State of the art and new directions of Quantitative Electroencephalography use in Differential Diagnosis of ADHD

Advances in technology in recent years have made the use of quantitative electroencephalogram more accessible to clinicians. The incorporation of normative databases in QEEG studies and the possibility of detecting different electroencephalographic patterns in patients with a given pathology, despite showing an apparent symptomatology homogeneity, make it an interesting source of information. The relationship of these patterns with a possible response to treatment or with prognostic estimates would justify its inclusion as a routine test in the process of the differential diagnosis of ADHD. In this paper, we present the possible benefits of the use of QEEG in the differential diagnosis of ADHD, the different electroencephalographic patterns associated with ADHD most common in the literature, and a case showcasing the use of the technique in a patient with ADHDEstado de la cuestión y uso de la electroencefalografía cuantitativa en el diagnóstico diferencial del TDAH. El avance de la tecnología en los últimos años ha hecho que el uso del electroencefalograma cuantitativo sea más accesible a los clínicos. La incorporación de bases de datos normativas en los estudios de QEEG y la posibilidad de detectar diferentes patrones electroencefalográficos en pacientes con una patología determinada, a pesar de mostrar una aparente homogeneidad sintomatológica, hacen que sea una fuente de información interesante. La relación de estos patrones con una posible respuesta a tratamientos o con estimaciones pronósticas justificarían su inclusión como prueba rutinaria en el proceso de diagnóstico diferencial del TDAH. En este trabajo se presentan los posibles beneficios del uso del QEEG en el diagnóstico diferencial del TDAH, los diferentes patrones electroencefalográficos asociados al TDAH más comunes en la literatura y un caso ilustrativo del uso de la técnica en un paciente con TDA

Spatiotemporal dynamics of single-letter reading: a combined ERP-FMRI study

This work investigates the neural correlates of single-letter reading by combining event-related potentials (ERPs) and functional magnetic resonance imaging (fMRI), thus exploiting their complementary spatiotemporal resolutions. Three externally-paced reading tasks were administered with an event-related design: passive observation of letters and symbols and active reading aloud of letters. ERP and fMRI data were separately recorded from 8 healthy adults during the same experimental conditions. Due to the presence of artifacts in the EEG signals, two subjects were discarded from further analysis. Independent Component Analysis was applied to ERPs, after dimensionality reduction by Principal Component Analysis: some independent components were clearly related to specific reading functions and the associated current density distributions in the brain were estimated with Low Resolution Electromagnetic Tomography Analysis method (LORETA). The impulse hemodynamic response function was modeled as a linear combination of linear B-spline functions and fMRI statistical analysis was performed by multiple linear regression. fMRI and LORETA maps were superimposed in order to identify the overlapping activations and the activated regions specifically revealed by each modality. The results showed the existence of neuronal networks functionally specific for letter processing and for explicit verbal-motor articulation, including the temporo-parietal and frontal regions. Overlap between fMRI and LORETA results was observed in the inferior temporal-middle occipital gyrus, suggesting that this area has a crucial and multifunctional role for linguistic and reading processes, likely because its spatial location and strong interconnection with the main visual and auditory sensory systems may have favored its specialization in grapheme-phoneme matching

SPARC expression in CML is associated to imatinib treatment and to inhibition of leukemia cell proliferation

BACKGROUND: SPARC is a matricellular glycoprotein with growth-inhibitory and antiangiogenic activity in some cell types. The study of this protein in hematopoietic malignancies led to conflicting reports about its role as a tumor suppressor or promoter, depending on its different functions in the tumor microenvironment. In this study we investigated the variations in SPARC production by peripheral blood cells from chronic myeloid leukemia (CML) patients at diagnosis and after treatment and we identified the subpopulation of cells that are the prevalent source of SPARC. METHODS: We evaluated SPARC expression using real-time PCR and western blotting. SPARC serum levels were detected by ELISA assay. Finally we analyzed the interaction between exogenous SPARC and imatinib (IM), in vitro, using ATP-lite and cell cycle analysis. RESULTS: Our study shows that the CML cells of patients at diagnosis have a low mRNA and protein expression of SPARC. Low serum levels of this protein are also recorded in CML patients at diagnosis. However, after IM treatment we observed an increase of SPARC mRNA, protein, and serum level in the peripheral blood of these patients that had already started at 3 months and was maintained for at least the 18 months of observation. This SPARC increase was predominantly due to monocyte production. In addition, exogenous SPARC protein reduced the growth of K562 cell line and synergized in vitro with IM by inhibiting cell cycle progression from G1 to S phase. CONCLUSION: Our results suggest that low endogenous SPARC expression is a constant feature of BCR/ABL positive cells and that IM treatment induces SPARC overproduction by normal cells. This exogenous SPARC may inhibit CML cell proliferation and may synergize with IM activity against CML

A Psychophysiological Investigation of the Von Restorff Paradigm in Children

Ten 5th-grade children were asked to memorize series of words. In some of the series, a word was isolated by presenting it in larger font. Event-related brain potentials, elicited by each word were recorded. The subjects showed an enhanced recall of the isolated words in comparison to non-isolated words matched for serial position (the von Restorff effect). The isolated words also elicited P300\u27s of larger amplitude than the non-isolated words. Furthermore, isolated words which were subsequently recalled elicited larger P300\u27s than did isolated words that were not recalled. Finally, the subjects showed an above-chance performance in a following \u27size-recall\u27 test. The results are discussed in terms of a model of the von Restorff effect that emphasizes the special encoding of isolated items. Children show a large von Restorff effect because because they do not make extensive use of elaborative rehearsal strategies that may override the effects of the special encoding processes

Early dysfunction of perceptual processes in developmental dyslexia

Objective: Single-letter reading is an early predictor of later reading success and identifies adult dyslexics [1]. This work investigates the differences between healthy and dyslexic children in brain activity during single-letter reading. Methods: Event-related potentials (ERPs) were recorded from 45 healthy and 45 dyslexic children (age range 8–10 years) during self-paced letter recognition (SPLR), i.e. active reading aloud of letters presented at a self-determined pace. Standardized Low Resolution Electromagnetic Tomography (sLORETA) [2] was applied to individual ERPs and unpaired voxel-by-voxel t-test analysis (P < 0.05) was performed to compare the sLORETA maps between groups of subjects corresponding with the latency of the main grand average peaks. Results: At middle latencies, dyslexics were characterized by a greater activation in the right middle-inferior frontal, insular and superior temporal regions and by impaired engagement of the left middle parietal lobe as compared to the healthy controls. At middle-long latencies, a significantly reduced activation in the left occipital gyrus was observed in dyslexic children compared to controls. Conclusions: Distributed source imaging applied to ERPs describes the spatiotemporal dynamics of cerebral reading functions and allows inference regarding at which stage of the reading process the activation of the involved brain regions is disrupted in impaired readers. The existence of specific compensatory mechanisms may explain why dyslexic children who are characterized by impaired activation of left parietal and occipital regions show a significantly greater involvement of right temporal–parietal regions and premature engagement of right middle–inferior frontal regions as compared to controls

Clinical and Electrophysiological Differences between Subjects with Dysphonetic Dyslexia and Non-Specific Reading Delay

Reading is essentially a two-channel function, requiring the integration of intact visual and auditory processes both peripheral and central. It is essential for normal reading that these component processes go forward automatically. Based on this model, Boder described three main subtypes of dyslexia: dysphonetic dyslexia (DD), dyseidetic, mixed and besides a fourth group defined non-specific reading delay (NSRD). The subtypes are identified by an algorithm that considers the reading quotient and the % of errors in the spelling test. Chiarenza and Bindelli have developed the Direct Test of Reading and Spelling (DTRS), a computerized, modified and validated version to the Italian language of the Boder test. The sample consisted of 169 subjects with DD and 36 children with NSRD. The diagnosis of dyslexia was made according to the DSM-V criteria. The DTRS was used to identify the dyslexia subtypes and the NSRD group. 2&ndash;5 min of artefact-free EEG (electroencephalogram), recorded at rest with eyes closed, according to 10&ndash;20 system were analyzed. Stability based Biomarkers identification methodology was applied to the DTRS and the quantitative EEG (QEEG). The reading quotients and the errors of the reading and spelling test were significantly different in the two groups. The DD group had significantly higher activity in delta and theta bands compared to NSRD group in the frontal, central and parietal areas bilaterally. The classification equation for the QEEG, both at the scalp and the sources levels, obtained an area under the robust Receiver Operating Curve (ROC) of 0.73. However, we obtained a discrimination equation for the DTRS items which did not participate in the Boder classification algorithm, with a specificity and sensitivity of 0.94 to discriminate DD from NSRD. These results demonstrate for the first time the existence of different neuropsychological and neurophysiological patterns between children with DD and children with NSRD. They may also provide clinicians and therapists warning signals deriving from the anamnesis and the results of the DTRS that should lead to an earlier diagnosis of reading delay, which is usually very late diagnosed and therefore, untreated until the secondary school level

Modulation of specific brain activity by the perceptual analysis of very subtle geometrical relationships of the Mangina-Test stimuli: a functional magnetic resonance imaging (fMRI) investigation in young healthy adults

The Mangina-Test provides a neuropsychometric assessment of varying degrees of “Analytical-Specific Visual Perception”, i.e., the ability to identify simple stimuli inserted into more complex ones according to their exact geometrical properties in a limited span of time. Perceptual analysis of stimuli dealing with the exact discrimination of size and dimension is related more to mathematical abilities (MATH), while perceptual analysis of direction and spatial orientation is related more to abilities in reading and reading comprehension (READ). Some stimuli are {MIXED} since they deal with both of the above features combined. We previously determined the distributed neuronal network of analytical-specific visual perceptual processes as measured by the Mangina-Test. Here, we aim at further assessing as to how brain activity is differentially modulated by the discrimination of very subtle category-specific perceptual relationships. Brain activity was measured by functional magnetic resonance imaging in 12 young healthy subjects while they performed a computer-adapted version of the Mangina-Test. Behavioral results of the present study indicate that performance was not different among stimulus categories. However, brain functional data show that analytical-specific perceptual processes for MATH, {READ} and {MIXED} stimuli rely on partially distinct brain circuits. Bilateral posterior parietal, premotor and prefrontal regions along with the anterior cingulate appeared to be more activated by {MATH} stimuli, while {READ} stimuli predominantly activated bilateral medial occipito-temporal, amygdala/parahippocampal and sensorimotor cortices, and the right inferior frontal cortex. Moreover, the posterior parahippocampal cortex showed a higher activity specifically for {MIXED} stimuli. Altogether, these findings demonstrate that in the Mangina-Test, the exact discrimination of very subtle perceptual relationships between geometrical stimuli distinctly modulates cerebral activity, so that category-specific brain responses can be related to identifiable cognitive abilities