Anterior cingulate cortex (ACC) and striatum (STR) contain neurons encoding not only the expected values of actions, but also the value of stimulus features irrespective of actions. Values about stimulus features in ACC or STR might contribute to adaptive behavior by guiding fixational information sampling and biasing choices toward relevant objects, but they might also have indirect motivational functions by enabling subjects to estimate the value of putting effort into choosing objects. Here, we tested these possibilities by modulating neuronal activity in ACC and STR of nonhuman primates using transcranial ultrasound stimulation while subjects learned the relevance of objects in situations with varying motivational and cognitive demands. Motivational demand was indexed by varying gains and losses during learning, while cognitive demand was varied by increasing the uncertainty about which object features could be relevant during learning. We found that ultrasound stimulation of the ACC, but not the STR, reduced learning efficiency and prolonged information sampling when the task required averting losses and motivational demands were high. Reduced learning efficiency was particularly evident at high cognitive demands and immediately after subjects experienced a loss of already attained tokens. These results suggest that the ACC supports flexible learning of feature values when loss experiences impose a motivational challenge and when uncertainty about the relevance of objects is high. Taken together, these findings provide causal evidence that the ACC facilitates resource allocation and improves visual information sampling during adaptive behavior.
Neural activity in anterior cingulate cortex and the anterior striatum predicts which visual objects are sampled and how likely objects are paired with positive or aversive outcomes. We causally tested whether these neural signals contribute to behavioral flexibility. Disrupting with transcranial ultrasound the ACC, but not striatum, prolonged information sampling when attentional demands were high, impaired flexible learning, and reduced the ability to avoid losses. These results support a role of the ACC in guiding attention and information sampling to overcome motivational conflict during adaptive behaviors.
Rare cancers are an understudied and deadly public health problem. Estimates for the percentage of cancer diagnoses that are rare vary depending upon the source cited and the definition of what constitutes a rare cancer. A frequently cited report states that 25% of all adult cancers are rare. However, given the ever-changing landscape of cancer biology and as a result of changes in disease classification, oft-cited percentages underestimate the burden of rare cancers. To address this discrepancy, we reviewed the most recent publicly available data regarding the incidence of all cancers in the United States. Following the NCI definition of a rare disease as one affecting fewer than 15 persons per 100,000 per year, for 2017, a cancer affecting 48,952 or fewer is classified as rare. We considered each cancer individually, acknowledging subtypes based upon the criteria of scientifically accepted definitions, treatments, and histology. We then compiled statistics for each type and subtype. By this method, the total number of estimated new cancer patients in 2017 was 1,685,346, which differed only 0.2% from the Cancer.gov's publicly available estimate of 1,688,780. However, in contrast to previously published data that indicated that 60 of 71 cancer types were rare, we identified a total of 347 cancers, of which 337 were rare. The estimate for rare cancer diagnoses in the U.S. per year was therefore 875,084. Ultimately, 51.9% of all cancer diagnoses are classified as rare cancers by this method. In addition, of 52 major groupings of cancer, 35 (67.3%) disproportionately affect minorities in terms of incidence or overall survival. Seven groupings exclusively or almost exclusively affect women, and 7 additional groups display disproportionate incidence or negative outcomes in women. In addition, while many cancers affect children, and while all cancer in children is rare, at least 55 cancers exclusively or frequently affect children. This analysis clearly shows that the incidence of rare cancer in the United States is widely misunderstood and that cancer in total disproportionately affects historically underserved populations. Treatment options are needed for each form of cancer and should be developed based on a thorough understanding of each disease's biology. In addition, efforts to understand and address the origins of demographic disparities can help reduce disease burden. Citation Format: Katherine Arline, Emily Zeme, Robert L. Treuting, Rodrigo Bravo, Jamie Barber, Christopher Higginson, Jon Goetz, William Siders, Johanne Kaplan. Rare isn't rare: Rare cancers compose over 50% of all U.S. diagnoses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1198.
During transcranial focused ultrasound (FUS) procedures, accurate targeting is important and neuronavigation with optically tracked tools is used to estimate the free-field focal location on pre-acquired images. Offline neuronavigation systems do not typically incorporate aberrating effects of the skull known to displace and distort the focus. Here, we developed a pipeline that integrated patient-specific acoustic simulations informed by transformations from optically tracked FUS procedures as a tool to evaluate transcranial pressure fields and demonstrated its use in three FUS scenarios: magnetic resonance imaging-guided (MR-guided) phantom experiments, MR-guided non-human primate (NHP) experiments, an offline behaving NHP experiments. Distance vectors between the estimated focus from optical tracking and peak intracranial location from simulations were less than 1 mm for all groups (Phantom: 0.6 ± 0.3 mm, NHP: 0.7 ± 0.3 mm, Behaving NHP: 0.5 ± 0.2 mm). Comparisons of the target registration error of MR measurements with the optically tracked focus (TRETracked) and simulated focus (TRESimulated) suggest that focal location errors are dominated by optical tracking errors rather than aberration through the skull in the NHP (Phantom: TRETracked: 3.3 ± 1.4 mm, Phantom TRESimulated: 3.3 ± 1.9 mm, NHP TRETracked: 3.9 ± 1.9 mm, NHP TRESimulated: 4.1 ± 1.6 mm). Our software pipeline provides patient-specific estimates of the acoustic field during transcranial FUS procedures.
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