Showing papers by "Fabio Apicella published in 2016"

Gut to brain interaction in Autism Spectrum Disorders: a randomized controlled trial on the role of probiotics on clinical, biochemical and neurophysiological parameters

Abstract: A high prevalence of a variety of gastrointestinal (GI) symptoms is frequently reported in patients with Autism Spectrum Disorders (ASD). The GI disturbances in ASD might be linked to gut dysbiosis representing the observable phenotype of a “gut-brain axis” disruption. The exploitation of strategies which can restore normal gut microbiota and reduce the gut production and absorption of toxins, such as probiotics addition/supplementation in a diet, may represent a non-pharmacological option in the treatment of GI disturbances in ASD. The aim of this randomized controlled trial is to determine the effects of supplementation with a probiotic mixture (Vivomixx®) in ASD children not only on specific GI symptoms, but also on the core deficits of the disorder, on cognitive and language development, and on brain function and connectivity. An ancillary aim is to evaluate possible effects of probiotic supplementation on urinary concentrations of phthalates (chemical pollutants) which have been previously linked to ASD. A group of 100 preschoolers with ASD will be classified as belonging to a GI group or to a Non-GI (NGI) group on the basis of a symptom severity index specific to GI disorders. In order to obtain four arms, subjects belonging to the two groups (GI and NGI) will be blind randomized 1:1 to regular diet with probiotics or with placebo for 6 months. All participants will be assessed at baseline, after three months and after six months from baseline in order to evaluate the possible changes in: (1) GI symptoms; (2) autism symptoms severity; (3) affective and behavioral comorbid symptoms; (4) plasmatic, urinary and fecal biomarkers related to abnormal intestinal function; (5) neurophysiological patterns. The effects of treatments with probiotics on children with ASD need to be evaluated through rigorous controlled trials. Examining the impact of probiotics not only on clinical but also on neurophysiological patterns, the current trial sets out to provide new insights into the gut-brain connection in ASD patients. Moreover, results could add information to the relationship between phthalates levels, clinical features and neurophysiological patterns in ASD. ClinicalTrials.gov Identifier: NCT02708901 . Retrospectively registered: March 4, 2016.

Difference in Visual Social Predispositions between Newborns at Low-and High-risk for Autism

Abstract: Some key behavioural traits of Autism Spectrum Disorders (ASD) have been hypothesized to be due to impairments in the early activation of subcortical orienting mechanisms, which in typical development bias newborns to orient to relevant social visual stimuli. A challenge to testing this hypothesis is that autism is usually not diagnosed until a child is at least 3 years old. Here, we circumvented this difficulty by studying for the very first time, the predispositions to pay attention to social stimuli in newborns with a high familial risk of autism. Results showed that visual preferences to social stimuli strikingly differed between high-risk and low-risk newborns. Significant predictors for high-risk newborns were obtained and an accurate biomarker was identified. The results revealed early behavioural characteristics of newborns with familial risk for ASD, allowing for a prospective approach to the emergence of autism in early infancy.

The effect of gender on the neuroanatomy of children with autism spectrum disorders: A support vector machine case-control study

Abstract: Genetic, hormonal, and environmental factors contribute since infancy to sexual dimorphism in regional brain structures of subjects with typical development. However, the neuroanatomical differences between male and female children with autism spectrum disorders (ASD) are an intriguing and still poorly investigated issue. This study aims to evaluate whether the brain of young children with ASD exhibits sex-related structural differences and if a correlation exists between clinical ASD features and neuroanatomical underpinnings. A total of 152 structural MRI scans were analysed. Specifically, 76 young children with ASD (38 males and 38 females; 2–7 years of age; mean = 53 months, standard deviation = 17 months) were evaluated employing a support vector machine (SVM)-based analysis of the grey matter (GM). Group comparisons consisted of 76 age-, gender- and non-verbal-intelligence quotient-matched children with typical development or idiopathic developmental delay without autism. For both genders combined, SVM showed a significantly increased GM volume in young children with ASD with respect to control subjects, predominantly in the bilateral superior frontal gyrus (Brodmann area –BA– 10), bilateral precuneus (BA 31), bilateral superior temporal gyrus (BA 20/22), whereas less GM in patients with ASD was found in right inferior temporal gyrus (BA 37). For the within gender comparisons (i.e., females with ASD vs. controls and males with ASD vs. controls), two overlapping regions in bilateral precuneus (BA 31) and left superior frontal gyrus (BA 9/10) were detected. Sex-by-group analyses revealed in males with ASD compared to matched controls two male-specific regions of increased GM volume (left middle occipital gyrus—BA 19—and right superior temporal gyrus—BA 22). Comparisons in females with and without ASD demonstrated increased GM volumes predominantly in the bilateral frontal regions. Additional regions of significantly increased GM volume in the right anterior cingulate cortex (BA 32) and right cerebellum were typical only of females with ASD. Despite the specific behavioural correlates of sex-dimorphism in ASD, brain morphology as yet remains unclear and requires future dedicated investigations. This study provides evidence of structural brain gender differences in young children with ASD that possibly contribute to the different phenotypic disease manifestations in males and females.

Pre-linguistic Vocal Trajectories at 6–18 Months of Age As Early Markers of Autism

Abstract: This study explores pre-linguistic vocal trajectories in infants with autism spectrum disorder (ASD) during caregiver-infant interaction. Home videos were obtained from 10 infants with ASD and 10 typically developing infants (TD), covering three time periods: 0-6 months (T1, 47 video sequences), 6-12 months (T2, 47 video sequences), and 12-18 months (T3, 48 video sequences). In total 142 video sequences were analyzed. Vocalizations, long reduplicated babbling, 2-syllable babbling, and first words were investigated longitudinally. Face-gazing was also analyzed, to evaluate the social quality of vocal behaviors. Results show a lower rate of vocalizations in the ASD group at T2, and a lower rate of first words at T3, compared to the TD group. However, the prevalence of non-social babbling, appeared higher in the ASD group. The implications of these findings for screening programs are discussed.

Temporal lobe connects regression and macrocephaly to autism spectrum disorders.

Abstract: Interictal electroencephalogram (EEG) abnor- malities are frequently associated with autism spectrum disorders (ASD), although their relationship with the clinical features of ASD, particularly the regressive onset, remains controversial. The aim of this study was to inves- tigate whether the characteristics of interictal EEG abnor- malities might help to distinguish and predict definite phe - notypes within the heterogeneity of ASD. We reviewed the awake and sleep interictal EEGs of 220 individuals with idiopathic ASD, either with or without a history of seizures. EEG findings were analyzed with respect to a set of clini - cal variables to explore significant associations. A brain morphometry study was also carried out on a subgroup of patients. EEG abnormalities were seen in 154/220 individ- uals (70 %) and were mostly focal (p < 0.01) with an ante- rior localization (p < 0.001). They were detected more fre- quently during sleep (p < 0.01), and were associated with a regressive onset of ASD (p < 0.05), particularly in individu- als with focal temporal localization (p < 0.05). This asso- ciation was also stronger in regressive patients with con- current macrocephaly, together with a relative volumetric reduction of the right temporal cortex (p < 0.05). Indeed,

Using Brain Connectivity Measure of EEG Synchrostates for Discriminating Typical and Autism Spectrum Disorder

Abstract: In this paper we utilized the concept of stable phase synchronization topography - synchrostates - over the scalp derived from EEG recording for formulating brain connectivity network in Autism Spectrum Disorder (ASD) and typically-growing children. A synchronization index is adapted for forming the edges of the connectivity graph capturing the stability of each of the synchrostates. Such network is formed for 11 ASD and 12 control group children. Comparative analyses of these networks using graph theoretic measures show that children with autism have a different modularity of such networks from typical children. This result could pave the way to a new modality for possible identification of ASD from non-invasively recorded EEG data.

On the Existence of Synchrostates in Multichannel EEG Signals during Face-perception Tasks

Abstract: Phase synchronisation in multichannel EEG is known as the manifestation of functional brain connectivity. Traditional phase synchronisation studies are mostly based on time average synchrony measures hence do not preserve the temporal evolution of the phase difference. Here we propose a new method to show the existence of a small set of unique phase synchronised patterns or "states" in multi-channel EEG recordings, each "state" being stable of the order of ms, from typical and pathological subjects during face perception tasks. The proposed methodology bridges the concepts of EEG microstates and phase synchronisation in time and frequency domain respectively. The analysis is reported for four groups of children including typical, Autism Spectrum Disorder (ASD), low and high anxiety subjects - a total of 44 subjects. In all cases, we observe consistent existence of these states - termed as synchrostates - within specific cognition related frequency bands (beta and gamma bands), though the topographies of these synchrostates differ for different subject groups with different pathological conditions. The inter-synchrostate switching follows a well-defined sequence capturing the underlying inter-electrode phase relation dynamics in stimulus- and person-centric manner. Our study is motivated from the well-known EEG microstate exhibiting stable potential maps over the scalp. However, here we report a similar observation of quasi-stable phase synchronised states in multichannel EEG. The existence of the synchrostates coupled with their unique switching sequence characteristics could be considered as a potentially new field over contemporary EEG phase synchronisation studies.