Magnetoencephalography as a putative biomarker for Alzheimer's disease.

Alzheimer’s Disease (AD) is the most common dementia in the elderly and is estimated to affect tens of millions of people worldwide. AD is believed to have a prodromal stage lasting ten or more years. While amyloid deposits, tau filaments, and loss of brain cells are characteristics of the disease, the loss of dendritic spines and of synapses predate such changes. Popular preclinical detection strategies mainly involve cerebrospinal fluid biomarkers, magnetic resonance imaging, metabolic PET scans, and amyloid imaging. One strategy missing from this list involves neurophysiological measures, which might be more sensitive to detect alterations in brain function. The Magnetoencephalography International Consortium of Alzheimer’s Disease arose out of the need to advance the use of Magnetoencephalography (MEG), as a tool in AD and pre-AD research. This paper presents a framework for using MEG in dementia research, and for short-term research priorities

Aesthetic appreciation: event-related field and time-frequency analyses

Improvements in neuroimaging methods have afforded significant advances in our knowledge of the cognitive and neural foundations of aesthetic appreciation. We used magnetoencephalography (MEG) to register brain activity while participants decided about the beauty of visual stimuli. The data were analyzed with event-related field (ERF) and Time-Frequency (TF) procedures. ERFs revealed no significant differences between brain activity related with stimuli rated as “beautiful” and “not beautiful.” TF analysis showed clear differences between both conditions 400 ms after stimulus onset. Oscillatory power was greater for stimuli rated as “beautiful” than those regarded as “not beautiful” in the four frequency bands (theta, alpha, beta, and gamma). These results are interpreted in the frame of synchronization studies.

Early dysfunction of functional connectivity in healthy elderly with subjective memory complaints

It is still an open question whether subjective memory complaints (SMC) can actually be considered to be clinically relevant predictors for the development of an objective memory impairment and even dementia. There is growing evidence that suggests that SMC are associated with an increased risk of dementia and with the presence of biological correlates of early Alzheimer's disease. In this paper, in order to shed some light on this issue, we try to discern whether subjects with SMC showed a different profile of functional connectivity compared with subjects with mild cognitive impairment (MCI) and healthy elderly subjects. In the present study, we compare the degree of synchronization of brain signals recorded with magnetoencephalography between three groups of subjects (56 in total): 19 with MCI, 12 with SMC and 25 healthy controls during a memory task. Synchronization likelihood, an index based on the theory of nonlinear dynamical systems, was used to measure functional connectivity. Briefly, results show that subjects with SMC have a very similar pattern of connectivity to control group, but on average, they present a lower synchronization value. These results could indicate that SMC are representing an initial stage with a hypo-synchronization (in comparison with the control group) where the brain system is still not compensating for the failing memory networks, but behaving as controls when compared with the MCI subjects.

Alterations of cross-frequency coupling in MEG resting state recordings in Mild Cognitive Impairment patients

The default mode network (DMN) has received growing attention in recent years because it seems to be involved in the neuropathology of psychiatric and neurodegenerative disorders such as autism, schizophrenia and Alzheimer Disease. It has been defined as a task negative network, beca use the activity of all its brain regions is increased during the resting state and suspended during external or goal directed tasks.

Brain dynamics of mild cognitive impairment during face encoding

Brain oscillations are closely correlated with human information processing and fundamental aspects of cognition. Previous literature shows that due to the relation between brain oscillations and memory processes, spectral dynamics during such tasks are good candidates to study and characterize memory related pathologies. Mild cognitive impairment (MCI), defined as a clinical condition characterized by memory impairment and/ or deterioration of additional cognitive domains, is considered a preliminary stage in the dementia process. In consequence, the study of its brain patterns could help to achieve an early diagnosis of Alzheimer Disease.

Resting state functional connectivity patterns associated with ApoE genotype. A MEG study in Mild Cognitive Impairment (MCI)

Alteration of brain communication due to abnormal patterns of synchronization is nowadays one of the most suitable mechanisms for having a better understanding of brain pathologies. Very recently, it has been proved that abnormal changes in both local and long range functional interactions underlie the cognitive deficits associated with different brain disorders. Mild cognitive impairment (MCI) is a state characterized for cognitive dysfunction, such as the memory. The study of the spatial and dynamic alterations in MCI subjects' functional networks could provide important evidences of the brain mechanisms responsible for such impairment.

Mild cognitive impairment subtypes: An MEG study

Previous studies of the dementia continuum have characterized the early disruption of the brain oscillatory activity at the stage of Mild cognitive impairment (MCI). Reduction in power in posterior regions in the alpha band has been one of the landmarks of the Alzheimer Disease accompanied by the anteriorization of the theta band power. However, little is known about the neurophysiological differences between single and multidomain MCI patients.Our goal is to study the differences in oscillatory magnetic activity between amnestic single and multidomain MCI. This will allow us to test whether the effect of the impairment in a single cognitive domain or in a more widespread functional impairment can be reflected in specific neurophysiological profiles.

Cognitive reserve benefits brain efficiency in healthy aging

The concept of cognitive reserve (CR) describes the mind’s resistance to the progressive damage of the brain and probably this can be reflected as the ability to recruit brain networks in an effective way. It is as- sociated with the abilityto copewith the deleterious effects of brain damage,brain degeneration, or age-related changes on cognitive performance.

Cognitive reserve is associated with the functional organization of brain networks in healthy aging: a MEG study

The proportion of elderly people in the population has increased rapidly in the last century and consequently "healthy aging" is expected to become a critical area of research in neuroscience. Evidence reveals how healthy aging depends on three main behavioral factors: social lifestyle, cognitive activity and physical activity. In this study, we focused on the role of cognitive activity, concentrating specifically on educational and occupational attainment factors, which were considered two of the main pillars of cognitive reserve. 21 subjects with similar rates of social lifestyle, physical and cognitive activity were selected from a sample of 55 healthy adults. These subjects were divided into two groups according to their level of cognitive reserve; one group comprised subjects with high cognitive reserve (9 members) and the other contained those with low cognitive reserve (12 members). To evaluate the cortical brain connectivity network, all participants were recorded by Magnetoencephalography (MEG) while they performed a memory task (modified version of the Sternberg¿s Task). We then applied two algorithms (Phase Locking Value & Phase-Lag Index) to study the dynamics of functional connectivity. In response to the same task, the subjects with lower cognitive reserve presented higher functional connectivity than those with higher cognitive reserve. These results may indicate that participants with low cognitive reserve needed a greater 'effort' than those with high cognitive reserve to achieve the same level of cognitive performance. Therefore, we conclude that cognitive reserve contributes to the modulation of the functional connectivity patterns of the aging brain.

TMS- EEG Signatures of GABAergic Neurotransmission in the Human Cortex

Combining transcranial magnetic stimulation (TMS) and electroencephalography (EEG) constitutes a powerful tool to directly assess human cortical excitability and connectivity. TMS of the primary motor cortex elicits a sequence of TMS-evoked EEG potentials (TEPs). It is thought that inhibitory neurotransmission through GABA-A receptors (GABAAR) modulates early TEPs (<50 ms after TMS), whereas GABA-B receptors (GABABR) play a role for later TEPs (at ∼100 ms after TMS). However, the physiological underpinnings of TEPs have not been clearly elucidated yet. Here, we studied the role of GABAA/B-ergic neurotransmission for TEPs in healthy subjects using a pharmaco-TMS-EEG approach. In Experiment 1, we tested the effects of a single oral dose of alprazolam (a classical benzodiazepine acting as allosteric-positive modulator at α1, α2, α3, and α5 subunit-containing GABAARs) and zolpidem (a positive modulator mainly at the α1 GABAAR) in a double-blind, placebo-controlled, crossover study. In Experiment 2, we tested the influence of baclofen (a GABABR agonist) and diazepam (a classical benzodiazepine) versus placebo on TEPs. Alprazolam and diazepam increased the amplitude of the negative potential at 45 ms after stimulation (N45) and decreased the negative component at 100 ms (N100), whereas zolpidem increased the N45 only. In contrast, baclofen specifically increased the N100 amplitude. These results provide strong evidence that the N45 represents activity of α1-subunit-containing GABAARs, whereas the N100 represents activity of GABABRs. Findings open a novel window of opportunity to study alteration of GABAA-/GABAB-related inhibition in disorders, such as epilepsy or schizophrenia.

MedVir: an interactive representation system of multidimensional medical data applied to Traumatic Brain Injury's rehabilitation prediction

Clinicians could model the brain injury of a patient through his brain activity. However, how this model is defined and how it changes when the patient is recovering are questions yet unanswered. In this paper, the use of MedVir framework is proposed with the aim of answering these questions. Based on complex data mining techniques, this provides not only the differentiation between TBI patients and control subjects (with a 72% of accuracy using 0.632 Bootstrap validation), but also the ability to detect whether a patient may recover or not, and all of that in a quick and easy way through a visualization technique which allows interaction.