While rehabilitation therapies always help patients with ataxia, there are currently no FDA-approved treatments for ataxia. Medications are available to treat symptoms that may complicate an ataxic ...illness, e.g., tremor, myoclonus, dystonia, and rigidity, which are discussed elsewhere in this volume. Spasticity, pain, fatigue, depression, sleep disturbances, cognitive decline, and bowel and bladder dysfunction, if they occur, all have multiple available drugs and therapies for symptomatic use. There is also an extensive literature on off-label uses of various medications to improve imbalance. The pipeline of emerging therapies for symptomatic and possible disease-modifying management of ataxia gives hope that we will soon see the first of many FDA-approved drugs for ataxic illnesses.
The experience of frustration is common in early childhood, yet some children seem to possess a lower tolerance for frustration than others. Characterizing the biological mechanisms underlying a wide ...range of frustration tolerance observed in early childhood may inform maladaptive behavior and psychopathology that is associated with this construct. The goal of this study was to measure prefrontal correlates of frustration in 3–5-year-old children, who are not readily adaptable for typical neuroimaging approaches, using functional near infrared spectroscopy (fNIRS). fNIRS of frontal regions were measured as frustration was induced in children through a computer game where a desired and expected prize was “stolen” by an animated dog. A fNIRS general linear model (GLM) was used to quantify the correlation of brain regions with the task and identify areas that were statistically different between the winning and frustrating test conditions. A second-level voxel-based ANOVA analysis was then used to correlate the amplitude of each individual's brain activation with measure of parent-reported frustration. Experimental results indicated increased activity in the middle prefrontal cortex during winning of a desired prize, while lateral prefrontal cortex activity increased during frustration. Further, activity increase in lateral prefrontal cortex during frustration correlated positively with parent-reported frustration tolerance. These findings point to the role of the lateral prefrontal cortex as a potential region supporting the regulation of emotion during frustration.
•fNIRS is an effective method for brain imaging in preschool children.•A novel paradigm was designed to induce frustration in 3–5-year-old children.•Frustration was linked to increased hemoglobin in the lateral PFC.•Low frustration tolerance correlated with increased hemoglobin in lateral PFC.
In cognitive neuroscience, measurements of “resting baseline” are often considered stable across age and used as a reference point against which to judge cognitive state. The task-based ...approach—comparing resting baseline to task conditions—implies that resting baseline is an equalizer across participants and—in the case of studies of developmental changes in cognition—across age groups. In contrast, network neuroscience explicitly examines the development of “resting state” networks across age, at odds with the idea of a consistent resting baseline. Little attention has been paid to how cognition during rest may shift across development, particularly in children under the age of eight. Childhood is marked by striking maturation of neural systems, including a protracted developmental period for cognitive control systems. To grow and shape these cognitive systems, children have a developmental imperative to engage their neural circuitry at every possible opportunity. Thus, periods of “rest” without specific instructions may require additional control for children as they fight against developmental expectation to move, speak, or otherwise engage. We therefore theorize that the child brain does not rest in a manner consistent with the adult brain as longer rest periods may represent increased cognitive control. To shape this theory, we first review the extant literature on neurodevelopment across early childhood within the context of cognitive development. Next, we present nascent evidence for a destabilized baseline for comparisons across age. Finally, we present recommendations for designing, analyzing, and interpreting tasks conducted with young children as well as for resting state. Future work must aim to tease apart the cognitive context under which we examine functional brain development in young children and take considerations into account unique to each age.
•During tasks, resting cognition is often considered stable across age and used for comparisons.•Little attention has examined how resting cognition develops, particularly in early childhood.•We present nascent cognitive and neurobiological evidence that children do NOT rest like adults.•We provide guidance for current and future work and highlight areas in need of systematic study.
The arrival of the Journal's 175th anniversary occurs at a time of recent advances in research, providing an ideal opportunity to present a neurodevelopmental roadmap for understanding, preventing, ...and treating psychiatric disorders. Such a roadmap is particularly relevant for early-childhood-onset neurodevelopmental conditions, which emerge when experience-dependent neuroplasticity is at its peak. Employing a novel developmental specification approach, this review places recent neurodevelopmental research on early childhood disruptive behavior within the historical context of the Journal. The authors highlight irritability and callous behavior as two core exemplars of early disruptive behavior. Both phenotypes can be reliably differentiated from normative variation as early as the first years of life. Both link to discrete pathophysiology: irritability with disruptions in prefrontal regulation of emotion, and callous behavior with abnormal fear processing. Each phenotype also possesses clinical and predictive utility. Based on a nomologic net of evidence, the authors conclude that early disruptive behavior is neurodevelopmental in nature and should be reclassified as an early-childhood-onset neurodevelopmental condition in DSM-5. Rapid translation from neurodevelopmental discovery to clinical application has transformative potential for psychiatric approaches of the millennium.AJP at 175: Remembering Our Past As We Envision Our FutureNovember 1938: Electroencephalographic Analyses of Behavior Problem ChildrenHerbert Jasper and colleagues found that brain abnormalities revealed by EEG are a potential causal factor in childhood behavioral disorders. (Am J Psychiatry 1938; 95:641–658)
The neural underpinnings of working memory are hypothesized to develop incrementally across preschool and early school age, coinciding with the rapid maturation of executive function occurring during ...this period. This study investigates the development of prefrontal cortex function between the ages of 3 and 7. Children (n = 68) participated in a novel spatial working memory task while their middle and lateral prefrontal cortex (LPFC) was monitored using functional near infrared spectroscopy (fNIRS). We found increased activation of the LPFC when comparing working memory to rest. Greater LPFC increase was noted for longer compared with shorter delay periods. Increase in LPFC activation, accuracy, and response speed were positively correlated with child age, suggesting that developmental changes in prefrontal function might underlie effective development of executive function in this age range.
Genomic technologies such as next-generation sequencing (NGS) are revolutionizing molecular diagnostics and clinical medicine. However, these approaches have proven inefficient at identifying ...pathogenic repeat expansions. Here, we apply a collection of bioinformatics tools that can be utilized to identify either known or novel expanded repeat sequences in NGS data. We performed genetic studies of a cohort of 35 individuals from 22 families with a clinical diagnosis of cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS). Analysis of whole-genome sequence (WGS) data with five independent algorithms identified a recessively inherited intronic repeat expansion (AAGGG)exp in the gene encoding Replication Factor C1 (RFC1). This motif, not reported in the reference sequence, localized to an Alu element and replaced the reference (AAAAG)11 short tandem repeat. Genetic analyses confirmed the pathogenic expansion in 18 of 22 CANVAS-affected families and identified a core ancestral haplotype, estimated to have arisen in Europe more than twenty-five thousand years ago. WGS of the four RFC1-negative CANVAS-affected families identified plausible variants in three, with genomic re-diagnosis of SCA3, spastic ataxia of the Charlevoix-Saguenay type, and SCA45. This study identified the genetic basis of CANVAS and demonstrated that these improved bioinformatics tools increase the diagnostic utility of WGS to determine the genetic basis of a heterogeneous group of clinically overlapping neurogenetic disorders.
The genetic ataxias have no cures and no proven ways to delay progression (no disease-modifying therapies). The acquired ataxias may have treatments that address the underlying cause and may slow or ...stop progression, but will not reverse damage already sustained. The idiopathic ataxias (of unknown genetic or acquired cause) also have no proven disease-modifying therapies. However, for all patients with ataxia of any cause, there is always something that can be done to improve quality of life-treat associated symptoms, provide information and resources, counsel patient and family, help with insurance and disability concerns, be available to listen and answer the many questions they will have.
The regulation of affective arousal is a critical aspect of children’s social and cognitive development. However, few studies have examined the brain mechanisms involved in the development of this ...aspect of “hot” executive functioning. This process has been conceptualized as involving prefrontal control of the amygdala. Here, using functional magnetic resonance imaging (fMRI), we investigated the brain mechanisms involved in the development of affective regulation in typically developing 5- to 11-year-olds and an adult comparison sample. Children and adults displayed differing patterns of increased anterior cingulate cortex and decreased amygdala activation during episodes in which emotion regulation was required. Specifically, amygdala activation increased in adults but decreased in children during recovery from a frustrating episode. In addition, we used effective connectivity analyses to investigate differential correlations between key emotional brain areas in response to the regulatory task demands. We found reliable increases in effective connectivity between the anterior cingulate cortex and the amygdala during periods of increased demand for emotion regulation. This effective connectivity increased with age.
The importance of dimensional approaches is widely recognized, but an empirical base for clinical application is lacking. This is particularly true for irritability, a dimensional phenotype that cuts ...across many areas of psychopathology and manifests early in life. We examine longitudinal, dimensional patterns of irritability and their clinical import in early childhood.
Irritability was assessed longitudinally over an average of 16 months in a clinically enriched, diverse community sample of preschoolers (N = 497; mean = 4.2 years; SD = 0.8). Using the Temper Loss scale of the Multidimensional Assessment Profile of Disruptive Behavior (MAP-DB) as a developmentally sensitive indicator of early childhood irritability, we examined its convergent/divergent, clinical, and incremental predictive validity, and modeled its linear and nonlinear associations with clinical risk.
The Temper Loss scale demonstrated convergent and divergent validity to child and maternal factors. In multivariate analyses, Temper Loss predicted mood (separation anxiety disorder SAD, generalized anxiety disorder GAD, and depression/dysthymia), disruptive (oppositional defiant disorder ODD, attention-deficit/hyperactivity disorder ADHD, and conduct disorder CD) symptoms. Preschoolers with even mildly elevated Temper Loss scale scores showed substantially increased risk of symptoms and disorders. For ODD, GAD, SAD, and depression, increases in Temper Loss scale scores at the higher end of the dimension had a greater impact on symptoms relative to increases at the lower end. Temper Loss scale scores also showed incremental validity over DSM-IV disorders in predicting subsequent impairment. Finally, accounting for the substantial heterogeneity in longitudinal patterns of Temper Loss significantly improved prediction of mood and disruptive symptoms.
Dimensional, longitudinal characterization of irritability informs clinical prediction. A vital next step will be empirically generating parameters for the incorporation of dimensional information into clinical decision-making with reasonable certainty.
Background
Research to date has largely conceptualized irritability in terms of intraindividual differences. However, the role of interpersonal dyadic processes has received little consideration. ...Nevertheless, difficulties in how parent–child dyads synchronize during interactions may be an important correlate of irritably in early childhood. Innovations in developmentally sensitive neuroimaging methods now enable the use of measures of neural synchrony to quantify synchronous responses in parent–child dyads and can help clarify the neural underpinnings of these difficulties. We introduce the Disruptive Behavior Diagnostic Observation Schedule: Biological Synchrony (DB‐DOS:BioSync) as a paradigm for exploring parent–child neural synchrony as a potential biological mechanism for interpersonal difficulties in preschool psychopathology.
Methods
Using functional near‐infrared spectroscopy (fNIRS) 4‐ to 5‐year‐olds (N = 116) and their mothers completed the DB‐DOS:BioSync while assessing neural synchrony during mild frustration and recovery. Child irritability was measured using a latent irritability factor that was calculated from four developmentally sensitive indicators.
Results
Both the mild frustration and the recovery contexts resulted in neural synchrony. However, less neural synchrony during the recovery context only was associated with more child irritability.
Conclusions
Our results suggest that recovering after a frustrating period might be particularly challenging for children high in irritability and offer support for the use of the DB‐DOS:BioSync task to elucidate interpersonal neural mechanisms of developmental psychopathology.
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