Functional network disruption in cognitively unimpaired autosomal dominant Alzheimer's disease: a magnetoencephalography study.

Understanding the nature and onset of neurophysiological changes, and the selective vulnerability of central hub regions in the functional network, may aid in managing the growing impact of Alzheimer's disease on society. However, the precise neurophysiological alterations occurring in the pre-clinical stage of human Alzheimer's disease remain controversial. This study aims to provide increased insights on quantitative neurophysiological alterations during a true early stage of Alzheimer's disease.

Erratum: Network-level permutation entropy of resting-state MEG recordings: A novel biomarker for early-stage Alzheimer's disease?

[This corrects the article DOI: 10.1162/netn_a_00224.].

Local signal variability and functional connectivity: Sensitive measures of the excitation-inhibition ratio?

Unlabelled: A novel network version of permutation entropy, the inverted joint permutation entropy (JPE), holds potential as non-invasive biomarker of abnormal excitation-inhibition (E-I) ratio in Alzheimer's disease (AD). In this computational modelling study, we test the hypotheses that this metric, and related measures of signal variability and functional connectivity, are sensitive to altered E-I ratios. The E-I ratio in each neural mass of a whole-brain computational network model was systematically varied.

Risk factors for neurophysiological events related to intraoperative halo-femoral traction in spinal deformity surgery.

Purpose: This study identifies risk factors for neurophysiological events caused by intraoperative halo-femoral traction (IOHFT) in patients with adolescent idiopathic scoliosis (AIS), and neuromuscular scoliosis (NMS).

Methods: Neurophysiological integrity was monitored using motor evoked potentials (MEPs). IONM event was defined as a decreased MEP amplitude of more than 80% of baseline in, at least, one muscle.

Surgical treatment options for spasticity in children and adolescents with hereditary spastic paraplegia.

Purpose: To provide an overview of outcome and complications of selective dorsal rhizotomy (SDR) and intrathecal baclofen pump implantation (ITB) for spasticity treatment in children with hereditary spastic paraplegia (HSP).

Methods: Retrospective study including children with HSP and SDR or ITB. Gross motor function measure (GMFM-66) scores and level of spasticity were assessed.

Neurophysiological alterations in mice and humans carrying mutations in APP and PSEN1 genes.

Background: Studies in animal models of Alzheimer's disease (AD) have provided valuable insights into the molecular and cellular processes underlying neuronal network dysfunction. Whether and how AD-related neurophysiological alterations translate between mice and humans remains however uncertain.

Methods: We characterized neurophysiological alterations in mice and humans carrying AD mutations in the APP and/or PSEN1 genes, focusing on early pre-symptomatic changes.

Tau protein spreads through functionally connected neurons in Alzheimer's disease: a combined MEG/PET study.

Recent studies on Alzheimer's disease (AD) suggest that tau proteins spread through the brain following neuronal connections. Several mechanisms could be involved in this process: spreading between brain regions that interact strongly (functional connectivity); through the pattern of anatomical connections (structural connectivity); or simple diffusion. Using magnetoencephalography (MEG), we investigated which spreading pathways influence tau protein spreading by modelling the tau propagation process using an epidemic spreading model.

Resting-state oscillations reveal disturbed excitation-inhibition ratio in Alzheimer's disease patients.

An early disruption of neuronal excitation-inhibition (E-I) balance in preclinical animal models of Alzheimer's disease (AD) has been frequently reported, but is difficult to measure directly and non-invasively in humans. Here, we examined known and novel neurophysiological measures sensitive to E-I in patients across the AD continuum. Resting-state magnetoencephalography (MEG) data of 86 amyloid-biomarker-confirmed subjects across the AD continuum (17 patients diagnosed with subjective cognitive decline, 18 with mild cognitive impairment (MCI) and 51 with dementia due to probable AD (AD dementia)), 46 healthy elderly and 20 young control subjects were reconstructed to source-space.

A multiscale brain network model links Alzheimer's disease-mediated neuronal hyperactivity to large-scale oscillatory slowing.

Background: Neuronal hyperexcitability and inhibitory interneuron dysfunction are frequently observed in preclinical animal models of Alzheimer's disease (AD). This study investigates whether these microscale abnormalities explain characteristic large-scale magnetoencephalography (MEG) activity in human early-stage AD patients.

Methods: To simulate spontaneous electrophysiological activity, we used a whole-brain computational network model comprised of 78 neural masses coupled according to human structural brain topology.

Network-level permutation entropy of resting-state MEG recordings: A novel biomarker for early-stage Alzheimer's disease?

Increasing evidence suggests that measures of signal variability and complexity could present promising biomarkers for Alzheimer's disease (AD). Earlier studies have however been limited to the characterization of local activity. Here, we investigate whether a network version of permutation entropy could serve as a novel biomarker for early-stage AD.

Oscillatory Activity of the Hippocampus in Prodromal Alzheimer's Disease: A Source-Space Magnetoencephalography Study.

Background: In Alzheimer's disease (AD), oscillatory activity of the human brain slows down. However, oscillatory slowing varies between individuals, particularly in prodromal AD. Cortical oscillatory changes have shown suboptimal accuracy as diagnostic markers.

Sensitive and reproducible MEG resting-state metrics of functional connectivity in Alzheimer's disease.

Background: Analysis of functional brain networks in Alzheimer's disease (AD) has been hampered by a lack of reproducible, yet valid metrics of functional connectivity (FC). This study aimed to assess both the sensitivity and reproducibility of the corrected amplitude envelope correlation (AEC-c) and phase lag index (PLI), two metrics of FC that are insensitive to the effects of volume conduction and field spread, in two separate cohorts of patients with dementia due to AD versus healthy elderly controls.

Methods: Subjects with a clinical diagnosis of AD dementia with biomarker proof, and a control group of subjective cognitive decline (SCD), underwent two 5-min resting-state MEG recordings.

Generating diagnostic profiles of cognitive decline and dementia using magnetoencephalography.

Accurate identification of the underlying cause(s) of cognitive decline and dementia is challenging due to significant symptomatic overlap between subtypes. This study presents a multi-class classification framework for subjects with subjective cognitive decline, mild cognitive impairment, Alzheimer's disease, dementia with Lewy bodies, fronto-temporal dementia and cognitive decline due to psychiatric illness, trained on source-localized resting-state magnetoencephalography data. Diagnostic profiles, describing probability estimates for each of the 6 diagnoses, were assigned to individual subjects.

EEG Alpha and Beta Band Functional Connectivity and Network Structure Mark Hub Overload in Mild Cognitive Impairment During Memory Maintenance.

While decreased alpha and beta-band functional connectivity (FC) and changes in network topology have been reported in Alzheimer's disease, it is not yet entirely known whether these differences can mark cognitive decline in the early stages of the disease. Our study aimed to analyze electroencephalography (EEG) FC and network differences in the alpha and beta frequency band during visuospatial memory maintenance between Mild Cognitive Impairment (MCI) patients and healthy elderly with subjective memory complaints. Functional connectivity and network structure of 17 MCI patients and 20 control participants were studied with 128-channel EEG during a visuospatial memory task with varying memory load.

Routine magnetoencephalography in memory clinic patients: A machine learning approach.

Introduction: We report the routine application of magnetoencephalography (MEG) in a memory clinic, and its value in the discrimination of patients with Alzheimer's disease (AD) dementia from controls.

Methods: Three hundred sixty-six patients visiting our memory clinic underwent MEG recording. Source-reconstructed MEG data were visually assessed and evaluated in the context of clinical findings and other diagnostic markers.

The predictive value of normal EEGs in dementia due to Alzheimer's disease.

Objective: To determine differences in clinical presentation and disease progression between patients with dementia due to AD with visually normal and abnormal EEG recordings. We hypothesized that patients with normal electroencephalographs (EEGs) are a representation of the heterogeneity of AD. We expected this group to have a phenotype with relatively predominant hippocampal atrophy, memory deficits, and a slower disease progression.

In vivo tau pathology is associated with synaptic loss and altered synaptic function.

Background: The mechanism of synaptic loss in Alzheimer's disease is poorly understood and may be associated with tau pathology. In this combined positron emission tomography (PET) and magnetoencephalography (MEG) study, we aimed to investigate spatial associations between regional tau pathology ([F]flortaucipir PET), synaptic density (synaptic vesicle 2A [C]UCB-J PET) and synaptic function (MEG) in Alzheimer's disease.

Methods: Seven amyloid-positive Alzheimer's disease subjects from the Amsterdam Dementia Cohort underwent dynamic 130-min [F]flortaucipir PET, dynamic 60-min [C]UCB-J PET with arterial sampling and 2 × 5-min resting-state MEG measurement.

Profound regional spectral, connectivity, and network changes reflect visual deficits in posterior cortical atrophy: an EEG study.

Patients with posterior cortical atrophy (PCA-AD) show more severe visuospatial and perceptual deficits than those with typical AD (tAD). The aim of this study was to investigate whether functional alterations measured by electroencephalography can help understand the mechanisms that explain this clinical heterogeneity. 21-channel electroencephalography recordings of 29 patients with PCA-AD were compared with 29 patients with tAD and 29 controls matched for age, gender, and disease severity.

Diagnostic and prognostic value of EEG in prodromal dementia with Lewy bodies.

Objective: Early biomarkers for dementia with Lewy bodies (DLB) are lacking. To determine whether EEG differentiates the prodromal phase of DLB from other causes of mild cognitive impairment (MCI) and whether EEG is predictive for time to conversion from MCI to DLB, we compared EEGs and clinical follow-up of patients with MCI due to DLB with those of patients with MCI due to Alzheimer disease (MCI-AD).

Methods: We compared 37 patients with MCI who developed DLB during follow-up or had an abnormal I-PF-CIT SPECT scan (MCI-DLB) with 67 age-matched patients with MCI-AD.

Characterization of EEG-based functional brain networks in myotonic dystrophy type 1.

Objective: In the autosomal dominant, multisystem, chronic progressive disease myotonic dystrophy type 1 (DM1), cognitive deficits may originate from disrupted functional brain networks. We aimed to use network analysis of resting-state electro-encephalography (EEG) recordings of patients with DM1 and matched unaffected controls to investigate changes in network organization in large-scale functional brain networks and correlations with cognitive deficits.

Methods: In this cross-sectional study, 28 adult patients with genetically confirmed DM1 and 26 age-, sex- and education-matched unaffected controls underwent resting-state EEG and neuropsychological assessment.

The degree of prematurity affects functional brain activity in preterm born children at school-age: An EEG study.

Prematurely born children are at higher risk for long-term adverse motor and cognitive outcomes. The aim of this paper was to compare quantitative measures derived from electroencephalography (EEG) between extremely (EP) and very prematurely (VP) born children at 9-10 years of age. Fifty-five children born <32 weeks' of gestation underwent EEG at 9-10 years of age and were assessed for motor development and cognitive outcome.

Reproducibility of EEG functional connectivity in Alzheimer's disease.

Background: Although numerous electroencephalogram (EEG) studies have described differences in functional connectivity in Alzheimer's disease (AD) compared to healthy subjects, there is no general consensus on the methodology of estimating functional connectivity in AD. Inconsistent results are reported due to multiple methodological factors such as diagnostic criteria, small sample sizes and the use of functional connectivity measures sensitive to volume conduction. We aimed to investigate the reproducibility of the disease-associated effects described by commonly used functional connectivity measures with respect to the amyloid, tau and neurodegeneration (A/T/N) criteria.

The road ahead in clinical network neuroscience.

Clinical network neuroscience, the study of brain network topology in neurological and psychiatric diseases, has become a mainstay field within clinical neuroscience. Being a multidisciplinary group of clinical network neuroscience experts based in The Netherlands, we often discuss the current state of the art and possible avenues for future investigations. These discussions revolve around questions like "How do dynamic processes alter the underlying structural network?" and "Can we use network neuroscience for disease classification?" This opinion paper is an incomplete overview of these discussions and expands on ten questions that may potentially advance the field.

Safety, tolerability and efficacy of the glutaminyl cyclase inhibitor PQ912 in Alzheimer's disease: results of a randomized, double-blind, placebo-controlled phase 2a study.

Background: PQ912 is an inhibitor of the glutaminyl cyclase enzyme that plays a central role in the formation of synaptotoxic pyroglutamate-A-beta oligomers. We report on the first clinical study with PQ912 in subjects with biomarker-proven Alzheimer's disease (AD). The aim was to determine the maximal tolerated dose, target occupancy and treatment-related pharmacodynamic effects.