Spatio-Temporal Fluctuations of Neural Dynamics in Mild Cognitive Impairment and Alzheimer's Disease.

BACKGROUND: An accurate characterization of neural dynamics in mild cognitive impairment (MCI) is of paramount importance to gain further insights into the underlying neural mechanisms in Alzheimer's disease (AD). Nevertheless, there has been relatively little research on brain dynamics in prodromal AD. As a consequence, its neural substrates remain unclear. METHODS: In the present research, electroencephalographic (EEG) recordings from patients with dementia due to AD, subjects with MCI due to AD and healthy controls (HC) were analyzed using relative power (RP) in conventional EEG frequency bands and a novel parameter useful to explore the spatio-temporal fluctuations of neural dynamics: the spectral flux (SF). RESULTS: Our results suggest that dementia due to AD is associated with a significant slowing of EEG activity and several significant alterations in spectral fluctuations at low (i.e. theta) and high (i.e. beta and gamma) frequency bands compared to HC (p < 0.05). Furthermore, subjects with MCI due to AD exhibited a specific frequency-dependent pattern of spatio-temporal abnormalities, which can help identify neural mechanisms involved in cognitive impairment preceding AD. Classification analyses using linear discriminant analysis with a leave-one-out cross-validation procedure showed that the combination of RP and within-electrode SF at the beta band was useful to obtain a 77.3 % of accuracy to discriminate between HC and AD patients. In the case of comparison between HC and MCI subjects, the classification accuracy reached a value of 79.2 %, combining within-electrode SF at beta and gamma bands. SF has proven to be a useful measure to obtain an original description of brain dynamics at different stages of AD. CONCLUSION: Consequently, SF may contribute to gain a more comprehensive understanding into neural substrates underlying MCI, as well as to develop potential early AD biomarkers.

Analysis of spontaneous EEG activity in Alzheimer's disease using cross-sample entropy and graph theory.

The aim of this pilot study was to analyze spontaneous electroencephalography (EEG) activity in Alzheimer's disease (AD) by means of Cross-Sample Entropy (Cross-SampEn) and two local measures derived from graph theory: clustering coefficient (CC) and characteristic path length (PL). Five minutes of EEG activity were recorded from 37 patients with dementia due to AD and 29 elderly controls. Our results showed that Cross-SampEn values were lower in the AD group than in the control one for all the interactions among EEG channels. This finding indicates that EEG activity in AD is characterized by a lower statistical dissimilarity among channels. Significant differences were found mainly for fronto-central interactions (p <; 0.01, permutation test). Additionally, the application of graph theory measures revealed diverse neural network changes, i.e. lower CC and higher PL values in AD group, leading to a less efficient brain organization. This study suggests the usefulness of our approach to provide further insights into the underlying brain dynamics associated with AD.

Pressure pain sensitivity map of multifocal nummular headache: a case report.

BACKGROUND: Nummular headache (NH) is most commonly a localized unifocal headache; however, some patients infrequently exhibit multifocal symptomatic painful head areas retaining all features of NH. We present the pressure pain sensitivity map of an adolescent with multifocal NH. CASE PRESENTATION: We describe a case of a 14 year-old-girl with a 3-year history of continuous pain in four rounded areas, all of them with the same size and shape. Pressure pain thresholds (PPT) were assessed on 21 points over the scalp and over the symptomatic areas. A pressure pain sensitivity map of the head was constructed. The neurological exam was unremarkable, with neither sensory symptoms nor trophic changes within the painful areas. As previously shown, symptomatic points exhibited lower PPTs compared to the surrounding areas. The map reflected 4 restricted areas of mechanical hyperalgesia confined just to the painful areas. Treatment with gabapentin achieved complete remission. CONCLUSION: This is the first pain sensitivity map of a patient with multifocal NH. Our results support peripheral mechanisms are maintained in multifocal NH.

Characterization of the spontaneous electroencephalographic activity in Alzheimer's disease using disequilibria and graph theory.

The aim of this research was to study the changes that Alzheimer's disease (AD) elicits in the organization of brain networks. For this task, the electroencephalographic (EEG) activity from 32 AD patients and 25 healthy controls was analyzed. In a first step, a disequilibrium measure, the Euclidean distance (ED), was used to estimate the similarity between the spectral content of each pair of electrodes. In a second step, the similarity matrices were used to generate the corresponding graphs, from which two parameters were computed to characterize the network structure: the mean clustering coefficient and the mean path length. Results revealed significant changes (p<0.05) in ED values, as well as in the mean clustering coefficient and the mean path length, though they depend on the specific frequency band. Our findings suggest that AD is accompanied by a significant frequency-dependent alteration of brain network organization.

Pattern of neurofilament expression in the developing cochleovestibular ganglia in vivo, and modulation by neurotrophin 3 in vitro / Patrón de expresión de neurofilamentos en los ganglios cocleo-vestibulares en desarrollo in vivo y modulación por neurotrofina 3 in vitro

Neurofilaments are the cytoskeletal intermediate filaments in neurons. They consist of three proteins (NFPs) with estimated molecular masses of 68, 160 and 200 kDa. The expression of NFPs by cells is regarded as a hallmark of neuronal differentiation and evolution. In the present study we analyzed the pattern of NFP expression in the neurons of the chicken cochleo-vestibular ganglion (CVG) during development and early post-hatching stages. We also investigated the expression of NFPs "in vitro" and their regulation by the neurotrophic factor NT3 to assess the participation of NFPs in neurotrophin-induced effects. The occurrence of NFP immunoreactivity (IR) "in vivo" and "in vitro" was studied using both Western-blot and immunohistochemistry on whole mount embryos, tissue sections and primary cultures. The 68 kDa NFP subunit was expressed as from stage E4 to E10, while the 160 kDa NFP subunit was found in all developmental stages and on the early post-hatching days (P10). The 200 kDa NFP subunit was observed at later developmental stages from E10 to P30. The immunoreactivity for each NFP subunit detected in inner ear sections was consistent with the data obtained by immunoblotting. NFPs were localized in the neuronal perikarya and their processes, allowing us to establish the temporal pattern of innervation of the sensory neuroepithelia located in the inner ear. Primary cultures with NT3 reproduced the "in vivo" pattern of NFP expression. The present results demonstrate that NFP subunits are developmentally regulated, suggesting that they may be specifically involved in the maturation of CVG neurons. Furthermore, the findings obtained in cultured neurons point to a regulation of NFP expression by neurotrophin-3 (AU)

Los neurofilamentos son los filamentos intermedios citoesqueléticos en las neuronas. Constan de tres proteínas (NFPs) con masas moleculares estimadas de 68, 160 y 200 kDa. La expresión de NFPs por las células se considera típica de la diferenciación y evolución neuronal. En este estudio analizamos el patrón de expresión de NFP en las neuronas del ganglio cocleo-vestibular (GCV) del pollo durante la fase de desarrollo y la fase temprana post-eclosión. También investigamos la expresión de NFPs in vitro y su regulación por el factor neurotrófico NT3 (neurotrofina 3) para evaluar la participación de NFPs en los efectos inducidos por la neurotrofina. La presencia de inmunorreactividad (IR) a las NFPs in vivo e in vitro se estudió utilizando tanto el método de Western-blot como la inmunohistoquímica sobre preparaciones completas de embriones, secciones tisulares y cultivos primarios. La subunidad de NPF de 68kDa fue expresada a partir de la fase E4 hasta la E10, mientras que la subunidad de NPF de 160 kDa se encontró en todas las fases de desarrollo y en los días tempranos post-eclosión (P10). La subunidad de NFP de 200 kDa se observó en fases posteriores de desarrollo a partir de E10 hasta P30. La inmunorreactividad hacia cada subunidad detectada en secciones del oído interno fue consistente con los datos obtenidos con la inmunotransferencia. Los NFPs estaban localizados en los pericarion neuronales y sus procesos, permitiéndonos establecer el patrón temporal de inervación de los neuroepitelios sensoriales ubicados en el oído interno. Los cultivos primarios con NT3 reprodujeron el patrón “in vivo” de expresión de NFP. Los resultados aquí obtenidos demuestran que las subunidades de NFP son reguladas según su grado de desarrollo, lo cual sugiere que es posible que estén implicadas específicamente en la maduración de neuronas del GCV. Además, los hallazgos encontrados en neuronas en cultivo apuntan hacia una regulación de la expresión de NFP por la neurotrofina 3 (AU)