Decoding Continuous Variables from Neuroimaging Data: Basic and Clinical Applications

The application of statistical machine learning techniques to neuroimaging data has allowed researchers to decode the cognitive and disease states of participants. The majority of studies using these techniques have focused on pattern classification to decode the type of object a participant is viewing, the type of cognitive task a participant is completing, or the disease state of a participant's brain. However, an emerging body of literature is extending these classification studies to the decoding of values of continuous variables (such as age, cognitive characteristics, or neuropsychological state) using high-dimensional regression methods. This review details the methods used in such analyses and describes recent results. We provide specific examples of studies which have used this approach to answer novel questions about age and cognitive and disease states. We conclude that while there is still much to learn about these methods, they provide useful information about the relationship between neural activity and age, cognitive state, and disease state, which could not have been obtained using traditional univariate analytical methods

Decoding Developmental Differences and Individual Variability in Response Inhibition Through Predictive Analyses Across Individuals

Response inhibition is thought to improve throughout childhood and into adulthood. Despite the relationship between age and the ability to stop ongoing behavior, questions remain regarding whether these age-related changes reflect improvements in response inhibition or in other factors that contribute to response performance variability. Functional neuroimaging data shows age-related changes in neural activity during response inhibition. While traditional methods of exploring neuroimaging data are limited to determining correlational relationships, newer methods can determine predictability and can begin to answer these questions. Therefore, the goal of the current study was to determine which aspects of neural function predict individual differences in age, inhibitory function, response speed, and response time variability. We administered a stop-signal task requiring rapid inhibition of ongoing motor responses to healthy participants aged 9–30. We conducted a standard analysis using GLM and a predictive analysis using high-dimensional regression methods. During successful response inhibition we found regions typically involved in motor control, such as the ACC and striatum, that were correlated with either age, response inhibition (as indexed by stop-signal reaction time; SSRT), response speed, or response time variability. However, when examining which variables neural data could predict, we found that age and SSRT, but not speed or variability of response execution, were predicted by neural activity during successful response inhibition. This predictive relationship provides novel evidence that developmental differences and individual differences in response inhibition are related specifically to inhibitory processes. More generally, this study demonstrates a new approach to identifying the neurocognitive bases of individual differences

Post-traumatic stress disorder in children and adolescents one year after a super-cyclone in Orissa, India: exploring cross-cultural validity and vulnerability factors

BACKGROUND: It has been asserted that psychological responses to disasters in children and adolescents vary widely across cultures, but this has rarely been investigated. The objectives of the study were to clinically evaluate the construct of traumatic stress symptoms and disorder in children and adolescents after a super-cyclone in Orissa, India; to find out the prevalence at one year; compare the effect in high and low exposure areas and study the factors associated with it. METHODS: Clinical examination of children and adolescents (n = 447) was done, supplemented by a symptoms checklist based on International Classification of Mental and Behavioural Disorders, Diagnostic Criteria for Research and a semi-structured questionnaire for disaster related experiences. RESULTS: A majority of children had post-traumatic symptoms. Post-traumatic stress disorder (PTSD) was present in 30.6% (95% confidence interval: 26.4 to 34.9), and an additional 13.6% had sub-syndromal PTSD. Parents or teachers reported mental health concerns in 7.2% subjects, who were a minor proportion (12.8%) of subjects with any syndromal diagnosis (n = 196). Significantly more (43.7%) children in high exposure areas had PTSD than that (11.2%) in low exposure areas (p < 0.001). Depression was significantly associated with PTSD. Binary logistic regression analysis indicated that high exposure, lower educational level and middle socioeconomic status significantly predicted the outcome of PTSD. Extreme fear and perceived threat to life during the disaster, death in family, damage to home, or staying in shelters were not significantly associated with PTSD. CONCLUSION: Following natural disaster PTSD is a valid clinical construct in children and adolescents in Indian set up; and though highly prevalent it may be missed without clinical screening. Its manifestation and associated factors resembled those in other cultures

Reduced antioxidant defense in early onset first-episode psychosis: a case-control study

Background:Our objective is to determine the activity of the antioxidant defense system at admission in patients with early onset first psychotic episodes compared with a control group. Methods: Total antioxidant status (TAS) and lipid peroxidation (LOOH) were determined in plasma. Enzyme activities and total glutathione levels were determined in erythrocytes in 102 children and adolescents with a first psychotic episode and 98 healthy controls. Results: A decrease in antioxidant defense was found in patients, measured as decreased TAS and glutathione levels. Lipid damage (LOOH) and glutathione peroxidase activity was higher in patients than controls. Our study shows a decrease in the antioxidant defense system in early onset first episode psychotic patients. Conclusions: Glutathione deficit seems to be implicated in psychosis, and may be an important indirect biomarker of oxidative stress in early-onset schizophrenia. Oxidative damage is present in these patients, and may contribute to its pathophysiology

The UCLA Study of Children with Moderate-to-Severe Traumatic Brain Injury: Event-Related Potential Measure of Interhemispheric Transfer Time

Traumatic brain injury (TBI) frequently results in diffuse axonal injury and other white matter damage. The corpus callosum (CC) is particularly vulnerable to injury following TBI. Damage to this white matter tract has been associated with impaired neurocognitive functioning in children with TBI. Event-related potentials can identify stimulus-locked neural activity with high temporal resolution. They were used in this study to measure interhemispheric transfer time (IHTT) as an indicator of CC integrity in 44 children with moderate/severe TBI at 3-5 months post-injury, compared with 39 healthy control children. Neurocognitive performance also was examined in these groups. Nearly half of the children with TBI had IHTTs that were outside the range of the healthy control group children. This subgroup of TBI children with slow IHTT also had significantly poorer neurocognitive functioning than healthy controls-even after correction for premorbid intellectual functioning. We discuss alternative models for the relationship between IHTT and neurocognitive functioning following TBI. Slow IHTT may be a biomarker that identifies children at risk for poor cognitive functioning following moderate/severe TBI

The benefit of directly comparing autism and schizophrenia for revealing mechanisms of social cognitive impairment

Autism and schizophrenia share a history of diagnostic conflation that was not definitively resolved until the publication of the DSM-III in 1980. Though now recognized as heterogeneous disorders with distinct developmental trajectories and dissociative features, much of the early nosological confusion stemmed from apparent overlap in certain areas of social dysfunction. In more recent years, separate but substantial literatures have accumulated for autism and schizophrenia demonstrating that abnormalities in social cognition directly contribute to the characteristic social deficits of both disorders. The current paper argues that direct comparison of social cognitive impairment can highlight shared and divergent mechanisms underlying pathways to social dysfunction, a process that can provide significant clinical benefit by informing the development of tailored treatment efforts. Thus, while the history of diagnostic conflation between autism and schizophrenia may have originated in similarities in social dysfunction, the goal of direct comparisons is not to conflate them once again but rather to reveal distinctions that illuminate disorder-specific mechanisms and pathways that contribute to social cognitive impairment