Musical training does not enhance neural sound encoding at early stages of the auditory system: A large-scale multisite investigation.

Musical training has been associated with enhanced neural processing of sounds, as measured via the frequency following response (FFR), implying the potential for human subcortical neural plasticity. We conducted a large-scale multi-site preregistered study (n > 260) to replicate and extend the findings underpinning this important relationship. We failed to replicate any of the major findings published previously in smaller studies. Musical training was related neither to enhanced spectral encoding strength of a speech stimulus (/da/) in babble nor to a stronger neural-stimulus correlation. Similarly, the strength of neural tracking of a speech sound with a time-varying pitch was not related to either years of musical training or age of onset of musical training. Our findings provide no evidence for plasticity of early auditory responses based on musical training and exposure.

Imaging and analytical methods as applied to the evaluation of vasculature and hypoxia in human brain tumors.

Tissue hypoxia results from the interaction of cellular respiration, vascular oxygen carrying capacity, and vessel distribution. We studied the relationship between tumor vasculature and regions of low pO(2) using quantitative analysis of binding of the 2-nitroimidazole EF5 given to patients intravenously (21 mg/kg) approximately 24 h preceding surgery. We describe new computer algorithms for determining EF5 binding as a function of radial distance from individual blood vessels and converting this value to tissue pO(2). Tissues from six human brain tumors were assessed. In a hemangiopericytoma, a WHO Grade 2 and WHO Grade 3 glial brain tumor, all tissue pO(2) values calculated by EF5 binding were >20 mmHg (described as "physiologically oxygenated"). In these three tumors, EF5 binding gradients (measured as a function of distance from each observed vessel) were low, with small positive and negative values averaging close to zero. Much lower tissue oxygen levels were found, including near some vessels, in glioblastomas. Gradients of EF5 binding away from vessels were larger in glioblastomas than in the low-grade tumors, but positive and negative values again averaged to near zero. Based on these preliminary data, we hypothesize a new paradigm for tumor blood flow in human brain tumors whereby in-flowing and out-flowing blood patterns may have contrasting effects on average tissue EF5 (and by inference, oxygen) gradients. Our studies also imply that neither distance to the nearest blood vessel nor distance from each observed blood vessel provide reliable estimates of tissue pO(2).

Oxygen levels in normal and previously irradiated human skin as assessed by EF5 binding.

The oxygen status of skin is a controversial topic. Skin is radiosensitive, suggesting it is well-oxygenated. However, it can be further sensitized with nitroimidazole drugs, implying that it is partially hypoxic. Skin oxygen levels are difficult to measure with either electrodes or the hypoxia-monitoring agent (3)H-misonidazole. For the latter, binding has previously been reported to be high in murine skin, but this could be attributed to either non-oxygen-dependent variations in nitroreductase activity, drug metabolism, and/or actual oxygen gradients. We obtained tumor and skin from patients given EF5, a 2-nitroimidazole tissue hypoxia monitor. We performed immunohistochemical studies using highly specific monoclonal antibodies for the hypoxia-dependent production of EF5 tissue adducts. Some tissue sections were counterstained using either Ki67 for proliferation or CD31 for vessels. We found that the human dermis is well-oxygenated, the epidermis is modestly hypoxic and portions of some sebaceous glands and hair follicles are moderately to severely hypoxic. Normal and irradiated skin had similar oxygenation patterns. Control studies demonstrated that these observations are not due to tissue variations in nitroreductase activity. The importance of the highly heterogeneous distribution of oxygen in skin requires further study, but recent investigations suggest that skin hypoxia may have important clinical ramifications including mediating cellular transformation.