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The middle Eocene Cibrone Formation of Brianza (central-western Lombardy) represents an important stratigraphic record to understand a key step of the tectonic evolution of the Alpine range poorly recorded elsewhere. Quantitative petrographic analysis of turbidite arenites, well-constrained in age by the biostratigraphy of interlayered marlstones based on calcareous foraminifera and nannoplankton, allowed us to identify a possible vertical compositional trend within the Cibrone Fm. and to document the NP17 nannofossil Zone (Bartonian) in central Lombardy exposures, east of the Ternate Formation outcrop area. Variable arenite compositions are interpreted to reflect contributions from different source areas, i.e., recycled orogen, island arc, and starved continental shelf. In a paleogeographic scenario still open to different interpretations, the proposed reconstruction supports a classical plate tectonics model for arc-trench systems. The stratigraphic gap, recorded everywhere in Lombardy, between the Eocene succession and the base of the Gonfolite Lombarda Group (upper NP24 nannofossil Zone, early Chattian), corresponds to the earliest stage of continental collision, uplift and erosion that climaxed in the Neo-Alpine Phase.

Abstract Neuronal activity in the brain reflects an excitation–inhibition balance that is regulated predominantly by glutamatergic and GABAergic neurotransmission, and often disturbed in neuropsychiatric disorders. Here, we tested the effects of a single oral dose of two anti-glutamatergic drugs (dextromethorphan, an NMDA receptor antagonist; perampanel, an AMPA receptor antagonist) and an L-type voltage-gated calcium channel blocker (nimodipine) on transcranial magnetic stimulation (TMS)-evoked electroencephalographic (EEG) potentials (TEPs) and TMS-induced oscillations (TIOs) in 16 healthy adults in a pseudorandomized, double-blinded, placebo-controlled crossover design. Single-pulse TMS was delivered to the hand area of left primary motor cortex. Dextromethorphan increased the amplitude of the N45 TEP, while it had no effect on TIOs. Perampanel reduced the amplitude of the P60 TEP in the non-stimulated hemisphere, and increased TIOs in the beta-frequency band in the stimulated sensorimotor cortex, and in the alpha-frequency band in midline parietal channels. Nimodipine and placebo had no effect on TEPs and TIOs. The TEP results extend previous pharmaco-TMS-EEG studies by demonstrating that the N45 is regulated by a balance of GABAAergic inhibition and NMDA receptor-mediated glutamatergic excitation. In contrast, AMPA receptor-mediated glutamatergic neurotransmission contributes to propagated activity reflected in the P60 potential and midline parietal induced oscillations. This pharmacological characterization of TMS-EEG responses will be informative for interpreting TMS-EEG abnormalities in neuropsychiatric disorders with pathological excitation–inhibition balance.

Abstract Objective Transcranial magnetic stimulation (TMS) produces characteristic deflections in the EEG signal named TMS‐evoked EEG potentials (TEPs), which can be used to assess drug effects on cortical excitability. TMS can also be used to determine the resting motor threshold (RMT) for eliciting a minimal muscle response, as a biomarker of corticospinal excitability. XEN1101 is a novel potassium channel opener undergoing clinical development for treatment of epilepsy. We used TEPs and RMT to measure the effects of XEN1101 in the human brain, to provide evidence that XEN1101 alters cortical excitability at doses that might be used in future clinical trials. Methods TMS measurements were incorporated in this Phase I clinical trial to evaluate the extent to which XEN1101 modulates TMS parameters of cortical and corticospinal excitability. TEPs and RMT were collected before and at 2‐, 4‐, and 6‐hours post drug intake in a double‐blind, placebo‐controlled, randomized, two‐period crossover study of 20 healthy male volunteers. Results Consistent with previous TMS investigations of antiepileptic drugs (AEDs) targeting ion channels, the amplitude of TEPs occurring at early (15–55 msec after TMS) and at late (150–250 msec after TMS) latencies were significantly suppressed from baseline by 20 mg of XEN1101. Furthermore, the RMT showed a significant time‐dependent increase that correlated with the XEN1101 plasma concentration. Interpretation Changes from baseline in TMS measures provided evidence that 20 mg of XEN1101 suppressed cortical and corticospinal excitability, consistent with the effects of other AEDs. These results support the implementation of TMS as a tool to inform early‐stage clinical trials.

A detailed Upper Cretaceous/Paleocene stratigraphic section was measured from the Spanboth Chu Valley, High Himalaya Nappes. Placement Of the Cretaceous—Tertiary boundary was refined, but some uncertitudes still remain because of poor exposure in this portion of the sequence. The Maastrichtian is characterized by floral and faunal assemblages consisting of Cymopolia, Ornphalocyclus, Siderolites and Odon togryphaea. The Lower Paleocene seems to be missing, whilst the Middle to Upper Paleocene is characterized by Rotalia, Daviesina, Lockhartia and Furcoporella assemblages. Sandstone petrography and carbonate microfacies were analyzed for environmental interpretation. Moreover, a reconsideration of the recent published data on the Upper Cretaceous/ Paleocene from the Zanskar mountains allows us to delineate a tentative depositional history of this part of the Indian continental margin during the considered time.

Face and body perception is mediated by configural mechanisms, which allow the perception of these stimuli as a whole, rather than the sum of individual parts. Indirect measures of configural processing in visual cognition are the face and body inversion effects (FIE and BIE), which refer to the drop in performance when these stimuli are perceived upside-down. Albeit FIE and BIE have been well characterized at the behavioral level, much still needs to be understood in terms of the neurophysiological correlates of these effects. Thus, in the current study, the brain’s electrical activity has been recorded by a 128 channel electroencephalogram (EEG) in 24 healthy participants while perceiving (upright and inverted) faces, bodies and houses. EEG data were analyzed in both the time domain (i.e., event-related potentials—ERPs) and the frequency domain [i.e., induced theta (5–7 Hz) and gamma (28–45 Hz) oscillations]. ERPs amplitude results showed increased N170 amplitude for inverted faces and bodies (compared to the same stimuli presented in canonical position) but not for houses. ERPs latency results showed delayed N170 components for inverted (vs. upright) faces, houses, but not bodies. Spectral analysis of induced oscillations indicated physiological FIE and BIE; that is decreased gamma-band synchronization over right occipito-temporal electrodes for inverted (vs. upright) faces, and increased bilateral frontoparietal theta-band synchronization for inverted (vs. upright) faces. Furthermore, increased left occipito-temporal and right frontal theta-band synchronization for upright (vs. inverted) bodies was found. Our findings, thus, demonstrate clear differences in the neurophysiological correlates of face and body perception. The neurophysiological FIE suggests disruption of feature binding processes (decrease in occipital gamma oscillations for inverted faces), together with enhanced feature-based attention (increase in frontoparietal theta oscillations for inverted faces). In contrast, the BIE may suggest that structural encoding for bodies is mediated by the first stages of configural processing (decrease in occipital theta oscillations for inverted bodies).

Biserial heterohelicid foraminifera are paleohydrographic indices for open ocean oxygen minimum zones. Comparison of the depletion of biserial heterohelicid carbon isotope ratios with the carbon isotope contrast through the water column is used to describe the strength of Eocene oxygen minima. Combining stable isotope values and percentages of planktonic foraminiferal index species, we describe the following boundary condition for early, middle and latest Eocene oxygen minimum zones in the Atlantic Ocean. Early Eocene - low meridional and vertical thermal contrasts, reduced upwelling and circulation vigor in a moderately war m, stable thermospheric ocean accompany a poorly developed, spatially restricted oxygen minimum. Middle Eocene - invigorated upwelling, large vertical and spatial thermal contrasts caused by cooling at the bottom but not at the surface together with increased ventilation of the water column accompany a strong, widely developed oxygen minimum; and Late Eocene - in a psychrospheric ocean low meridional and vertical thermal contrasts, reduced equatorial upwelling and atmospheric circulation with decreased current circulation vigor correlate with a homogeneous mixed layer in which an oxygen minimum is poorly developed above the thermocline, but not at mid depths.

People with Parkinson’s disease (PD) experience significant impairments to gait and balance; as a result, the rate of falls in people with Parkinson’s disease is much greater than that of the general population. Falls can have a catastrophic impact on quality of life, often resulting in serious injury and even death. The number (or rate) of falls is often used as a primary outcome in clinical trials on PD. However, falls data can be unreliable, expensive and time-consuming to collect. We sought to validate and test a novel digital biomarker for PD that uses wearable sensor data obtained during the Timed Up and Go (TUG) test to predict the number of falls that will be experienced by a person with PD. Three datasets, containing a total of 1057 (671 female) participants, including 71 previously diagnosed with PD, were included in the analysis. Two statistical approaches were considered in predicting falls counts: the first based on a previously reported falls risk assessment algorithm, and the second based on elastic net and ensemble regression models. A predictive model for falls counts in PD showed a mean R2 value of 0.43, mean error of 0.42 and a mean correlation of 30% when the results were averaged across two independent sets of PD data. The results also suggest a strong association between falls counts and a previously reported inertial sensor-based falls risk estimate. In addition, significant associations were observed between falls counts and a number of individual gait and mobility parameters. Our preliminary research suggests that the falls counts predicted from the inertial sensor data obtained during a simple walking task have the potential to be developed as a novel digital biomarker for PD, and this deserves further validation in the targeted clinical population.

Electroencephalographic (EEG) signals evoked by transcranial magnetic stimulation (TMS) are usually recorded with passive electrodes (PE). Active electrode (AE) systems have recently become widely available; compared to PE, they allow for easier electrode preparation and a higher-quality signal, due to the preamplification at the electrode stage, which reduces electrical line noise. The performance between the AE and PE can differ, especially with fast EEG voltage changes, which can easily occur with TMS-EEG; however, a systematic comparison in the TMS-EEG setting has not been made. Therefore, we recorded TMS-evoked EEG potentials (TEPs) in a group of healthy subjects in two sessions, one using PE and the other using AE. We stimulated the left primary motor cortex and right medial prefrontal cortex and used two different approaches to remove early TMS artefacts, Independent Component Analysis and Signal Space Projection—Source Informed Recovery. We assessed statistical differences in amplitude and topography of TEPs, and their similarity, by means of the concordance correlation coefficient (CCC). We also tested the capability of each system to approximate the final TEP waveform with a reduced number of trials. The results showed that TEPs recorded with AE and PE do not differ in amplitude and topography, and only few electrodes showed a lower-than-expected CCC between the two methods of amplification. We conclude that AE are a viable solution for TMS-EEG recording.

The Aptian-Albian Scisti a Fucoidi Formation, cropping out widely in the Umbrian-Marchean Basin (Italy), consists of a varicolored pelagic sequence of thinly interbedded red and green marlstones and calcareous marlstones, dark gray to black Corg-rich calcareous shales, and light green-gray marly limestones and limestones. The variable colored lithotypes appear to be rhythmically deposited. In order to investigate in detail such rhythmicity and the mechanism leading to the accumulation of Corg-rich sediments, a core, the Piobbico core, was specifically cut through the Scisti a Fucoidi.

Evoked potentials (EPs) are well established in clinical practice for diagnosis and prognosis in multiple sclerosis (MS). However, their value is limited to the assessment of their respective functional systems. Here, we used transcranial magnetic stimulation (TMS) coupled with electroencephalography (TMS-EEG) to investigate cortical excitability and spatiotemporal dynamics of TMS-evoked neural activity in MS patients. Thirteen patients with early relapsing–remitting MS (RRMS) with a median Expanded Disability Status Scale (EDSS) of 1.0 (range 0–2.5) and 16 age- and gender-matched healthy controls received single-pulse TMS of left and right primary motor cortex (L-M1 and R-M1), respectively. Resting motor threshold for L-M1 and R-M1 was increased in MS patients. Latencies and amplitudes of N45, P70, N100, P180, and N280 TMS-evoked EEG potentials (TEPs) were not different between groups, except a significantly increased amplitude of the N280 TEP in the MS group, both for L-M1 and R-M1 stimulation. Interhemispheric signal propagation (ISP), estimated from the area under the curve of TEPs in the non-stimulated vs. stimulated M1, also did not differ between groups. In summary, findings show that ISP and TEPs were preserved in early-stage RRMS, except for an exaggerated N280 amplitude. Our findings indicate that TMS-EEG is feasible in testing excitability and connectivity in cortical neural networks in MS patients, complementary to conventional EPs. However, relevance and pathophysiological correlates of the enhanced N280 will need further study.

Neuromodulation techniques such as tDCS have provided important insight into the neurophysiological mechanisms that mediate cognition. Albeit anodal tDCS (a-tDCS) often enhances cognitive skills, the role of cathodal tDCS (c-tDCS) in visual cognition is largely unexplored and inconclusive. Here, in a single-blind, sham-controlled study, we investigated the offline effects of 1.5 mA c-tDCS over the right occipital cortex of 86 participants on four tasks assessing perception and memory of both faces and objects. Results demonstrated that c-tDCS does not overall affect performance on the four tasks. However, post-hoc exploratory analysis on participants' race (Caucasian vs. non-Caucasians), showed a “face-specific” performance decrease (≈10%) in non-Caucasian participants only. This preliminary evidence suggests that c-tDCS can induce “other-race effect (ORE)-like” behavior in non-Caucasian participants that did not show any ORE before stimulation (and in case of sham stimulation). Our results add relevant information about the breadth of cognitive processes and visual stimuli that can be modulated by c-tDCS, about the design of effective neuromodulation protocols, and have important implications for the potential neurophysiological bases of ORE.

The combination of transcranial magnetic stimulation and electroencephalography (TMS-EEG) has uncovered underlying mechanisms of two anti-epileptic medications: levetiracetam and lamotrigine. Despite their different mechanism of action, both drugs modulated TMS-evoked EEG potentials (TEPs) in a similar way. Since both medications increase resting motor threshold (RMT), the current aim was to examine the similarities and differences in post-drug TEPs, depending on whether stimulation intensity was adjusted to take account of post-drug RMT increase. The experiment followed a placebo controlled, double blind, crossover design, involving a single dose of either lamotrigine or levetiracetam. When a drug-induced increase of RMT occurred, post-drug measurements involved two blocks of stimulations, using unadjusted and adjusted stimulation intensity. A cluster based permutation analysis of differences in TEP amplitude between adjusted and unadjusted stimulation intensity showed that lamotrigine induced a stronger modulation of the N45 TEP component compared to levetiracetam. Results highlight the impact of adjusting stimulation intensity.

Detailed biostratigraphic study of mid-Cretaceous Tethys Himalayan pelagic units shed new light on the evolution of the northern India passive continental margin. After a major episode of alkaline magmatism recorded from Zanskar to Nepal in the Early Cretaceous, condensed glauco-phosphorites were deposited during the Rotalipora subticinensis Subzone, and were overlain unconformably by pelagic mudstones during the Rotalipora ticinensis to Rotalipora appenninica Zones (Fatu La Formation in Zanskar and Muding Formation in Nepal). Throughout the Tethys Himalaya drowning of clastic shelves thus occurred with the same modalities and synchronously in Late Albian time. The base of the Chikkim Formation in Zanskar is younger, and overlies palimpsest arenites and reworked glauco-phosphorires deposited during the latest Cenomanian Whiteinella archaeocretacea Zone. Hiatuses several million years long, mainly coeval and similar in duration in the Chikkim and Fatu La Formations, characterize the Cenomanian and the Late Turonian to Campanian sections throughout the Zanskar Range. These hiatuses are ascribed to continuous resuspension of pelagic sediments on the upper slope, caused by the action of strong eastbound oceanic currents. Much higher accumulation rates were recorded in the early-middle Turonian, when deposition occurred at grearer depths below the mudline. Accumulation rates increased greatly in the Maastrichtian, when offshore marls with sparsc phosphate nodules were gradually rcplaced by inner shelf carbonate facies at the close of the Cretaceous. The studied succession shows a mirrorlike repetition of sedimentary facies, interpreted as part of a 65 to 70 my long Cretaceous supersequence. Sedimentary evolution reflected a complex interplay of global and regional phenomena, including the extensional and magmatic episodes leading to thc final fragmentarion of Gondwana-Land and opening of the Indian Ocean, a long-term tendency to eustatic rise, changing paleooceanographic circulation, and oceanic anoxic events.

Transcranial magnetic stimulation (TMS) of the primary motor cortex (M1) can excite both cortico-cortical and cortico-spinal axons resulting in TMS-evoked potentials (TEPs) and motor-evoked potentials (MEPs), respectively. Despite this remarkable difference with other cortical areas, the influence of motor output and its amplitude on TEPs is largely unknown. Here we studied TEPs resulting from M1 stimulation and assessed whether their waveform and spectral features depend on the MEP amplitude. To this aim, we performed two separate experiments. In experiment 1, single-pulse TMS was applied at the same supra-threshold intensity on primary motor, prefrontal, premotor and parietal cortices and the corresponding TEPs were compared by means of local mean field power and time-frequency spectral analysis. In experiment 2 we stimulated M1 at resting motor threshold in order to elicit MEPs characterized by a wide range of amplitudes. TEPs computed from high-MEP and low-MEP trials were then compared using the same methods applied in experiment 1. In line with previous studies, TMS of M1 produced larger TEPs compared to other cortical stimulations. Notably, we found that only TEPs produced by M1 stimulation were accompanied by a late event-related desynchronization (ERD-peaking at ~300 ms after TMS), whose magnitude was strongly dependent on the amplitude of MEPs. Overall, these results suggest that M1 produces peculiar responses to TMS possibly reflecting specific anatomo-functional properties, such as the re-entry of proprioceptive feedback associated with target muscle activation.

Calcareous nannofossil biostratigraphic investigations have been carried out on samples collected from the Tabiago section, Brianza, northern Italy. This section records early Maastrichtian (CC23b nannofossil zone) to early Eocene (NP10 nannofossil zone) calcareous nannofossil assemblages. The Cretaceous-Tertiary transition is characterized by major changes in sedimentation rates and two likely stratigraphic gaps. The Cretaceous Brenno Formation was deposited with a high sedimentation rate (~20 m/m.y.), whilst the Tabiago Formation of Paleogene age records a drastic decrease (~10 m/m.y.). The absence of the CC26 zonal marker Micula prinsii may indicate a stratigraphic hiatus or an extremely condensed level in the latest Maastrichtian. However, only two samples have been collected and analyzed in this interval due to low exposure of the outcrop, and the absence of M. prinsii could be the result of diagenetic overprint or insufficient sampling. A stratigraphic hiatus or a very condensed interval corresponds to the upper part of NP1 nannofossil zone and PĄ foraminiferal Zone and P1a Subzone in the early Paleocene. The poor exposure of the outcrop prevents to precisely locate the zonal boundaries between NP4 and NP5 and between NP9 and NP10 and impedes the documentation of possible further stratigraphic gaps or condensed intervals.

This short notes deals with the re-description and re-illustration of the holotypes of Thalmanninella brotzeni Sigal, 1948 and Rotalipora globotruncanoides Sigal, 1948, from Sidi Aissa, Algeria, middle Cenomanian. Both species are attributed to the genus Thalmanninella.

The middle Eocene Cibrone Formation of Brianza (central-western Lombardy) represents an important stratigraphic record to understand a key step of the tectonic evolution of the Alpine range poorly recorded elsewhere. Quantitative petrographic analysis of turbidite arenites, well-constrained in age by the biostratigraphy of interlayered marlstones based on calcareous foraminifera and nannoplankton, allowed us to identify a possible vertical compositional trend within the Cibrone Fm. and to document the NP17 nannofossil Zone (Bartonian) in central Lombardy exposures, east of the Ternate Formation outcrop area. Variable arenite compositions are interpreted to reflect contributions from different source areas, i.e., recycled orogen, island arc, and starved continental shelf. In a paleogeographic scenario still open to different interpretations, the proposed reconstruction supports a classical plate tectonics model for arc-trench systems. The stratigraphic gap, recorded everywhere in Lombardy, between the Eocene succession and the base of the Gonfolite Lombarda Group (upper NP24 nannofossil Zone, early Chattian), corresponds to the earliest stage of continental collision, uplift and erosion that climaxed in the Neo-Alpine Phase. [ABSTRACT FROM AUTHOR]

We present new stable (C, O) isotopic, biostratigraphic and organic geochemical data for the Vigla Shale Member of the Ionian Zone in NW Greece, in order to characterize organic carbon-rich strata that potentially record the impact of Cretaceous Oceanic Anoxic Events (OAEs). In a section exposed near Gotzikas (NW Epirus), we sampled a number of decimetre-thick, organic carbon-rich units enclosed within marly, locally silicified, Vigla Limestone (Berriasian-Turonian). All these units are characterized by largely comparable bulk geochemical characteristics, indicating a common marine origin and low thermal maturity. However, the stratigraphically highest of these black shales is further distinguished by its much higher total organic-carbon (TOC) content (28.9 wt%) and Hydrogen Index (HI) (529), and much enriched [[delta].sup.13][C.sub.org] value (-22.1 [per thousand]). Planktonic foraminiferal and calcareous nannofossil biostratigraphy indicate a lower to middle Albian age for the strata immediately above, and a lower Aptian age for the strata below, the uppermost black shale. In terms of molecular organic geochemistry, the latter black shale is also relatively enriched in specific isoprenoidal compounds (especially monocyclic isoprenoids), whose isotopic values are as high as -15 [per thousand], indicating a substantial archaeal contribution to the organic matter. The striking similarities between the molecular signatures of the uppermost Vigla black shale and coeval organic-rich strata from SE France and the North Atlantic (ODP Site 1049C) indicate that this level constitutes a record of the Paquier Event (OAE 1b). Keywords: Cretaceous, Albian, stratigraphy, isotopes, carbon.

A palynological and organic geochemical study of the early Aptian Selli unit (oceanic anoxic event 1a) of the western Tethys provides new information about paleoceanography and documents pronounced changes in the regional climate pattern. It also emphasizes the role of oxic degradation of organic matter, even at horizons with the highest rates of organic carbon ([C.sub.org]) accumulation. The absence of anoxia indicates that enhanced primary production is the main reason for these organic carbon accumulations, and variations in preservation are related to pulses in primary production and nutrient recycling. Despite the high-productivity character of the Selli unit black shales, the [[Delta].sup.13][C.sub.carb] values are not marked by a positive shift, but by an interval of unchanged values. Warm climatic conditions for deposition of the Selli unit are inferred from the presence of southern provenance pollen and low [[Delta].sup.18]O values. For the interval above the Selli unit, changes in the pollen spectrum and an increase in [[Delta].sup.18]O values reflect a hitherto undocumented late early Aptian cooler and more humid climate and/or a reorganization of the Tethyan oceanographic circulation pattern.

The planktonic foraminiferal genera Morozovella and Acarinina rapidly (in [approximately]10 k.y.) diversified during the late Paleocene thermal maximum (LPTM), giving rise to such morphotypes as M. allisonensis (new species), M. africana, and A. sibaiyaensis. Single-specimen isotopic analysis confirms that M. allisonensis and A. sibaiyaensis are restricted to the LPTM carbon isotope excursion recorded at Ocean Drilling Program Site 865 (equatorial Pacific Ocean). The short-lived (50 to several 100 k.y.) 'excursion' taxa attest to the ephemeral effects of the LPTM on the calcareous plankton. Single-specimen oxygen isotope data show that evolution of M. allisonensis and A. sibaiyaensis was accompanied by migration to deeper water depths. Ancestral M. velascoensis and A. soldadoensis were extremely rare or absent during the early stages of the LPTM, but immigrated back into the study area to coexist with their descendants in later LPTM horizons. Photosymbiosis may have facilitated the morozovellid and acarininid diversifications during the oligotrophic conditions of the LPTM.