Leonardo C. deAzevedo

Human cord blood transplantation in a neonatal rat model of hypoxic–ischemic brain damage: functional outcome related to neuroprotection in the striatum

Human umbilical cord blood mononuclear cells (HUCB) have been shown to have a therapeutic role in different models of central nervous system (CNS) damage, including stroke. We evaluated the possible therapeutic potential of HUCB in P7 rats submitted to the Rice-Vannucci model of neonatal hypoxic-ischemic (HI) brain damage. Our results demonstrated that intraperitoneal transplantation of HUCB, 3 h after the HI insult, resulted in better performance in two developmental sensorimotor reflexes, in the first week after the injury. We also showed a neuroprotective effect in the striatum, and a decrease in the number of activated microglial cells in the cerebral cortex of treated animals. We suggest that HUCB transplantation might rescue striatal neurons from cell death after a neonatal HI injury resulting in better functional recovery.

Immune allergic response in asperger syndrome

Aspergers syndrome is a subgroup of autism characterized by social deficits without language delay, and high cognitive performance. The biological nature of autism is still unknown but there are controversial evidence associating an immune imbalance and autism. Clinical findings, including atopic family history, serum IgE levels as well as cutaneous tests showed that incidence of atopy was higher in the Asperger group compared to the healthy controls. These findings suggest that atopy is frequent in this subgroup of autism implying that allergic inflammation might be an important feature in Asperger syndrome.

EEG photic driving: right-hemisphere reactivity deficit in childhood autism. A pilot study.

In 14 autistic boys, aged 6-14 years, free of drug treatment, with relatively intact verbal functions and without severe or moderate mental retardation (I.Q. 91.4+/-22.8), intermittent photic stimulation at 11 fixed frequencies of 3-24 Hz revealed latent deficiency of the right hemisphere in the photic driving reactivity, predominantly at the fast alpha and beta frequencies of stimulation. The left-side prevalence was observed: 1) in the total number of driving peaks evaluated for the first four harmonics in the EEG spectra of 14 cortical areas and 2) in the driving amplitude in the spectra of the 2 occipital areas. As compared to 21 normally developing boys matched on age who did not show interhemispheric asymmetry in the driving reactivity, the autistic patients had significantly lower driving characteristics only in the right hemisphere. There were no significant differences between the autistic and control groups in the spontaneous EEG spectra of the occipital areas in the resting state.

Electrophysiological Correlates of Morphological Neuroplasticity in Human Callosal Dysgenesis

In search for the functional counterpart of the alternative Probst and sigmoid bundles, considered as morphological evidence of neuroplasticity in callosal dysgenesis, electroencephalographic (EEG) coherence analysis was combined with high resolution and diffusion tensor magnetic resonance imaging. Data of two patients with callosal agenesis, plus two with typical partial dysgenesis with a remnant genu, and one atypical patient with a substantially reduced genu were compared to those of fifteen neurotypic controls. The interhemispheric EEG coherence between homologous nontemporal brain regions corresponded to absence or partial presence of callosal connections. A generalized coherence reduction was observed in complete acallosal patients, as well as coherence preservation in the anterior areas of the two patients with a remnant genu. jThe sigmoid bundles found in three patients with partial dysgenesis correlated with augmented EEG coherence between anterior regions of one hemisphere and posterior regions of the other. These heterologous (crossed) interhemispheric connections were asymmetric in both imaging and EEG patterns, with predominance of the right-anterior-to-left-posterior connections over the mirror ones. The Probst bundles correlated with higher intrahemispheric long-distance coherence in all patients. The significant correlations observed for the delta, theta and alpha bands indicate that these alternative pathways are functional, although the neuropsychological nature of this function is still unknown.

Estimating DSM accuracy for Attention Deficit Hyperactivity Disorder Based on Neurophysiological, Psychological, and Behavioral Correlates

Objective: To find objective evidence of accuracy of the Diagnostic and Statistical Manual of Mental Disorders (DSM) in the diagnosis of Attention Deficit Hyperactivity Disorder (ADHD), by comparing classifications of subjects based on behavioral (Attentional Network Test - ANT), psychological (Wechsler Intelligence Scale for Children - WISC-III), and neurophysiological (ANT-related potentials) data. Methods: Twenty typically developing (TD) boys and 19 boys diagnosed with ADHD according to DSM-IV-TR, aged 10-13 years, were examined using the ANT with simultaneous recording of the respective event-related potentials (ERPs). They also performed the Block Design, Digit Spam, Vocabulary and Arithmetic subtests of the WISC-III. A total of 815 variables of interest (VOI) obtained from the ANT, WISC-III scores, and ERP parameters were grouped by hierarchical clustering and integrated in 2 to 6 resultant vectors (RVs), from clusters at hierarchical levels 1 to 5. These RVs were used for the reclassification of subjects using the k-means method. Results: Regarding DSM-IV-TR diagnostics, the RVs from behavioral and psychological data and ERPs from the mid-frontal, mid-parietal plus right frontal, right central, and right temporal channels showed accuracy rates from 0.64 to 0.82 using the k-means reclassification. Among reclassifications with higher agreement (0.82), six subjects were reclassified (4 from the TD group, and 2 from the ADHD group). Assuming the reclassification of these six subjects, the estimated agreement between DSM and biological data was 84.61% with kappa index of 0.69. Conclusion: Results suggest biological validity and efficiency of DSM as a tool for ADHD diagnostics.Background. Psychiatric nosology lacks objective biological foundation, as well as typical biomarkers for diagnoses, which raises questions about its validity. The problem is particularly evident concerning Attention Deficit/Hyperactivity Disorder (ADHD). The objective of this study is to estimate whether the “Diagnostic and Statistical Manual of Mental Disorders” (DSM) is biologically valid for ADHD diagnosis using a multivariate analysis for small samples from a large dataset concerning neurophysiological, behavioral, and psychological variables. Methods: Twenty typically developing boys and 19 boys diagnosed with ADHD, aged 10-13 years, were examined using the Attentional Network Test (ANT) with records of event-related potentials (ERPs). From 815 variables, a reduced number of latent variables (LVs) were extracted with a clustering method, for further reclassification of subjects using the k-means method. This approach allowed multivariate analysis to be applied to a significantly larger number of variables than the number of cases (E. Wigneau et al., 2003, 2015) Results: From datasets including ERPs from the mid-frontal, mid-parietal, right frontal, and central channels, only seven subjects were miss-reclassified by the LVs. An estimated specificity of 75.00% and sensitivity of 89.47% for DSM were found in the reclassification. The kappa index between DSM and behavioral/psychological/neurophysiological data was 0.75, which is regarded as a “substantial level of agreement”. Discussion: Results showed that CLV is a useful method for diagnostic classification using a large dataset of small samples, suggesting the biological validity of DSM for ADHD diagnosis, in accordance to alterations in fronto-striatal networks previously related to ADHD.

Functional Asymmetry In The Central Brain Regions In Boys With Attention Deficit Hyperactivity Disorder Detected By Event Related Potentials During Performance Of The Attentional Network Test

Background Various functional asymmetries detected by different neurophysiological and neuroimaging methods have been reported in the literature on the Attention Deficit Hyperactivity Disorder (ADHD), some of them pointing to the right hemisphere activity. In our attempt to discriminate the ADHD patients from normal subjects by hierarchical clustering of behavioural, psychological and event related potential (ERP) variables, the late P3 component of potentials from the right central region (C4) proved to be one of the most informative parameters (in preparation for publication). Here, we have studied the differences in ERPs between the left (C3) and right (C4) central leads and relation of this asymmetry to ADHD diagnosed using DSM. Methods 16 typically developing (TD) boys and 16 boys diagnosed with ADHD according to DSM-IV-TR, aged 10-13 years, were examined by the Attentional Network Test (ANT), with simultaneous recording of the respective ERPs. The intergroup differences in the ERP amplitude parameters in the left (C3) and right (C4) central channels and in the difference in these parameters between the two channels (‘C3 minus C4’) were accessed. These characteristics were compared to the subjects’ DSM scores and ANT performance. Results The target-related potentials’ late characteristics from the C4 showed significant difference between the groups, while no difference was observed for the C3. Only in the ADHD patients, both the left and right late target ERP characteristics correlated with the reaction time, while the DSM scores did not show any correlations in both groups. The difference between ERPs of the C3 and C4 channels inside the interval of 40-290 ms after target onset was positive in the ADHD group and negative in the control group. This asymmetry correlated with DSM scores, mainly to hyperactive and impulsive criteria. Conclusion In ADHD patients, the results suggest ERP pattern of right-side functional predominance in the motor control, which correlates to DSM scores, mainly to hyperactive and impulsive criteria.