Neuroimage phenotyping for psychiatric and neurological disorders is performed using voxelwise analyses also known as voxel based analyses or morphometry (VBM). A typical voxelwise analysis treats measurements at each voxel (e.g., fractional anisotropy, gray matter probability) as outcome measures to study the effects of possible explanatory variables (e.g., age, group) in a linear regression setting. Furthermore, each voxel is treated independently until the stage of correction for multiple comparisons. Recently, multi-voxel pattern analyses (MVPA), such as classification, have arisen as an alternative to VBM. The main advantage of MVPA over VBM is that the former employ multivariate methods which can account for interactions among voxels in identifying significant patterns. They also provide ways for computer-aided diagnosis and prognosis at individual subject level. However, compared to VBM, the results of MVPA are often more difficult to interpret and prone to arbitrary conclusions. In this paper, first we use penalized likelihood modeling to provide a unified framework for understanding both VBM and MVPA. We then utilize statistical learning theory to provide practical methods for interpreting the results of MVPA beyond commonly used performance metrics, such as leave-one-out-cross validation accuracy and area under the receiver operating characteristic (ROC) curve. Additionally, we demonstrate that there are challenges in MVPA when trying to obtain image phenotyping information in the form of statistical parametric maps (SPMs), which are commonly obtained from VBM, and provide a bootstrap strategy as a potential solution for generating SPMs using MVPA. This technique also allows us to maximize the use of available training data. We illustrate the empirical performance of the proposed framework using two different neuroimaging studies that pose different levels of challenge for classification using MVPA.
<p>Virtually all developmental neuropsychiatric disorders involve some dysfunction or dysregulation of emotion. Moreover, many psychiatric disorders with adult onset have early subclinical manifestations in children. This essay selectively reviews the literature on the neuroimaging of affect and disorders of affect in children. Some critical definitional and conceptual issues are first addressed, including the distinctions between the perception and production of emotion and between emotional states and traits. Developmental changes in morphometric measures of brain structure are then discussed and the implications of such findings for studies of functional brain activity are considered. Data on functional neuroimaging and childhood depression are then reviewed. While the extant data in this area are meager, they are consistent with studies in adults that have observed decreased left-sided anterolateral prefrontal cortex activation in depression. Studies in children on the recognition of emotion and affective intent in faces using functional magnetic resonance imaging are then reviewed. These findings indicate that the amygdala plays an important role in such affective face processing in children, similar to the patterns of activation observed in adults. Moreover, one study has reported abnormalities in amygdala activation during a task requiring the judgment of affective intent from the eye region of the face in subjects with autism. Some of the methodological complexities of developmental research in this area are discussed, and directions for future research are suggested.</p>
Differences between dyslexics and controls in the unimanual and bimanual conditions of the peg placement section of the Purdue Pegboard Test were examined. Twenty-three disabled and twenty-three normal readers were studied. The groups were carefully screened on a neuropsychological battery. The disabled readers were comprised of a relatively homogeneous language-disordered subgroup exhibiting deficits in naming. Significant Group X Condition interactions were obtained for both raw and percentile scores and indicated that disabled readers performed worse than controls in the unimanual compared to bimanual conditions. The dyslexics performed particularly poorly compared with controls on the left hand condition. The implications of these data for hypotheses which argue for left hemisphere dysfunction, as well as those which posit interhemispheric transfer deficits in reading disabled children, are discussed.
Mindfulness-based cognitive therapy for children (MBCT-C) is a manualized group psychotherapy for children ages 9–13 years old, which was developed specifically to increase social-emotional resiliency through the enhancement of mindful attention. Program development is described along with results of the initial randomized controlled trial. We tested the hypotheses that children randomized to participate in MBCT-C would show greater reductions in (a) attention problems, (b) anxiety symptoms, and (c) behavior problems than wait-listed age and gender-matched controls. Participants were boys and girls aged 9–13 (N = 25), mostly from low-income, inner-city households. Twenty-one of 25 children were ethnic minorities. A randomized cross-lagged design provided a wait-listed control group, a second trial of MBCT-C, and a 3-month follow-up of children who completed the first trial. Measures included the Child Behavior Checklist, State-Trait Anxiety Inventory for Children, and Multidimensional Anxiety Scale for Children. Participants who completed the program showed fewer attention problems than wait-listed controls and those improvements were maintained at three months following the intervention [F (1, 1, 18) = 5.965, p = .025, Cohen’s d = .42]. A strong relationship was found between attention problems and behavior problems (r = .678, p < .01). Reductions in attention problems accounted for 46% of the variance of changes in behavior problems, although attention changes proved to be a non-significant mediator of behavior problems (p = .053). Significant reductions in anxiety symptoms and behavior problems were found for those children who reported clinically elevated levels of anxiety at pretest (n = 6). Results show that MBCT-C is a promising intervention for attention and behavior problems, and may reduce childhood anxiety symptoms.
<p>This experiment was designed to test whether reading disabled boys differ from matched controls on behavioral measures of interhemispheric transfer time (IHTT). Specifically, we proposed that language-disordered reading disabled children who had deficits in naming would show either faster or slower IHTTs compared with controls. From an initial group of 118 right-handed males, we selected a group of 25 disabled and 25 normal readers, matched on age. All subjects had to obtain a full scale IQ of 90 or above, a PIQ score of 85 or above, and a scaled score of 7 or above on the Block Design Subtest of the WISC-R. After meeting additional criteria for group assignment, manual reaction time (RT) measures of IHTT were obtained in response to simple visual and tactile stimuli during two laboratory testing sessions. Half the trials were conducted with the hands in an uncrossed orientation and half with the hands crossed in order to examine the effects of spatial compatibility on estimates of IHTT. The results revealed no overall group differences in IHTT for any of the conditions. However, correlations between IHTT measures and indices of cognitive performance indicated that faster IHTTs were significantly correlated with poorer performance on measures of reading and language function in the dyslexic group. These data are discussed within the context of a model of interhemispheric transfer deficits in disabled readers.</p>
High rates of child abuse and neglect occur in many families in which either or both parents abuse illicit drugs. This study reports on the results of a randomized controlled trial with families having a parent on methadone maintenance (N = 64), in which an intensive, home-based intervention, the Parents Under Pressure (PUP) program, was compared to standard care. A second brief intervention control group of families received a two-session parenting education intervention. The PUP intervention draws from the ecological model of child development by targeting multiple domains of family functioning including the psychological functioning of individuals in the family, parent–child relationships, and social contextual factors. Mindfulness skills were included to address parental affect regulation, a significant problem for this group of parents. At 3- and 6-month follow-up, PUP families showed significant reductions in problems across multiple domains of family functioning, including a reduction in child abuse potential, rigid parenting attitudes, and child behavior problems. Families in the brief intervention group showed a modest reduction in child abuse potential but no other changes in family function. There were no improvements found in the standard care group and some significant worsening was observed. Results are discussed in terms of their implications for improved treatment.
<p>OBJECTIVES: The study objectives were to develop and objectively assess the therapeutic effect of a novel movement-based complementary and alternative medicine approach for children with an autism-spectrum disorder (ASD). DESIGN: A within-subject analysis comparing pre- to post-treatment scores on two standard measures of childhood behavioral problems was used. SETTINGS AND LOCATION: The intervention and data analysis occurred at a tertiary care, medical school teaching hospital. SUBJECTS: Twenty-four (24) children aged 3-16 years with a diagnosis of an ASD comprised the study group. INTERVENTION: The efficacy of an 8-week multimodal yoga, dance, and music therapy program based on the relaxation response (RR) was developed and examined. OUTCOME MEASURES: The study outcome was measured using The Behavioral Assessment System for Children, Second Edition (BASC-2) and the Aberrant Behavioral Checklist (ABC). RESULTS: Robust changes were found on the BASC-2, primarily for 5-12-year-old children. Unexpectedly, the post-treatment scores on the Atypicality scale of the BASC-2, which measures some of the core features of autism, changed significantly (p=0.003). CONCLUSIONS: A movement-based, modified RR program, involving yoga and dance, showed efficacy in treating behavioral and some core features of autism, particularly for latency-age children.</p>
Given the central role of the amygdala in fear perception and expression and its likely abnormality in affective disorders and autism, there is great demand for a technique to measure differences in neurochemistry of the human amygdala. Unfortunately, it is also a technically complex target for magnetic resonance spectroscopy (MRS) due to a small volume, high field inhomogeneity and a shared boundary with hippocampus, which can undergo opposite changes in response to stress. We attempted to achieve reliable PRESS-localized single-voxel MRS at 3T of the isolated human amygdala by using anatomy to guide voxel size and location. We present data from 106 amygdala-MRS sessions from 58 volunteers aged 10 to 52 years, including two tests of one-week stability and a feasibility study in an adolescent sample. Our main outcomes were indices of spectral quality, repeated measurement variability (within- and between-subject standard deviations), and sensitivity to stable individual differences measured by intra-class correlation (ICC). We present metrics of amygdala-MRS reliability for n-acetyl-aspartate, creatine, choline, myo-Inositol, and glutamate+glutamine (Glx). We found that scan quality suffers an age-related difference in field homogeneity and modified our protocol to compensate. We further identified an effect of anatomical inclusion near the endorhinal sulcus, a region of high synaptic density, that contributes up to 29% of within-subject variability across 4 sessions (n=14). Remaining variability in line width but not signal-to-noise also detracts from reliability. Statistical correction for partial inclusion of these strong neurochemical gradients decreases n-acetyl-aspartate reliability from an intraclass correlation of 0.84 to 0.56 for 7-minute acquisitions. This suggests that systematic differences in anatomical inclusion can contribute greatly to apparent neurochemical concentrations and could produce false group differences in experimental studies. Precise, anatomically-based prescriptions that avoid age-related sources of inhomogeneity and use longer scan times may permit study of individual differences in neurochemistry throughout development in this late-maturing structure.
This study, based on a sample of 172 children, examined the relation between average afternoon salivary cortisol levels measured at home at age 4.5 years and socioemotional adjustment a year and a half later, as reported by mothers, fathers, and teachers. Cortisol levels were hypothesized to be positively associated with withdrawal-type behaviors (e.g., internalizing, social wariness) and inversely related to approach-type behaviors, both negative and positive (e.g., externalizing, school engagement). Higher cortisol levels at age 4.5 predicted more internalizing behavior and social wariness as reported by teachers and mothers, although child gender moderated the relation between cortisol and mother report measures. An inverse relation was found between boys' cortisol levels and father report of externalizing behavior. A marginal inverse relation was found between child cortisol levels and teacher report of school engagement. Behavior assessed concurrently with cortisol collection did not account for the prospective relations observed,suggesting that cortisol adds uniquely to an understanding of behavioral development.
Our objective was to conduct the first randomized controlled trial of the efficacy of a group mindfulness program aimed at reducing and preventing depression in an adolescent school-based population. For each of 12 pairs of parallel classes with students (age range 13–20) from five schools (N = 408), one class was randomly assigned to the mindfulness condition and one class to the control condition. Students in the mindfulness group completed depression assessments (the Depression Anxiety Stress Scales) prior to and immediately following the intervention and 6 months after the intervention. Control students completed the questionnaire at the same times as those in the mindfulness group. Hierarchical linear modeling showed that the mindfulness intervention showed significantly greater reductions (and greater clinically significant change) in depression compared with the control group at the 6-month follow-up. Cohen's d was medium sized (>.30) for both the pre-to-post and pre-to-follow-up effect for depressive symptoms in the mindfulness condition. The findings suggest that school-based mindfulness programs can help to reduce and prevent depression in adolescents.
The tensor-based morphometry (TBM) has been widely used in characterizing tissue volume difference between populations at voxel level. We present a novel computational framework for investigating the white matter connectivity using TBM. Unlike other diffusion tensor imaging (DTI) based white matter connectivity studies, we do not use DTI but only T1-weighted magnetic resonance imaging (MRI). To construct brain network graphs, we have developed a new data-driven approach called the e-neighbor method that does not need any predetermined parcellation. The proposed pipeline is applied in detecting the topological alteration of the white matter connectivity in maltreated children.
Although tantrums are among the most common behavioral problems of young children and may predict future antisocial behavior, little is known about them. To develop a model of this important phenomenon of early childhood, behaviors reported in parental narratives of the tantrums of 335 children aged 18 to 60 months were encoded as present or absent in consecutive 30-second periods. Principal Component (PC) analysis identified Anger and Distress as major, independent emotional and behavioral tantrum constituents. Anger-related behaviors formed PCs at three levels of intensity. High-intensity anger decreased with age, and low-intensity anger increased. Distress, the fourth PC, consisted of whining, crying, and comfort-seeking. Coping Style, the fifth PC, had high but opposite loadings on dropping down and running away, possibly reflecting the tendency to either "submit" or "escape." Model validity was indicated by significant correlations of the PCs with tantrum variables that were, by design, not included in the PC analysis.
This article completes the analysis of parental narratives of tantrums had by 335 children aged 18 to 60 months. Modal tantrum durations were 0.5 to 1 minute; 75% of the tantrums lasted 5 minutes or less. If the child stamped or dropped to the floor in the first 30 seconds, the tantrum was likely to be shorter and the likelihood of parental intervention less. A novel analysis of behavior probabilities that permitted grouping of tantrums of different durations converged with our previous statistically independent results to yield a model of tantrums as the expression of two independent but partially overlapping emotional and behavioral processes: Anger and Distress. Anger rises quickly, has its peak at or near the beginning of the tantrum, and declines thereafter. Crying and comfort-seeking, components of Distress, slowly increase in probability across the tantrum. This model indicates that tantrums can provide a window on the intense emotional processes of childhood.
Several randomised controlled trials suggest that mindfulness-based approaches are helpful in preventing depressive relapse and recurrence, and the UK Government’s National Institute for Health and Clinical Excellence has recommended these interventions for use in the National Health Service. There are good grounds to suggest that mindfulness-based approaches are also helpful with anxiety disorders and a range of chronic physical health problems, and there is much clinical and research interest in applying mindfulness approaches to other populations and problems such as people with personality disorders, substance abuse, and eating disorders. We review the UK context for developments in mindfulness-based approaches and set out criteria for mindfulness teacher competence and training steps, as well as some of the challenges and future directions that can be anticipated in ensuring that evidence-based mindfulness approaches are available in health care and other settings.
OBJECTIVES: Affective neuroscience research that investigates core symptoms of pediatric bipolar disorder (PBD) may be effective in differentiating PBD phenotypes. The current study used affect-modulated startle to examine potential differences in reactivity to emotional stimuli (reward and punishment) in narrow and broad phenotype PBD and controls. METHODS: Thirty children meeting DSM-IV bipolar disorder criteria (i.e. narrow phenotype PBD with defined manic episodes with elevated/expansive mood), 19 children meeting criteria for severe mood dysregulation (i.e. broad phenotype with chronic irritability, hyper-reactivity, and hyperarousal), and 19 controls completed a lottery startle paradigm involving reward (money) and punishment (loud noise). Startle probes were presented during anticipation of the emotional stimulus, immediately following the presentation of the stimulus, or during return to baseline following the stimulus. RESULTS: By self-report, patients and controls found the putative punishment to be preferable to the neutral condition. In the reward condition, patient samples reported greater arousal than did controls, but no between-group differences were found on the magnitude of startle response during the reward, punishment, or neutral conditions. CONCLUSIONS: The failure to find differences in affect-modulated startle between control children and those with narrow or broad PBD phenotypes speaks to the methodological challenges associated with studying reward mechanisms in PBD. Alternative paradigms that focus on different aspects of reward mechanisms are discussed.
For survivors of childhood sexual abuse (CSA), verbal disclosure is often complex and painful. The authors examined the voluntary disclosure-nondisclosure of CSA in relation to nonverbal expressions of emotion in the face. Consistent with hypotheses derived from recent theorizing about the moral nature of emotion, CSA survivors who did not voluntarily disclose CSA showed greater facial expressions of shame, whereas CSA survivors who voluntarily disclosed CSA expressed greater disgust. Expressions of disgust also signaled sexual abuse accompanied by violence. Consistent with recent theorizing about smiling behavior, CSA nondisclosers made more polite smiles, whereas nonabused participants expressed greater genuine positive emotion. Discussion addressed the implications of these findings for the study of disclosure of traumatic events, facial expression, and the links between morality and emotion.