240 research outputs found

    Calibration approaches for distributed hydrologic models in poorly gaged basins: implication for streamflow projections under climate change

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    Abstract. This study tests the performance and uncertainty of calibration strategies for a spatially distributed hydrologic model in order to improve model simulation accuracy and understand prediction uncertainty at interior ungaged sites of a sparsely gaged watershed. The study is conducted using a distributed version of the HYMOD hydrologic model (HY-MOD_DS) applied to the Kabul River basin. Several calibration experiments are conducted to understand the benefits and costs associated with different calibration choices, including (1) whether multisite gaged data should be used simultaneously or in a stepwise manner during model fitting, (2) the effects of increasing parameter complexity, and (3) the potential to estimate interior watershed flows using only gaged data at the basin outlet. The implications of the different calibration strategies are considered in the context of hydrologic projections under climate change. To address the research questions, high-performance computing is utilized to manage the computational burden that results from high-dimensional optimization problems. Several interesting results emerge from the study. The simultaneous use of multisite data is shown to improve the calibration over a stepwise approach, and both multisite approaches far exceed a calibration based on only the basin outlet. The basin outlet calibration can lead to projections of mid-21st century streamflow that deviate substantially from projections under multisite calibration strategies, supporting the use of caution when using distributed models in data-scarce regions for climate change impact assessments. Surprisingly, increased parameter complexity does not substantially increase the uncertainty in streamflow projections, even though parameter equifinality does emerge. The results suggest that increased (excessive) parameter complexity does not always lead to increased predictive uncertainty if structural uncertainties are present. The largest uncertainty in future streamflow results from variations in projected climate between climate models, which substantially outweighs the calibration uncertainty

    Bias Correction of Hydrologic Projections Strongly Impacts Inferred Climate Vulnerabilities in Institutionally Complex Water Systems

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    Water-resources planners use regional water management models (WMMs) to identify vulnerabilities to climate change. Frequently, dynamically downscaled climate inputs are used in conjunction with land-surface models (LSMs) to provide hydrologic streamflow projections, which serve as critical inputs for WMMs. Here, we show how even modest projection errors can strongly affect assessments of water availability and financial stability for irrigation districts in California. Specifically, our results highlight that LSM errors in projections of flood and drought extremes are highly interactive across timescales, path-dependent, and can be amplified when modeling infrastructure systems (e.g., misrepresenting banked groundwater). Common strategies for reducing errors in deterministic LSM hydrologic projections (e.g., bias correction) can themselves strongly distort projected climate vulnerabilities and misrepresent their inferred financial consequences. Overall, our results indicate a need to move beyond standard deterministic climate projection and error management frameworks that are dependent on single simulated climate change scenario outcomes

    TGF-Ξ²1 modulates microglial phenotype and promotes recovery after intracerebral hemorrhage

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    Intracerebral hemorrhage (ICH) is a devastating form of stroke that results from the rupture of a blood vessel in the brain, leading to a mass of blood within the brain parenchyma. The injury causes a rapid inflammatory reaction that includes activation of the tissue-resident microglia and recruitment of blood-derived macrophages and other leukocytes. In this work, we investigated the specific responses of microglia following ICH with the aim of identifying pathways that may aid in recovery after brain injury. We used longitudinal transcriptional profiling of microglia in a murine model to determine the phenotype of microglia during the acute and resolution phases of ICH in vivo and found increases in TGF-Ξ²1 pathway activation during the resolution phase. We then confirmed that TGF-Ξ²1 treatment modulated inflammatory profiles of microglia in vitro. Moreover, TGF-Ξ²1 treatment following ICH decreased microglial Il6 gene expression in vivo and improved functional outcomes in the murine model. Finally, we observed that patients with early increases in plasma TGF-Ξ²1 concentrations had better outcomes 90 days after ICH, confirming the role of TGF-Ξ²1 in functional recovery from ICH. Taken together, our data show that TGF-Ξ²1 modulates microglia-mediated neuroinflammation after ICH and promotes functional recovery, suggesting that TGF-Ξ²1 may be a therapeutic target for acute brain injury

    Spatial characterization of interictal high frequency oscillations in epileptic neocortex

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    Interictal high frequency oscillations (HFOs), in particular those with frequency components in excess of 200 Hz, have been proposed as important biomarkers of epileptic cortex as well as the genesis of seizures. We investigated the spatial extent, classification and distribution of HFOs using a dense 4 Γ— 4 mm2 two dimensional microelectrode array implanted in the neocortex of four patients undergoing epilepsy surgery. The majority (97%) of oscillations detected included fast ripples and were concentrated in relatively few recording sites. While most HFOs were limited to single channels, ∼10% occurred on a larger spatial scale with simultaneous but morphologically distinct detections in multiple channels. Eighty per cent of these large-scale events were associated with interictal epileptiform discharges. We propose that large-scale HFOs, rather than the more frequent highly focal events, are the substrates of the HFOs detected by clinical depth electrodes. This feature was prominent in three patients but rarely seen in only one patient recorded outside epileptogenic cortex. Additionally, we found that HFOs were commonly associated with widespread interictal epileptiform discharges but not with locally generated β€˜microdischarges’. Our observations raise the possibility that, rather than being initiators of epileptiform activity, fast ripples may be markers of a secondary local response

    Common Fronto-temporal Effective Connectivity in Humans and Monkeys

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    Cognitive pathways supporting human language and declarative memory are thought to have uniquely evolutionarily differentiated in our species. However, cross-species comparisons are missing on site-specific effective connectivity between regions important for cognition. We harnessed a new approach using functional imaging to visualize the impact of direct electrical brain stimulation in human neurosurgery patients. Applying the same approach with macaque monkeys, we found remarkably comparable patterns of effective connectivity between auditory cortex and ventro-lateral prefrontal cortex (vlPFC) and parahippocampal cortex in both species. Moreover, in humans electrical tractography revealed rapid evoked potentials in vlPFC from stimulating auditory cortex and speech sounds drove vlPFC, consistent with prior evidence in monkeys of direct projections from auditory cortex to vocalization responsive regions in vlPFC. The results identify a common effective connectivity signature that from auditory cortex is equally direct to vlPFC and indirect to the hippocampus (via parahippocampal cortex) in human and nonhuman primates

    Common Fronto-temporal Effective Connectivity in Humans and Monkeys

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    Human brain pathways supporting language and declarative memory are thought to have differentiated substantially during evolution. However, cross-species comparisons are missing on site-specific effective connectivity between regions important for cognition. We harnessed functional imaging to visualize the effects of direct electrical brain stimulation in macaque monkeys and human neurosurgery patients. We discovered comparable effective connectivity between caudal auditory cortex and both ventro-lateral prefrontal cortex (VLPFC, including area 44) and parahippocampal cortex in both species. Human-specific differences were clearest in the form of stronger hemispheric lateralization effects. In humans, electrical tractography revealed remarkably rapid evoked potentials in VLPFC following auditory cortex stimulation and speech sounds drove VLPFC, consistent with prior evidence in monkeys of direct auditory cortex projections to homologous vocalization-responsive regions. The results identify a common effective connectivity signature in human and nonhuman primates, which from auditory cortex appears equally direct to VLPFC and indirect to the hippocampus

    Individual Differences in Sound-in-Noise Perception Are Related to the Strength of Short-Latency Neural Responses to Noise

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    Important sounds can be easily missed or misidentified in the presence of extraneous noise. We describe an auditory illusion in which a continuous ongoing tone becomes inaudible during a brief, non-masking noise burst more than one octave away, which is unexpected given the frequency resolution of human hearing. Participants strongly susceptible to this illusory discontinuity did not perceive illusory auditory continuity (in which a sound subjectively continues during a burst of masking noise) when the noises were short, yet did so at longer noise durations. Participants who were not prone to illusory discontinuity showed robust early electroencephalographic responses at 40–66 ms after noise burst onset, whereas those prone to the illusion lacked these early responses. These data suggest that short-latency neural responses to auditory scene components reflect subsequent individual differences in the parsing of auditory scenes

    Discordant effect of body mass index on bone mineral density and speed of sound

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    BACKGROUND: Increased BMI may affect the determination of bone mineral density (BMD) by dual X-ray absorptiometry (DXA) and speed of sound (SOS) measured across bones. Preliminary data suggest that axial SOS is less affected by soft tissue. The purpose of this study is to evaluate the effect of body mass index (BMI) on BMD and SOS measured along bones. METHODS: We compared axial BMD determined by DXA with SOS along the phalanx, radius and tibia in 22 overweight (BMI > 27 kg/m(2)), and 11 lean (BMI = 21 kg/m(2)) postmenopausal women. Serum bone specific alkaline phosphatase and urinary deoxypyridinoline excretion determined bone turnover. RESULTS: Mean femoral neck – but not lumbar spine BMD was higher in the overweight – as compared with the lean group (0.70 Β± 0.82, -0.99 Β± 0.52, P < 0.00001). Femoral neck BMD in the overweight – but not in the lean group highly correlated with BMI (R = 0.68. P < 0.0001). Mean SOS at all measurement sites was similar in both groups and did not correlate with BMI. Bone turnover was similar in the two study groups. CONCLUSIONS: The high BMI of postmenopausal women may result in spuriously high BMD. SOS measured along bones may be a more appropriate means for evaluating bones of overweight women

    Discrimination of Timbre in Early Auditory Responses of the Human Brain

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    The issue of how differences in timbre are represented in the neural response still has not been well addressed, particularly with regard to the relevant brain mechanisms. Here we employ phasing and clipping of tones to produce auditory stimuli differing to describe the multidimensional nature of timbre. We investigated the auditory response and sensory gating as well, using by magnetoencephalography (MEG).Thirty-five healthy subjects without hearing deficit participated in the experiments. Two different or same tones in timbre were presented through conditioning (S1) – testing (S2) paradigm as a pair with an interval of 500 ms. As a result, the magnitudes of auditory M50 and M100 responses were different with timbre in both hemispheres. This result might support that timbre, at least by phasing and clipping, is discriminated in the auditory early processing. The second response in a pair affected by S1 in the consecutive stimuli occurred in M100 of the left hemisphere, whereas both M50 and M100 responses to S2 only in the right hemisphere reflected whether two stimuli in a pair were the same or not. Both M50 and M100 magnitudes were different with the presenting order (S1 vs. S2) for both same and different conditions in the both hemispheres.Our results demonstrate that the auditory response depends on timbre characteristics. Moreover, it was revealed that the auditory sensory gating is determined not by the stimulus that directly evokes the response, but rather by whether or not the two stimuli are identical in timbre
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