Single Trial Decoding of Movement Intentions Using Functional Ultrasound Neuroimaging

Brain-machine interfaces (BMI) are powerful devices for restoring function to people living with paralysis. Leveraging significant advances in neurorecording technology, computational power, and understanding of the underlying neural signals, BMI have enabled severely paralyzed patients to control external devices, such as computers and robotic limbs. However, high-performance BMI currently require highly invasive recording techniques, and are thus only available to niche populations. Here, we show that a minimally invasive neuroimaging approach based on functional ultrasound (fUS) imaging can be used to detect and decode movement intention signals usable for BMI. We trained non-human primates to perform memory-guided movements while using epidural fUS imaging to record changes in cerebral blood volume from the posterior parietal cortex, a brain area important for spatial perception, multisensory integration, and movement planning. Using hemodynamic signals acquired during movement planning, we classified left-cued vs. right-cued movements, establishing the feasibility of ultrasonic BMI. These results demonstrate the ability of fUS-based neural interfaces to take advantage of the excellent spatiotemporal resolution, sensitivity, and field of view of ultrasound without breaching the dura or physically penetrating brain tissue

A Cystine-Rich Whey Supplement (Immunocal®) Provides Neuroprotection from Diverse Oxidative Stress-Inducing Agents In Vitro

Oxidative stress is a principal mechanism underlying the pathophysiology of neurodegeneration. Therefore, nutritional enhancement of endogenous antioxidant defenses may represent a viable treatment option. We investigated the neuroprotective properties of a unique whey protein supplement (Immunocal®) that provides an essential precursor (cystine) for synthesis of the endogenous antioxidant, glutathione (GSH). Primary cultures of rat cerebellar granule neurons (CGNs), NSC34 motor neuronal cells, or HT22 hippocampal cells were preincubated in medium containing Immunocal and then subsequently treated with agents known to induce oxidative stress. Immunocal protected CGNs against neurotoxicity induced by the Bcl-2 inhibitor, HA14-1, the nitric oxide donor, sodium nitroprusside, CuCl2, and AlCl3. Immunocal also significantly reduced NSC34 cell death due to either H2O2 or glutamate and mitigated toxicity in HT22 cells overexpressing β-amyloid1-42. The neuroprotective effects of Immunocal were blocked by inhibition of γ-glutamyl-cysteine ligase, demonstrating dependence on de novo GSH synthesis. These findings indicate that sustaining GSH with Immunocal significantly protects neurons against diverse inducers of oxidative stress. Thus, Immunocal is a nutritional supplement worthy of testing in preclinical animal models of neurodegeneration and in future clinical trials of patients afflicted by these diseases

Geographic patterns in fruit colour diversity: do leaves constrain the colour of fleshy fruits?

7 pages, 2 figures.-- Supplementary material available: The list of fruit species, their colour as perceived by humans, their provenance and main disperser types. The dispersal category "mixed" refers to species consumed by birds and mammals (XLS, 43 kb).We tested for geographic patterns in fruit colour diversity. Fruit colours are thought to promote detection by seed dispersers. Because seed dispersers differ in their spectral sensitivities, we predicted that fruit colour diversity would be higher in regions with higher seed disperser diversity (i.e. the tropics). We collected reflectance data on 232 fruiting plant species and their natural backgrounds in seven localities in Europe, North and South America, and analysed fruit colour diversity according to the visual system of birds—the primary consumer types of these fruits. We found no evidence that fruit colours are either more conspicuous or more diverse in tropical areas characterised by higher seed disperser diversity. Instead, fruit colour diversity was lowest in central Brazil, suggesting that fruit colours may be more diverse in temperate regions. Although we found little evidence for geographic variation in fruit hues, the spectral properties of fruits were positively associated with the spectral properties of backgrounds. This result implies that fruit colours may be influenced by selection on the reflectance properties of leaves, thus constraining the evolution of fruit colour. Overall, the results suggest that fruit colours in the tropics are neither more diverse nor more conspicuous than temperate fruits, and that fruit colours may be influenced by correlated selection on leaf reflectance properties.H.M.S. was sponsored by a Deutsche Forschungsgemeinschaft (DFG) grant (Scha 1008/4-1). E.C. was sponsored by Fundaçao de Amparo à Pesquisa do Estado de Sao Paulo (Fapesp) and a Deutscher Akademischer Austausch Dienst (DAAD) fellowship. M.G. was sponsored by Fapesp and receives a research fellowship from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and E.C. a Fapesp fellowship. A.V. was supported by the Marie Curie European programme (grant MERG-CT-2004-510260), I3P [Consejo Superior de Investigaciones Científicas (CSIC)] and Acción Integrada (HA2006-0038; Ministerio de Educación y Ciencia).Peer reviewe

Evaluating predictive factors for toxicities experienced by head & neck cancer patients undergoing radiotherapy.

PurposeThe purpose of this study was to evaluate if HPV status serves as an independent predictor of early and late dysphagia outcomes when considered alongside standard patient characteristics and dose metrics for head and neck cancer patients treated with radiotherapy.Methods and materialsThe age, sex, smoking history, cancer type (oropharyngeal vs non-oropharyngeal), HPV status, and early and late dysphagia outcomes were obtained for 99 retrospective head and neck cancer patients treated at our clinic with radiotherapy. Additionally for each patient, the mean radiation dose to the pharynx, superior/middle/inferior pharyngeal constrictor muscles, and cricopharyngeus was calculated. The predictive power of these clinical characteristics and radiation metrics was evaluated using chi-square tests for categorical variables and t-tests for continuous variables. Then multi-variate logistic models were built for each outcome using a single dose metric at a time, and either HPV status, cancer type, or both. Multi-variate models were built using both top-down and bottom-up technique to establish the most predictive independent covariates.ResultsIn the univariate analysis for early dysphagia, cancer type (p = 0.04) and four dose metrics (p ≤ 0.02) were significantly associated with outcome, while for late dysphagia, only cancer type (p = 0.04) was associated with outcome. In the multivariate analysis for early dysphagia, cancer type, smoking history, and mean dose to the five structures were consistently selected as covariates. For late dysphagia, either HPV status or cancer type was selected in each model and the mean dose to the cricopharyngeus was selected in one model.ConclusionWhile HPV is a known contributing factor for tumor prognosis in oropharyngeal cancers, its role in normal tissue toxicities for head and neck cancers has not previously been evaluated. Our results indicate having an oropharyngeal cancer may increase a patient's risk of high-grade early and late dysphagia while HPV status was seldom selected

Adaptive replanning using cone beam CT for deformation of original CT simulation

BackgroundDuring a course of radiation therapy, anatomical changes such as a decrease in tumour size or weight loss can trigger the need for repeating a computed tomography (CT) simulation scan in order to generate a new treatment plan. This adaptive approach requires a separate appointment for an additional CT scan which generates additional burden, cost, and radiation exposure for patients.Case presentationHere, we present a case of a head and neck cancer patient who required palliative radiation for a large neck mass. During treatment, he had a remarkable response which required a replan due to rapid tumour downsizing. In this case, we used a novel technique to avoid repeating the planning CT simulation by using a mid-treatment high-quality cone beam CT (CBCT) to deform the secondary image (plan CT) of the original planning CT and generate a new adapted treatment plan.ConclusionThis is the first report to our knowledge using a Halcyon CBCT to deform the original planning CT in order to generate a new radiation treatment plan, and this novel technique represents a new potential method of adaptive replanning for select patients

Gene alterations as predictors of radiation-induced toxicity in head and neck squamous cell carcinoma.

BackgroundOptimizing the therapeutic ratio for radiation therapy (RT) in head and neck squamous cell carcinoma (HNSCC) is uniquely challenging owing to high rates of early and late toxicity involving nearby organs at risk. These toxicities have a profound impact on treatment compliance and quality of life. Emerging evidence suggests that RT dose alone cannot fully account for the variable severity of RT-related adverse events (rtAEs) observed in HNSCC patients. Next-generation sequencing has become an increasingly valuable tool with widespread use in the oncology field and is being robustly explored for predicting rtAEs beyond dosimetric data.MethodsPatients who had Foundation Medicine sequencing data and received RT for primary or locally recurrent HNSCC were selected for this study. Early and late toxicity data were collected and reported based on Common Terminology Criteria for Adverse Events version 5.0. Dosimetric parameters were collected for pertinent structures.ResultsA total of HNSCC 37 patients were analyzed in this study. Genetic alterations in BRCA2, ERBB3, NOTCH1 and CCND1 were all associated with higher mean grade of toxicity with BRCA2 alteration implicated in all toxicity parameters evaluated including mucositis, early dysphagia, xerostomia and to a lesser extent, late dysphagia. Interestingly, patients who exhibited alterations in both BRCA2 and ERBB3 experienced a twofold or greater increase in early dysphagia, early xerostomia and late dysphagia compared to ERBB3 alteration alone. Furthermore, several gene alterations were associated with improved toxicity outcomes. Within an RT supersensitive patient subset, alterations were found in TNFAIP3, HNF1A, SPTA1 and CASP8. All of these alterations were not found in the RT insensitive patient subset. We found 17 gene alterations in the RT insensitive patient subset that were not found in the RT supersensitive patient subset.ConclusionDespite consistent RT dosimetric parameters, patients with HNSCC experience heterogeneous patterns of rtAEs. Identifying factors associated with toxicity outcomes offers a new avenue for personalized precision RT therapy and prophylactic management. Here, next-generation sequencing in a population of HNSCC patients correlates several genetic alterations with severity of rtAEs. Further analysis is urgently needed to identify genetic patterns associated with rtAEs in order to reduce harmful outcomes in this challenging population