Positive effects of auditory cue in locomotor pattern of people with Parkinson's disease (off and on medication)

Gait disorders are identified in people with Parkinson’s disease. The aim of this study was to investigate the effect of auditory cues and medication on kinematic, kinetic and EMG parameters, during different gait phases of people with PD and healthy elderly. Thirty subjects distributed in two groups (Group 1, PD patients off and on medication; Group 2, healthy elderly) participated in this study and were instructed to walk in two experimental conditions: non-cued and cued. Therefore, kinematic, kinetic and electromyography analyses were utilized to investigate the locomotor pattern. Changes in locomotor pattern (greater muscular activity) with auditory cue were observed for PD patients. Regarding the medication, locomotor parameter improvement was observed after levodopa intake in association with the auditory cue. These results confirm the hypothesis about the external cues therapy that could be used as a complement to drug therapy to achieve improvement in the locomotor pattern of PD patients.

Comportamento locomotor, quadro clínico, incidência de quedas e nível de atividade física em pacientes com doença de Parkinson: um estudo longitudinal de dois anos

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Daily rhythms of native Brazilians in summer and winter

Access to electricity, granting relative independence of human activity on the dark phase of the day, has been pointed out as an important cause for the absence of seasonal changes in the daily rhythms of humans living in urban areas. Featuring a population of adult Guarani natives living without access to electricity, the present naturalistic study was designed to explore possible effects of different natural photoperiods and temperature on human circadian rhythms. We compared time series of wrist temperature (WT) and motor activity in winter and summer, respectively, 01 24 individuals aged 18 to 80. Twenty-four-hour rhythms of WT showed lower amplitudes and higher mean levels in summer, with no significant seasonal differences in acrophase. In contrast, rest-activity (RA) rhythms exhibited a significantly later rest on-and offset in summer, but no seasonal changes in duration, amplitude and mean level. We furthermore identified a phase advance of both the WT acrophase and rest onset with increasing age of the individuals. We concluded that in our study the effect of different seasons was reflected in the amplitude and mean level of the WT rhythm, as well the onset of nighttime rest, which was delayed in summer. (C) 2011 Elsevier Inc. All rights reserved.

Maternal immune activation in late gestation enhances locomotor response to acute but not chronic amphetamine treatment in male mice offspring: Role of the D1 receptor

Exposure to elevated levels of maternal cytokines can lead to functional abnormalities of the dopaminergic system in the adult offspring, including enhanced amphetamine (AMPH)-induced locomotion. Therefore, it seems reasonable to consider that offspring of challenged mothers would behave differently in models of addictive behavior, such as behavioral sensitization. Thus, we sought to evaluate the effects of prenatal exposure to lipopolysaccharide (LPS) on the locomotor response to acute and chronic AMPH treatment in male mice offspring. For this purpose, LPS (Escherichia coli 0127:B8; 120 mu g/kg) was administered intraperitoneally to pregnant Swiss mice on gestational day 17. At adulthood, male offspring were studied under one of the following conditions: (1) locomotor response to acute AMPH treatment (2.5 or 5.0 mg/kg) in an open field test; (2) behavioral sensitization paradigm, which consists of a daily injection of AMPH (1.0 mg/kg) for 10 days and observation of locomotion in the open field on days 1, 5, 10 (development phase), 15 and 17 (expression phase). The LPS stimulated offspring showed enhancement of the locomotor-stimulant effect after an acute AMPH challenge in comparison to baseline and saline pre-treated mice. They also showed development of behavioral sensitization earlier than the saline pre-treated group, although no changes between saline and LPS pre-treated groups were observed on development or expression of locomotor behavioral sensitization to AMPH. Furthermore, there was up-regulation of D1 receptor protein level within striatum in the LPS-stimulated offspring which was strongly correlated with increased grooming behavior. Taken together, our results indicate that motor and dopaminergic alterations caused by maternal immune activation are restricted to the acute AMPH challenge, mostly due to up-regulation of the D1 receptor within the mesolimbic and nigrostriatal pathways, but no locomotor differences were observed for behavioral sensitization to AMPH. (C) 2012 Elsevier B.V. All rights reserved.

Evolution of form and function: morphophysiological relationships and locomotor performance in tropidurine lizards

Locomotor capacity is often considered an excellent measure of whole animal performance because it requires the integrated functioning of many morphological, physiological (and biochemical) traits. However, because studies tend to focus on either structural or functional suits of traits, we know little on whether and how morphological and physiological traits coevolve to produce adequate locomotor capacities. Hence, we investigate the evolutionary relationships between morphological and physiological parameters related to exercise physiology, using tropidurine lizards as a model. We employ a phylogenetic principal component analysis (PCA) to identify variable clusters (factors) related to morphology, energetic metabolism and muscle metabolism, and then analyze the relationships between these clusters and measures of locomotor performance, using two models (star and hierarchical phylogenies). Our data indicate that sprint performance is enhanced by simultaneous evolutionary tendencies affecting relative limb and tail size and physiological traits. Specifically, the high absolute sprint speeds exhibited by tropidurines from the sand dunes are explained by longer limbs, feet and tails and an increased proportion of glycolytic fibers in the leg muscle, contrasting with their lower capacity for overall oxidative metabolism [principal component (PC1)]. However, when sprint speeds are corrected for body size, performance correlates with a cluster (PC3) composed by moderate loads for activity metabolic rate and body size. The simultaneous measurement of morphological and physiological parameters is a powerful tool for exploring patterns of coadaptation and proposing morphophysiological associations that are not directly predictable from theory. This approach may trigger novel directions for investigating the evolution of form and function, particularly in the context of organismal performance.

Citrus aurantium L. essential oil exhibits anxiolytic-like activity mediated by 5-HT1A-receptors and reduces cholesterol after repeated oral treatment

Abstract Background The current treatments for anxiety disorders and depression have multiple adverse effects in addition to a delayed onset of action, which has prompted efforts to find new substances with potential activity in these disorders. Citrus aurantium was chosen based on ethnopharmacological data because traditional medicine refers to the Citrus genus as useful in diminishing the symptoms of anxiety or insomnia, and C. aurantium has more recently been proposed as an adjuvant for antidepressants. In the present work, we investigated the biological activity underlying the anxiolytic and antidepressant effects of C. aurantium essential oil (EO), the putative mechanism of the anxiolytic-like effect, and the neurochemical changes in specific brain structures of mice after acute treatment. We also monitored the mice for possible signs of toxicity after a 14-day treatment. Methods The anxiolytic-like activity of the EO was investigated in a light/dark box, and the antidepressant activity was investigated in a forced swim test. Flumazenil, a competitive antagonist of benzodiazepine binding, and the selective 5-HT1A receptor antagonist WAY100635 were used in the experimental procedures to determine the mechanism of action of the EO. To exclude false positive results due to motor impairment, the mice were submitted to the rotarod test. Results The data suggest that the anxiolytic-like activity observed in the light/dark box procedure after acute (5 mg/kg) or 14-day repeated (1 mg/kg/day) dosing was mediated by the serotonergic system (5-HT1A receptors). Acute treatment with the EO showed no activity in the forced swim test, which is sensitive to antidepressants. A neurochemical evaluation showed no alterations in neurotransmitter levels in the cortex, the striatum, the pons, and the hypothalamus. Furthermore, no locomotor impairment or signs of toxicity or biochemical changes, except a reduction in cholesterol levels, were observed after treatment with the EO. Conclusion This work contributes to a better understanding of the biological activity of C. aurantium EO by characterizing the mechanism of action underlying its anxiolytic-like activity.

Disruption of endogenous tidal rhythms of larval release linked to food supply and heat stress in an intertidal barnacle

The timing of larval release may greatly affect the survivorship and distribution of pelagic stages and reveal important aspects of life history tactics in marine invertebrates. Endogenous rhythms of breeding individuals and populations are valuable indicators of selected strategies because they are free of the neutral effect of stochastic environmental variation. The high-shore intertidal barnacle Chthamalus bisinuatus exhibits endogenous tidal and tidal amplitude rhythms in a way that larval release would more likely occur during fortnightly neap periods at high tide. Such timing would minimize larval loss due to stranding and promote larval retention close to shore. This fully explains temporal patterns in populations facing the open sea and inhabiting eutrophic areas. However, rhythmic activity breaks down to an irregular pattern in a population within the São Sebastião Channel subjected to large variation of food supply around a mesotrophic average. Peaks of chl a concentration precede release events by 6 d, suggesting resource limitation for egg production within the channel. Also, extreme daily temperatures imposing mortality risk correlate to release rate just 1 d ahead, suggesting a terminal reproductive strategy. Oceanographic conditions apparently dictate whether barnacles follow a rhythmic trend of larval release supported by endogenous timing or, alternatively, respond to the stochastic variation of key environmental factors, resulting in an erratic temporal pattern.

Models for the study of neuronal activity during cognitive tasks

Assessment of brain connectivity among different brain areas during cognitive or motor tasks is a crucial problem in neuroscience today. Aim of this research study is to use neural mass models to assess the effect of various connectivity patterns in cortical EEG power spectral density (PSD), and investigate the possibility to derive connectivity circuits from EEG data. To this end, two different models have been built. In the first model an individual region of interest (ROI) has been built as the parallel arrangement of three populations, each one exhibiting a unimodal spectrum, at low, medium or high frequency. Connectivity among ROIs includes three parameters, which specify the strength of connection in the different frequency bands. Subsequent studies demonstrated that a single population can exhibit many different simultaneous rhythms, provided that some of these come from external sources (for instance, from remote regions). For this reason in the second model an individual ROI is simulated only with a single population. Both models have been validated by comparing the simulated power spectral density with that computed in some cortical regions during cognitive and motor tasks. Another research study is focused on multisensory integration of tactile and visual stimuli in the representation of the near space around the body (peripersonal space). This work describes an original neural network to simulate representation of the peripersonal space around the hands, in basal conditions and after training with a tool used to reach the far space. The model is composed of three areas for each hand, two unimodal areas (visual and tactile) connected to a third bimodal area (visual-tactile), which is activated only when a stimulus falls within the peripersonal space. Results show that the peripersonal space, which includes just a small visual space around the hand in normal conditions, becomes elongated in the direction of the tool after training, thanks to a reinforcement of synapses.

Models for the Study of Cortical Activity During Cognitive ans Motor Tasks

This thesis is mainly devoted to show how EEG data and related phenomena can be reproduced and analyzed using mathematical models of neural masses (NMM). The aim is to describe some of these phenomena, to show in which ways the design of the models architecture is influenced by such phenomena, point out the difficulties of tuning the dozens of parameters of the models in order to reproduce the activity recorded with EEG systems during different kinds of experiments, and suggest some strategies to cope with these problems. In particular the chapters are organized as follows: chapter I gives a brief overview of the aims and issues addressed in the thesis; in chapter II the main characteristics of the cortical column, of the EEG signal and of the neural mass models will be presented, in order to show the relationships that hold between these entities; chapter III describes a study in which a NMM from the literature has been used to assess brain connectivity changes in tetraplegic patients; in chapter IV a modified version of the NMM is presented, which has been developed to overcomes some of the previous version’s intrinsic limitations; chapter V describes a study in which the new NMM has been used to reproduce the electrical activity evoked in the cortex by the transcranial magnetic stimulation (TMS); chapter VI presents some preliminary results obtained in the simulation of the neural rhythms associated with memory recall; finally, some general conclusions are drawn in chapter VII.

Melanopsin Retinal Ganglion Cells: relevance to circadian rhythms and sleep in neurodegeneration

In this PhD thesis 3 projects were addressed focusing on the melanopsin retinal ganglion cells (mRGCs) system and its relevance for circadian rhythms and sleep in neurodegeneration. The first project was aimed at completing the characterization of mRGCs system in hereditary optic neuropathies (LHON and DOA). We confirmed that mRGCs are relatively spared also in post-mortem retinal specimens of a DOA case and pupillometric evaluation of LHON patients showed preservation of the pupillary light reflex, with attenuated responses compared to controls. Cell studies failed to indicate a protective role exerted by melanopsin itself. The second project was aimed at characterizing the possible occurrence of optic neuropathy and rest-activity circadian rhythm dysfunction in Alzheimer (AD) and Parkinson disease (PD), as well as, at histological level, the possible involvement of mRGCs in AD. OCT studies demonstrated a subclinical optic neuropathy in both AD and PD patients, with a different pattern involving the superior and nasal quadrants in AD and the temporal quadrant in PD. Actigraphic studies demonstrated a tendency towards an increased intradaily variability (IV) and reduced relative amplitude (RA) of rest-activity circadian rhythm in AD and a significant increased IV a reduced RA in PD. Immunohistochemical analysis of post-mortem retinal specimens and optic nerve cross-sections of neuropathologically confirmed AD cases demonstrated a significant loss of mRGCs and a nearly significant loss of axons in AD compared to controls. The mRGCs were affected in AD independently from age and magnitude of axonal loss. Overall these results suggest a role of the mRGCs system in the pathogenesis of circadian dysfunction in AD. The third project was aimed at evaluating the possible association between a single nucleotide polymorphism of the OPN4 gene and chronotype or SAD, failing to find any significant association with chronotype, but showing a non-significant increment of TT genotype in SAD.

Swimming as a model of task-specific locomotor retraining after spinal cord injury in the rat

BACKGROUND: The authors have shown that rats can be retrained to swim after a moderately severe thoracic spinal cord contusion. They also found that improvements in body position and hindlimb activity occurred rapidly over the first 2 weeks of training, reaching a plateau by week 4. Overground walking was not influenced by swim training, suggesting that swimming may be a task-specific model of locomotor retraining. OBJECTIVE: To provide a quantitative description of hindlimb movements of uninjured adult rats during swimming, and then after injury and retraining. METHODS: The authors used a novel and streamlined kinematic assessment of swimming in which each limb is described in 2 dimensions, as 3 segments and 2 angles. RESULTS: The kinematics of uninjured rats do not change over 4 weeks of daily swimming, suggesting that acclimatization does not involve refinements in hindlimb movement. After spinal cord injury, retraining involved increases in hindlimb excursion and improved limb position, but the velocity of the movements remained slow. CONCLUSION: These data suggest that the activity pattern of swimming is hardwired in the rat spinal cord. After spinal cord injury, repetition is sufficient to bring about significant improvements in the pattern of hindlimb movement but does not improve the forces generated, leaving the animals with persistent deficits. These data support the concept that force (load) and pattern generation (recruitment) are independent and may have to be managed together with respect to postinjury rehabilitation.

Biostimulation methods associated with early weaning and reproductive rhythms in primiparous rabbit does

El objetivo general de esta Tesis Doctoral ha sido tratar de mejorar los parámetros reproductivos de las conejas primíparas lactantes, empleando dos métodos de manejo (destete temprano y extensificación del ritmo reproductivo), que están directamente relacionados con su balance energético. Para ello, se diseñaron 2 experimentos en este tipo de hembras. En el primero, se estudió el efecto del destete a 25 días post-parto (dpp) sobre la actividad ovárica y el metabolismo energético de las conejas una semana más tarde (32 dpp). Un total de 34 primíparas lactantes con 8 gazapos fueron distribuidas en tres grupos: 10 conejas se sacrificaron a los 25 dpp (grupo L25), 13 fueron destetadas a los 25 dpp y sacrificadas a los 32 dpp (grupo NL32), y 11 conejas no se destetaron y fueron sacrificadas a los 32 dpp (grupo L32). No se observaron diferencias significativas entre grupos en el peso corporal, el peso del ovario, ni en las concentraciones séricas de ácidos grasos no esterificados y de proteínas totales. A pesar de que el grupo NL32 presentó un bajo consumo de alimento (122 ± 23,5 g / día, p <0,001), su contenido corporal estimado de lípidos (16,9 ± 1,09%, P <0,008), proteínas (19,7 ± 0,07%, P <0,0001), y energía (1147 ± 42,7 MJ / kg, p <0,006) fueron más elevados y las concentraciones séricas de glucosa (158 ± 24,5 mg/dl, p <0,04) más bajas que en los grupos L25 (11,9 ± 1,3%, 18,5 ± 0,08%, 942 ± 51,3 MJ/kg y 212 ± 27,9 mg/dl) y L32 (13,4 ± 1,03%, 18,5 ± 0,1%, 993 ± 40,4 MJ/kg y 259 ± 29,5 mg/dl), respectivamente. En el grupo L25 se observó un menor número medio de folículos ≥ 1 mm en la superficie ovárica en comparación con los grupos NL32 y L32 (12,7 ± 1,5 vs. 18,0 ± 1,45 y 17,6 ± 1,67, p <0,05). La población folicular ovárica en las secciones histológicas y la inmunolocalización de los receptores de prolactina fueron similares en todos los grupos. En el grupo L25, tanto la maduración nuclear de oocitos, medida en términos de tasas alcanzadas de Metafase II (67,0 vs. 79,7 y 78,3%, P <0.05) y la maduración citoplasmática, medida por el porcentaje de gránulos corticales (GC) total o parcialmente migrados en los oocitos, fueron significativamente menores que en los grupos NL32 y L32 (16,0 vs 38,3 y 60,0%, P <0.05). En conclusión, a pesar de que el destete precoz a 25 dpp pareció mejorar las reservas de energía de las conejas primíparas, este hecho no se reflejó claramente a nivel ovárico a los 32 dpp y fue similar independientemente del destete, por lo que éste último podría llevarse a cabo más tarde. En el segundo experimento, se compararon dos ritmos reproductivos. Se utilizaron un total de 48 conejas primíparas lactantes con 8 gazapos que se asignaron al azar en dos grupos experimentales: a) lactantes sacrificadas a comienzos del post-parto (11 dpp) de acuerdo a un ritmo semi-intensivo (n = 24), y b) lactantes sacrificadas al final del período post-parto (25 dpp) de acuerdo con un ritmo más extensivo (n = 24). En ellas, se estudió el peso vivo, la composición corporal estimada, parámetros metabólicos y endocrinos (estradiol y progesterona) y características ováricas como la población folicular y la tasa de atresia, así como la maduración nuclear y citoplásmica de los oocitos. En este estudio, el peso vivo, el contenido de energía corporal, los depósitos grasos y los ácidos grasos no esterificados disminuyeron a lo largo del post-parto con respecto al momento del parto (P <0,05). Las concentraciones séricas de proteínas y glucosa aumentaron en el mismo periodo post-parto (P <0,05). Se observaron similares niveles de estradiol y progesterona en ambos ritmos, así como una población folicular, tasas de maduración nuclear (tasa de oocitos en metafase II) y citoplasmática (porcentaje de oocitos con gránulos corticales migrados), similares en ambos momentos del post-parto. Sin embargo, el número de folículos preovulatorios en la superficie ovárica fue menor (P <0,05) y la tasa de atresia tendió a ser mayor con un porcentaje también menor de folículos sanos (P <0,1) en los ovarios de las hembras sometidas al ritmo extensivo. En conclusión, al final del post-parto (25 días), las conejas primíparas sin destetar muestran un deterioro de sus reservas corporales, de sus parámetros metabólicos séricos y de la calidad de sus oocitos; incluso se ha observado una ligera influencia negativa en el desarrollo de sus folículos ováricos. Por esta razón, se considera que en las conejas primíparas lactantes el manejo reproductivo extensivo (25 dpp) no presenta ninguna ventaja en comparación con el semi-intensivo (11 dpp). A la vista de los resultados de estos dos experimentos, podemos decir que ni el destete temprano, ni la extensificación del ritmo reproductivo han conseguido una mejora en los parámetros reproductivos de una hembra primípara. Por ello, son necesarios más estudios sobre el estado metabólico de la coneja primípara lactante para conseguir métodos o estrategias que lo mejoren y tengan consecuencias directas sobre la actividad reproductiva y sobre su éxito productivo. The general aim of this Thesis was to study two management methods (early weaning and extensive reproductive rhythm) linked to the energy balance of the primiparous rabbit does to improve their reproductive performance. In this sense, 2 experiments were conducted using this kind of females. In the first experiment, the effect of weaning at 25 days post-partum (dpp) on ovarian activity and energetic metabolism one week later (32 dpp) was studied. A total of 34 primiparous lactating rabbit does were used and distributed among three groups: 10 does euthanized at 25 dpp (group L25), 13 does weaned at 25 dpp and euthanized at 32 dpp (group NL32), and 11 non weaned does euthanized at 32 dpp (group L32). No significant differences were observed in live body weight, ovary weight, serum non esterified fatty acids (NEFA) and total protein concentration among groups. Although NL32 does had a low feed intake (122±23.5 g/Day; P < 0.001), their estimated lipids (16.9±1.09%, P < 0.008), protein (19.7±0.07%, P < 0.0001), and energy (1147±42.7 MJ/kg, P < 0.006) body contents were higher and their serum glucose concentrations (158±24.5 mg/dl, P < 0.04) were lower compared to L25 does (11.9±1.3%, 18.5±0.08%, 942±51.3 MJ/kg and 212±27.9 mg/dl) and L32 does (13.4±1.03%, 18.5±0.1%, 993±40.4 MJ/kg and 259±29.5 mg/dl, respectively). A lower number of follicles ≥1mm was observed compared to NL32 and L32 groups (12.7±1.5 vs. 18.0±1.45 and 17.6 ±1.67; P < 0.05) in the ovarian surface of L25 does. Follicular population in the histological ovarian sections and immunolocalization of prolactin receptor were similar in all groups. In group L25, both nuclear maturation of oocytes in terms of Metaphase II rate (67.0 vs. 79.7 and 78.3%; P < 0.05) and cytoplasmic maturation measured by percentage of cortical granules (CG), totally or partially migrated in oocytes were significantly lower than in groups NL32 and L32 (16.0 vs. 38.3 and 60.0%; P < 0.05). Consequently, a higher rate of oocytes with non-migrated CGs was found in group L25 than in groups NL32 and L32 (76.0 vs. 46.8 and 33.3%; P < 0.05). In conclusion, even though early weaning at 25 dpp seemed to improve body energy stored in primiparous does, this fact was not well reflected on the ovarian status at 32 dpp, which was similar regardless of weaning time. In the second experiment, two reproductive rhythms were compared. A total of 48 primiparous Californian x New Zealand White rabbit does suckling 8 kits were randomly allocated in two experimental groups: a) lactating does euthanized at early post-partum period (11 dpp) according to a semi-intensive rhythm (n = 24), and b) lactating does euthanized on later post-partum period (25 dpp) according to a more extensive rhythm (n = 24). Live weight, estimated body composition, serum metabolic and endocrine parameters (oestradiol and progesterone concentrations) and ovarian features like follicle population and atresia rate, and oocyte maturation were studied. Live weight, body energy content, lipid depots and serum non esterified fatty acids (NEFA) concentrations diminished from parturition time to post-partum period (P < 0.05). In addition, serum protein and glucose concentrations increased along postpartum time (P < 0.05). Similar oestradiol and progesterone levels were shown in rhythms as well as similar follicle population and nuclear and cytoplasmic maturation rates measured as metaphase II and cortical granule migration, respectively in both postpartum times. However, number of preovulatory follicles on the ovarian surface was lower (P < 0.05) and atresia rate tended to be higher with also lower percentage of healthy follicles (P < 0.1) in ovaries of females of extensive group. In conclusion, primiparous non-weaned rabbits does at late post-partum time (25 days), Did no show any improvement regarding body reserves, serum metabolic parameters and oocyte quality; even a slight negative influence has been observed in the development of their ovarian follicles. Thus this reproductive management does not present any advantage compared to earlier post-partum (11 days) reproductive rhythm. In summary, according to the obtained results from these two experiments, we can say that the application of early weaning and the extensive rhythms did not achieve an improvement in the reproductive performance of primiparous does. Thus, it is necessary to conduct more studies about the metabolic status of the primiparous lactating doe to achieve strategies in order to improve it and consequently, to improve the reproductive activity and their productive success.

Analysis of spontaneous MEG activity in mild cognitive impairment and Alzheimer's disease using spectral entropies and statistical complexity measures

Alzheimer's disease (AD) is the most common cause of dementia. Over the last few years, a considerable effort has been devoted to exploring new biomarkers. Nevertheless, a better understanding of brain dynamics is still required to optimize therapeutic strategies. In this regard, the characterization of mild cognitive impairment (MCI) is crucial, due to the high conversion rate from MCI to AD. However, only a few studies have focused on the analysis of magnetoencephalographic (MEG) rhythms to characterize AD and MCI. In this study, we assess the ability of several parameters derived from information theory to describe spontaneous MEG activity from 36 AD patients, 18 MCI subjects and 26 controls. Three entropies (Shannon, Tsallis and Rényi entropies), one disequilibrium measure (based on Euclidean distance ED) and three statistical complexities (based on Lopez Ruiz–Mancini–Calbet complexity LMC) were used to estimate the irregularity and statistical complexity of MEG activity. Statistically significant differences between AD patients and controls were obtained with all parameters (p < 0.01). In addition, statistically significant differences between MCI subjects and controls were achieved by ED and LMC (p < 0.05). In order to assess the diagnostic ability of the parameters, a linear discriminant analysis with a leave-one-out cross-validation procedure was applied. The accuracies reached 83.9% and 65.9% to discriminate AD and MCI subjects from controls, respectively. Our findings suggest that MCI subjects exhibit an intermediate pattern of abnormalities between normal aging and AD. Furthermore, the proposed parameters provide a new description of brain dynamics in AD and MCI.

Brain-wide slowing of spontaneous alpha rhythms in mild cognitive impairment

The neurophysiological changes associated with Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI) include an increase in low frequency activity, as measured with electroencephalography or magnetoencephalography (MEG). A relevant property of spectral measures is the alpha peak, which corresponds to the dominant alpha rhythm. Here we studied the spatial distribution of MEG resting state alpha peak frequency and amplitude values in a sample of 27 MCI patients and 24 age-matched healthy controls. Power spectra were reconstructed in source space with linearly constrained minimum variance beamformer. Then, 88 Regions of Interest (ROIs) were defined and an alpha peak per ROI and subject was identified. Statistical analyses were performed at every ROI, accounting for age, sex and educational level. Peak frequency was significantly decreased (p < 0.05) in MCIs in many posterior ROIs. The average peak frequency over all ROIs was 9.68 ± 0.71 Hz for controls and 9.05 ± 0.90 Hz for MCIs and the average normalized amplitude was (2.57 ± 0.59)·10−2 for controls and (2.70 ± 0.49)·10−2 for MCIs. Age and gender were also found to play a role in the alpha peak, since its frequency was higher in females than in males in posterior ROIs and correlated negatively with age in frontal ROIs. Furthermore, we examined the dependence of peak parameters with hippocampal volume, which is a commonly used marker of early structural AD-related damage. Peak frequency was positively correlated with hippocampal volume in many posterior ROIs. Overall, these findings indicate a pathological alpha slowing in MCI.

The protein kinase CK2 is involved in regulation of circadian rhythms in Arabidopsis

A wide range of processes in plants, including expression of certain genes, is regulated by endogenous circadian rhythms. The circadian clock-associated 1 (CCA1) and the late elongated hypocotyl (LHY) proteins have been shown to be closely associated with clock function in Arabidopsis thaliana. The protein kinase CK2 can interact with and phosphorylate CCA1, but its role in the regulation of the circadian clock remains unknown. Here we show that plants overexpressing CKB3, a regulatory subunit of CK2, display increased CK2 activity and shorter periods of rhythmic expression of CCA1 and LHY. CK2 is also able to interact with and phosphorylate LHY in vitro. Additionally, overexpression of CKB3 shortened the periods of four known circadian clock-controlled genes with different phase angles, demonstrating that many clock outputs are affected. This overexpression also reduced phytochrome induction of an Lhcb gene. Finally, we found that the photoperiodic flowering response, which is influenced by circadian rhythms, was diminished in the transgenic lines, and that the plants flowered earlier on both long-day and short-day photoperiods. These data demonstrate that CK2 is involved in regulation of the circadian clock in Arabidopsis.