The full neural circuits of conscious perception remain unknown. Using a visual perception task, we directly recorded a subcortical thalamic awareness potential (TAP). We also developed a unique paradigm to classify perceived versus not perceived stimuli using eye measurements to remove confounding signals related to reporting on conscious experiences. Using fMRI, we discovered three major brain networks driving conscious visual perception independent of report: first, increases in signal detection regions in visual, fusiform cortex, and frontal eye fields; and in arousal/salience networks involving midbrain, thalamus, nucleus accumbens, anterior cingulate, and anterior insula; second, increases in frontoparietal attention and executive control networks and in the cerebellum; finally, decreases in the default mode network. These results were largely maintained after excluding eye movement-based fMRI changes. Our findings provide evidence that the neurophysiology of consciousness is complex even without overt report, involving multiple cortical and subcortical networks overlapping in space and time.

Lay Summary Higher ustekinumab concentrations were associated with improved radiologic (Simplified Magnetic Resonance Index of Activity for Crohn’s Disease) and stringent biomarker (calprotectin) outcomes. The high concentration needed for these novel endpoints validates previous studies using the same assay.

Purpose of the Review. In this review, we bring together recent developments in the detection and management of radiation retinopathy. Recent Findings Research into OCT-angiography for radiation retinopathy has led to the identification of biomarkers of early radiation-induced changes in the retinal microvasculature including focal capillary loss and vascular remodeling. These microvasculature changes are detectable after exposure to radiation but prior to the emergence of classical clinical markers historically used to diagnose radiation retinopathy. The ability to detect subclinical changes may present the need to redefine radiation retinopathy diagnostic criteria which may ultimately impact management. Additionally, explorations into prophylactic treatment following radiation exposure and development of newer anti-VEGF agents may present more options for retinal specialists to prevent or treat vision loss and retinal vasculopathy from radiation exposure. Summary Currently, anti-VEGF injections and/or intravitreal steroids remain the primary treatment following a diagnosis of radiation retinopathy. However, a mainstay treatment and management strategy have not yet been identified. In the future, new anatomical endpoints for radiation retinopathy may be identified with OCT-angiography while prophylactic treatment with anti-VEGF agents following radiation therapy may reduce initial vision loss and changes to the retina.

Introduction: Controversy exists for ustekinumab concentrations needed in Crohn's disease (CD). No data exist comparing ustekinumab concentrations and validated radiologic outcomes. We characterized these relationships and clarified concentrations needed. Methods: CD patients on maintenance ( . 16 weeks) ustekinumab with both ustekinumab concentrations and simplified magnetic resonance index of activity (sMaRIA) scoring were included. Ustekinumab concentrations were compared between those with and without (1) radiologic remission (sMaRIA , 2), (2) severe radiologic inflammation (sMaRIA , 3) and (3) fecal calprotectin (FCP) biomarker remission (FCP , 50 mg/g). Area under the receiver-operating characteristic (AUROC) curve determined optimal ustekinumab concentrations. Outcomes were compared between patients above and below identified ustekinumab thresholds. Results: Thirty-eight paired ustekinumab concentrations and MRE were included. Ustekinumab concentrations were higher with radiologic remission (11.4 mg/mL vs. 6.4 mg/mL, P5.005) and had good diagnostic accuracy for radiologic remission (AUROC 0.76, 95% CI 0.60 -0.91) and for absence of severe inflammation (AUROC 0.71, 95% CI 0.55 -0.88, optimal concentration 8.4 mg/mL). With ustekinumab $ 8.4 mg/mL, higher proportions had radiologic remission (63.2% vs. 21.1%, P5.01) and absence of severe inflammation (78.9% vs. 36.8%, P5.01) compared to patients with lower concentrations. Ustekinumab concentrations had good diagnostic accuracy (AUROC 0.73, 95% CI 0.52 -0.94) for FCP biomarker remission (optimal concentration: 6.1 mg/mL). Patients with ustekinumab concentrations $ 6.1 mg/mL had higher proportions with biomarker remission (72.2% vs. 12.5% P , .01) compared to those with lower concentrations. (Figure ) Conclusion: Ustekinumab concentrations are associated with radiologic and biomarker outcomes in CD. These data validate the need for higher ustekinumab concentrations.

Understanding consciousness is one of the most important and challenging questions in modern science. Existing theories have pursued single unifying mechanisms but do not succeed in explaining consciousness. Importantly, the neural circuits that distinguish messages that arrive from the outside world and attain consciousness have remained unknown. Here we identify signals throughout the entire brain at high spatiotemporal resolution specifically related to consciousness. To accomplish this, we combined a large sample size of electrical and neuroimaging data with a novel experimental approach to remove confounding signal unrelated to consciousness1-3. We discovered three major brain networks driving conscious visual perception. First, we found increases in signal detection regions in visual, fusiform cortex, and frontal eye fields; and in arousal/salience networks involving midbrain, thalamus, nucleus accumbens, anterior cingulate, and anterior insula. Second, we found increases in frontoparietal attention and executive control networks and in the cerebellum. Finally, we found decreases in the default mode network. Our results identify subcortical and cortical networks designed for signal detection, attentional amplification, and perceptual processing that together can explain visual consciousness. These findings provide evidence that understanding consciousness can be reframed as requiring multiple overlapping brain networks to produce consciousness of visual events4.