Coordinated optimization of visual cortical maps (II) Numerical studies

It is an attractive hypothesis that the spatial structure of visual cortical architecture can be explained by the coordinated optimization of multiple visual cortical maps representing orientation preference (OP), ocular dominance (OD), spatial frequency, or direction preference. In part (I) of this study we defined a class of analytically tractable coordinated optimization models and solved representative examples in which a spatially complex organization of the orientation preference map is induced by inter-map interactions. We found that attractor solutions near symmetry breaking threshold predict a highly ordered map layout and require a substantial OD bias for OP pinwheel stabilization. Here we examine in numerical simulations whether such models exhibit biologically more realistic spatially irregular solutions at a finite distance from threshold and when transients towards attractor states are considered. We also examine whether model behavior qualitatively changes when the spatial periodicities of the two maps are detuned and when considering more than 2 feature dimensions. Our numerical results support the view that neither minimal energy states nor intermediate transient states of our coordinated optimization models successfully explain the spatially irregular architecture of the visual cortex. We discuss several alternative scenarios and additional factors that may improve the agreement between model solutions and biological observations.Comment: 55 pages, 11 figures. arXiv admin note: substantial text overlap with arXiv:1102.335

Coordinated optimization of visual cortical maps (I) Symmetry-based analysis

In the primary visual cortex of primates and carnivores, functional architecture can be characterized by maps of various stimulus features such as orientation preference (OP), ocular dominance (OD), and spatial frequency. It is a long-standing question in theoretical neuroscience whether the observed maps should be interpreted as optima of a specific energy functional that summarizes the design principles of cortical functional architecture. A rigorous evaluation of this optimization hypothesis is particularly demanded by recent evidence that the functional architecture of OP columns precisely follows species invariant quantitative laws. Because it would be desirable to infer the form of such an optimization principle from the biological data, the optimization approach to explain cortical functional architecture raises the following questions: i) What are the genuine ground states of candidate energy functionals and how can they be calculated with precision and rigor? ii) How do differences in candidate optimization principles impact on the predicted map structure and conversely what can be learned about an hypothetical underlying optimization principle from observations on map structure? iii) Is there a way to analyze the coordinated organization of cortical maps predicted by optimization principles in general? To answer these questions we developed a general dynamical systems approach to the combined optimization of visual cortical maps of OP and another scalar feature such as OD or spatial frequency preference.Comment: 90 pages, 16 figure

Association of daily tar and nicotine intake with incident myocardial infarction: Results from the population-based MONICA/KORA Augsburg Cohort Study 1984 - 2002

<p>Abstract</p> <p>Background</p> <p>Cigarette smoking has been shown to be one of the most important risk factors for cardiovascular diseases. However, little is known about cumulative effects of daily tar and nicotine intake on the risk of incident myocardial infarction (MI) so far. To bridge this gap, we conducted an analysis in a large prospective study from Southern Germany investigating associations of daily tar and nicotine intake with an incident MI event.</p> <p>Methods</p> <p>The study was based on 4,099 men and 4,197 women participating in two population-based MONICA Augsburg surveys between 1984 and 1990 and followed up within the KORA framework until 2002. During a mean follow-up of 13.3 years, a number of 307 men and 80 women developed an incident MI event. Relative risks were calculated as hazard ratios (HRs) estimated by Cox proportional hazards models adjusted for cardiovascular risk factors.</p> <p>Results</p> <p>In the present study, male regular smokers consumed on average more cigarettes per day than female regular smokers (20 versus 15) and had a higher tar and nicotine intake per day. In men, the MI risk compared to never-smokers increased with higher tar intake: HRs were 2.24 (95% CI 1.40-3.56) for 1-129 mg/day, 2.12 (95% CI 1.37-3.29) for 130-259 mg/day and 3.01 (95% CI 2.08-4.36) for ≥ 260 mg/day. In women, the corresponding associations were comparable but more pronounced for high tar intake (HR 4.67, 95% CI 1.76-12.40). Similar associations were observed for nicotine intake.</p> <p>Conclusions</p> <p>The present study based on a large population-based sample adds important evidence of cumulative effects of tar and nicotine intake on the risk of incident MI. Even low or medium tar and nicotine intake revealed substantial risk increases as compared to never-smokers. Therefore, reduction of tar and nicotine contents in cigarettes cannot be seen as a suitable public health policy in preventing myocardial infarction.</p

Discovery of Sexual Dimorphisms in Metabolic and Genetic Biomarkers

Metabolomic profiling and the integration of whole-genome genetic association data has proven to be a powerful tool to comprehensively explore gene regulatory networks and to investigate the effects of genetic variation at the molecular level. Serum metabolite concentrations allow a direct readout of biological processes, and association of specific metabolomic signatures with complex diseases such as Alzheimer's disease and cardiovascular and metabolic disorders has been shown. There are well-known correlations between sex and the incidence, prevalence, age of onset, symptoms, and severity of a disease, as well as the reaction to drugs. However, most of the studies published so far did not consider the role of sexual dimorphism and did not analyse their data stratified by gender. This study investigated sex-specific differences of serum metabolite concentrations and their underlying genetic determination. For discovery and replication we used more than 3,300 independent individuals from KORA F3 and F4 with metabolite measurements of 131 metabolites, including amino acids, phosphatidylcholines, sphingomyelins, acylcarnitines, and C6-sugars. A linear regression approach revealed significant concentration differences between males and females for 102 out of 131 metabolites (p-values<3.8 x 10(-4); Bonferroni-corrected threshold). Sex-specific genome-wide association studies (GWAS) showed genome-wide significant differences in beta-estimates for SNPs in the CPS1 locus (carbamoyl-phosphate synthase 1, significance level: p<3.8 x 10(-10); Bonferroni-corrected threshold) for glycine. We showed that the metabolite profiles of males and females are significantly different and, furthermore, that specific genetic variants in metabolism-related genes depict sexual dimorphism. Our study provides new important insights into sex-specific differences of cell regulatory processes and underscores that studies should consider sex-specific effects in design and interpretation

Distributed processing and temporal codes in neuronal networks

The cerebral cortex presents itself as a distributed dynamical system with the characteristics of a small world network. The neuronal correlates of cognitive and executive processes often appear to consist of the coordinated activity of large assemblies of widely distributed neurons. These features require mechanisms for the selective routing of signals across densely interconnected networks, the flexible and context dependent binding of neuronal groups into functionally coherent assemblies and the task and attention dependent integration of subsystems. In order to implement these mechanisms, it is proposed that neuronal responses should convey two orthogonal messages in parallel. They should indicate (1) the presence of the feature to which they are tuned and (2) with which other neurons (specific target cells or members of a coherent assembly) they are communicating. The first message is encoded in the discharge frequency of the neurons (rate code) and it is proposed that the second message is contained in the precise timing relationships between individual spikes of distributed neurons (temporal code). It is further proposed that these precise timing relations are established either by the timing of external events (stimulus locking) or by internal timing mechanisms. The latter are assumed to consist of an oscillatory modulation of neuronal responses in different frequency bands that cover a broad frequency range from <2 Hz (delta) to >40 Hz (gamma) and ripples. These oscillations limit the communication of cells to short temporal windows whereby the duration of these windows decreases with oscillation frequency. Thus, by varying the phase relationship between oscillating groups, networks of functionally cooperating neurons can be flexibly configurated within hard wired networks. Moreover, by synchronizing the spikes emitted by neuronal populations, the saliency of their responses can be enhanced due to the coincidence sensitivity of receiving neurons in very much the same way as can be achieved by increasing the discharge rate. Experimental evidence will be reviewed in support of the coexistence of rate and temporal codes. Evidence will also be provided that disturbances of temporal coding mechanisms are likely to be one of the pathophysiological mechanisms in schizophrenia

Knowing with Which Eye We See: Utrocular Discrimination and Eye-Specific Signals in Human Visual Cortex

Neurophysiological and behavioral reports converge to suggest that monocular neurons in the primary visual cortex are biased toward low spatial frequencies, while binocular neurons favor high spatial frequencies. Here we tested this hypothesis with functional magnetic resonance imaging (fMRI). Human participants viewed flickering gratings at one of two spatial frequencies presented to either the left or the right eye, and judged which of the two eyes was being stimulated (utrocular discrimination). Using multivoxel pattern analysis we found that local spatial patterns of signals in primary visual cortex (V1) allowed successful decoding of the eye-of-origin. Decoding was above chance for low but not high spatial frequencies, confirming the presence of a bias reported by animal studies in human visual cortex. Behaviorally, we found that reliable judgment of the eye-of-origin did not depend on spatial frequency. We further analyzed the mean response in visual cortex to our stimuli and revealed a weak difference between left and right eye stimulation. Our results are thus consistent with the interpretation that participants use overall levels of neural activity in visual cortex, perhaps arising due to local luminance differences, to judge the eye-of-origin. Taken together, we show that it is possible to decode eye-specific voxel pattern information in visual cortex but, at least in healthy participants with normal binocular vision, these patterns are unrelated to awareness of which eye is being stimulated

Patterns of Multimorbidity in the Aged Population. Results from the KORA-Age Study

Multimorbidity is a common problem in aged populations with a wide range of individual and societal consequences. The objective of the study was to explore patterns of comorbidity and multimorbidity in an elderly population using different analytical approaches. Data were gathered from the population-based KORA-Age project, which included 4,127 persons aged 65–94 years living in the city of Augsburg and its two surrounding counties in Southern Germany. Information on the presence of 13 chronic conditions was collected in a standardized telephone interview and a self-administered questionnaire. Patterns of comorbidity and multimorbidity were analyzed using prevalence figures, logistic regression models and exploratory tetrachoric factor analysis. The prevalence of multimorbidity (≥2 diseases) was 58.6% in the total sample. Hypertension and diabetes (Odds Ratio [OR] 2.95, 99.58% confidence interval [CI] [2.19–3.96]), as well as hypertension and stroke (OR 2.00, 99.58% CI [1.26–3.16]) most often occurred in combination. This association was independent of age, sex and the presence of other conditions. Using factor analysis, we identified four patterns of multimorbidity: the first pattern includes cardiovascular and metabolic diseases, the second includes joint, liver, lung and eye diseases, the third covers mental and neurologic diseases and the fourth pattern includes gastrointestinal diseases and cancer. 44% of the persons were assigned to at least one of the four multimorbidity patterns; 14% could be assigned to both the cardiovascular/metabolic and the joint/liver/lung/eye pattern. Further common pairs were the mental/neurologic pattern combined with the cardiovascular/metabolic pattern (7.2%) or the joint/liver/lung/eye pattern (5.3%), respectively. Our results confirmed the existence of co-occurrence of certain diseases in elderly persons, which is not caused by chance. Some of the identified patterns of multimorbidity and their overlap may indicate common underlying pathological mechanisms

Dorsal Visual Pathway Changes in Patients with Comitant Extropia

BACKGROUND: Strabismus is a disorder in which the eyes are misaligned. Persistent strabismus can lead to stereopsis impairment. The effect of strabismus on human brain is not unclear. The present study is to investigate whether the brain white structures of comitant exotropia patients are impaired using combined T1-weighted imaging and diffusion tensor imaging (DTI). PRINCIPAL FINDINGS: Thirteen patients with comitant strabismus and twelve controls underwent magnetic resonance imaging (MRI) with acquisition of T1-weighted and diffusion tensor images. T1-weighted images were used to analyze the change in volume of white matter using optimized voxel-based morphology (VBM) and diffusion tensor images were used to detect the change in white matter fibers using voxel-based analysis of DTI in comitant extropia patients. VBM analysis showed that in adult strabismus, white matter volumes were smaller in the right middle occipital gyrus, right occipital lobe/cuneus, right supramarginal gyrus, right cingulate gyrus, right frontal lobe/sub-gyral, right inferior temporal gyrus, left parahippocampa gyrus, left cingulate gyrus, left occipital lobe/cuneus, left middle frontal gyrus, left inferior parietal lobule, and left postcentral gyrus, while no brain region with greater white matter volume was found. Voxel-based analysis of DTI showed lower fractional anisotropy (FA) values in the right middle occipital gyrus and right supramarginal gyrus in strabismus patients, while brain region with increased FA value was found in the right inferior frontal gyrus. CONCLUSION: By combining VBM and voxel-based analysis of DTI results, the study suggests that the dorsal visual pathway was abnormal or impaired in patients with comitant exotropia

Neural network model of the primary visual cortex: From functional architecture to lateral connectivity and back

The role of intrinsic cortical dynamics is a debatable issue. A recent optical imaging study (Kenet et al., 2003) found that activity patterns similar to orientation maps (OMs), emerge in the primary visual cortex (V1) even in the absence of sensory input, suggesting an intrinsic mechanism of OM activation. To better understand these results and shed light on the intrinsic V1 processing, we suggest a neural network model in which OMs are encoded by the intrinsic lateral connections. The proposed connectivity pattern depends on the preferred orientation and, unlike previous models, on the degree of orientation selectivity of the interconnected neurons. We prove that the network has a ring attractor composed of an approximated version of the OMs. Consequently, OMs emerge spontaneously when the network is presented with an unstructured noisy input. Simulations show that the model can be applied to experimental data and generate realistic OMs. We study a variation of the model with spatially restricted connections, and show that it gives rise to states composed of several OMs. We hypothesize that these states can represent local properties of the visual scene

Hormone replacement therapy, body mass, and the risk of colorectal cancer among postmenopausal women from Germany

Previous studies have reported inconsistent results regarding the modifying effect of hormone replacement therapy (HRT) on the association of body mass index (BMI) and the risk of colorectal cancer (CRC) among postmenopausal women. We assessed the use of HRT and BMI in 208 postmenopausal women with histologically confirmed incident CRC and 246 controls in a population-based case–control study in Germany (DACHS study). Ever use of HRT was strongly associated with reduction of CRC risk (adjusted odds ratio 0.41, 95% confidence interval 0.25–0.67). Among nonusers of HRT, risk of CRC was strongly increased in women with BMI 27 to <30 kg m−2 (2.76, 1.07–7.12) and obese women (3.30, 1.25–8.72), when compared with women with BMI <23 kg m−2 (P for trend <0.01). BMI was not associated with risk of CRC among HRT users (P for interaction <0.01). In contrast to most other studies, a positive association of BMI and CRC risk was found among nonusers of HRT, but not among users of HRT. The reasons for the inconsistency of results regarding the potential risk modifying effect of postmenopausal hormones in the association of BMI with CRC remain inconclusive and require further study