (aBR), and nonaction-oriented body representations (NaBR), and affective, cognitive, and motor empathy. A higher tendency to be self-focused on interoceptive signals predicted higher affective, cognitive, and motor empathy levels. A better performance in tasks probing aBR and NaBR predicted, respectively, higher motor and cognitive empathy levels.These findings support the view that the various facets of the empathic response are differently grounded in the body since they diversely involve representations with a different bodily format.Individual differences in the focus on one's internal body state representation can directly modulate all the components of the empathic experience. Instead, a body representation used interpersonally to represent both one's own body and others' bodies, in particular in its spatial specificity, could be necessary to accurately understand other people's minds (cognitive empathy), while a sensorimotor body representation used to represent both one's own body and others' bodies actions, could be fundamental for the self-awareness of feelings expressed in actions (motor empathy).

Sensitivity of conventional cognitive tests in multiple sclerosis: Application of item response theory.

BACKGROUND: Cognitive impairment (CI) is common in Multiple Sclerosis (MS), and its prevalence rate ranges between 22% and 70%. Because CI significantly impacts vocational status, caregiver burden, and quality of life, an accurate neuropsychological assessment is required. Three widely used and validated batteries for MS-associated CI are the Brief Repeatable Neuropsychological Battery (BRN-B), the Minimal Assessment of Cognitive Function (MACFIMS), and the Brief International Cognitive Assessment (BICAMS). Although similar, these batteries differ in time-consuming and in specific tests employed. This study aims to assess the sensitivity of cognitive tests included in these batteries through an Item Response Theory approach. METHODS: Ninety-seven patients with MS and 91 demographically matched controls (HC) were consecutively assessed using the three neuropsychological batteries (i.e., BRN-B, MACFIMS, and BICAMS). Continuous Response Model (CRM) was used to identify the cognitive test(s) that best discriminate patients with MS from HC. Receiver Operating Characteristic (ROC) curve analysis was used to determine the accuracy of the CRM results. RESULTS: Cognitive tests loaded on two different latent variables: the 'higher-order executive functioning,' consisting of tests assessing concept formation, problem-solving, and inhibitory control, and the 'memory and information processing speed,' comprising tests assessing long-term, working memory, and information processing speed. The Delis Kaplan Executive Functioning System-Sorting Test and the Stroop Test were the most sensitive tests in differentiating cognitive functioning between MS and HC. CONCLUSIONS: This study confirms the importance of including a more extensive executive assessment in MS clinical practice since higher-order executive functions (e.g., abstraction and inhibitory control) significantly impact patients' quality of life and functional autonomy. Clinical implications of careful dissection of executive functioning in MS neuropsychological assessment are discussed.

On the Embodiment of Social Cognition Skills: The Inner and Outer Body Processing Differently Contributes to the Affective and Cognitive Theory of Mind.

A specific interpretation of embodiment assigns a central role to the body representations (BR) in cognition. In the social cognition domain, BR could be pivotal in representing others' actions and states. However, empirical evidence on the relationship between different BR and social cognition, in terms of Theory of Mind (ToM), in the same sample of participants is missing. Here, this relationship was explored considering individual differences in the action-oriented BR (aBR), nonaction-oriented BR (NaBR), and subjective predisposition toward internal bodily sensations (interoceptive sensibility, ISe). Eighty-two healthy adults were given behavioral measures probing aBR, NaBR, ISe, and affective/cognitive ToM. The results suggest that NaBR, which mainly relies on exteroceptive signals, predicts individual differences in cognitive ToM, possibly because it can allow differentiating between the self and others. Instead, the negative association between affective ToM and ISe suggests that an alteration of the internal body state representation (i.e., over-reporting interoceptive sensations) can affect emotional processing in social contexts. The finding that distinct aspects of the body processing from within (ISe) and from the outside (NaBR) differently contribute to ToM provides empirical support to the BR role in social cognition and can be relevant for developing interventions in clinical settings.

Where Am I? Searching for the Tangle in the Developmental Topographical Disorientation.

The Developmental Topographical Disorientation (DTD) is a pathological condition that impairs an individual's ability to orient in space, even in the most familiar environments. It is a lifelong selective condition in individuals without brain damage or without impaired general cognitive functions. Here, we aimed at characterizing 54 individuals with DTD identified in a previous study, aged between 18 and 35 years and assessed through a 4-year-long online survey. To this purpose, we compared them with 54 matched healthy participants. We described the demographics, sense of direction, town knowledge, navigational strategies, left-right confusion as well as agnosic disorders (for landmarks, faces and objects). This novel study attempts to characterize the phenotype of DTD, providing an important contribution to the worldwide definition of a condition that was first described only 13 years ago, but which, considering the growing number of cases complaining of the disorder, deserves continuous and increasing attention.

"Where am I?" A snapshot of the developmental topographical disorientation among young Italian adults.

In the last decade, several cases affected by Developmental Topographical Disorientation (DTD) have been described. DTD consists of a neurodevelopmental disorder affecting the ability to orient in the environment despite well-preserved cognitive functions, and in the absence of a brain lesion or other neurological or psychiatric conditions. Described cases showed different impairments in navigational skills ranging from topographic memory deficits to landmark agnosia. All cases lacked a mental representation of the environment that would allow them to use high-order spatial orientation strategies. In addition to the single case studies, a group study performed in Canada showed that the disorder is more widespread than imagined. The present work intends to investigate the occurrence of the disorder in 1,698 young Italian participants. The sample is deliberately composed of individuals aged between 18 and 35 years to exclude people who could manifest the loss of the ability to navigate as a result of an onset of cognitive decline. The sample was collected between 2016 and 2019 using the Qualtrics platform, by which the Familiarity and Spatial Cognitive Style Scale and anamnestic interview were administered. The data showed that the disorder is present in 3% of the sample and that the sense of direction is closely related to town knowledge, navigational strategies adopted, and gender. In general, males use more complex navigational strategies than females, although DTD is more prevalent in males than in females, in line with the already described cases. Finally, the paper discusses which protective factors can reduce DTD onset and which intervention measures should be implemented to prevent the spread of navigational disorders, which severely impact individuals' autonomy and social relationships.

Congenital lack and extraordinary ability in object and spatial imagery: An investigation on sub-types of aphantasia and hyperphantasia.

Studies that have shown a distinction between object and spatial imagery suggest more than one type of aphantasia and hyperphantasia, yet this has not been systematically investigated in studies on imagery ability extremes. Also, if the involuntary imagery is preserved in aphantasia and how this condition affects other skills is not fully clear. We collected data on spatial and object imagery, retrospective, and prospective memory, face recognition, and sense of direction (SOD), suggesting a distinction between two subtypes of aphantasia/hyperphantasia. Spatial aphantasia is associated with difficulties in visuo-spatial mental imagery and SOD. Instead, in object aphantasia there are difficulties in imaging single items and events - with no mental visualization of objects, out-of-focus, and black-and-white mental images more frequent than expected - in SOD and face recognition. Furthermore, associative involuntary imagery can be spared in aphantasia. The opposite pattern of performance was found in spatial and object hyperphantasia.

Body Representation Alterations in Patients with Unilateral Brain Damage.

OBJECTIVE: Systematic studies about the impact of unilateral brain damage on the different body representations (body schema, body structural representation, and body semantics) are still rare. Aim of this study was to evaluate body representation deficits in a relatively large sample of patients with unilateral brain damage and to investigate the impact of right or left brain damage on body representations (BRs), independently from deficits in other cognitive processes. METHOD: Sixty-four patients with unilateral stroke (22 with left brain damage, LBD; 31 with right brain damage without neglect, RBD-N; 11 with right brain damage with neglect, RBD+N) and 41 healthy individuals underwent a specific battery including BR as well as control tasks. RESULTS: In more than a third of the sample, selective (37.5%) and pure (31%) deficits of BR were presented and equally distributed among the different BRs (˜10% for each representation), with selective (27.2%) and pure (22.7%) body schema deficit mainly presented after left brain damage. As a group, patients with unilateral brain damage, independently of the side of lesion (LBD, RBD-N, RBD+N), had significantly worse performance on body structural representation with respect to healthy individuals, whereas LBD had numerically worse performance on body schema with respect to healthy individuals and RBD-N. No significant differences among groups were found on body semantics. CONCLUSION: BR deficits are not a rare consequence of unilateral brain damage and are independent of a more general cognitive dysfunction. Accordingly, the need for an accurate assessment and specific neuropsychological training in clinical settings is discussed.

Psychological Distress and Work Environment Perception by Physical Therapists from Southern Italy during COVID-19 Pandemic: The C.A.L.A.B.R.I.A Study.

The psychosocial impact of the work environment during the COVID-19 pandemic on health professionals is a growing issue. The present study examined specific psychosocial work environment indicators during the COVID-19 pandemic, through a multiple regression model of a self-administered cross-sectional online survey in a cohort of physical therapists from a region of Southern Italy from March 2020 to May 2021. The questionnaire contained items on work and healthcare issues related to COVID-19. Eighty physical therapists (29 male and 51 female), mean age 32.5 ± 10.1 years, were involved in this survey. The multiple regression analysis showed that "management activity" was significantly correlated to "therapist frustration" during the COVID-19 pandemic (ΔR2 = 0.16; p < 0.03). Findings of this study underline the importance of a healthy psychosocial work environment to enhance job satisfaction of all health professionals and to avoid role conflict and burnout syndrome during the COVID-19 pandemic.

The Body across the Lifespan: On the Relation between Interoceptive Sensibility and High-Order Body Representations.

BACKGROUND: Interoceptive information plays a pivotal role in building higher-order cognitive body representations (BR) that neuropsychological and neuroimaging evidence classifies as action-oriented (i.e., body schema) or non-action-oriented (i.e., visuo-spatial body map). This study aimed to explore the development of BR, considering the association with the interoceptive sensibility throughout the lifespan. METHODS: Two hundred thirty-nine healthy participants divided into five age groups (7 to 8 years; 9 to 10 years; 18 to 40 years; 41 to 60 years; over 60 years) completed a self-report measure of interoceptive sensibility (the Self-Awareness Questionnaire; SAQ) and were given tasks assessing the two BR (action-oriented: hand laterality task; non-action-oriented: frontal body evocation task). RESULTS: Both children (7-8 and 9-10 years) and older adults (over 60 years) performed worse than young (18-40 years) and middle-aged adults (41-60 years) in action- and non-action-oriented BR tasks. Moderation analyses showed that the SAQ score significantly moderated the relationship between age and action-oriented BR. CONCLUSIONS: The current results are consistent with inverted U-shaped developmental curves for action- and non-action-oriented BR. As an innovative aspect, the ability to mentally represent one's own body parts in diverse states could be negatively affected by higher interoceptive sensibility levels in childhood and late adulthood.

The Body Across Adulthood: On the Relation Between Interoception and Body Representations.

Interoceptive information plays a pivotal role in building body representations (BR), but the association between interoception and the different types of BR in healthy individuals has never been systematically investigated. Thus, this study aimed to explore the association between BR and interoceptive sensibility (IS) throughout adulthood. One hundred thirty-seven healthy participants (50 aged from 18 to 40 years old; 50 aged from 41 to 60 years old; and 37 over 60 years old) were given a self-report tool for assessing IS (the Self-Awareness Questionnaire; SAQ), and a specific battery including tasks evaluating three different BR (i.e., the body schema, using the Hand Laterality Task; the body structural representation, using the Frontal Body Evocation task, FBE; and body semantics, using the Object-Body Part Association Task) as well as control tasks (i.e., tasks with non-body stimuli). The older age group (aged over 60 years old) showed lower performances on the tasks probing the body schema and body structural representation than younger groups (aged 18 to 40 and 41 to 60 years old). More interestingly, worse performances on a task assessing the body schema were significantly associated with higher IS with older age, suggesting that higher awareness of one's inner body sensations would decrease the plasticity of this BR. These findings are interpreted according to the neuropsychological model of BR development and the effects of aging on the brain.

The development of body representations in school-aged children.

Following the triadic taxonomy, three different body representations do exist, namely the body semantics, the body structural representation and the body schema. The development of these body representations has been widely investigated in toddlers, but several issues remain to be addressed in school age. To assess age- and gender-related changes in different body representations and to investigate the presence of different patterns of interplay between these representations of the body, 90 children (age range: 7-10) and 37 young adults (age range: 18-35) were given tasks assessing the body semantics, the body structural representation and the body schema as well as control tasks. The present results suggested that the body schema, evaluated by means of hand laterality judgments, was still not completely developed in school-aged children, whereas the body structural representation reached an adult-like pattern by the age of 9-10 years. Finally, body semantics was fully developed in school-aged children. These findings were discussed in terms of their theoretical implications, for a better understanding of body representation development; also, implications for clinical assessment of body representation disorders were discussed.

Cognitive Outcomes and Relationships with Phenylalanine in Phenylketonuria: A Comparison between Italian and English Adult Samples.

We aimed to assess if the same cognitive batteries can be used cross-nationally to monitor the effect of Phenylketonuria (PKU). We assessed whether a battery, previously used with English adults with PKU (AwPKU), was also sensitive to impairments in Italian AwPKU. From our original battery, we selected a number of tasks that comprehensively assessed visual attention, visuo-motor coordination, executive functions (particularly, reasoning, planning, and monitoring), sustained attention, and verbal and visual memory and learning. When verbal stimuli/or responses were involved, stimuli were closely matched between the two languages for psycholinguistic variables. We administered the tasks to 19 Italian AwPKU and 19 Italian matched controls and compared results from with 19 English AwPKU and 19 English matched controls selected from a previously tested cohort. Participant election was blind to cognitive performance and metabolic control, but participants were closely matched for age and education. The Italian AwPKU group had slightly worse metabolic control but showed levels of performance and patterns of impairment similar to the English AwPKU group. The Italian results also showed extensive correlations between adult cognitive measures and metabolic measures across the life span, both in terms of Phenylalanine (Phe) levels and Phe fluctuations, replicating previous results in English. These results suggest that batteries with the same and/or matched tasks can be used to assess cognitive outcomes across countries allowing results to be compared and accrued. Future studies should explore potential differences in metabolic control across countries to understand what variables make metabolic control easier to achieve.

Topological and hodological aspects of body representation in right brain damaged patients.

The triadic taxonomy posits that three distinct types of body representations do exist, namely the body schema (BS), which corresponds to the representation derived from multiple sensory and motor inputs, the body structural representation (BSR), which corresponds to the structural description of spatial relations among the body parts, and the body semantics (SEM), which corresponds to the lexical-semantic representation of the body. Although several studies have assessed neural correlates of these representations, no study has compared them in brain-damaged patients, controlling for deficits in other cognitive domains. Also, little is known about the contribution of the right hemisphere to different body representations. Here we used a computerized battery to test these three body representations in twenty-six right brain damaged patients, controlling for other cognitive deficits by means of tests tapping similar spatial and lexical processes on non-body related stimuli. Residual scores corresponding to the BS, the BSR and the SEM were used to test neural correlates, which were assessed by integrating topological and hodological approaches to lesion-deficit analyses. We found that the BSR was associated with lesion of the superior temporal gyrus, the insula, the supramarginal gyrus and the temporo-parietal junction, extending also to the Rolandic operculum and the inferior frontal gyrus. Also, it was associated with the disconnection probability of the posterior arcuate segment. The BS was associated with a small cluster of voxels in the precentral and postcentral gyri, whereas the SEM was associated with white matter lesion at the boundary between the parietal and temporal lobes. Overall, these results provide strong support to the regional and connectional contribution of the right hemisphere to body representation, and more specifically to the BSR.