What Electrophysiology Tells Us About Alzheimer’s Disease::A Window into the Synchronization and Connectivity of Brain Neurons

Electrophysiology provides a real-time readout of neural functions and network capability in different brain states, on temporal (fractions of milliseconds) and spatial (micro, meso, and macro) scales unmet by other methodologies. However, current international guidelines do not endorse the use of electroencephalographic (EEG)/magnetoencephalographic (MEG) biomarkers in clinical trials performed in patients with Alzheimer’s disease (AD), despite a surge in recent validated evidence. This Position Paper of the ISTAART Electrophysiology Professional Interest Area endorses consolidated and translational electrophysiological techniques applied to both experimental animal models of AD and patients, to probe the effects of AD neuropathology (i.e., brain amyloidosis, tauopathy, and neurodegeneration) on neurophysiological mechanisms underpinning neural excitation/inhibition and neurotransmission as well as brain network dynamics, synchronization, and functional connectivity reflecting thalamocortical and cortico-cortical residual capacity. Converging evidence shows relationships between abnormalities in EEG/MEG markers and cognitive deficits in groups of AD patients at different disease stages. The supporting evidence for the application of electrophysiology in AD clinical research as well as drug discovery pathways warrants an international initiative to include the use of EEG/MEG biomarkers in the main multicentric projects planned in AD patients, to produce conclusive findings challenging the present regulatory requirements and guidelines for AD studies

Fluid storage and migration properties of sheared Neptunian dykes

Neptunian dykes are widely reported along the Tethyan carbonate platforms and are commonly considered as subsurface baffles or barriers to fluid flow. However, the fluid storage and migration properties of sheared Neptunian dykes are poorly known. For this reason, we investigate the inner structure and fluid flow properties of two Neptunian dykes, which can be characterized by different architectures if involved or not in brittle shearing processes. The dykes strike ca. WNW-ESE and crosscutting the tight Jurassic limestones exposed at Maranfusa Mt., NW Sicily, Italy. The unsheared and sheared Neptunian dykes are almost sub-vertical and at high-angle with respect to the horizontal plane, respectively. The first one includes a homogeneous pelagic limestone infill whereas the second one includes a heterogeneous, marl-rich pelagic limestone infill and also thin veneers of tectonic breccias vertically persistent throughout the investigated outcrop. The sheared Neptunian dyke shows evidences of transtensional faulting, which likely occurred during the early Jurassic up to middle Cretaceous times, with throw up to 2 m. The amount of fracture porosity and equivalent permeability are computed by integrating geological and structural field data with petrographic data obtained from selected samples and Discrete Fracture Network modelling of geocellular volumes representative of the study outcrops. Results are consistent with the sheared Neptunian dyke forming a combined barrier-conduit permeability structure, in which the low-permeability and low\u2013porosity cataclastic core is flanked by a fractured damage zone that enhance the dyke-parallel fluid flow in the subsurface. Accordingly, the amount of fluid storage in the fractured damage zone is sensitively higher than in the surrounding limestone host rock. Data we present highlight that the m-offset, sheared Neptunian dyke, due to its inherited sedimentary infill, is characterized by a permeability structure that it is often associated to large fault zones made up of cataclastic fault cores that impede the cross-fault fluid flow

Geomorphological and Morphometric Analyses of the Catanzaro Trough (Central Calabrian Arc, Southern Italy): Seismotectonic Implications

In this work, we investigated the landscape response to the recent activity of the faults affecting the Catanzaro Trough, a seismically active structural basin that developed transversally to the Calabrian Arc (Southern Italy) during the Neogene–Quaternary. We carried out a geomorphological and morphometric study of the drainage networks and basins intercepted by the Quaternary faults that were previously mapped through remote and field analyses. The study confirms the occurrence north of the Catanzaro Trough of a WNW–ESE-oriented left-lateral strike-slip fault system (here named the South Sila Piccola Fault System), which accommodates the differential SE-ward migration of the upper crustal sectors of the Calabrian Arc, and of a south-dipping WNW–ESE-oriented oblique fault system (the Lamezia-Catanzaro Fault System), characterized by a predominant normal component of movement. The latter delimits the Catanzaro Trough and accommodates the transition from a strike-slip regime to an extensional regime in the south. Inside the Catanzaro Trough, we detected for the first time a NNE–SSW-trending, WNW-dipping fault system (here named the Caraffa Fault System). This system contributes to accommodate the extension that occurs orthogonally to the southern sector of the Calabrian Arc. The geomorphological and morphometric analysis revealed the recent activity of these fault systems. In particular, the activity of the Caraffa Fault System is evidenced by the differential uplift and tilting of discrete areas inside the basin. Given its location, geometry, and kinematics, the Caraffa Fault System could be responsible for the occurrence of large historical earthquakes

Boulder coastal deposits at Favignana Island rocky coast (Sicily, Italy): Litho-structural and hydrodynamic control

Boulders are frequently dislodged from rock platforms, transported and deposited along coastal zones by high-magnitude storm waves or tsunamis. Their size and shape are often controlled by the thickness of bedding planes as well as by high-angle to bedding fracture network. We investigate these processes along two coastal areas of Favignana Island by integrating geological data for 81 boulders, 49 rupture surfaces (called sockets) and fracture orientation and spacing with four radiocarbon dates, numerical hydrodynamic analysis, and hindcast numerical simulation data. Boulders are scattered along the carbonate platform as isolated blocks or in small groups, which form, as a whole, a discontinuous berm. Underwater surveys also highlight free boulders with sharp edges and sockets carved out in the rock platform. Boulders are composed of ruditic- to arenitic-size clastic carbonates. Their size ranges from 0.6 to 3.7 m, 0.55 to 2.4 m, and 0.2 to 1 m on the major (A), medium (B), and minor (C) axes, respectively. The highest value of mass estimation is 12.5 t. Almost all of boulders and sockets are characterized by a tabular or bladed shape. The comparisons between a) the fractures spacing and the length of A- and B-axes, and b) the frequency peaks of C-axis with the recurrent thickness of beds measured along the coastal zone demonstrate the litho-structural control in the size and shape of joint-bounded boulders. These comparisons, together with the similarity between the shapes of the boulders and those of the sockets as well as between the lithology of boulders and the areas surrounding the sockets, suggest that blocks originate by detachment from the platform edge. Thus, the most common pre-transport setting is the joint-bounded scenario. Hydrodynamic equations estimate that the storm wave heights necessary to initiate the transport of blocks diverge from ~ 2 m to ~ 8 m for joint-bounded boulders and from few tens of centimeters up to ~ 11 m for submerged boulders. The comparison between the wave heights at the breaking point of the coastal zones with the results of hydrodynamic equations shows that waves approaching the coastline are able to transport all surveyed boulders. Our data suggest that boulders have been transported by several storm events, even in very recent times

Alpha rhythm induces attenuation-amplification dynamics in neural activity cascades

Rhythmical cortical activity has long been recognized as a pillar in the architecture of brain functions. Yet, the dynamic organization of its underlying neuronal population activity remains elusive. Here we uncover a unique organizational principle regulating collective neural dynamics associated with the alpha rhythm in the awake resting-state. We demonstrate that cascades of neural activity obey attenuation-amplification dynamics (AAD), with a transition from the attenuation regime—within alpha cycles—to the amplification regime—across a few alpha cycles—that correlates with the characteristic frequency of the alpha rhythm. We find that this short-term AAD is part of a large-scale, size-dependent temporal structure of neural cascades that obeys the Omori law: Following large cascades, smaller cascades occur at a rate that decays as a power-law of the time elapsed from such events—a long-term AAD regulating brain activity over the timescale of seconds. We show that such an organization corresponds to the "waxing and waning" of the alpha rhythm. Importantly, we observe that short- and long-term AAD are unique to the awake resting-state, being absent during NREM sleep. These results provide a quantitative, dynamical description of the so-far-qualitative notion of the "waxing and waning" phenomenon, and suggest the AAD as a key principle governing resting-state dynamics across timescales

Beyond pulsed inhibition: Alpha oscillations modulate attenuation and amplification of neural activity in the awake resting state

Alpha oscillations are a distinctive feature of the awake resting state of the human brain. However, their functional role in resting-state neuronal dynamics remains poorly understood. Here we show that, during resting wakefulness, alpha oscillations drive an alternation of attenuation and amplification bouts in neural activity. Our analysis indicates that inhibition is activated in pulses that last for a single alpha cycle and gradually suppress neural activity, while excitation is successively enhanced over a few alpha cycles to amplify neural activity. Furthermore, we show that long-term alpha amplitude fluctuations—the “waxing and waning” phenomenon—are an attenuation-amplification mechanism described by a power-law decay of the activity rate in the “waning” phase. Importantly, we do not observe such dynamics during non-rapid eye movement (NREM) sleep with marginal alpha oscillations. The results suggest that alpha oscillations modulate neural activity not only through pulses of inhibition (pulsed inhibition hypothesis) but also by timely enhancement of excitation (or disinhibition)

Elusive active faults in a low strain rate region (Sicily, Italy): Hints from a multidisciplinary land-to-sea approach

Low Strain Rate regions (LSRrs), i.e., areas undergoing tectonic deformation at rates of 1 mm/yr or less, often host important cities and highly vulnerable anthropogenic assets, and due to their subdued topography and relatively infrequent seismicity, are often considered low seismic hazard areas. Despite this, infrequent but high-magnitude earthquakes in such regions suggest that identifying active structures in the LSRr is one of the primary challenges for both the scientific community and modern societies. In such regions, one of the main issues in identifying active faults is the lack of valuable outcrop data due to erosional/sedimentation rates overwhelming the fault deformation, causing the hidden morphological signature of the tectonic structures. This work proposes a multidisciplinary approach designed to detect active geological structures and their related deformation in such areas. Our approach consists of quantitative morphotectonic, offshore and onshore tectonostratigraphic and GNSS joint analyses. To test this approach, we selected as a natural laboratory the partially offshore northern Sicilian LSRr (southern Italy) in the coastal sector located between the two major cities of Palermo and Termini Imerese. This area includes the compressional structures of the northern sector of the Apennine-Maghrebian fold and thrust belt, presently accommodating the slow Africa-Europe plate convergence. The main results we achieved are 1) new evidence of active tectonic deformation in this region; 2) the 3D modelling of two NNW-trending active faults; 3) the slip rate of a segment of the westernmost of the two detected faults; 4) a newly recorded relative GNSS velocity field; 5) a new morphotectonic map and morphotectonic evolution model of the study area. Our multidisciplinary approach allowed us to shed new light on the active tectonic framework of a slowly deforming area that crosses the physical limit of the coastline

Long-term earthquake potential of active faults by using coastal and off-shore geological and morphological indicators

Seismogenic fault models and active deformation ones coupled with models of both earthquake rate and earthquake probability were recently used in a time-independent modelling. The integration of models allows to estimates the magnitude, location, and likelihood of potentially damaging earthquake ruptures in regions with high natural seismic hazard. Improvements of these models imply the recognition of the spatial geometry of the larger, active faults, deemed to be the source of the most damaging future earthquakes. However, identifying active faults and calculating their geologic slip rates for deriving earthquake rates are not easy tasks in regions inaccessible to direct field studies like active offshore areas. To improve the ability to define seismogenic fault models and active deformation models in offshore areas, we aim to develop a geophysical/geological method that allows to (a) identify the spatial geometry of active faults and fault systems in coastal areas, and (b) deduce the average long-term slip rates and recurrence interval, displacement per event, and elapsed time since the last event along the fault plane. The approach consists of innovative combination of geological and geophysical dataset, sampling methodology and GIS based on morphometric analysis. Preliminary results of this multidisciplinary approach applied to the coastal area of north Sicily document active deformation in an on-land sector of the Sicilian Maghrebian Chain and in its off-shore prolongation. Here we present results concerning the Palermo-Termini Imerese coastal sector based on a combination of: 1) structural data, 2) high-resolution reflection seismic data, 3) time series of GNSS data of the permanent stations of Palermo, Partinico, Prizzi, and Termini compared to the IGS station of Noto, 4) morphometric analysis of high-resolution digital elevation data for the hydrographic basins of the Oreto, Eleuterio, Milicia, San Leonardo, Torto and Imera Settentrionale rivers, and 5) seismological data. In the area of the Capo Zafferano promontory, Pleistocene conglomerates and grainstones are affected by recent tectonic deformation. In particular, at two sites near the village of Porticello we observed two sets of N-S to NNW-SSE and NE-SW striking deformation bands. Both sets have an almost vertical dip and show mutual cross-cutting relationships, suggesting their contemporaneous development. The N-S to NNW-SSE striking set shows left-lateral strike slip kinematic. At place, the deformation bands affect also Upper Pleistocene (Tyrrhenian) bio-calcarenites. In the off-shore, a number of seismic units, bounded by unconformities, were identified on seismic lines. The unit of inferred late Pleistocene age appears to be folded and faulted. Faults generally have an inclination of ca. 50°, small displacements up to 10 m and are sealed by the unit of inferred post-LGM age. Only a limited number of these faults are observed moving ca. 3 km offshore towards the NE. The average values of the velocity vectors obtained for the Palermo, Partinico, Prizzi, and Termini Imerese stations are 4.55, 2.97, 2.96, and 2.15 mm/yr, respectively. The direction of the velocity vectors for all stations is oriented towards the IGS reference station of Noto. The relative displacements of the Termini Imerese, Partinico and Prizzi stations respect to Palermo station are most equal to 0.5 mm/yr. Also, the directions of vectors suggest a clockwise rotation. The drainage network analysis highlights that the trunk streams of Eleuterio and San Leonardo drainage networks are asymmetric towards SE and the absolute asymmetry are ~ 3 and ~ 2 km, respectively. On the contrary, the trunk streams of the Milicia, Torto and Imera Settentrionale rivers are asymmetric towards W-NW with an asymmetry ranging from 3.5 up to 4 km. The Oreto stream does not show any evidence of lateral shift. Hypsometric analysis shows two types of statistical distributions of elevation classes. The latter have a bi-modal distribution for the Eleuterio, Oreto and Torto basins while uni-modal for the Milicia and San Leonardo basins. Values of the hypsometric integral are ~ 0.4 for the Milicia, San Leonardo and Torto basins, ~ 0.5 for the Eleuterio basin and 0.35 for the Oreto basin. The study area has been struck in the past centuries by several significant earthquakes of I0 ≥ 6. Mainly low-to-moderate magnitude seismicity, instead, occurred in this sector in the more recent times, showing highest earthquake concentration in the Tyrrhenian off-shore of the study area with respect to the onshore sector. To furnish a first constraint on seismogenic sources lying in this area, we performed hypocenter location and focal mechanism computation of the seismicity that occurred in the last thirty years. Then, we jointly evaluated data and information coming from historical seismicity with the results obtained by the geophysical, geological, and seismological analyses performed in order to better characterize the possible seismogenic sources present in the study region