Human Hippocampal Ripples Signal Encoding of Episodic Memories.

Direct human brain recordings have confirmed the presence of high-frequency oscillatory events, termed ripples, during awake behavior. While many prior studies have focused on medial temporal lobe (MTL) ripples during memory retrieval, here we investigate ripples during memory encoding. Specifically, we ask whether ripples during encoding predict whether and how memories are subsequently recalled.

MTL neurons phase-lock to human hippocampal theta.

Memory formation depends on neural activity across a network of regions, including the hippocampus and broader medial temporal lobe (MTL). Interactions between these regions have been studied indirectly using functional MRI, but the bases for interregional communication at a cellular level remain poorly understood. Here, we evaluate the hypothesis that oscillatory currents in the hippocampus synchronize the firing of neurons both within and outside the hippocampus.

A neural code for time and space in the human brain.

Time and space are primary dimensions of human experience. Separate lines of investigation have identified neural correlates of time and space, yet little is known about how these representations converge during self-guided experience. Here, 10 subjects with intracranially implanted microelectrodes play a timed, virtual navigation game featuring object search and retrieval tasks separated by fixed delays.

Spatial Relationships between Molecular Pathology and Neurodegeneration in the Alzheimer's Disease Continuum.

A deeper understanding of the spatial relationships of β-amyloid (Aβ), tau, and neurodegeneration in Alzheimer's disease (AD) could provide insight into pathogenesis and clinical trial design. We included 81 amyloid-positive patients (age 64.4 ± 9.

Structural, geometric and genetic factors predict interregional brain connectivity patterns probed by electrocorticography.

Electrocorticography (ECoG) data can be used to estimate brain-wide connectivity patterns. Yet, the invasiveness of ECoG, incomplete cortical coverage, and variability in electrode placement across individuals make the network analysis of ECoG data challenging. Here, we show that the architecture of whole-brain ECoG networks and the factors that shape it can be studied by analysing whole-brain, interregional and band-limited ECoG networks from a large cohort-in this case, of individuals with medication-resistant epilepsy.

Tau covariance patterns in Alzheimer's disease patients match intrinsic connectivity networks in the healthy brain.

According to the network model of neurodegeneration, the spread of pathogenic proteins occurs selectively along connected brain regions. We tested in vivo whether the distribution of filamentous tau (measured with [F]flortaucipir-PET), fibrillar amyloid-β ([C]PIB-PET) and glucose hypometabolism ([F]FDG-PET) follows the intrinsic functional organization of the healthy brain. We included 63 patients with Alzheimer's disease (AD; 30 male, 63 ± 8 years) who underwent [F]flortaucipir, [C]PIB and [F]FDG PET, and 1000 young adults (427 male, 21 ± 3 years) who underwent task-free fMRI.

Associations Between Tau, β-Amyloid, and Cognition in Parkinson Disease.

Importance: Multiple disease processes are associated with cognitive impairment in Parkinson disease (PD), including Lewy bodies, cerebrovascular disease, and Alzheimer disease. It remains unknown whether tau pathology relates to cognition in patients with PD without dementia.

Objective: To compare tau aggregation in patients with PD who are cognitively normal (PD-CN), patients with PD with mild cognitive impairment (PD-MCI), and healthy control participants, and evaluate the relationships between β-amyloid (Aβ), tau, and cognition in patients with PD who did not have dementia.

Local and distant relationships between amyloid, tau and neurodegeneration in Alzheimer's Disease.

The relationships between β-amyloid (Aβ), tau and neurodegeneration within Alzheimer's Disease pathogenesis are not fully understood. To explore these associations , we evaluated 30 Aβ PET-positive patients (mean ± sd age 62.4 ± 8.

Tau pathology and neurodegeneration contribute to cognitive impairment in Alzheimer's disease.

Neuropathological and in vivo studies have revealed a tight relationship between tau pathology and cognitive impairment across the Alzheimer's disease spectrum. However, tau pathology is also intimately associated with neurodegeneration and amyloid pathology. The aim of the present study was therefore to assess whether grey matter atrophy and amyloid pathology contribute to the relationship between tau pathology, as measured with 18F-AV-1451-PET imaging, and cognitive deficits in Alzheimer's disease.

F-flortaucipir tau positron emission tomography distinguishes established progressive supranuclear palsy from controls and Parkinson disease: A multicenter study.

Objective: F-flortaucipir (formerly F-AV1451 or F-T807) binds to neurofibrillary tangles in Alzheimer disease, but tissue studies assessing binding to tau aggregates in progressive supranuclear palsy (PSP) have yielded mixed results. We compared in vivo F-flortaucipir uptake in patients meeting clinical research criteria for PSP (n = 33) to normal controls (n = 46) and patients meeting criteria for Parkinson disease (PD; n = 26).

Methods: Participants underwent magnetic resonance imaging and positron emission tomography for amyloid-β ( C-PiB or F-florbetapir) and tau ( F-flortaucipir).

Frontotemporal dementia with the V337M mutation: Tau-PET and pathology correlations.

Objective: To assess the efficacy of [F]AV1451 PET in visualizing tau pathology in vivo in a patient with frontotemporal dementia (FTD) associated with the V337M microtubule-associated protein tau ( mutation.

Methods: mutations are associated with the deposition of hyperphosphorylated tau protein in neurons and glia. The PET tracer [F]AV1451 binds with high affinity to paired helical filaments tau that comprises neurofibrillary tangles in Alzheimer disease (AD), while postmortem studies suggest lower or absent binding to the tau filaments of the majority of non-AD tauopathies.

Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer's disease.

SEE SARAZIN ET AL DOI101093/BRAIN/AWW041 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: The advent of the positron emission tomography tracer (18)F-AV1451 provides the unique opportunity to visualize the regional distribution of tau pathology in the living human brain. In this study, we tested the hypothesis that tau pathology is closely linked to symptomatology and patterns of glucose hypometabolism in Alzheimer's disease, in contrast to the more diffuse distribution of amyloid-β pathology. We included 20 patients meeting criteria for probable Alzheimer's disease dementia or mild cognitive impairment due to Alzheimer's disease, presenting with a variety of clinical phenotypes, and 15 amyloid-β-negative cognitively normal individuals, who underwent (18)F-AV1451 (tau), (11)C-PiB (amyloid-β) and (18)F-FDG (glucose metabolism) positron emission tomography, apolipoprotein E (APOE) genotyping and neuropsychological testing.

PET Imaging of Tau Deposition in the Aging Human Brain.

Tau pathology is a hallmark of Alzheimer's disease (AD) but also occurs in normal cognitive aging. Using the tau PET agent (18)F-AV-1451, we examined retention patterns in cognitively normal older people in relation to young controls and AD patients. Age and β-amyloid (measured using PiB PET) were differentially associated with tau tracer retention in healthy aging.

Tau, amyloid, and hypometabolism in a patient with posterior cortical atrophy.

Determining the relative contribution of amyloid plaques and neurofibrillary tangles to brain dysfunction in Alzheimer disease is critical for therapeutic approaches, but until recently could only be assessed at autopsy. We report a patient with posterior cortical atrophy (visual variant of Alzheimer disease) who was studied using the novel tau tracer [(18) F]AV-1451 in conjunction with [(11) C]Pittsburgh compound B (PIB; amyloid) and [(18) F]fluorodeoxyglucose (FDG) positron emission tomography. Whereas [(11) C]PIB bound throughout association neocortex, [(18) F]AV-1451 was selectively retained in posterior brain regions that were affected clinically and showed markedly reduced [(18) F]FDG uptake.