Abnormal EEG Synchronization Correlates with Demyelination in Alzheimer's Disease

Introduction : The pathological processes caused by Alzheimer's disease (AD) supposedly disrupt communication between and within the distributed cortical networks due to the dysfunction/loss of synapses and myelination breakdown. Indeed, recently (Knyazeva et al. 2008), we have revealed the whole-head topography of EEG synchronization specific to AD. Here we analyze whether and how these abnormalities of synchronization are related to the demyelination of cortico-cortical fibers. Methods : Fifteen newly diagnosed AD patients (CDR 0.5-1) and 15 controls matched for age, participated in the study. Their multichannel (128) EEGs were recorded during 3-5 min at rest. They were submitted to the multivariate phase synchronization (MPS) analysis for mapping regional synchronization. To obtain individual whole-head maps, the MPS was computed for each sensor considering its 2nd nearest topographical neighbors. Separate calculations were performed for the delta, theta, alpha-1/−2, and beta-1/−2 EEG bands. The same subjects were scanned on a 3 Tesla Philips scanner. The protocol included a high-resolution T1-weighted sequence and a Magnetization Transfer Imaging (MTI) acquisition. For each subject, we defined a 3mm thick layer of white matter exactly below the cortical gray matter. The magnetization transfer ratio (MTR) - an estimator of myelination - was calculated for this layer in 39 Brodmann-defined ROIs per hemisphere. To assess the between-group differences, we used a permutation version of Hotelling's T2 test or two-sample T-test (Pcorrected <0.05). For correlation analysis, Spearman Rank Correlation was calculated. Results : In AD patients, we have found an abnormal landscape of synchronization characterized by a decrease in MPS over the fronto-temporal region of the left hemisphere and an increase over the temporo-parieto-occipital regions bilaterally. Also, we have shown a widespread decrease in regional MTR in the AD patients for all the areas excluding motor, premotor, and primary sensory ones. Assuming that AD-related changes in synchronization are associated with demyelination, we hypothesized a correlation between the regional MTR values and MPS values in the hypo- and hyper-synchronized clusters. We found that MPS in the left fronto-temporal hypo-synchronized cluster directly correlates with myelination in BA42-46 of the left hemisphere: the lower the myelination in individual patients, the lower the EEG synchronization. By contrast, in the posterior hyper-synchronized cluster, MPS inversely correlated with myelination, i.e., the lower the myelination, the higher the synchronization. This posterior hyper-synchronization, more characteristic for early-onset AD, probably, results from the initial effect of the disease on cortical inhibition, reducing cortical capacity for decoupling irrelevant connections. Remarkably, it showed different topography of correlations in early- vs. late-onset patients. In the early-onset patients, hyper-synchronization was mainly related to demyelination in posterior BAs, the effect being significant in all the EEG frequency bands. In the late-onset patients, widely distributed correlations were significant for the EEG delta band, suggesting an interaction between the cerebral manifestations of AD and the age of its onset, i.e., topographically selective impairment of cortical inhibition in early-onset AD vs. its wide-spread weakening in old age. Conclusions : Overall, our results document that the degradation of white matter is a significant factor of AD pathogenesis leading to functional dysconnection, the latter being reflected in EEG synchronization abnormalities.

Reliability and validity of physiological data obtained within a cycle-run transition test in age-group triathletes.

This study examined the validity and reliability of a sequential "Run-Bike-Run" test (RBR) in age-group triathletes. Eight Olympic distance (OD) specialists (age 30.0 ± 2.0 years, mass 75.6 ± 1.6 kg, run VO2max 63.8 ± 1.9 ml· kg(-1)· min(-1), cycle VO2peak 56.7 ± 5.1 ml· kg(-1)· min(-1)) performed four trials over 10 days. Trial 1 (TRVO2max) was an incremental treadmill running test. Trials 2 and 3 (RBR1 and RBR2) involved: 1) a 7-min run at 15 km· h(-1) (R1) plus a 1-min transition to 2) cycling to fatigue (2 W· kg(-1) body mass then 30 W each 3 min); 3) 10-min cycling at 3 W· kg(-1) (Bsubmax); another 1-min transition and 4) a second 7-min run at 15 km· h(-1) (R2). Trial 4 (TT) was a 30-min cycle - 20-min run time trial. No significant differences in absolute oxygen uptake (VO2), heart rate (HR), or blood lactate concentration ([BLA]) were evidenced between RBR1 and RBR2. For all measured physiological variables, the limits of agreement were similar, and the mean differences were physiologically unimportant, between trials. Low levels of test-retest error (i.e. ICC <0.8, CV<10%) were observed for most (logged) measurements. However [BLA] post R1 (ICC 0.87, CV 25.1%), [BLA] post Bsubmax (ICC 0.99, CV 16.31) and [BLA] post R2 (ICC 0.51, CV 22.9%) were least reliable. These error ranges may help coaches detect real changes in training status over time. Moreover, RBR test variables can be used to predict discipline specific and overall TT performance. Cycle VO2peak, cycle peak power output, and the change between R1 and R2 (deltaR1R2) in [BLA] were most highly related to overall TT distance (r = 0.89, p < 0. 01; r = 0.94, p < 0.02; r = 0.86, p < 0.05, respectively). The percentage of TR VO2max at 15 km· h(-1), and deltaR1R2 HR, were also related to run TT distance (r = -0.83 and 0.86, both p < 0.05).

High throughput 3D super-resolution microscopy reveals Caulobacter crescentus in vivo Z-ring organization.

We created a high-throughput modality of photoactivated localization microscopy (PALM) that enables automated 3D PALM imaging of hundreds of synchronized bacteria during all stages of the cell cycle. We used high-throughput PALM to investigate the nanoscale organization of the bacterial cell division protein FtsZ in live Caulobacter crescentus. We observed that FtsZ predominantly localizes as a patchy midcell band, and only rarely as a continuous ring, supporting a model of "Z-ring" organization whereby FtsZ protofilaments are randomly distributed within the band and interact only weakly. We found evidence for a previously unidentified period of rapid ring contraction in the final stages of the cell cycle. We also found that DNA damage resulted in production of high-density continuous Z-rings, which may obstruct cytokinesis. Our results provide a detailed quantitative picture of in vivo Z-ring organization.

L'examen neuropsychologique en pratique quotidienne [Neuropsychological test in daily practice]

Neuropsychology is a scientific discipline, born in the XIX century, and bridges the fields of neurology and psychology. Neuropsychologists apply scientific knowledge about the relationship between brain function and mental performances. The major clinical role of a neuropsychological evaluation is to help to establish medical and functional diagnosis in patients (adults or infants) with different neurological pathologies such as stroke, traumatic brain injury, dementia, epilepsy.... Such analysis necessitates accurate observation of behaviour and administration of tests of mental abilities (e.g. language, memory...). Test results can also help to clarify the nature of cognitive difficulties and to support the formulation of plans for neuropsychological therapy and functional adjustment in every day life.