Abstract

Accurate classification or prediction of the brain state across individual subject, i.e., healthy, or with brain disorders, is generally a more difficult task than merely finding group differences. The former must be approached with highly informative and sensitive biomarkers as well as effective pattern classification/feature selection approaches. In this paper, we propose a systematic methodology to discriminate attention deficit hyperactivity disorder (ADHD) patients from healthy controls on the individual level. Multiple neuroimaging markers that are proved to be sensitive features are identified, which include multiscale characteristics extracted from blood oxygenation level dependent (BOLD) signals, such as regional homogeneity (ReHo) and amplitude of low-frequency fluctuations. Functional connectivity derived from Pearson, partial, and spatial correlation is also utilized to reflect the abnormal patterns of functional integration, or, dysconnectivity syndromes in the brain. These neuroimaging markers are calculated on either voxel or regional level. Advanced feature selection approach is then designed, including a brain-wise association study (BWAS). Using identified features and proper feature integration, a support vector machine (SVM) classifier can achieve a cross-validated classification accuracy of 76.15% across individuals from a large dataset consisting of 141 healthy controls and 98 ADHD patients, with the sensitivity being 63.27% and the specificity being 85.11%. Our results show that the most discriminative features for classification are primarily associated with the frontal and cerebellar regions. The proposed methodology is expected to improve clinical diagnosis and evaluation of treatment for ADHD patient, and to have wider applications in diagnosis of general neuropsychiatric disorders.

Highlights

  • Attention deficit hyperactivity disorder (ADHD) is characterized by clinical symptoms of inattention, impulsivity, and hyperactivity

  • The main reason is that the number of healthy controls (141) is larger than that of ADHD patients (98), which renders the hyper plane in support vector machine (SVM) to be biased that favors the correct classification of healthy controls

  • Using neuroimaging markers derived at different scales, such as fractional amplitude of low frequency fluctuations (fALFF), regional homogeneity (ReHo), and various kinds of functional connectivity measures, we have identified the most discriminative features for accurate classification on the individual level

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Summary

Introduction

Attention deficit hyperactivity disorder (ADHD) is characterized by clinical symptoms of inattention, impulsivity, and hyperactivity. It is one of the most common brain and behavioral disorders among children, which affects 5–8% school age children. A number of neuroimaging studies have demonstrated the abnormalities in both structure and function of the brain for ADHD patients (Seidman et al, 2005; Bassett et al, 2006). Functional connectivity alterations of ADHD patients include fronto-parietal (Dickstein et al, 2006), fronto-striatal (Castellanos et al, 2006), and frontotemporal-parietal network (Smith et al, 2006), and anterior cingulate (Tian et al, 2006)

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