Saturating Nonlinearities of Contrast Response in Human Visual Cortex

Response nonlinearities are ubiquitous throughout the brain, especially within sensory cortices where changes in stimulus intensity typically produce compressed responses. Although this relationship is well established in electrophysiological measurements, it remains controversial whether the same nonlinearities hold for population-based measurements obtained with human fMRI. We propose that these purported disparities are not contingent on measurement type and are instead largely dependent on the visual system state at the time of interrogation. We show that deploying a contrast adaptation paradigm permits reliable measurements of saturating sigmoidal contrast response functions (10 participants, 7 female). When not controlling the adaptation state, our results coincide with previous fMRI studies, yielding nonsaturating, largely linear contrast responses. These findings highlight the important role of adaptation in manifesting measurable nonlinear responses within human visual cortex, reconciling discrepancies reported in vision neuroscience, re-establishing the qualitative relationship between stimulus intensity and response across different neural measures and the concerted study of cortical gain control.SIGNIFICANCE STATEMENT Nonlinear stimulus–response relationships govern many essential brain functions, ranging from the sensory to cognitive level. Certain core response properties previously shown to be nonlinear with nonhuman electrophysiology recordings have yet to be reliably measured with human neuroimaging, prompting uncertainty and reconsideration. The results of this study stand to reconcile these incongruencies in the vision neurosciences, demonstrating the profound impact adaptation can have on brain activation throughout the early visual cortex. Moving forward, these findings facilitate the study of modulatory influences on sensory processing (i.e., arousal and attention) and help establish a closer link between neural recordings in animals and hemodynamic measurements from human fMRI, resuming a concerted effort to understand operations in the mammalian cortex.     

Early wheezing phenotypes and cognitive development of 3‐yr‐olds. Community‐recruited birth cohort study

Jedrychowski W, Perera FP, Jankowski J, Maugeri U, Mrozek‐Budzyn D, Mroz E, Flak E, Skarupa A, Edwards S, Lisowska‐Miszczyk I. Early wheezing phenotypes and cognitive development of 3‐yr‐olds. Community‐recruited birth cohort study.
Pediatr Allergy Immunol 2010: 21: 550–556.
© 2009 John Wiley & Sons A/S The main purpose of the study was to answer the question whether young children without clinical diagnosis of asthma but experiencing early wheezing disorders and therefore being at high risk of developing asthma may have cognitive deficits. In the ongoing birth cohort study wheezing symptoms were recorded postpartum over two first years of age and subsequently cognitive status of children at the age of 3 yr was assessed with the Bayley Mental Development Index (MDI). In the statistical analysis a wide range of modifying and confounding factors (maternal education, gender of children, prenatal exposure to lead and environmental tobacco smoke (ETS) were considered to assess the independent effect of early wheezing phenotypes on cognitive development of children. The MDI score correlated inversely with the number of wheezing days recorded over 24 months (r = ?0.13, p = 0.007), lead cord blood concentration (r = ?0.12, p = ?0.02), number of siblings (r = ?0.17, p = 0.0006) and the number of cigarettes smoked daily by other household members at home over the pregnancy period (r = ?0.18, p = 0.0002). While the children who experienced wheezing over the first year of age showed deficit of 2 MDI scores (beta coeff. = ?2.31, 95%CI: ?4.63 to 0.02), those with persistent wheezing had the score deficit of 4 points (beta coeff. = ?4.41, 95%CI: ?8.27 to ?0.55). To our knowledge, it is the first report in the iterature showing that early wheezing is associated the cognitive deficit in a community‐recruited very young children. Observed cognitive deficit in early wheezers may be caused by RSV infections or can be related to lower lung function attributed to persistent wheezing, which reducing oxygen supply would affect rapidly developing brain.     

TP53 and RAS mutations in metachronous tumors from patients with cancer of the upper aerodigestive tract

Patients who initially develop an upper aerodigestive tract cancer have an increased risk of second primary cancers. We examined TP53 and RAS mutations and p53 protein in 21 tumors from 10 patients with upper aerodigestive tract cancer who developed a metachronous tumor, to assess the genetic changes that occur in multiple primary tumors from the same individual. Thirteen of 21 (62%) tumors were found to have mis-sense mutations of either TP53 or RAS. Six tumors had TP53 mutations in codons 5 to 8 and 10 tumors from 7 patients had mutations of codons 12 or 13 of K-RAS. Only one patient had concordance of a mutation in 2 tumors; this mutation occurred in K-RAS and was accompanied by discordance of TP53 mutation. Three patients had tumors discordant for both T53 and RAS mutations. Smoking-related tumors had TP53 and RAS mutations which were transversions in 11 (9 G:C to T:A and 2 G:C to C:G) and transitions in 3 (2 G:C to A:T and 1 A:T to G:C). Tumors not associated with smoking contained only transitions (both G:C to A:T). p53 protein was detected by immunohisto-chemistry in 7 of 13 (54%) tumors and was concordant in the multiple tumors of 3 patients. Three of the 7 tumors staining for p53 also had TP53 mutations. Thus, genetic alterations are discordant in multiple primary cancers and the pattern of mutations is similar to that found in patients with a single primary tumor, supporting the concept that these cancers arise independently. © 1995 Wiley-Liss, Inc.     

Short-term carcinogenicity testing of 2-amino-1-methyl-6-phenylimidazo[4, 5-b]pyridine (PhIP) and 2-amino-3-methylimidazo[4, 5-f]quinoline (IQ) in E{micro}-pim-1 transgenic mice

The usefulness of transgenic Eµ-pim-1 mice over-expressingthe pim-1 oncogene in lymphoid tissues, as sensitive test organismswas studied in a short-term carcinogenicity study. The micewere fed standard diet Altromin 1314 supplemented either with0.03% 2-amino-1-methyl-6-phenylimidazo[4, 5-b]pyridine (PhIP)for 7 months or with 0.03% 2-amino-3-methylimidazo[4, 5-f] quinoline(IQ) for 6 months. PhIP and IQ are heterocyclic amines formedduring cooking of meat and fish and are mutagenic to bacteriaand cultured mammalian cells. PhIP is a potent mouse lymphomagen,while IQ is a liver carcinogen and also causes lung tumors andtumors of the forestomach in mice. We found that transgenicEµ-pim-1 mice are highly susceptible to PhIP induced lymphomagenesisbut do not respond to the IQ treatment. PhIP feeding of Eµ-pim-1mice not only increased the total number of T-cell lymphomasbut also decreased the latency time compared to either transgenicor wild-type controls. The effect was most pronounced in thetreated female Eµ-pim-1 mice, which showed a higher incidenceof PhIP induced T-cell lymphomas than transgenic males and astrongly reduced latency period after PhIP treatment comparedto non-transgenic mice. Our results suggest that the transgenicEµ-pim-1 mouse may be a useful model for short-term carcinogenicityscreening of potential genotoxic carcinogens having the lymphoidsystem as target tissue. The carcinogen IQ which does not havethe lymphoid system as a target was not recognized in this model.     

First results with wavefront-guided photorefractive keratectomy for hyperopia

PURPOSE: To compare the results of traditional laser photoablation and wavefront-supported customized ablation (WASCA) in hyperopic photorefractive keratectomy (H-PRK). METHODS: This was a prospective study, comparing two treatment groups, each comprising 40 eyes of 20 patients. Wavefront aberrations were examined using a Shack-Hartmann aberrometer. Preoperative refraction was similar in the two groups; in the traditional H-PRK group (Group 1) it was +3.10 +/- 0.85 D, and in the WASCA-guided group (Group 2) it was +2.90 +/- 0.80 D. H-PRK was performed with the Asclepion-Meditec MEL 70 flying-spot excimer laser. The follow-up time was 6 months. RESULTS: In Group 1, mean postoperative refraction was +0.14 +/- 0.24 D, and in Group 2, -0.10 +/- 0.25 D; mean uncorrected visual acuity was 0.92 +/- 0.16 in Group 1 and 0.95 +/- 0.18 in Group 2. Mean best spectacle-corrected visual acuity was 0.96 +/- 0.04 in Group 1 and 1.06 +/- 0.13 in Group 2. In Group 1, 67.5% (27 of 40 eyes), and in Group 2, 85% (34 of 40 eyes) were within +/-0.50 D of target refraction. Regarding change of spectacle-corrected visual acuity in Group 1, 5% (2 of 40 eyes), and in Group 2, 20% (8 of 40 eyes) gained one Snellen line compared to the preoperative; in Group 1, 10% (4 of 40 eyes), and in Group 2, 12.5% (5 of 40 eyes) lost two Snellen lines. In Group 2, the root mean square value for the higher order aberration increased from the initial 0.134 to 0.257 microm at 6 months after surgery. CONCLUSIONS: WASCA-guided hyperopic-PRK treatment was found to be safe and predictable. The results were better than those achieved with traditional PRK performed using the same flying-spot type excimer laser.     

Gonadal hormone-induced changes in adult male and female rats exposed to early postnatal handling are not altered by prenatal morphine exposure

The purpose of the present study was to investigate the long-term effects of early postnatal handling in several gonadal hormone conditions in adult male and female rats exposed prenatally to morphine or saline. An open-field apparatus was used to test locomotor activities such as line crossing, rearing, grooming, and anxiety-like behaviors such as visiting squares alongside the walls of the open field and boli dropping. Postnatal handling increased locomotor activities in gonadally intact males and in all groups of hormone-manipulated females, but did not change them in gonadectomized (GNX) males. Additionally, there was a decrease in anxiety-like behavior in ovariectomized (OVX) females after estradiol benzoate (EB) or EB and progesterone (P) replacement due to handling. Handling did not affect anxiety-like behaviors in OVX females or in GNX or gonadally intact males. Prenatal morphine exposure did not alter any open-field measures in handled or nonhandled animals when compared to saline controls. Thus, the present study demonstrates that early postnatal handling induces long-lasting changes in locomotor and anxiety-like behaviors of adult male and female rats regardless of their prenatal exposure to morphine. These changes are gonadal hormone specific.