Transcranial Direct Current Stimulation in Child and Adolescent Psychiatry.

OBJECTIVES: Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that consists of applying a weak electric current over the scalp to modulate cortical excitability. tDCS has been extensively investigated in adults with psychiatric disorders. The aim of this study was to review the current literature regarding the use of tDCS in children and adolescents with psychiatric disorders. METHODS: We searched MEDLINE and EMBASE databases for studies evaluating the safety and efficacy of tDCS in children and adolescents from age 0 to 18 years with psychiatric disorders. RESULTS: We found six studies that evaluated patients with different psychiatric disorders, with diverse study designs and stimulation parameters, including three small randomized clinical trials (RCTs), one evaluating childhood-onset schizophrenia, one RCT with patients with autism spectrum disorders (ASD), and one study in attention-deficit/hyperactivity disorder (ADHD); three open-label studies, two evaluating patients with ASD, and one study of feasibility of the technique in children and adolescents with language disorders and diverse psychiatric disorders, including ASD, intellectual disability, and ADHD. We also found three studies of dosage considerations in the general pediatric population. The technique was well tolerated, with no reports of serious side effects. CONCLUSION: Preliminary research suggests that tDCS may be well tolerated and safe for children and adolescents with psychiatric and neurodevelopmental disorders. Nevertheless, because the literature regarding tDCS in child and adolescent psychiatry is scarce and there exist limited numbers of randomized controlled trials, it is not possible to draw definite conclusions. Future studies should investigate the technique with regard to specific psychiatric conditions in comparison with standard treatments. In addition, long-term efficacy and safety should be monitored.

Structural and functional rich club organization of the brain in children and adults.

Recent studies using Magnetic Resonance Imaging (MRI) have proposed that the brain's white matter is organized as a rich club, whereby the most highly connected regions of the brain are also highly connected to each other. Here we use both functional and diffusion-weighted MRI in the human brain to investigate whether the rich club phenomena is present with functional connectivity, and how this organization relates to the structural phenomena. We also examine whether rich club regions serve to integrate information between distinct brain systems, and conclude with a brief investigation of the developmental trajectory of rich-club phenomena. In agreement with prior work, both adults and children showed robust structural rich club organization, comprising regions of the superior medial frontal/dACC, medial parietal/PCC, insula, and inferior temporal cortex. We also show that these regions were highly integrated across the brain's major networks. Functional brain networks were found to have rich club phenomena in a similar spatial layout, but a high level of segregation between systems. While no significant differences between adults and children were found structurally, adults showed significantly greater functional rich club organization. This difference appeared to be driven by a specific set of connections between superior parietal, insula, and supramarginal cortex. In sum, this work highlights the existence of both a structural and functional rich club in adult and child populations with some functional changes over development. It also offers a potential target in examining atypical network organization in common developmental brain disorders, such as ADHD and Autism.

Developments and challenges in the diagnosis and treatment of ADHD.

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder, often associated with other psychiatric comorbidities, functional impairments, and poor long-term outcomes. The objective of this selected review is to describe current advances and challenges in the diagnosis and treatment of ADHD. The disorder is associated with neurobiological underpinnings and is highly heterogeneous in various aspects, such as symptom profiles, cognitive impairments, and neurobiological and genetic features. The efficacy and safety of short-term pharmacological treatments across the life cycle is well studied, but further research investigating long-term treatment, impact of treatment in preschoolers, and non-pharmacological interventions is needed. Future research is also needed to better characterize the neurodevelopmental pathways of the disorder, linking clinical and neurobiological information, less investigated populations, and new interventions.

Altered cortico-striatal-thalamic connectivity in relation to spatial working memory capacity in children with ADHD.

INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) captures a heterogeneous group of children, who are characterized by a range of cognitive and behavioral symptoms. Previous resting-state functional connectivity MRI (rs-fcMRI) studies have sought to understand the neural correlates of ADHD by comparing connectivity measurements between those with and without the disorder, focusing primarily on cortical-striatal circuits mediated by the thalamus. To integrate the multiple phenotypic features associated with ADHD and help resolve its heterogeneity, it is helpful to determine how specific circuits relate to unique cognitive domains of the ADHD syndrome. Spatial working memory has been proposed as a key mechanism in the pathophysiology of ADHD. METHODS: We correlated the rs-fcMRI of five thalamic regions of interest (ROIs) with spatial span working memory scores in a sample of 67 children aged 7-11 years [ADHD and typically developing children (TDC)]. In an independent dataset, we then examined group differences in thalamo-striatal functional connectivity between 70 ADHD and 89 TDC (7-11 years) from the ADHD-200 dataset. Thalamic ROIs were created based on previous methods that utilize known thalamo-cortical loops and rs-fcMRI to identify functional boundaries in the thalamus. RESULTS/CONCLUSION: Using these thalamic regions, we found atypical rs-fcMRI between specific thalamic groupings with the basal ganglia. To identify the thalamic connections that relate to spatial working memory in ADHD, only connections identified in both the correlational and comparative analyses were considered. Multiple connections between the thalamus and basal ganglia, particularly between medial and anterior dorsal thalamus and the putamen, were related to spatial working memory and also altered in ADHD. These thalamo-striatal disruptions may be one of multiple atypical neural and cognitive mechanisms that relate to the ADHD clinical phenotype.

Atypical default network connectivity in youth with attention-deficit/hyperactivity disorder.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a major public health concern. It has been suggested that the brain's default network may provide a crucial avenue for understanding the neurobiology of attention deficit/hyperactivity disorder. Evaluations of the default network have increased over recent years with the applied technique of resting-state functional connectivity magnetic resonance imaging (rs-fcMRI). These investigations have established that spontaneous activity in this network is highly correlated at rest in young adult populations. This coherence seems to be reduced in adults with ADHD. This is an intriguing finding, as coherence in spontaneous activity within the default network strengthens with age. Thus, the pathophysiology of ADHD might include delayed or disrupted maturation of the default network. If so, it is important to determine whether an altered developmental picture can be detected using rs-fcMRI in children with ADHD. METHODS: This study used the typical developmental context provided previously by Fair et al. (2008) to examine coherence of brain activity within the default network using rs-fcMRI in children with (n = 23) and without attention deficit/hyperactivity disorder (n = 23). RESULTS: We found that functional connections previously shown as developmentally dynamic in the default network were atypical in children with attention deficit/hyperactivity disorder-consistent with perturbation or failure of the maturational processes. CONCLUSIONS: These findings are consistent with the hypothesis that atypical consolidation of this network over development plays a role in attention deficit/hyperactivity disorder.

Maturing thalamocortical functional connectivity across development.

Recent years have witnessed a surge of investigations examining functional brain organization using resting-state functional connectivity MRI (rs-fcMRI). To date, this method has been used to examine systems organization in typical and atypical developing populations. While the majority of these investigations have focused on cortical-cortical interactions, cortical-subcortical interactions also mature into adulthood. Innovative work by Zhang et al. (2008) in adults have identified methods that utilize rs-fcMRI and known thalamo-cortical topographic segregation to identify functional boundaries in the thalamus that are remarkably similar to known thalamic nuclear grouping. However, despite thalamic nuclei being well formed early in development, the developmental trajectory of functional thalamo-cortical relations remains unexplored. Thalamic maps generated by rs-fcMRI are based on functional relationships, and should modify with the dynamic thalamo-cortical changes that occur throughout maturation. To examine this possibility, we employed a strategy as previously described by Zhang et al. to a sample of healthy children, adolescents, and adults. We found strengthening functional connectivity of the cortex with dorsal/anterior subdivisions of the thalamus, with greater connectivity observed in adults versus children. Temporal lobe connectivity with ventral/midline/posterior subdivisions of the thalamus weakened with age. Changes in sensory and motor thalamo-cortical interactions were also identified but were limited. These findings are consistent with known anatomical and physiological cortical-subcortical changes over development. The methods and developmental context provided here will be important for understanding how cortical-subcortical interactions relate to models of typically developing behavior and developmental neuropsychiatric disorders.

Developments and challenges in the diagnosis and treatment of ADHD

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder, often associated with other psychiatric comorbidities, functional impairments, and poor long-term outcomes. The objective of this selected review is to describe current advances and challenges in the diagnosis and treatment of ADHD. The disorder is associated with neurobiological underpinnings and is highly heterogeneous in various aspects, such as symptom profiles, cognitive impairments, and neurobiological and genetic features. The efficacy and safety of short-term pharmacological treatments across the life cycle is well studied, but further research investigating long-term treatment, impact of treatment in preschoolers, and non-pharmacological interventions is needed. Future research is also needed to better characterize the neurodevelopmental pathways of the disorder, linking clinical and neurobiological information, less investigated populations, and new interventions.