Multiple sessions of transcranial direct current stimulation to the intact hemisphere improves visual function after unilateral ablation of visual cortex

Damage to cerebral systems is frequently followed by the emergence of compensatory mechanisms, which serve to reduce the effects of brain damage and allow recovery of function. Intrinsic recovery, however, is rarely complete. Non-invasive brain stimulation technologies have the potential to actively shape neural circuits and enhance recovery from brain damage. In this study, a stable deficit for detecting and orienting to visual stimuli presented in the contralesional visual hemifield was generated by producing unilateral brain damage of the right posterior parietal and contiguous visual cortical areas. A long regimen of inhibitory non-invasive transcranial directcurrent stimulation (cathodal 2mA, 20 min) was applied to the contralateral (intact) posterior parietal cortex over 14 weeks (total of 70 sessions, one per day, five days per week) and behavioral outcomes were periodically assessed. In three out of four stimulated cats, lasting recovery of visuospatial function was observed. Recovery started after 2-3 weeks of stimulation, and recovered targets were located first in the periphery, and moved to more central visual field locations with the accrual of stimulation sessions. Recovery for moving tasks followed a biphasic pattern before reaching plateau levels. Recovery did not occur for more difficult visual tasks. These findings highlight the ability of multiple sessions of transcranial direct-current stimulation to produce recovery of visuospatial function after unilateral brain damage

Causal frequency-specific contributions of frontal spatiotemporal patterns induced by non-invasive neurostimulation to human visual performance

Neural oscillatory activity is known to play a crucial role in brain function. In the particular domain of visual perception, specific frequency bands in different brain regions and networks, from sensory areas to large-scale frontoparietal systems, have been associated with distinct aspects of visual behavior. Nonetheless, their contributions to human visual cognition remain to be causally demonstrated. We hereby used non-uniform (and thus non-frequency-specific) and uniform (frequency-specific) high-beta and gamma patterns of noninvasive neurostimulation over the right frontal eye field (FEF) to isolate the behavioral effects of oscillation frequency and provide causal evidence that distinct visual behavioral outcomes could be modulated by frequency-specific activity emerging from a single cortical region. In a visual detection task using near-threshold targets, high-beta frequency enhanced perceptual sensitivity (d ) without changing response criterion (beta), whereas gamma frequency shifted response criterion but showed no effects on perceptual sensitivity. The lack of behavioral modulations by non-frequency-specific patterns demonstrates that these behavioral effects were specifically driven by burstfrequency. We hypothesizethat suchfrequency-coded behavioral impact of oscillatory activity may reflect a general brain mechanism to multiplex functions within the same neural substrate. Furthermore, pathological conditions involving impaired cerebral oscillations could potentially benefit in the near future from the use of neurostimulation to restore the characteristic oscillatory patterns of healthy systems

On the use of fast blue, fluoro-gold and diamidino yellow for retrograde tracing after peripheral nerve injury: uptake, fading, dye interactions, and toxicity

The usefulness of three retrograde fluorescent dyes for tracing injured peripheral axons was investigated. The rat sciatic was transected bilaterally and the proximal end briefly exposed to either Fast Blue (FB), Fluoro-Gold (FG) or to Diamidino Yellow (DY) on the right side, and to saline on the left side, respectively. The nerves were then resutured and allowed to regenerate. Electrophysiological tests 3 months later showed similar latencies and amplitudes of evoked muscle and nerve action potentials between tracer groups. The nerves were then cut distal to the original injury and exposed to a second (different) dye. Five days later, retrogradely labelled neurones were counted in the dorsal root ganglia (DRGs) and spinal cord ventral horn, The number of neurones labelled by the first tracer was similar for all three dyes in the DRG and ventral horn except for FG, which labelled fewer motoneurones. When used as second tracer, DY labelled fewer neurones than FG and FB in some experimental situations. The total number of neurotics labelled by the first and/or second tracer was reduced by about 30% compared with controls. The contributions of cell death as well as different optional tracer combinations for studies of nerve regeneration are discussed

Fluvio-deltaic record of increased sediment transport during the Middle Eocene Climatic Optimum (MECO), Southern Pyrenees, Spain

The early Cenozoic marine sedimentary record is punctuated by several brief episodes (&lt;200 kyr) of abrupt global warming, called hyperthermals, that have disturbed ocean life and water physicochemistry. Moreover, recent studies of fluvial–deltaic systems, for instance at the Palaeocene–Eocene Thermal Maximum, revealed that these hyperthermals also impacted the hydrologic cycle, triggering an increase in erosion and sediment transport at the Earth's surface. Contrary to the early Cenozoic hyperthermals, the Middle Eocene Climatic Optimum (MECO), lasting from 40.5 to 40.0 Ma, constitutes an event of gradual warming that left a highly variable carbon isotope signature and for which little data exist about its impact on Earth surface systems. In the South Pyrenean foreland basin (SPFB), an episode of prominent deltaic progradation (Belsué–Atarés and Escanilla formations) in the middle Bartonian has been usually associated with increased Pyrenean tectonic activity, but recent magnetostratigraphic data suggest a possible coincidence between the progradation and the MECO warming period. To test this hypothesis, we measured the stable-isotope composition of carbonates (δ13Ccarb and δ18Ocarb) and organic matter (δ13Corg) of 257 samples in two sections of SPFB fluvial–deltaic successions covering the different phases of the MECO and already dated with magnetostratigraphy. We find a negative shift in δ18Ocarb and an unclear signal in δ13Ccarb around the transition from magnetic chron C18r to chron C17r (middle Bartonian). These results allow, by correlation with reference sections in the Atlantic and Tethys, the MECO to be identified and its coincident relationship with the Belsué–Atarès fluvial–deltaic progradation to be documented. Despite its long duration and a more gradual temperature rise, the MECO in the South Pyrenean foreland basin may have led, like lower Cenozoic hyperthermals, to an increase in erosion and sediment transport that is manifested in the sedimentary record. The new data support the hypothesis of a more important hydrological response to the MECO than previously thought in mid-latitude environments, including those around the Tethys.</p

Impact of brain tissue filtering on neurostimulation fields: A modeling study

Electrical neurostimulation techniques, such as deep brain stimulation (DBS) and transcranial magnetic stimulation (TMS), are increasingly used in the neurosciences, e.g., for studying brain function, and for neurotherapeutics, e.g., for treating depression, epilepsy, and Parkinson's disease. The characterization of electrical properties of brain tissue has guided our fundamental understanding and application of these methods, from electrophysiologic theory to clinical dosing-metrics. Nonetheless, prior computational models have primarily relied on ex-vivo impedance measurements. We recorded the in-vivo impedances of brain tissues during neurosurgical procedures and used these results to construct MRI guided computational models of TMS and DBS neurostimulatory fields and conductance-based models of neurons exposed to stimulation. We demonstrated that tissues carry neurostimulation currents through frequency dependent resistive and capacitive properties not typically accounted for by past neurostimulation modeling work. We show that these fundamental brain tissue properties can have significant effects on the neurostimulatory-fields (capacitive and resistive current composition and spatial/temporal dynamics) and neural responses (stimulation threshold, ionic currents, and membrane dynamics). These findings highlight the importance of tissue impedance properties on neurostimulation and impact our understanding of the biological mechanisms and technological potential of neurostimulatory methods.United States. Defense Advanced Research Projects Agency (Contract W31P4Q-09-C-0117)National Institute of Neurological Disorders and Stroke (U.S.) (Award R43NS062530)National Institute of Neurological Disorders and Stroke (U.S.) (Award 1R44NS080632

TRIB3 silencing promotes the downregulation of Akt pathway and PAX3-FOXO1 in high-risk rhabdomyosarcoma

Fusion protein; RhabdomyosarcomaProteïna de fusió; RabdomiosarcomaProteína de fusión; RabdomiosarcomaRhabdomyosarcoma (RMS), such as other childhood tumors, has witnessed treatment advancements in recent years. However, high-risk patients continue to face poor survival rates, often attributed to the presence of the PAX3/7-FOXO1 fusion proteins, which has been associated with metastasis and treatment resistance. Despite efforts to directly target these chimeric proteins, clinical success remains elusive. In this study, the main aim was to address this challenge by investigating regulators of FOXO1. Specifically, we focused on TRIB3, a potential regulator of the fusion protein in RMS. Our findings revealed a prominent TRIB3 expression in RMS tumors, highlighting its correlation with the presence of fusion protein. By conducting TRIB3 genetic inhibition experiments, we observed an impairment on cell proliferation. Notably, the knockdown of TRIB3 led to a decrease in PAX3-FOXO1 and its target genes at protein level, accompanied by a reduction in the activity of the Akt signaling pathway. Additionally, inducible silencing of TRIB3 significantly delayed tumor growth and improved overall survival in vivo. Based on our analysis, we propose that TRIB3 holds therapeutic potential for treating the most aggressive subtype of RMS. The findings herein reported contribute to our understanding of the underlying molecular mechanisms driving RMS progression and provide novel insights into the potential use of TRIB3 as a therapeutic intervention for high-risk RMS patients.This research was funded by grants from Institut Català d’Oncologia (ICO), Instituto de Salud Carlos III (PI21/00640), Fundació la Marató de TV3, Fundació BOSCH, Iniciativa Tot per tu, Fundació Amics Joan Petit, Fundación Inocente, and Mi compañero de viaje

Manipulation of Pre-Target Activity on the Right Frontal Eye Field Enhances Conscious Visual Perception in Humans

The right Frontal Eye Field (FEF) is a region of the human brain, which has been consistently involved in visuo-spatial attention and access to consciousness. Nonetheless, the extent of this cortical site’s ability to influence specific aspects of visual performance remains debated. We hereby manipulated pre-target activity on the right FEF and explored its influence on the detection and categorization of low-contrast near-threshold visual stimuli. Our data show that pre-target frontal neurostimulation has the potential when used alone to induce enhancements of conscious visual detection. More interestingly, when FEF stimulation was combined with visuo-spatial cues, improvements remained present only for trials in which the cue correctly predicted the location of the subsequent target. Our data provide evidence for the causal role of the right FEF pre-target activity in the modulation of human conscious vision and reveal the dependence of such neurostimulatory effects on the state of activity set up by cue validity in the dorsal attentional orienting network