EEG-fMRI Signal Coupling Is Modulated in Subjects With Mild Cognitive Impairment and Amyloid Deposition.

Cognitive impairment indicates disturbed brain physiology which can be due to various mechanisms including Alzheimer's pathology. Combined functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) recordings (EEG-fMRI) can assess the interplay between complementary measures of brain activity and EEG changes to be localized to specific brain regions. We used a two-step approach, where we first examined changes related to a syndrome of mild cognitive impairment irrespective of pathology and then studied the specific impact of amyloid pathology.

Increased cerebral blood volume in small arterial vessels is a correlate of amyloid-β-related cognitive decline.

The protracted accumulation of amyloid-β (Aβ) is a major pathologic hallmark of Alzheimer's disease and may trigger secondary pathological processes that include neurovascular damage. This study was aimed at investigating long-term effects of Aβ burden on cerebral blood volume of arterioles and pial arteries (CBVa), possibly present before manifestation of dementia. Aβ burden was assessed by 11C Pittsburgh compound-B positron emission tomography in 22 controls and 18 persons with mild cognitive impairment (MCI), [ages: 75(±6) years].

Low cortical iron and high entorhinal cortex volume promote cognitive functioning in the oldest-old.

The aging brain is characterized by an increased presence of neurodegenerative and vascular pathologies. However, there is substantial variation regarding the relationship between an individual's pathological burden and resulting cognitive impairment. To identify correlates of preserved cognitive functioning at highest age, the relationship between β-amyloid plaque load, presence of small vessel cerebrovascular disease (SVCD), iron-burden, and brain atrophy was investigated.

Brain amyloid burden and cerebrovascular disease are synergistically associated with neurometabolism in cognitively unimpaired older adults.

Alzheimer's disease (AD) is the most common cause of cognitive dysfunction in older adults. The pathological hallmarks of AD such as beta amyloid (Aβ) aggregation and neurometabolic change, as indicated by altered myo-inositol (mI) and N-acetylaspartate (NAA) levels, typically precede the onset of cognitive dysfunction by years. Furthermore, cerebrovascular disease occurs early in AD, but the interplay between vascular and neurometabolic brain change is largely unknown.

Changes of Functional and Directed Resting-State Connectivity Are Associated with Neuronal Oscillations, ApoE Genotype and Amyloid Deposition in Mild Cognitive Impairment.

The assessment of effects associated with cognitive impairment using electroencephalography (EEG) power mapping allows the visualization of frequency-band specific local changes in oscillatory activity. In contrast, measures of coherence and dynamic source synchronization allow for the study of functional and effective connectivity, respectively. Yet, these measures have rarely been assessed in parallel in the context of mild cognitive impairment (MCI) and furthermore it has not been examined if they are related to risk factors of Alzheimer's disease (AD) such as amyloid deposition and apolipoprotein ε4 (ApoE) allele occurrence.

Memory performance-related dynamic brain connectivity indicates pathological burden and genetic risk for Alzheimer's disease.

Background: The incidence of Alzheimer's disease (AD) strongly relates to advanced age and progressive deposition of cerebral amyloid-beta (Aβ), hyperphosphorylated tau, and iron. The purpose of this study was to investigate the relationship between cerebral dynamic functional connectivity and variability of long-term cognitive performance in healthy, elderly subjects, allowing for local pathology and genetic risk.

Methods: Thirty seven participants (mean (SD) age 74 (6.

Subcortical Shape Changes, Hippocampal Atrophy and Cortical Thinning in Future Alzheimer's Disease Patients.

Efficacy of future treatments depends on biomarkers identifying patients with mild cognitive impairment at highest risk for transitioning to Alzheimer's disease. Here, we applied recently developed analysis techniques to investigate cross-sectional differences in subcortical shape and volume alterations in patients with stable mild cognitive impairment (MCI) ( = 23, age range 59-82, 47.8% female), future converters at baseline ( = 10, age range 66-84, 90% female) and at time of conversion (age range 68-87) compared to group-wise age and gender matched healthy control subjects ( = 23, age range 61-81, 47.

Microstructural Integrity of Hippocampal Subregions Is Impaired after Mild Traumatic Brain Injury.

Mild traumatic brain injury (mTBI) affects a large number of individuals and diffusion tensor imaging can be used to investigate microstructural integrity of brain tissue after mTBI. However, results have varied considerably between studies and gray matter (GM) integrity has been largely neglected in these investigations. Given impaired working memory processing after mTBI and its possible association with Alzheimer's disease, we investigated hippocampal integrity and parcellated this structure into five subregions: subiculum, cornu ammonis (CA) 1, CA 2/3, CA 4/dentate gyrus, and stratum radiatum/lacunosum-moleculare.

Low episodic memory performance in cognitively normal elderly subjects is associated with increased posterior cingulate gray matter N-acetylaspartate: a H MRSI study at 7 Tesla.

Low episodic memory performance characterizes elderly subjects at increased risk for Alzheimer's disease (AD) and may reflect neuronal dysfunction within the posterior cingulate cortex and precuneus (PCP) region. To investigate a potential association between cerebral neurometabolism and low episodic memory in the absence of cognitive impairment, tissue-specific magnetic resonance spectroscopic imaging at ultrahigh field strength of 7 Tesla was used to investigate the PCP region in a healthy elderly study population (n = 30, age 70 ± 5.7 years, Mini-Mental State Examination 29.

Hippocampal shape alterations are associated with regional Aβ load in cognitively normal elderly individuals.

Aβ deposition is a driving force of Alzheimer's disease pathology and can be detected early by amyloid positron emission tomography. Identifying presymptomatic structural brain changes associated with Aβ deposition might lead to a better understanding of its consequences and provide early diagnostic information. In this respect we analyzed measures of cortical thickness and subcortical volumes along with hippocampal, thalamic and striatal shape and surface area by applying novel analysis strategies for structural magnetic resonance imaging.

Arterial spin labeling imaging reveals widespread and Aβ-independent reductions in cerebral blood flow in elderly apolipoprotein epsilon-4 carriers.

Changes in cerebral blood flow are an essential feature of Alzheimer's disease and have been linked to apolipoprotein E-genotype and cerebral amyloid-deposition. These factors could be interdependent or influence cerebral blood flow via different mechanisms. We examined apolipoprotein E-genotype, amyloid beta-deposition, and cerebral blood flow in amnestic mild cognitive impairment using pseudo-continuous arterial spin labeling MRI in 27 cognitively normal elderly and 16 amnestic mild cognitive impairment participants.

Volumetric and shape analysis of the thalamus and striatum in amnestic mild cognitive impairment.

Alterations in brain structures, including progressive neurodegeneration, are a hallmark in patients with Alzheimer's disease (AD). However, pathological mechanisms, such as the accumulation of amyloid and the proliferation of tau, are thought to begin years, even decades, before the initial clinical manifestations of AD. In this study, we compare the brain anatomy of amnestic mild cognitive impairment patients (aMCI, n = 16) to healthy subjects (CS, n = 22) using cortical thickness, subcortical volume, and shape analysis, which we believe to be complimentary to volumetric measures.

Regional cerebral blood flow estimated by early PiB uptake is reduced in mild cognitive impairment and associated with age in an amyloid-dependent manner.

Early uptake of [(11)C]-Pittsburgh Compound B (ePiB, 0-6 minutes) estimates cerebral blood flow. We studied ePiB in 13 PiB-negative and 10 PiB-positive subjects with mild cognitive impairment (MCI, n = 23) and 11 PiB-positive and 74 PiB-negative cognitively healthy elderly control subjects (HCS, n = 85) in 6 bilateral volumes of interest: posterior cingulate cortex (PCC), hippocampus (hipp), temporoparietal region, superior parietal gyrus, parahippocampal gyrus (parahipp), and inferior frontal gyrus (IFG) for the associations with cognitive status, age, amyloid deposition, and apolipoprotein E ε4-allele. We observed no difference in ePiB between PiB-positive and -negative subjects and carriers and noncarriers.

Regional Fluid-Attenuated Inversion Recovery (FLAIR) at 7 Tesla correlates with amyloid beta in hippocampus and brainstem of cognitively normal elderly subjects.

Background: Accumulation of amyloid beta (Aβ) may occur during healthy aging and is a risk factor for Alzheimer Disease (AD). While individual Aβ-accumulation can be measured non-invasively using Pittsburgh Compund-B positron emission tomography (PiB-PET), Fluid-attenuated inversion recovery (FLAIR) is a Magnetic Resonance Imaging (MRI) sequence, capable of indicating heterogeneous age-related brain pathologies associated with tissue-edema. In the current study cognitively normal elderly subjects were investigated for regional correlation of PiB- and FLAIR intensity.

Posterior cingulate γ-aminobutyric acid and glutamate/glutamine are reduced in amnestic mild cognitive impairment and are unrelated to amyloid deposition and apolipoprotein E genotype.

The biomarker potential of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) for the in vivo characterization of preclinical stages in Alzheimer's disease has not yet been explored. We measured GABA, glutamate + glutamine (Glx), and N-acetyl-aspartate (NAA) levels by single-voxel MEGA-PRESS magnetic resonance spectroscopy in the posterior cingulate cortex of 21 elderly subjects and 15 patients with amnestic mild cognitive impairment. Participants underwent Pittsburgh Compound B positron emission tomography, apolipoprotein E (APOE) genotyping, and neuropsychological examination.

Superior colliculi involvement in poststroke unilateral spatial neglect: a pilot study.

Purpose: The neural mechanisms underlying unilateral spatial neglect (USN) are unclear. The superior colliculi (SC) may be involved in USN expression, and the spatial summation effect (SSE), where reaction times to bilateral stimuli are faster than to unilateral, may be a behavioral index of SC function. We determined the feasibility of investigating SC contribution to poststroke USN using the SSE in 3 groups.

The neural circuitry of executive functions in healthy subjects and Parkinson's disease.

In our constantly changing environment, we are frequently faced with altered circumstances requiring generation and monitoring of appropriate strategies, when novel plans of action must be formulated and conducted. The abilities that we call upon to respond accurately to novel situations are referred to as 'executive functions', and are frequently engaged to deal with conditions in which routine activation of behavior would not be sufficient for optimal performance. Here, we summarize important findings that may help us understand executive functions and their underlying neuronal correlates.

Blindsight mediated by an S-cone-independent collicular pathway: an fMRI study in hemispherectomized subjects.

The purpose of our study was to investigate the ability to process achromatic and short-wavelength-sensitive cone (S-cone)-isolating (blue-yellow) stimuli in the blind visual field of hemispherectomized subjects and to demonstrate that blindsight is mediated by a collicular pathway that is independent of S-cone inputs. Blindsight has been described as the ability to respond to visual stimuli in the blind visual field without conscious awareness [Weiskrantz, L., Warrington, E.

Right impairment of temporal order judgements in dyslexic children.

This study investigates the spatial bias of visual attention measured by a temporal order judgement (TOJ) task and the influence of a high attentional load condition in a group of dyslexic children compared to a control group with normal reading skills (each group N=10). The TOJ task (T2) was placed after a shape discrimination task (T1). In a low attentional load block participants worked only on T2, whereas in the high attentional load block they were required to process both T1 and T2.

The connectivity of the human pulvinar: a diffusion tensor imaging tractography study.

Previous studies in nonhuman primates and cats have shown that the pulvinar receives input from various cortical and subcortical areas involved in vision. Although the contribution of the pulvinar to human vision remains to be established, anatomical tracer and electrophysiological animal studies on cortico-pulvinar circuits suggest an important role of this structure in visual spatial attention, visual integration, and higher-order visual processing. Because methodological constraints limit investigations of the human pulvinar's function, its role could, up to now, only be inferred from animal studies.

Neural substrates of blindsight after hemispherectomy.

Blindsight is a visual phenomenon whereby hemianopic patients are able to process visual information in their blind visual field without awareness. Previous research demonstrating the existence of blindsight in hemianopic patients has been criticized for the nature of the paradigms used, for the presence of methodological artifacts, and for the possibility that spared islands of visual cortex may have sustained the phenomenon because the patients generally had small circumscribed lesions. To respond to these criticisms, the authors have been investigating for several years now residual visual abilities in the blind field of hemispherectomized patients in whom a whole cerebral hemisphere has been removed or disconnected from the rest of the brain.

Fronto-striatal connections in the human brain: a probabilistic diffusion tractography study.

Anatomical studies in animals have described multiple striatal circuits and suggested that sub-components of the striatum, although functionally related, project to distinct cortical areas. To date, anatomical investigations in humans have been limited by methodological constraints such that most of our knowledge of fronto-striatal networks relies on nonhuman primate studies. To better identify the fronto-striatal pathways in the human brain, we used Diffusion Tensor Imaging (DTI) tractography to reconstruct neural connections between the frontal cortex and the caudate nucleus and putamen in vivo.

Absence of S-cone input in human blindsight following hemispherectomy.

Destruction of the occipital cortex presumably leads to permanent blindness in the contralateral visual field. Residual abilities to respond to visual stimuli in the blind field without consciously experiencing them have, however, been described in cortically blind patients and are termed 'blindsight'. Although the neuronal basis of blindsight remains unknown, possible neuronal correlates have been proposed based on the nature of the residual vision observed.

Unconscious vision: new insights into the neuronal correlate of blindsight using diffusion tractography.

The existence of several types of unconscious vision, or 'blindsight', has convincingly been demonstrated in numerous studies, and their neuronal correlates have been hypothesized according to the nature of the residual vision observed. We used diffusion tensor imaging (DTI) tractography to demonstrate an association between the presence of 'Type I'- blindsight or 'attention blindsight' and reconstructed superior colliculi (SC) fibre tracts in hemispherectomized subjects, in support of the hypothesis that this subcortical structure plays a pivotal role in this type of blindsight. Before the DTI study, 'Type I' blindsight was identified in two of four hemispherectomized subjects by using a spatial summation effect paradigm, an indirect behavioural method, in which subjects were unaware of a stimulus presented in their blind visual field and were required to respond to an identical stimulus presented simultaneously in their intact field.