Spatiotemporal frequency and direction sensitivities of human visual areas measured using fMRI

Using functional magnetic resonance imaging (fMRI) we have studied the variation in response magnitude, in each visual area (V1-V5), as a function of spatial frequency (SF), temporal frequency (TF) and unidirectional motion versus counterphase flicker. Each visual area was identified in each subject using a combination of retinotopic mapping fMRI and cortical flattening techniques. A drifting (or counterphasing) sinusoidal grating was used as the stimulus in a study in which we parametrically varied SF between 0.4 and 7 cycles/degree and TF between 0 and 18 Hz. For each experiment we constructed fMRI amplitude tuning curves, averaged across subjects, for each visual area. The tuning curves that resulted are consistent with the known physiological properties of cells in the corresponding macaque visual areas, previous functional imaging studies, and in the case of V1, the psychophysically determined contrast sensitivity functions for spatial and temporal frequency. In the case of V3A, the SF tuning functions obtained were more similar to those found in single cell studies of macaque V3 rather than macaque V3A. All areas showed at least a moderate preference for directed versus counterphasing motion with V5 showing the largest preference. Visual areas V1, V2, V3, and V3A showed more direction sensitivity at low spatial frequencies, while VP, V4, and V5 had the highest drifting versus counterphasing ratios for higher spatial frequencies.     

Isolation and characterization of murine cell surface components. I. Purification of milligram quantities of Thy-1.1

The Thy-l.1 molecule was isolated from the BW5147 murine lymphoblastoid cell line. The initial step in purification was the preparation of a crude plasma membrane fraction followed by acetone precipitation. The acetone pellet was solubilized using deoxycholate (DOC) and Thy-1.1 was purified by use of a Lens culinaris lectin affinity column and an AcA-34 gel filtration column. The purified glycoprotein with Thy-1.1 activity had a mol wt of approximately 25,000 daltons. The isolation of this molecule was effected by detecting Thy-I activity utilizing rabbit anti- mouse brain serum tested on rat thymocytes. Congenic anti-Thy-l.1 serum was ineffective in detecting Thy-l.1 after DOC solubilization. An antiserum prepared in rabbits to the purified Thy-1.1 was found to be cytotoxic to mouse and rat thymocytes. The cytotoxic activity of this antisera could be completely absorbed with AKR/Jax brain and thymus but was not absorbed by liver. In addition, AKR/Jax thymocytes totally absorbed all cytotoxic activity of the rabbit anti-purified Thy-1 serum for BW5147 cells suggesting that the cell line shares identical specificities with normal thymocytes. The purified Thy-1.1 molecule was able to totally absorb the cytotoxic activity of mouse congenic anti-Thy-1. These studies serve as a model for the isolation of other murine lymphoid cell surface components in quantities for detailed structural and functional analysis.     

The Opportunity Loss of Boarding Admitted Patients in the Emergency Department

Objectives: Boarding admitted patients in emergency department (ED) treatment beds has been recognized as a major cause of ED crowding and ambulance diversions. When process delays impede the transfer of admitted patients from the ED to inpatient units, the department's capacity to accept new arrivals and to generate revenue from additional patient services is restricted. The objective of this study was to determine the amount of functional ED treatment capacity that was used to board inpatients during 12 months of operations at a community hospital and to estimate the value of that lost treatment capacity.
Methods: Historical data from 62,588 patient visits to the ED of a 450-bed nonprofit community teaching hospital in south central Pennsylvania between July 2004 and June 2005 were used to determine the amount of treatment bed occupancy lost to inpatient holding and the revenue potential of utilizing that blocked production capacity for additional patient visits.
Results: Transferring admitted patients from the ED to an inpatient unit within 120 minutes would have increased the functional treatment capacity of the ED by 10,397 hours during the 12 months of this study. By reducing admission process delays, the hospital could potentially have accommodated another 3,175 patient encounters in its existing treatment spaces. Providing emergency services to new patients in ED beds formerly used to board inpatients could have generated $3,960,264 in additional net revenue for the hospital.
Conclusions: Significantly higher operational revenues could be generated by reducing output delays that restrict optimal utilization of existing ED treatment capacity.     

Mild hemophilia A with factor VIII assay discrepancy: using thrombin generation assay to assess the bleeding phenotype

Summary.  Introduction:  In some patients with mild hemophilia A, there are discrepancies between 1-stage (1-st) and 2-stage (2-st) factor VIII (FVIII) clotting assays, and also chromogenic assays for FVIII activity (FVIII:C). We examined whether thrombography could provide a better evaluation of the hemostatic status of these patients. Methods:  Two families with such discrepancies and markedly contrasting clinical histories were studied. Family X had no serious bleedings, in contrast to family Y. Sixty-one moderate/mild hemophiliacs without discrepancy and 15 healthy subjects served as controls. Calibrated automated thrombography was performed with platelet-rich plasma after one freeze-thawing cycle and low tissue factor concentration. Results:  The chromogenic FVIII:C levels were higher (0.90 ± 0.15 and 0.47 ± 0.13 IU mL⁻¹) than the 1-st clotting ones (0.14 ± 0.05 and 0.10 ± 0.05 IU mL⁻¹) in family X and Y, respectively ( P  < 0.001). Mean endogenous thrombin potential (ETP) was 1579 ± 359 n m  min⁻¹ and 1060 ± 450 for healthy controls and hemophilic controls, respectively. For members of family X, the ETP values were 1188, 1317 and 2277 n m  min⁻¹, whereas for those of family Y they ranged from 447 to 1122 n m  min⁻¹. Two novel missense point mutations were evidenced: p.Ile369Thr in family X and p.Phe2127Ser in family Y. In family X, we postulate that the mutation is responsible for a delayed but non-deleterious FVIII activation. Conclusions:  Our results suggest that the hemostatic phenotype assessed by thrombography may be clinically relevant in moderate/mild hemophilic patients with discrepant FVIII:C results.     

Neural correlates of context‐dependent feature conjunction learning in visual search tasks

Many perceptual learning experiments show that repeated exposure to a basic visual feature such as a specific orientation or spatial frequency can modify perception of that feature, and that those perceptual changes are associated with changes in neural tuning early in visual processing. Such perceptual learning effects thus exert a bottom‐up influence on subsequent stimulus processing, independent of task‐demands or endogenous influences (e.g., volitional attention). However, it is unclear whether such bottom‐up changes in perception can occur as more complex stimuli such as conjunctions of visual features are learned. It is not known whether changes in the efficiency with which people learn to process feature conjunctions in a task (e.g., visual search) reflect true bottom‐up perceptual learning versus top‐down, task‐related learning (e.g., learning better control of endogenous attention). Here we show that feature conjunction learning in visual search leads to bottom‐up changes in stimulus processing. First, using fMRI, we demonstrate that conjunction learning in visual search has a distinct neural signature: an increase in target‐evoked activity relative to distractor‐evoked activity (i.e., a relative increase in target salience). Second, we demonstrate that after learning, this neural signature is still evident even when participants passively view learned stimuli while performing an unrelated, attention‐demanding task. This suggests that conjunction learning results in altered bottom‐up perceptual processing of the learned conjunction stimuli (i.e., a perceptual change independent of the task). We further show that the acquired change in target‐evoked activity is contextually dependent on the presence of distractors, suggesting that search array Gestalts are learned. Hum Brain Mapp 37:2319–2330, 2016. © 2016 Wiley Periodicals, Inc.     

Advanced magnetic resonance imaging in benign hereditary chorea: Study of two familial cases

No brain abnormalities are usually detected on conventional magnetic resonance imaging (MRI) in benign hereditary chorea (BHC); there are currently no studies with advanced techniques in literature. We investigated whether conventional and advanced MRI techniques could depict regional brain abnormalities in two familial BHC patients and 24 healthy controls. No brain abnormalities on conventional scans were detectable; also, no significant differences in fractional anisotropy of the basal nuclei were observed. Volumetric analysis showed a decreased volume of the striatum bilaterally compared with controls, whereas spectroscopy demonstrated a significant increased myoinositol/creatine ratio bilaterally, a reduction of choline/creatine ratio bilaterally, and of N‐acetyl‐aspartate/creatine in the right putamen. With the limits of the small sample size in the patient group, these data show that, despite the absence of macroscopic changes on conventional MRI, volumetric and metabolic abnormalities are present in the basal nuclei of BHC patients. © 2010 Movement Disorder Society.     

Discovery of SCH 900229, a Potent Presenilin 1 Selective γ-Secretase Inhibitor for the Treatment of Alzheimer’s Disease

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Acute surgical removal of low-grade (Spetzler-Martin I-II) bleeding arteriovenous malformations

Background

Early surgical removal of cerebral AVMs is a relatively infrequent therapeutic option when dealing with a cerebral hemorrhage caused by AVM rupture: even in the case of low-grade AVMs, delayed treatment is, if possible, preferred because it is considered safer for patients and more comfortable for surgeons. To assess whether acute surgery may be a safe and effective management, we conducted a retrospective analysis of our early surgery strategy for ruptured low-grade AVMs.

Methods

We reviewed 27 patients with SM grade I-II AVM treated during 2004 to 2008 in the acute stage of bleeding (within the first 6 days after bleed). All patients showed a cerebral AVM on DSA at admission, and surgical removal was controlled by postoperative angiography. Neurological outcomes were assessed with GOS. The average length of follow-up was 22 months (48-3 months).

Results

Before surgery, 16 (59%) patients showed a GCS of 8 or less, 2 of them presenting an acute rebleeding after first hemorrhage. All patients underwent radical AVM surgical removal and hematoma evacuation in a single-stage procedure. Most patients (78%) were operated within the first day of hemorrhage. A favorable functional outcome (GOS: good recovery or moderate disability) was observed in 23 patients (85%). Mortality was 7.4%. Outcome was not significantly correlated with GCS at presentation and with presence of preoperative anisocoria.

Conclusions

Early surgery for grade I-II AVMs is a safe and definitive treatment, achieving both immediate cerebral decompression and patient protection against rebleeding, reducing time of hospital stay and allowing a more rapid rehabilitative course whenever necessary.