Fetal brain MRI atlases and datasets: A review.

Fetal brain development is a complex process involving different stages of growth and organization which are crucial for the development of brain circuits and neural connections. Fetal atlases and labeled datasets are promising tools to investigate prenatal brain development. They support the identification of atypical brain patterns, providing insights into potential early signs of clinical conditions. In a nutshell, prenatal brain imaging and post-processing via modern tools are a cutting-edge field that will significantly contribute to the advancement of our understanding of fetal development. In this work, we first provide terminological clarification for specific terms (i.e., "brain template" and "brain atlas"), highlighting potentially misleading interpretations related to inconsistent use of terms in the literature. We discuss the major structures and neurodevelopmental milestones characterizing fetal brain ontogenesis. Our main contribution is the systematic review of 18 prenatal brain atlases and 3 datasets. We also tangentially focus on clinical, research, and ethical implications of prenatal neuroimaging.

Prolonged neural encoding of visual information in autism.

Autism spectrum disorder (ASD) is associated with a hyper-focused visual attentional style, impacting higher-order social and affective domains. The understanding of such peculiarity can benefit from the use of multivariate pattern analysis (MVPA) of high-resolution electroencephalography (EEG) data, which has proved to be a powerful technique to investigate the hidden neural dynamics orchestrating sensory and cognitive processes. Here, we recorded EEG in typically developing (TD) children and in children with ASD during a visuo-spatial attentional task where attention was exogenously captured by a small (zoom-in) or large (zoom-out) cue in the visual field before the appearance of a target at different eccentricities. MVPA was performed both in the cue-locked period, to reveal potential differences in the modulation of the attentional focus, and in the target-locked period, to reveal potential cascade effects on stimulus processing. Cue-locked MVPA revealed that while in the TD group the pattern of neural activity contained information about the cue mainly before the target appearance, the ASD group showed a temporally sustained and topographically diffuse significant decoding of the cue neural response even after the target onset, suggesting a delayed extinction of cue-related neural activity. Crucially, this delayed extinction positively correlated with behavioral measures of attentional hyperfocusing. Results of target-locked MVPA were coherent with a hyper-focused attentional profile, highlighting an earlier and stronger decoding of target neural responses in small cue trials in the ASD group. The present findings document a spatially and temporally overrepresented encoding of visual information in ASD, which can constitute one of the main reasons behind their peculiar cognitive style.

From neural noise to co-adaptability: Rethinking the multifaceted architecture of motor variability.

In the last decade, the source and the functional meaning of motor variability have attracted considerable attention in behavioral and brain sciences. This construct classically combined different levels of description, variable internal robustness or coherence, and multifaceted operational meanings. We provide here a comprehensive review of the literature with the primary aim of building a precise lexicon that goes beyond the generic and monolithic use of motor variability. In the pars destruens of the work, we model three domains of motor variability related to peculiar computational elements that influence fluctuations in motor outputs. Each domain is in turn characterized by multiple sub-domains. We begin with the domains of noise and differentiation. However, the main contribution of our model concerns the domain of adaptability, which refers to variation within the same exact motor representation. In particular, we use the terms learning and (social)fitting to specify the portions of motor variability that depend on our propensity to learn and on our largely constitutive propensity to be influenced by external factors. A particular focus is on motor variability in the context of the sub-domain named co-adaptability. Further groundbreaking challenges arise in the modeling of motor variability. Therefore, in a separate pars construens, we attempt to characterize these challenges, addressing both theoretical and experimental aspects as well as potential clinical implications for neurorehabilitation. All in all, our work suggests that motor variability is neither simply detrimental nor beneficial, and that studying its fluctuations can provide meaningful insights for future research.

Context expectation influences the gait pattern biomechanics.

Beyond classical aspects related to locomotion (biomechanics), it has been hypothesized that walking pattern is influenced by a combination of distinct computations including online sensory/perceptual sampling and the processing of expectations (neuromechanics). Here, we aimed to explore the potential impact of contrasting scenarios ("risky and potentially dangerous" scenario; "safe and comfortable" scenario) on walking pattern in a group of healthy young adults. Firstly, and consistently with previous literature, we confirmed that the scenario influences gait pattern when it is recalled concurrently to participants' walking activity (motor interference). More intriguingly, our main result showed that participants' gait pattern is also influenced by the contextual scenario when it is evoked only before the start of walking activity (motor expectation). This condition was designed to test the impact of expectations (risky scenario vs. safe scenario) on gait pattern, and the stimulation that preceded walking activity served as prior. Noteworthy, we combined statistical and machine learning (Support-Vector Machine classifier) approaches to stratify distinct levels of analyses that explored the multi-facets architecture of walking. In a nutshell, our combined statistical and machine learning analyses converge in suggesting that walking before steps is not just a paradox.

Neural dynamics driving audio-visual integration in autism.

Audio-visual (AV) integration plays a crucial role in supporting social functions and communication in autism spectrum disorder (ASD). However, behavioral findings remain mixed and, importantly, little is known about the underlying neurophysiological bases. Studies in neurotypical adults indicate that oscillatory brain activity in different frequencies subserves AV integration, pointing to a central role of (i) individual alpha frequency (IAF), which would determine the width of the cross-modal binding window; (ii) pre-/peri-stimulus theta oscillations, which would reflect the expectation of AV co-occurrence; (iii) post-stimulus oscillatory phase reset, which would temporally align the different unisensory signals. Here, we investigate the neural correlates of AV integration in children with ASD and typically developing (TD) peers, measuring electroencephalography during resting state and in an AV integration paradigm. As for neurotypical adults, AV integration dynamics in TD children could be predicted by the IAF measured at rest and by a modulation of anticipatory theta oscillations at single-trial level. Conversely, in ASD participants, AV integration/segregation was driven exclusively by the neural processing of the auditory stimulus and the consequent auditory-induced phase reset in visual regions, suggesting that a disproportionate elaboration of the auditory input could be the main factor characterizing atypical AV integration in autism.

The (a)typical burden of COVID-19 pandemic scenario in Autism Spectrum Disorder.

Psychological and mental health consequences of large-scale anti-contagion policies are assuming strong relevance in the COVID-19 pandemic. We proposed a specific focus on a large sample of children with Autism Spectrum Disorder (ASD), developing an ad hoc instrument to investigate changes occurred in specific (sub-)domains during a period of national lockdown (Italy). Our questionnaire, named AutiStress, is both context-specific (being set in the COVID-19 pandemic scenario) and condition-specific (being structured taking into account the autistic functioning peculiarities in the paediatric age). An age- and gender-matched group of neurotypical (TD) controls was also provided. As expected, the severe lockdown policies had a general negative impact both on ASD and TD children, reflecting the obvious burden of the pandemic situation. However, our findings also indicate that children with ASD experienced more positive changes than TD ones. Noteworthy, we report a thought-provoking double dissociation in the context-specific predictor (i.e., accessibility to private outdoor spaces), indicating that it impacts differently on the two groups. Focusing on the ASD group, results suggest a condition-specific impact of the COVID-19 pandemic on core autistic (sub-)domains. Taken together, our data call for a multi-layered, context- and condition-specific analysis of the pandemic burden beyond any oversimplification.

Neurotypical individuals fail to understand action vitality form in children with autism spectrum disorder.

Any defects of sociality in individuals diagnosed with autism spectrum disorder (ASD) are standardly explained in terms of those individuals' putative impairments in a variety of cognitive functions. Recently, however, the need for a bidirectional approach to social interaction has been emphasized. Such an approach highlights differences in basic ways of acting between ASD and neurotypical individuals which would prevent them from understanding each other. Here we pursue this approach by focusing on basic action features reflecting the agent's mood and affective states. These are action features Stern named "vitality forms," and which are widely assumed to substantiate core social interactions [D. N. Stern, The Interpersonal World of the Infant (1985); D. N. Stern, Forms of Vitality Exploring Dynamic Experience in Psychology, Arts, Psychotherapy, and Development (2010)]. Previously we demonstrated that, although ASD and typically developing (TD) children alike differentiate vitality forms when performing actions, ASD children express them in a way that is motorically dissimilar to TD children. To assess whether this motor dissimilarity may have consequences for vitality form recognition, we asked neurotypical participants to identify the vitality form of different types of action performed by ASD or TD children. We found that participants exhibited remarkable inaccuracy in identifying ASD children's vitality forms. Interestingly, their performance did not benefit from information feedback. This indicates that how people act matters for understanding others and for being understood by them. Because vitality forms pervade every aspect of daily life, our findings promise to open the way to a deeper comprehension of the bidirectional difficulties for both ASD and neurotypical individuals in interacting with one another.

Anomalous Perception of Biological Motion in Autism: A Conceptual Review and Meta-Analysis.

Despite its popularity, the construct of biological motion (BM) and its putative anomalies in autism spectrum disorder (ASD) are not completely clarified. In this article, we present a meta-analysis investigating the putative anomalies of BM perception in ASD. Through a systematic literature search, we found 30 studies that investigated BM perception in both ASD and typical developing peers by using point-light display stimuli. A general meta-analysis including all these studies showed a moderate deficit of individuals with ASD in BM processing, but also a high heterogeneity. This heterogeneity was explored in different additional meta-analyses where studies were grouped according to levels of complexity of the BM task employed (first-order, direct and instrumental), and according to the manipulation of low-level perceptual features (spatial vs. temporal) of the control stimuli. Results suggest that the most severe deficit in ASD is evident when perception of BM is serving a secondary purpose (e.g., inferring intentionality/action/emotion) and, interestingly, that temporal dynamics of stimuli are an important factor in determining BM processing anomalies in ASD. Our results question the traditional understanding of BM anomalies in ASD as a monolithic deficit and suggest a paradigm shift that deconstructs BM into distinct levels of processing and specific spatio-temporal subcomponents.

Altered neural oscillations and connectivity in the beta band underlie detail-oriented visual processing in autism.

Sensory and perceptual anomalies may have a major impact on basic cognitive and social skills in humans. Autism Spectrum Disorder (ASD) represents a special perspective to explore this relationship, being characterized by both these features. The present study employed electroencephalography (EEG) to test whether detail-oriented visual perception, a recognized hallmark of ASD, is associated with altered neural oscillations and functional connectivity in the beta frequency band, considering its role in feedback and top-down reentrant signalling in the typical population. Using a visual crowding task, where participants had to discriminate a peripheral target letter surrounded by flankers at different distances, we found that detail-oriented processing in children with ASD, as compared to typically developing peers, could be attributed to anomalous oscillatory activity in the beta band (15-30 Hz), while no differences emerged in the alpha band (8-12 Hz). Altered beta oscillatory response reflected in turn atypical functional connectivity between occipital areas, where the initial stimulus analysis is accomplished, and infero-temporal regions, where objects identity is extracted. Such atypical beta connectivity predicted both ASD symptomatology and their detail-oriented processing. Overall, these results might be explained by an altered feedback connectivity within the visual system, with potential cascade effects in visual scene parsing and higher order functions.

Stability and flexibility in multisensory sampling: insights from perceptual illusions.

Neural, oscillatory, and computational counterparts of multisensory processing remain a crucial challenge for neuroscientists. Converging evidence underlines a certain efficiency in balancing stability and flexibility of sensory sampling, supporting the general idea that multiple parallel and hierarchically organized processing stages in the brain contribute to our understanding of the (sensory/perceptual) world. Intriguingly, how temporal dynamics impact and modulate multisensory processes in our brain can be investigated benefiting from studies on perceptual illusions.

Insights from perceptual, sensory, and motor functioning in autism and cerebellar primary disturbances: Are there reliable markers for these disorders?

The contribution of cerebellar circuitry alterations in the pathophysiology of Autism Spectrum Disorder (ASD) has been widely investigated in the last decades. Yet, experimental studies on neurocognitive markers of ASD have not been attentively compared with similar studies in patients with cerebellar primary disturbances (e.g., malformations, agenesis, degeneration, etc). Addressing this neglected issue could be useful to underline unexpected areas of overlap and/or underestimated differences between these sets of conditions. In fact, ASD and cerebellar primary disturbances (notably, Cerebellar Cognitive Affective Syndrome, CCAS) can share atypical manifestations in perceptual, sensory, and motor functions, but neural subcircuits involved in these anomalies/difficulties could be distinct. Here, we specifically deal with this issue focusing on four paradigmatic neurocognitive functions: visual and biological motion perception, multisensory integration, and high stages of the motor hierarchy. From a research perspective, this represents an essential challenge to more deeply understand neurocognitive markers of ASD and of cerebellar primary disturbances/CCAS. Although we cannot assume definitive conclusions, and beyond phenotypical similarities between ASD and CCAS, clinical and experimental evidence described in this work argues that ASD and CCAS are distinct phenomena. ASD and CCAS seem to be characterized by different pathophysiological mechanisms and mediated by distinct neural nodes. In parallel, from a clinical perspective, this characterization may furnish insights to tackle the distinction between autistic functioning/autistic phenotype (in ASD) and dysmetria of thought/autistic-like phenotype (in CCAS).

Weak surround suppression of the attentional focus characterizes visual selection in the ventral stream in autism.

Neurophysiological findings in the typical population demonstrate that spatial scrutiny for visual selection determines a center-surround profile of the attentional focus, which is the result of recurrent processing in the visual system. Individuals with autism spectrum disorder (ASD) manifest several anomalies in their visual selection, with strengths in detail-oriented tasks, but also difficulties in distractor inhibition tasks. Here, we asked whether contradictory aspects of perception in ASD might be due to a different center-surround profile of their attentional focus. In two experiments, we tested two independent samples of children with ASD, comparing them with typically developing (TD) peers. In Experiment 1, we used a psychophysical task that mapped the entire spatial profile of the attentional focus. In Experiment 2, we used dense-array electroencephalography (EEG) to explore its neurophysiological underpinnings. Experiment 1 results showed that the suppression, surrounding the attentional focus, was markedly reduced in children with ASD. Experiment 2 showed that the center-surround profile in TD children resulted in a modulation of the posterior N2 ERP component, with cortical sources in the lateral-occipital and medial/inferior temporal areas. In contrast, children with ASD did not show modulation of the N2 and related activations in the ventral visual stream. Furthermore, behavioural and neurophysiological measures of weaker suppression predicted more severe autistic symptomatology. The present findings, showing an altered center-surround profile during attentional selection, give an important insight to understand superior visual processing in autism as well as the experiencing of sensory overload.

Are We "Motorically" Wired to Others? High-Level Motor Computations and Their Role in Autism.

High-level motor computations reflect abstract components far apart from the mere motor performance. Neural correlates of these computations have been explored both in nonhuman and human primates, supporting the idea that our brain recruits complex nodes for motor representations. Of note, these computations have exciting implications for social cognition, and they also entail important challenges in the context of autism. Here, we focus on these challenges benefiting from recent studies addressing motor interference, motor resonance, and high-level motor planning. In addition, we suggest new ideas about how one maps and shares the (motor) space with others. Taken together, these issues inspire intriguing and fascinating questions about the social tendency of our high-level motor computations, and this tendency may indicate that we are "motorically" wired to others. Thus, after furnishing preliminary insights on putative neural nodes involved in these computations, we focus on how the hypothesized social nature of high-level motor computations may be anomalous or limited in autism, and why this represents a critical challenge for the future.

Role of the cerebellum in high stages of motor planning hierarchy.

Motor planning is not a monolithic process, and distinct stages of motor planning are responsible for encoding different levels of abstractness. However, how these distinct components are mapped into different neural substrates remains an open question. We studied one of these high-level motor planning components, defined as second-order motor planning, in a patient (R.G.) with an extremely rare case of cerebellar agenesis but without any other cortical malformations. Second-order motor planning dictates that when two acts must be performed sequentially, planning of the second act can influence execution of the first. We used an optoelectronic system for kinematic analysis to compare R.G.'s performance with age-matched controls in a second-order motor planning task. The first act was to reach for an object, and the second was to place it into a small or large container. Our results showed that despite the expected difficulties in fine-motor skills, second-order motor planning (i.e., the ability to modulate the first act as a function of the nature of the second act) was preserved even in the patient with congenital absence of the cerebellum. These results open new intriguing speculations about the role of the cerebellum in motor planning abilities. Although prudence is imperative when suggesting conclusions made on the basis of single-case findings, this evidence suggests fascinating hypotheses about the neural circuits that support distinct stages of the motor planning hierarchy, and regarding the functional role of second-order motor planning in motor cognition and its potential dysfunction in autism.NEW & NOTEWORTHY Traditionally, the cerebellum was considered essential for motor planning. By studying an extremely rare patient with cerebellar agenesis and a group of neurotypical controls, we found that high stages of the motor planning hierarchy can be preserved even in this patient with congenital absence of the cerebellum. Our results provide interesting insights that shed light on the neural circuits supporting distinct levels of motor planning. Furthermore, the results are intriguing because of their potential clinical implications in autism.

The functional and developmental role of imitation in the (a)typical brain.

Keven & Akins (K&A) propose a biologically plausible view of neonatal imitation based on the analysis of sensorimotor development. Here, we consider imitation in the general context of motor cognition, taking examples from both typical and atypical development. Specifically, we will discuss the functional role of imitation, its multi-level nature, and its anomalous features in autism.

So close yet so far: Motor anomalies impacting on social functioning in autism spectrum disorder.

Difficulties in the social domain and motor anomalies have been widely investigated in Autism Spectrum Disorder (ASD). However, they have been generally considered as independent, and therefore tackled separately. Recent advances in neuroscience have hypothesized that the cortical motor system can play a role not only as a controller of elementary physical features of movement, but also in a complex domain as social cognition. Here, going beyond previous studies on ASD that described difficulties in the motor and in the social domain separately, we focus on the impact of motor mechanisms anomalies on social functioning. We consider behavioral, electrophysiological and neuroimaging findings supporting the idea that motor cognition is a critical "intermediate phenotype" for ASD. Motor cognition anomalies in ASD affect the processes of extraction, codification and subsequent translation of "external" social information into the motor system. Intriguingly, this alternative "motor" approach to the social domain difficulties in ASD may be promising to bridge the gap between recent experimental findings and clinical practice, potentially leading to refined preventive approaches and successful treatments.

The motor way: Clinical implications of understanding and shaping actions with the motor system in autism and drug addiction.

To understand others' minds is crucial for survival; however, it is quite puzzling how access to others' minds can be--to some extent--direct and not necessarily mediated by conceptual reasoning. Recent advances in neuroscience have led to hypothesize a role for motor circuits not only in controlling the elementary physical features of movement (e.g., force, direction, and amplitude), but also in understanding and shaping human behavior. The concept of "motor cognition" refers to these aspects, and neurophysiological, neuroimaging, and behavioral studies in human and nonhuman primates support this view. From a clinical perspective, motor cognition represents a challenge in several domains. A thorough investigation of the neural mechanisms mediating motor action/intention understanding and automatized/compulsive behaviors seems to be a promising way to tackle a range of neurodevelopmental and drug-related disorders. On the one hand, anomalies in motor cognition may have cascade effects on social functioning in individuals with autism spectrum disorder (ASD); on the other, motor cognition may help explain the pathophysiology of drug-seeking and drug-taking behaviors in the most severe phase of drug addiction (i.e., see drug dependence, motor low-order cue reactivity). This may represent a promising approach that could improve the efficacy of rehabilitative interventions. The only way to shed light on multifactorial disorders such as ASD and drug addiction is through the investigation of their multiple factors. This motor way can promote new theoretical and experimental perspectives that would help bridge the gap between the basic neuroscience approach and clinical practice.

Where there is a goal, there is a way: what, why and how the parieto-frontal mirror network can mediate imitative behaviours.

The relationships between mirror neurons (MNs) and motor imitation, and its clinical implications in autism spectrum disorder (ASD) have been widely investigated; however, the literature remains­at least partially­controversial. In this review we support a multi-level action understanding model focusing on the mirror-based understanding. We review the functional role of the parieto-frontal MNs (PFMN) network claiming that PFMNs function cannot be limited to imitation nor can imitation be explained solely by the activity of PFMNs. The distinction between movement, motor act and motor action is useful to characterize deeply both act(ion) understanding and imitation of act(ion). A more abstract representation of act(ion) may be crucial for clarifying what, why and how an imitator is imitating. What counts in social interactions is achieving goals: it does not matter which effector or string of motor acts you eventually use for achieving (proximal and distal) goals. Similarly, what counts is the ability to recognize/imitate the style of act(ion) regardless of the way in which it is expressed. We address this crucial point referring to its potential implications in ASD.