Facilitatory stimulation of the pre-SMA in healthy aging has distinct effects on task-based activity and connectivity

Semantic cognition is central to communication and our understanding of the world. It is usually well preserved in healthy aging. However, semantic control processes, which guide semantic access and retrieval, decline with age. The present study explored the potential of intermittent theta burst stimulation (iTBS) to enhance semantic cognition in healthy middle-aged to older adults. Using an individualized stimulation approach, we applied iTBS to the pre-supplementary motor area (pre-SMA) and assessed task-specific effects on semantic judgments in functional neuroimaging. We found increased activation after effective relative to sham stimulation only for the semantic task in visual and dorsal attention networks. Further, iTBS increased functional connectivity in domain-general executive networks. Notably, stimulation-induced changes in activation and connectivity related differently to behavior: While increased activation of the parietal dorsal attention network was linked to poorer semantic performance, its enhanced coupling with the pre-SMA was associated with more efficient semantic processing. Our findings indicate differential effects of iTBS on activity and connectivity. We show that iTBS modulates networks in a task-dependent manner and generates remote network effects. Stimulating the pre-SMA was linked to more efficient but not better performance, indicating a role in domain-general semantic control processes distinct to domain-specific semantic control

Tracing North Atlantic volcanism and seaway connectivity across the Paleocene–Eocene Thermal Maximum (PETM)

There is a temporal correlation between the peak activity of the North Atlantic Igneous Province (NAIP) and the Paleocene–Eocene Thermal Maximum (PETM), suggesting that the NAIP may have initiated and/or prolonged this extreme warming event. However, corroborating a causal relationship is hampered by a scarcity of expanded sedimentary records that contain both climatic and volcanic proxies. One locality hosting such a record is the island of Fur in Denmark, where an expanded pre- to post-PETM succession containing hundreds of NAIP ash layers is exceptionally well preserved. We compiled a range of environmental proxies, including mercury (Hg) anomalies, paleotemperature proxies, and lithium (Li) and osmium (Os) isotopes, to trace NAIP activity, hydrological changes, weathering, and seawater connectivity across this interval. Volcanic proxies suggest that NAIP activity was elevated before the PETM and appears to have peaked during the body of the δ13C excursion but decreased considerably during the PETM recovery. This suggests that the acme in NAIP activity, dominated by flood basalt volcanism and thermogenic degassing from contact metamorphism, was likely confined to just ∼ 200 kyr (ca. 56.0–55.8 Ma). The hundreds of thick (> 1 cm) basaltic ashes in the post-PETM strata likely represent a change from effusive to explosive activity, rather than an increase in NAIP activity. Detrital δ7Li values and clay abundances suggest that volcanic ash production increased the basaltic reactive surface area, likely enhancing silicate weathering and atmospheric carbon sequestration in the early Eocene. Signals in lipid biomarkers and Os isotopes, traditionally used to trace paleotemperature and weathering changes, are used here to track seaway connectivity. These proxies indicate that the North Sea was rapidly cut off from the North Atlantic in under 12 kyr during the PETM recovery due to NAIP thermal uplift. Our findings reinforce the hypothesis that the emplacement of the NAIP had a profound and complex impact on Paleocene–Eocene climate, both directly through volcanic and thermogenic degassing and indirectly by driving regional uplift and changing seaway connectivity

Effects of depressive symptoms and peripheral DAT methylation on neural reactivity to alcohol cues in alcoholism

In alcohol-dependent (AD) patients, alcohol cues induce strong activations in brain areas associated with alcohol craving and relapse, such as the nucleus accumbens (NAc) and amygdala. However, little is known about the influence of depressive symptoms, which are common in AD patients, on the brain’s reactivity to alcohol cues. The methylation state of the dopamine transporter gene (DAT) has been associated with alcohol dependence, craving and depression, but its influence on neural alcohol cue reactivity has not been tested. Here, we compared brain reactivity to alcohol cues in 38 AD patients and 17 healthy controls (HCs) using functional magnetic resonance imaging and assessed the influence of depressive symptoms and peripheral DAT methylation in these responses. We show that alcoholics with low Beck’s Depression Inventory scores (n=29) had higher cue-induced reactivity in NAc and amygdala than those with mild/moderate depression scores (n=9), though subjective perception of craving was higher in those with mild/moderate depression scores. We corroborated a higher DAT methylation in AD patients than HCs, and showed higher DAT methylation in AD patients with mild/moderate than low depression scores. Within the AD cohort, higher methylation predicted craving and, at trend level (P=0.095), relapse 1 year after abstinence. Finally, we show that amygdala cue reactivity correlated with craving and DAT methylation only in AD patients with low depression scores. These findings suggest that depressive symptoms and DAT methylation are associated with alcohol craving and associated brain processes in alcohol dependence, which may have important consequences for treatment. Moreover, peripheral DAT methylation may be a clinically relevant biomarker in AD patients

Effects of strontium ranelate and alendronate on bone microstructure in women with osteoporosis: Results of a 2-year study

Summary: Strontium ranelate appears to influence more than alendronate distal tibia bone microstructure as assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT), and biomechanically relevant parameters as assessed by micro-finite element analysis (μFEA), over 2years, in postmenopausal osteoporotic women. Introduction: Bone microstructure changes are a target in osteoporosis treatment to increase bone strength and reduce fracture risk. Methods: Using HR-pQCT, we investigated the effects on distal tibia and radius microstructure of strontium ranelate (SrRan; 2g/day) or alendronate (70mg/week) for 2years in postmenopausal osteoporotic women. This exploratory randomized, double-blind trial evaluated HR-pQCT and FEA parameters, areal bone mineral density (BMD), and bone turnover markers. Results: In the intention-to-treat population (n = 83, age: 64 ± 8years; lumbar T-score: −2.8 ± 0.8 [DXA]), distal tibia Cortical Thickness (CTh) and Density (DCort), and cancellous BV/TV increased by 6.3%, 1.4%, and 2.5%, respectively (all P < 0.005), with SrRan, but not with alendronate (0.9%, 0.4%, and 0.8%, NS) (P < 0.05 for all above between-group differences). Difference for CTh evaluated with a distance transformation method was close to significance (P = 0.06). The estimated failure load increased with SrRan (+2.1%, P < 0.005), not with alendronate (−0.6%, NS) (between-group difference, P < 0.01). Cortical stress was lower with SrRan (P < 0.05); both treatments decreased trabecular stress. At distal radius, there was no between-group difference other than DCort (P < 0.05). Bone turnover markers decreased with alendronate; bALP increased (+21%) and serum-CTX-I decreased (−1%) after 2years of SrRan (between-group difference at each time point for both markers, P < 0.0001). Both treatments were well tolerated. Conclusions: Within the constraints of HR-pQCT method, and while a possible artefactual contribution of strontium cannot be quantified, SrRan appeared to influence distal tibia bone microstructure and FEA-determined biomechanical parameters more than alendronate. However, the magnitude of the differences is unclear and requires confirmation with another metho

Pre-breakup magmatism on the Vøring margin: Insight from new sub-basalt imaging and results from Ocean Drilling program hole 642E

Highlights • Sub-basalt imaging improvement on the Vøring Margin • Definition of a new seismic facies unit: the Lower Series Flows • Significant organic carbon content within the melting crustal segment • Apectodinium augustum marker for the PETM is reworked into the Lower Series Flows • The Lower Series Flows, early Eocene in age, predate the Vøring Margin breakup Abstract Improvements in sub-basalt imaging combined with petrological and geochemical observations from the Ocean Drilling Program (ODP) Hole 642E core provide new constraints on the initial breakup processes at the Vøring Margin. New and reprocessed high quality seismic data allow us to identify a new seismic facies unit which we define as the Lower Series Flows. This facies unit is seismically characterized by wavy to continuous subparallel reflections with an internal disrupted and hummocky shape. Drilled lithologies, which we correlate to this facies unit, have been interpreted as subaqueous flows extruding and intruding into wet sediments. Locally, the top boundary of this facies unit is defined as a negative in polarity reflection, and referred as the K-Reflection. This reflection can be correlated with the spatial extent of pyroclastic deposits, emplaced during transitional shallow marine to subaerial volcanic activities during the rift to drift transition. The drilled Lower Series Flows consist of peraluminous, cordierite bearing peperitic basaltic andesitic to dacitic flows interbedded with thick volcano-sedimentary deposits and intruded sills. The peraluminous geochemistry combined with available C (from calcite which fills vesicles and fractures), Sr, Nd, and Pb isotopes data point towards upper crustal rock-mantle magma interactions with a significant contribution of organic carbon rich pelagic sedimentary material during crustal anatexis. From biostratigraphic analyses, Apectodinium augustum was found in the The Lower Series Flows. This species is a marker for the Paleocene – Eocene Thermal Maximum (PETM). However, the absence of very low carbon isotope values (from bulk organic matter), that characterize the PETM, imply that A.augustum was reworked into the early Eocene sediments of this facies unit which predate the breakup time of the Vøring Margin. Finally, a plausible conceptual emplacement model for the Lower Series Flows facies unit is proposed. This model comprises several stages: (1) the emplacement of subaqueous peperitic basaltic andesitic flows intruding and/or extruding wet sediments; (2) a subaerial to shallow marine volcanism and extrusion of dacitic flows; (3) a proto-breakup phase with intense shallow marine to subaerial explosive volcanism responsible for pyroclastic flow deposits which can be correlated with the seismic K-Reflection and (4) the main breakup stage with intense transitional tholeiitic MORB-type volcanism and large subsidence concomitant with the buildup of the Seaward Dipping Reflector wedge

Tracing North Atlantic volcanism and seaway connectivity across the Paleocene–Eocene Thermal Maximum (PETM)

Abstract. There is a temporal correlation between the peak activity of the North Atlantic Igneous Province (NAIP) and the Paleocene–Eocene Thermal Maximum (PETM), suggesting that the NAIP may have initiated and/or prolonged this extreme warming event. However, corroborating a causal relationship is hampered by a scarcity of expanded sedimentary records that contain both climatic and volcanic proxies. One locality hosting such a record is the island of Fur in Denmark, where an expanded pre- to post-PETM succession containing hundreds of NAIP ash layers is exceptionally well preserved. We compiled a range of environmental proxies, including mercury (Hg) anomalies, paleotemperature proxies, and lithium (Li) and osmium (Os) isotopes, to trace NAIP activity, hydrological changes, weathering, and seawater connectivity across this interval. Volcanic proxies suggest that NAIP activity was elevated before the PETM and appears to have peaked during the body of the δ13C excursion but decreased considerably during the PETM recovery. This suggests that the acme in NAIP activity, dominated by flood basalt volcanism and thermogenic degassing from contact metamorphism, was likely confined to just ∼ 200 kyr (ca. 56.0–55.8 Ma). The hundreds of thick (&gt; 1 cm) basaltic ashes in the post-PETM strata likely represent a change from effusive to explosive activity, rather than an increase in NAIP activity. Detrital δ7Li values and clay abundances suggest that volcanic ash production increased the basaltic reactive surface area, likely enhancing silicate weathering and atmospheric carbon sequestration in the early Eocene. Signals in lipid biomarkers and Os isotopes, traditionally used to trace paleotemperature and weathering changes, are used here to track seaway connectivity. These proxies indicate that the North Sea was rapidly cut off from the North Atlantic in under 12 kyr during the PETM recovery due to NAIP thermal uplift. Our findings reinforce the hypothesis that the emplacement of the NAIP had a profound and complex impact on Paleocene–Eocene climate, both directly through volcanic and thermogenic degassing and indirectly by driving regional uplift and changing seaway connectivity

Evidence for Low‐Pressure Crustal Anatexis During the Northeast Atlantic Break‐Up

While basaltic volcanism is dominant during rifting and continental breakup, felsic magmatism may be a significant component of some rift margins. During International Ocean Discovery Program (IODP) Expedition 396 on the continental margin of Norway, a graphite‐garnet‐cordierite bearing dacitic unit (the Mimir dacite) was recovered in two holes within early Eocene sediments on Mimir High (Site U1570), a marginal high on the Vøring Transform Margin. Here, we present a comprehensive textural, petrological, and geochemical study of the Mimir dacite in order to assess its origin and discuss the geodynamic implications. The major mineral phases (garnet, cordierite, quartz, plagioclase, alkali feldspar) are hosted in a fresh rhyolitic, vesicular, glassy matrix that is locally mingled with sediments. The major element chemistry of garnet and cordierite, the presence of zircon inclusions with inherited cores, and thermobarometric calculations all support an upper crustal metapelitic origin. While most magma‐rich margin models favor crustal anatexis in the lower crust, thermobarometric calculations performed here show that the Mimir dacite was produced at upper‐crustal depths (<5 kbar, 18 km depth) and high temperature (750–800°C) with up to 3 wt% water content. In situ U‐Pb analyses on zircon inclusions give a magmatic crystallization age of 54.6 ± 1.1 Ma, consistent with emplacement that post‐dates the Paleocene‐Eocene Thermal Maximum. Our results suggest that the opening of the Northeast Atlantic was associated with a phase of low‐pressure, high‐temperature crustal anatexis preceding the main phase of magmatism

Paleocene–Eocene age glendonites from the Mid-Norwegian Margin – indicators of cold snaps in the hothouse?

The International Ocean Discovery Program (IODP) Expedition 396 to the mid-Norwegian margin recovered &gt; 1300 m of pristinely preserved, volcanic-ash-rich sediments deposited during the late Paleocene and early Eocene from close to the centre of the North Atlantic Igneous Province (NAIP). Remarkably, many of these cores contain glendonites, pseudomorphs after the purported cold-water mineral ikaite, from sediments dated to the late Paleocene and early Eocene. These time intervals span some of the hottest climates of the Cenozoic, including the Paleocene–Eocene Thermal Maximum (PETM). Global deep-ocean temperatures are not thought to have dropped below 10 ∘C at any point during this time, making the occurrence of supposedly cold-water (near-freezing temperature) glendonite pseudomorphs seemingly paradoxical. This study presents a detailed sedimentological, geochemical, and microscopic study of the IODP Exp. 396 glendonites and presents an updated model for the ikaite-to-calcite transformation for these glendonites. Specifically, we show that early diagenesis of basaltic ashes of the NAIP appear to have chemically promoted ikaite growth in the sediments in this region. Together with existing knowledge of late Paleocene and early Eocene glendonites from Svalbard to the north and early Eocene glendonites from Denmark to the south, these new glendonite finds possibly imply episodic, short-duration, and likely localized cooling in the Nordic Seas region, which may have been directly or indirectly linked to the emplacement of the NAIP.</p