Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268

In this review, we consider the potential functional role of beta-band oscillations, which at present is not yet well understood. We discuss evidence from recent studies on top-down mechanisms involved in cognitive processing, on the motor system and on the pathophysiology of movement disorders that suggest a unifying hypothesis: beta-band activity seems related to the maintenance of the current sensorimotor or cognitive state. We hypothesize that beta oscillations and/or coupling in the beta-band are expressed more strongly if the maintenance of the status quo is intended or predicted, than if a change is expected. Moreover, we suggest that pathological enhancement of beta-band activity is likely to result in an abnormal persistence of the status quo and a deterioration of flexible behavioural and cognitive control.

Beta-band oscillations--signalling the status quo?

The blood-brain barrier (BBB) is a continuous endothelial membrane within brain microvessels that has sealed cell-to-cell contacts and is sheathed by mural vascular cells and perivascular astrocyte end-feet The BBB protects neurons from factors present in the systemic circulation and maintains the highly regulated CNS internal milieu, which is required for proper synaptic and neuronal functioning BBB disruption allows influx into the brain of neurotoxic blood-derived debris, cells and microbial pathogens and is associated with inflammatory and immune responses, which can initiate multiple pathways of neurodegeneration This Review discusses neuroimaging studies in the living human brain and post-mortem tissue as well as biomarker studies demonstrating BBB breakdown in Alzheimer disease, Parkinson disease, Huntington disease, amyotrophic lateral sclerosis, multiple sclerosis, HIV-1-associated dementia and chronic traumatic encephalopathy The pathogenic mechanisms by which BBB breakdown leads to neuronal injury, synaptic dysfunction, loss of neuronal connectivity and neurodegeneration are described The importance of a healthy BBB for therapeutic drug delivery and the adverse effects of disease-initiated, pathological BBB breakdown in relation to brain delivery of neuropharmaceuticals are briefly discussed Finally, future directions, gaps in the field and opportunities to control the course of neurological diseases by targeting the BBB are presented

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Blood–brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders

During the past decade, a conceptual shift occurred in the field of Alzheimer's disease (AD) considering the disease as a continuum. Thanks to evolving biomarker research and substantial discoveries, it is now possible to identify the disease even at the preclinical stage before the occurrence of the first clinical symptoms. This preclinical stage of AD has become a major research focus as the field postulates that early intervention may offer the best chance of therapeutic success. To date, very little evidence is established on this "silent" stage of the disease. A clarification is needed about the definitions and lexicon, the limits, the natural history, the markers of progression, and the ethical consequence of detecting the disease at this asymptomatic stage. This article is aimed at addressing all the different issues by providing for each of them an updated review of the literature and evidence, with practical recommendations.

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Preclinical Alzheimer's disease: Definition, natural history, and diagnostic criteria.

The blood-brain barrier (BBB) prevents neurotoxic plasma components, blood cells, and pathogens from entering the brain. At the same time, the BBB regulates transport of molecules into and out of t...

/pdf/blood-brain-barrier-from-physiology-to-disease-and-back-1xwjgb63cg.pdf

Blood-Brain Barrier: From Physiology to Disease and Back

Processing the head direction cell signal: A review and commentary

Previous research has shown that head direction (HD) cells in both the anterior dorsal thalamus (ADN) and the postsubiculum (PoS) in rats discharge in relation to familiar, visual landmarks in the environment. This study assessed whether PoS and ADN HD cells would be similarly responsive to nonvisual or unfamiliar environmental cues. After visual input was eliminated by blindfolding the rats, HD cells maintained direction-specific discharge, but their preferred firing directions became less stable. In addition, rotations of the behavioral apparatus indicated that some nonvisual cues (presumably tactile, olfactory, or both) exerted above chance stimulus control over a cell's preferred firing direction. However, a prominent auditory cue was not effective in exerting stimulus control over a cell's preferred direction. HD cell activity also was assessed after rotation of a novel visual cue exposed to the rat for 1, 3, or 8 min. An 8-min exposure was enough time for a novel visual cue to gain control over a cell's preferred direction, whereas an exposure of 1 or 3 min led to control in only about half the sessions. These latter results indicate that HD cells rely on a rapid learning mechanism to develop associations with landmark cues.

Cue Control and Head Direction Cells

A subset of neurons in the rat limbic system encodes head direction (HD) by selectively discharging when the rat points its head in a preferred direction in the horizontal plane. The preferred firi...

/pdf/passive-transport-disrupts-directional-path-integration-by-448niw0eld.pdf

Passive transport disrupts directional path integration by rat head direction cells.

Objective: To define changes in cortical function in persons inheriting familial Alzheimer disease (FAD) mutations before the onset of cognitive decline. Methods: Twenty-six subjects with a family history of FAD were divided into 2 subgroups according to genotype (FAD mutation carriers, n = 15; FAD noncarriers, n = 11). Subjects were given standardized tests of cognitive function and the Clinical Dementia Rating scale (CDR). Sensory (P50, N100, P200) and cognitive (N200, P300) event-related potentials were recorded during an auditory discrimination task. Amplitudes and latencies of cortical potentials were compared among FAD mutation carriers and noncarriers. Results: FAD mutation carriers and noncarriers did not significantly differ in age or on measures of cognitive function, but FAD carriers had a greater incidence of 0.5 CDR scores (1/10 noncarriers, 5/15 carriers). Relative to noncarriers, FAD mutation carriers had significantly longer latencies of the N100, P200, N200, and P300 components, and smaller slow wave amplitudes. Subanalyses of subjects having CDR scores of 0.0 also showed latency increases in FAD mutation carriers. Conclusions: Auditory sensory and cognitive cortical potentials in persons with familial Alzheimer disease (FAD) mutations are abnormal approximately 10 years before dementia will be manifest. Longer event-related potential latencies suggest slowing of cortical information processing in FAD mutation carriers.

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Cortical event-related potentials in preclinical familial Alzheimer disease

Purpose

To measure the cerebrovascular volume and blood-brain barrier (BBB) permeability indices in hippocampus and cerebellum of patients with mild cognitive impairment (MCI) using dynamic contrast-enhanced MRI (DCE-MRI), and compare to that of normal controls.



Materials and Methods

A total of 11 MCI subjects and 11 healthy elderly controls participated in this prospective study. DCE-MRI was performed to measure the contrast enhancement kinetics. The early enhancement percentage (at 50 seconds after injection) was defined as the vascular volume index, and the ratio between the four to five–minute enhancement relative to the 50-second enhancement was defined as the BBB permeability index.



Results

The enhancement kinetics measured from hippocampus of MCI individuals demonstrated a lower magnitude and slower decay than healthy controls, suggesting that they had a smaller vascular volume (significant in the right side; P <0.001) and a higher BBB permeability (not reaching significance level). The vascular volume index was significantly correlated with naming ability (P 0.05).



Conclusion

These results suggest that changes in cerebrovasculature may occur in hippocampus of MCI. DCE-MRI may provide a noninvasive means to measure the subtle BBB leakage associated with the cerebrovascular pathology commonly found in Alzheimer's disease. J. Magn. Reson. Imaging 2006. © 2006 Wiley-Liss, Inc.

Vascular volume and blood-brain barrier permeability measured by dynamic contrast enhanced MRI in hippocampus and cerebellum of patients with MCI and normal controls.

Edward J. Golob

Papers

Processing the head direction cell signal: A review and commentary

Cue Control and Head Direction Cells

Passive transport disrupts directional path integration by rat head direction cells.

Cortical event-related potentials in preclinical familial Alzheimer disease

Vascular volume and blood-brain barrier permeability measured by dynamic contrast enhanced MRI in hippocampus and cerebellum of patients with MCI and normal controls.