Non-invasive brain stimulation for the rehabilitation of children and adolescents with neurodevelopmental disorders: A systematic review

In the last years, there has been a growing interest in the application of different non-invasive brain stimulation techniques to induce neuroplasticity and to modulate cognition and behavior in adults. Very recently, different attempts have been made to induce functional plastic changes also in pediatric populations. Importantly, not only sensorimotor processing, but also higher-level functions have been addressed, with the aim to boost rehabilitation in different neurodevelopmental disorders. However, efficacy and safety of using these techniques in pediatric population is still debated. The current article aims to review the non-invasive brain stimulation studies conducted in pediatric populations using Transcranial Magnetic Stimulation or transcranial Direct Current Stimulation. Specifically, the available proofs concerning the efficacy and safety of these techniques on Autism Spectrum Disorder, Attention-deficit/hyperactivity disorder, Dyslexia, Tourette syndrome, and tic disorders are systematically reviewed and discussed. The article also aims to provide an overview about other possible applications of these and other stimulation techniques for rehabilitative purposes in children and adolescents

Feasibility of a home-based computerized cognitive training for pediatric patients with congenital or acquired brain damage: An explorative study

Pediatric brain damage is associated with various cognitive deficits. Cognitive rehabilitation may prevent and reduce cognitive impairment. In recent years, home-based computerized cognitive training (CCT) has been introduced in clinical practice to increase treatment opportunities for patients (telerehabilitation). However, limited research has been conducted thus far on investigating the effects of remote CCT for the juvenile population in contexts other than English-speaking countries. The aim of the present study was to investigate the feasibility of a home-based CCT in a group of Italian adolescents with brain damage. A commercially available CCT (Lumosity) developed in the English language was used due to the lack of telerehabilitation programs in the Italian language that allow stimulation of multiple cognitive domains and, at the same time, remote automatic collection of data. Thus, this investigation provides information on the possibility of introducing CCT programs available in foreign languages in countries with limited investment in the telerehabilitation field

Perceived Family Functioning Profile in Adolescents at Clinical High Risk for Psychosis: Rigidity as a Possible Preventive Target

: The presence of a positive family relationship has been suggested as a protective factor from parental stress and from the development of full-blown psychosis. However, to date, there is limited research on family functioning in adolescents with psychosis and at clinical high risk for psychosis (CHR-P). This study is aimed at comparing family functioning and perceived stress in parents of adolescents with either CHR-P, early onset psychosis (EOP), or other psychiatric disorders (no CHR-P). As a secondary aim, it will correlate family functioning with parental perceived stress in order to find critical targets of intervention. We conducted a Reporting of Studies Conducted Using Observational Routinely-Collected Health Data (RECORD)-compliant, real-world, cross-sectional study. One-hundred and eleven adolescents aged 12-17 who access the institute of hospitalization and care with scientific character (IRCCS) Mondino Foundation Neuropsychiatric services (Pavia, Italy) between 2017 and 2020 and their parents (n = 222) were included. Sociodemographic characteristics of adolescents and their parents were collected. Family functioning was evaluated through the Family Adaptability and Cohesion Evaluation Scale-IV (FACES-IV) and the level of stress through the Perceived Stress Scale (PSS). Twenty adolescents had EOP, 38 had CHR-P, and 59 had no CHR-P. In total, 2.6% of CHR-P adolescents were adopted, 76.3% had separated-divorced parents, and 34.2% of parents had a depressive disorder. Among the FACES-IV sub-scale, maternal rigidity was progressively increased from no-CHR-P to CHR-P to EOP group, with statistical differences between EOP and the other two groups (p = 0.01). CHR-P mothers and fathers showed a high level of PSS values, without group difference. Lastly, PSS values correlated positively with the Rigidity, Disengagement, and Chaos scale of FACES-IV and negatively with the Communication scale (p < 0.05). Our results suggest that family functioning has a central role and could represent a worthwhile target of intervention for adolescents at CHR-P, leading the way to new preventive approaches

Learning and Using Abstract Words: Evidence from Clinical Populations

Lorusso ML, Burigo M, Tavano A, et al. Learning and Using Abstract Words: Evidence from Clinical Populations. BioMed Research International. 2017;2017:1-8

Remote Technology-Based Training Programs for Children with Acquired Brain Injury: A Systematic Review and a Meta-Analytic Exploration

Introduction. Multidisciplinary rehabilitation interventions are considered to be a need for children with acquired brain injury (ABI), in order to remediate the important sequelae and promote adjustment. Technology-based treatments represent a promising field inside the rehabilitation area, as they allow delivering interventions in ecological settings and creating amusing exercises that may favor engagement. In this work, we present an overview of remote technology-based training programs (TP) addressing cognitive and behavioral issues delivered to children with ABI and complement it with the results of a meta-analytic exploration. Evidence Acquisition. We performed the review process between January and February 2019. 32 studies were included in the review, of which 14 were further selected to be included in the meta-analysis on TP efficacy. Evidence Synthesis. Based on the review process, the majority of TP addressing cognitive issues and all TP focusing on behavioral issues were found to be effective. Two meta-analytic models examining the means of either cognitive TP outcomes or behavioral TP outcomes as input outcome yielded a nonsignificant effect size for cognitive TP and a low-moderate effect size for behavioral TP. Additional models on outcomes reflecting the greatest beneficial effects of TP yielded significant moderate effect sizes for both types of TP. Nevertheless, consistent methodological heterogeneity was observed, pointing to cautious interpretation of findings. A subgroup analysis on visuospatial skill outcomes showed a smaller yet significant effect size of cognitive TP, with low heterogeneity, providing a more reliable estimation of overall cognitive TP effects. Conclusions. Promising results on remote cognitive and behavioral TP efficacy emerged both at the review process and at the meta-analytic investigation. Nevertheless, the high heterogeneity that emerged across studies prevents us from drawing definite conclusions. Further research is needed to identify whether specific training characteristics and population subgroups are more likely to be associated with greater training efficacy

Neurocognition and functioning in adolescents at clinical high risk for psychosis

BACKGROUND: Once psychosis has set in, it is difficult for patients to achieve full recovery. Prevention of psychosis and early intervention are promising for improving the outcomes of this disorder. In the last two decades, neurocognition has been studied as a biomarker for clinical-high risk for psychosis (CHR-P). However, neurocognitive functioning has been under-investigated in adolescents. METHODS: We enrolled 116 adolescents from 12 to 17years old (mean=15.27, SD=1.56; 76 females). This 3-year cohort study aimed to identify differences in neurocognitive and overall functioning in three groups of adolescent patients divided according to the semi-structured interview Comprehensive Assessment of At-Risk Mental States (CAARMS): adolescents with established psychosis, adolescents with CHR-P, and adolescents not meeting either criteria (non-CHR-P). To differentiate the profiles, clinicians administered cognitive evaluation and neuropsychological tasks. Moreover, they filled in scales to assess their global, social, and role functioning and a questionnaire to assess the severity of the disease. RESULTS: We made a between-group comparison on neurocognitive measures and found that the CHR-P and the psychosis groups differed in processing speed (TMT-A; p=.002 in BVN categorial fluency (p=.018), and Rey-Osterrieth complex figure drawing from memory task (p=.014), with psychosis group showing worse performance. No differences emerged between non-CHR-P and CHR-P (p=.014) individuals. CHR-P had better functioning than the psychosis group but worse than the non-CHR-P one. CONCLUSIONS: These results confirm that neurocognition can be a helpful biomarker in identifying specific subgroups of adolescents with emerging psychopathology and help clinicians develop stratified preventive approaches.The present study was supported by the Italian Ministry of Health (Ricerca Corrente)

Facial emotion recognition in Williams syndrome and Down syndrome: A matching and developmental study

In this study both the matching and developmental trajectories approaches were used to clarify questions that remain open in the literature on facial emotion recognition in Williams syndrome (WS) and Down syndrome (DS). The matching approach showed that individuals with WS or DS exhibit neither proficiency for the expression of happiness nor specific impairments for negative emotions. Instead, they present the same pattern of emotion recognition as typically developing (TD) individuals. Thus, the better performance on the recognition of positive compared to negative emotions usually reported in WS and DS is not specific of these populations but seems to represent a typical pattern. Prior studies based on the matching approach suggested that the development of facial emotion recognition is delayed in WS and atypical in DS. Nevertheless, and even though performance levels were lower in DS than in WS, the developmental trajectories approach used in this study evidenced that not only individuals with DS but also those with WS present atypical development in facial emotion recognition. Unlike in the TD participants, where developmental changes were observed along with age, in the WS and DS groups, the development of facial emotion recognition was static. Both individuals with WS and those with DS reached an early maximum developmental level due to cognitive constraints

Nuovi paradigmi e i disturbi del neurosviluppo: le linee di cambiamento che emergono dal dibattito

Il contributo qui presentato si propone come sintesi dei numerosi e ricchi contributi ricevuti a commento dell’articolo-bersaglio di Antonietti et al. (2022) sulla possibilità/necessità di cambiare paradigma per affrontare e comprendere i disturbi del neurosviluppo. Il dibattito, con l’integrazione con quanto disponibile in letteratura, ha permesso di evidenziare linee di cambiamento per affrontare la complessità che caratterizza le traiettorie di sviluppo a vari livelli d’analisi. L’approccio multi-livello è qui analizzato attraverso tre costrutti: 1) la vulnerabilità biologica e/o psicologica in interazione con l’ambiente; 2) lo sviluppo come organizzazione atipica delle connessioni del cervello; 3) la visione processuale della realtà. Gli approfondimenti proposti nel dibattito hanno consentito di evidenziare fattori che si ritengono rilevanti per la ricerca, per il lavoro clinico diagnostico e per l’intervento. La formazione accademica e degli operatori sanitari può essere lo strumento funzionale per promuovere conoscenze e competenze finalizzate a una maggiore consapevolezza del cambiamento che è in atto

Delineation and Diagnostic Criteria of Oral-Facial-Digital Syndrome Type VI

Oral-Facial-Digital Syndrome type VI (OFD VI) represents a rare phenotypic subtype of Joubert syndrome and related disorders (JSRD). In the original report polydactyly, oral findings, intellectual disability, and absence of the cerebellar vermis at post-mortem characterized the syndrome. Subsequently, the molar tooth sign (MTS) has been found in patients with OFD VI, prompting the inclusion of OFD VI in JSRD. We studied the clinical, neurodevelopmental, neuroimaging, and genetic findings in a cohort of 16 patients with OFD VI. We derived the following inclusion criteria from the literature: 1) MTS and one oral finding and polydactyly, or 2) MTS and more than one typical oral finding. The OFD VI neuroimaging pattern was found to be more severe than in other JSRD subgroups and includes severe hypoplasia of the cerebellar vermis, hypoplastic and dysplastic cerebellar hemispheres, marked enlargement of the posterior fossa, increased retrocerebellar collection of cerebrospinal fluid, abnormal brainstem, and frequently supratentorial abnormalities that occasionally include characteristic hypothalamic hamartomas. Additionally, two new JSRD neuroimaging findings (ascending superior cerebellar peduncles and fused thalami) have been identified. Tongue hamartomas, additional frenula, upper lip notch, and mesoaxial polydactyly are specific findings in OFD VI, while cleft lip/palate and other types of polydactyly of hands and feet are not specific. Involvement of other organs may include ocular findings, particularly colobomas. The majority of the patients have absent motor development and profound cognitive impairment. In OFD VI, normal cognitive functions are possible, but exceptional. Sequencing of known JSRD genes in most patients failed to detect pathogenetic mutations, therefore the genetic basis of OFD VI remains unknown. Compared with other JSRD subgroups, the neurological findings and impairment of motor development and cognitive functions in OFD VI are significantly worse, suggesting a correlation with the more severe neuroimaging findings. Based on the literature and this study we suggest as diagnostic criteria for OFD VI: MTS and one or more of the following: 1) tongue hamartoma(s) and/or additional frenula and/or upper lip notch; 2) mesoaxial polydactyly of one or more hands or feet; 3) hypothalamic hamartoma

Recurrent, founder and hypomorphic variants contribute to the genetic landscape of Joubert syndrome

Background Joubert syndrome (JS) is a neurodevelopmental ciliopathy characterised by a distinctive mid-hindbrain malformation, the 'molar tooth sign'. Over 40 JS-associated genes are known, accounting for two-thirds of cases.Methods While most variants are novel or extremely rare, we report on 11 recurring variants in seven genes, including three known 'founder variants' in the Ashkenazi Jewish, Hutterite and Finnish populations. We evaluated variant frequencies in similar to 550 European patients with JS and compared them with controls (&gt;15 000 Italian plus gnomAD), and with an independent cohort of similar to 600 JS probands from the USA.Results All variants were markedly enriched in the European JS cohort compared with controls. When comparing allele frequencies in the two JS cohorts, the Ashkenazim founder variant (TMEM216 c.218G&gt;T) was significantly enriched in American compared with European patients with JS, while MKS1 c.1476T&gt;G was about 10 times more frequent among European JS. Frequencies of other variants were comparable in the two cohorts. Genotyping of several markers identified four novel European founder haplotypes. Two recurrent variants (MKS1 c.1476T&gt;G and KIAA0586 c.428delG), have been detected in homozygosity in unaffected individuals, suggesting they could act as hypomorphic variants. However, while fibroblasts from a MKS1 c.1476T&gt;G healthy homozygote showed impaired ability to form primary cilia and mildly reduced ciliary length, ciliary parameters were normal in cells from a KIAA0586 c.428delG healthy homozygote.Conclusion This study contributes to understand the complex genetic landscape of JS, explain its variable prevalence in distinct geographical areas and characterise two recurrent hypomorphic variants