Complexity Analysis of Spontaneous Brain Activity in Attention-Deficit/Hyperactivity Disorder: Diagnostic Implications

Background: Attention-deficit/hyperactivity disorder (ADHD) is defined as the most common neurobehavioral disorder of childhood, but an objective diagnostic test is not available yet to date. Neurophychological, neuroimaging, and neurophysiological research offer ample evidence of brain and behavioral dysfunctions in ADHD, but these findings have not been useful as a diagnostic test. Methods: Whole-head magnetoencephalographic recordings were obtained from 14 diagnosed ADHD patients and 14 healthy children during resting conditions. Lempel-Ziv complexity (LZC) values were obtained for each channel and child and averaged in five sensor groups: anterior, central, left lateral, right lateral, and posterior. Results: Lempel-Ziv complexity scores were significantly higher in control subjects, with the maximum value in anterior region. Combining age and anterior complexity values allowed the correct classification of ADHD patients and control subjects with a 93% sensitivity and 79% specificity. Control subjects showed an age-related monotonic increase of LZC scores in all sensor groups, while children with ADHD exhibited a nonsignificant tendency toward decreased LZC scores. The age-related divergence resulted in a 100% specificity in children older than 9 years. Conclusions: Results support the role of a frontal hypoactivity in the diagnosis of ADHD. Moreover, the age-related divergence of complexity scores between ADHD patients and control subjects might reflect distinctive developmental trajectories. This interpretation of our results is in agreement with recent investigations reporting a delay of cortical maturation in the prefrontal corte

MEG analysis of neural dynamics in attention-deficit/hyperactivity disorder with fuzzy entropy

Producción CientíficaThe aim of this study was to analyze the neural dynamics in attention-deficit/hyperactivity disorder (ADHD). For this purpose, magnetoencephalographic (MEG) background activity was analyzed using fuzzy entropy (FuzzyEn), an entropy measure that quantifies signal irregularity, in 13 ADHD patients and 14 control children. Additionally, relative power (RP) was computed in conventional frequency bands (delta, theta, alpha, beta and gamma). FuzzyEn results showed that MEG activity was more regular in ADHD patients than in controls. Moreover, we found an increase of power in delta band and a decrease in the remaining frequency bands. Statistically significant differences (p-values <0.05; nonparametric permutation test for multiple comparisons) were detected for FuzzyEn in the posterior and left temporal regions, and for RP in the posterior, anterior and left temporal regions. Our results support the hypothesis that ADHD involves widespread functional brain abnormalities, affecting more areas than fronto-striatal circuits, such as the left temporal and posterior regions.Ministerio de Economía y Competitividad (project TEC2011-22987)Junta de Castilla y León (project BIO/VA38/14 and project VA059U13

Multimodal alterations of directed connectivity profiles in patients with attention-deficit/hyperactivity disorders

Functional and effective connectivity measures for tracking brain region interactions that have been investigated using both electroencephalography (EEG) and magnetoencephalography (MEG) bringing up new insights into clinical research. However, the differences between these connectivity methods, especially at the source level, have not yet been systematically studied. The dynamic characterization of coherent sources and temporal partial directed coherence, as measures of functional and effective connectivity, were applied to multimodal resting EEG and MEG data obtained from 11 young patients (mean age 13.2 ± 1.5 years) with attention-deficit/hyperactivity disorder (ADHD) and age-matched healthy subjects. Additionally, machine-learning algorithms were applied to the extracted connectivity features to identify biomarkers differentiating the two groups. An altered thalamo-cortical connectivity profile was attested in patients with ADHD who showed solely information outflow from cortical regions in comparison to healthy controls who exhibited bidirectional interregional connectivity in alpha, beta, and gamma frequency bands. We achieved an accuracy of 98% by combining features from all five studied frequency bands. Our findings suggest that both types of connectivity as extracted from EEG or MEG are sensitive methods to investigate neuronal network features in neuropsychiatric disorders. The connectivity features investigated here can be further tested as biomarkers of ADHD

The correlation between white-matter microstructure and the complexity of spontaneous brain activity: A difussion tensor imaging-MEG study

The advent of new signal processing methods, such as non-linear analysis techniques, represents a new perspective which adds further value to brain signals' analysis. Particularly, Lempel–Ziv's Complexity (LZC) has proven to be useful in exploring the complexity of the brain electromagnetic activity. However, an important problem is the lack of knowledge about the physiological determinants of these measures. Although acorrelation between complexity and connectivity has been proposed, this hypothesis was never tested in vivo. Thus, the correlation between the microstructure of the anatomic connectivity and the functional complexity of the brain needs to be inspected. In this study we analyzed the correlation between LZC and fractional anisotropy (FA), a scalar quantity derived from diffusion tensors that is particularly useful as an estimate of the functional integrity of myelinated axonal fibers, in a group of sixteen healthy adults (all female, mean age 65.56 ± 6.06 years, intervals 58–82). Our results showed a positive correlation between FA and LZC scores in regions including clusters in the splenium of the corpus callosum, cingulum, parahipocampal regions and the sagittal stratum. This study supports the notion of a positive correlation between the functional complexity of the brain and the microstructure of its anatomical connectivity. Our investigation proved that a combination of neuroanatomical and neurophysiological techniques may shed some light on the underlying physiological determinants of brain's oscillation

Lempel-Ziv complexity in schizophrenia: A MEG study

Objective The neurodevelopmental–neurodegenerative debate is a basic issue in the field of the neuropathological basis of schizophrenia (SCH). Neurophysiological techniques have been scarcely involved in such debate, but nonlinear analysis methods may contribute to it. Methods Fifteen patients (age range 23–42 years) matching DSM IV-TR criteria for SCH, and 15 sex- and age-matched control subjects (age range 23–42 years) underwent a resting-state magnetoencephalographic evaluation and Lempel–Ziv complexity (LZC) scores were calculated. Results Regression analyses indicated that LZC values were strongly dependent on age. Complexity scores increased as a function of age in controls, while SCH patients exhibited a progressive reduction of LZC values. A logistic model including LZC scores, age and the interaction of both variables allowed the classification of patients and controls with high sensitivity and specificity. Conclusions Results demonstrated that SCH patients failed to follow the “normal” process of complexity increase as a function of age. In addition, SCH patients exhibited a significant reduction of complexity scores as a function of age, thus paralleling the pattern observed in neurodegenerative diseases. Significance Our results support the notion of a progressive defect in SCH, which does not contradict the existence of a basic neurodevelopmental alteration. Highlights ► Schizophrenic patients show higher complexity values as compared to controls. ► Schizophrenic patients showed a tendency to reduced complexity values as a function of age while controls showed the opposite tendency. ► The tendency observed in schizophrenic patients parallels the tendency observed in Alzheimer disease patients

Resting state fMRI entropy probes complexity of brain activity in adults with ADHD

In patients with attention deficit hyperactivity disorder (ADHD), quantitative neuroimaging techniques have revealed abnormalities in various brain regions, including the frontal cortex, striatum, cerebellum, and occipital cortex. Nonlinear signal processing techniques such as sample entropy have been used to probe the regularity of brain magnetoencephalography signals in patients with ADHD. In the present study, we extend this technique to analyse the complex output patterns of the 4 dimensional resting state functional magnetic resonance imaging signals in adult patients with ADHD. After adjusting for the effect of age, we found whole brain entropy differences (P=0.002) between groups and negative correlation (r=-0.45) between symptom scores and mean whole brain entropy values, indicating lower complexity in patients. In the regional analysis, patients showed reduced entropy in frontal and occipital regions bilaterally and a significant negative correlation between the symptom scores and the entropy maps at a family-wise error corrected cluster level of P<0.05 (P=0.001, initial threshold). Our findings support the hypothesis of abnormal frontal-striatal-cerebellar circuits in ADHD and the suggestion that sample entropy is a useful tool in revealing abnormalities in the brain dynamics of patients with psychiatric disorders

Analysis of cross-correlations in electroencephalogram signals as an approach to proactive diagnosis of schizophrenia

We apply flicker-noise spectroscopy (FNS), a time series analysis method operating on structure functions and power spectrum estimates, to study the clinical electroencephalogram (EEG) signals recorded in children/adolescents (11 to 14 years of age) with diagnosed schizophrenia-spectrum symptoms at the National Center for Psychiatric Health (NCPH) of the Russian Academy of Medical Sciences. The EEG signals for these subjects were compared with the signals for a control sample of chronically depressed children/adolescents. The purpose of the study is to look for diagnostic signs of subjects' susceptibility to schizophrenia in the FNS parameters for specific electrodes and cross-correlations between the signals simultaneously measured at different points on the scalp. Our analysis of EEG signals from scalp-mounted electrodes at locations F3 and F4, which are symmetrically positioned in the left and right frontal areas of cerebral cortex, respectively, demonstrates an essential role of frequency-phase synchronization, a phenomenon representing specific correlations between the characteristic frequencies and phases of excitations in the brain. We introduce quantitative measures of frequency-phase synchronization and systematize the values of FNS parameters for the EEG data. The comparison of our results with the medical diagnoses for 84 subjects performed at NCPH makes it possible to group the EEG signals into 4 categories corresponding to different risk levels of subjects' susceptibility to schizophrenia. We suggest that the introduced quantitative characteristics and classification of cross-correlations may be used for the diagnosis of schizophrenia at the early stages of its development.Comment: 36 pages, 6 figures, 2 tables; to be published in "Physica A