Foetal growth restriction has negative influence on narrative skills in 8-10-year-old children.

AIM: The risk for neurocognitive difficulties is increased in children born with foetal growth restriction (FGR), but no data exist yet on their narrative skills. The narrative skills of 8- to 10-year-old children born with FGR between 24 and 40 weeks were compared with those of children born with appropriate growth for gestational age (AGA). METHODS: A prospectively collected cohort of 36 children with FGR was recruited prenatally at a Finnish tertiary hospital from 1998-2001, and 31 children with AGA served as controls. Narrative skills were assessed using a standardised test, and correlations between narrative, communication, reading and spelling skills were studied. RESULTS: Children born with FGR produced significantly less information and shorter utterances in their narratives than the AGA group. Children born preterm with FGR performed significantly more poorly in their narratives than the preterm AGA group. Poor narrative skills correlated with poor communication, reading and spelling skills. CONCLUSION: Children born with FGR had poorer narrative skills compared with their AGA peers at the age of 8-10 years, and narrative skills were linked to other language-based skills, which underlines the importance of early detection and preventive measures to optimise the educational outcome of children born with FGR.

Developing therapeutically more efficient Neurturin variants for treatment of Parkinson's disease.

In Parkinson's disease midbrain dopaminergic neurons degenerate and die. Oral medications and deep brain stimulation can relieve the initial symptoms, but the disease continues to progress. Growth factors that might support the survival, enhance the activity, or even regenerate degenerating dopamine neurons have been tried with mixed results in patients. As growth factors do not pass the blood-brain barrier, they have to be delivered intracranially. Therefore their efficient diffusion in brain tissue is of crucial importance. To improve the diffusion of the growth factor neurturin (NRTN), we modified its capacity to attach to heparan sulfates in the extracellular matrix. We present four new, biologically fully active variants with reduced heparin binding. Two of these variants are more stable than WT NRTN in vitro and diffuse better in rat brains. We also show that one of the NRTN variants diffuses better than its close homolog GDNF in monkey brains. The variant with the highest stability and widest diffusion regenerates dopamine fibers and improves the conditions of rats in a 6-hydroxydopamine model of Parkinson's disease more potently than GDNF, which previously showed modest efficacy in clinical trials. The new NRTN variants may help solve the major problem of inadequate distribution of NRTN in human brain tissue.

Feedback to distal dendrites links fMRI signals to neural receptive fields in a spiking network model of the visual cortex.

The blood oxygenation level-dependent (BOLD) response has been strongly associated with neuronal activity in the brain. However, some neuronal tuning properties are consistently different from the BOLD response. We studied the spatial extent of neural and hemodynamic responses in the primary visual cortex, where the BOLD responses spread and interact over much longer distances than the small receptive fields of individual neurons would predict. Our model shows that a feedforward-feedback loop between V1 and a higher visual area can account for the observed spread of the BOLD response. In particular, anisotropic landing of inputs to compartmental neurons were necessary to account for the BOLD signal spread, while retaining realistic spiking responses. Our work shows that simple dendrites can separate tuning at the synapses and at the action potential output, thus bridging the BOLD signal to the neural receptive fields with high fidelity.

Modeling fMRI signals can provide insights into neural processing in the cerebral cortex.

Every stimulus or task activates multiple areas in the mammalian cortex. These distributed activations can be measured with functional magnetic resonance imaging (fMRI), which has the best spatial resolution among the noninvasive brain imaging methods. Unfortunately, the relationship between the fMRI activations and distributed cortical processing has remained unclear, both because the coupling between neural and fMRI activations has remained poorly understood and because fMRI voxels are too large to directly sense the local neural events. To get an idea of the local processing given the macroscopic data, we need models to simulate the neural activity and to provide output that can be compared with fMRI data. Such models can describe neural mechanisms as mathematical functions between input and output in a specific system, with little correspondence to physiological mechanisms. Alternatively, models can be biomimetic, including biological details with straightforward correspondence to experimental data. After careful balancing between complexity, computational efficiency, and realism, a biomimetic simulation should be able to provide insight into how biological structures or functions contribute to actual data processing as well as to promote theory-driven neuroscience experiments. This review analyzes the requirements for validating system-level computational models with fMRI. In particular, we study mesoscopic biomimetic models, which include a limited set of details from real-life networks and enable system-level simulations of neural mass action. In addition, we discuss how recent developments in neurophysiology and biophysics may significantly advance the modelling of fMRI signals.

[Is there unused capacity in our brain?]. / Onko aivoissamme käyttämätöntä kapasiteettia?

Although a great deal of research has been performed on special abilities occurring in connection with developmental disorders and injuries, their biological background remains unknown. It is tempting to think that understanding of the mechanism of generation of special ability would help each of us to liberate our brain capacity and direct it in a desired manner. Poor knowledge of the general functioning principle of the brain remains an essential restriction against establishing whether there is extra capacity in the brain and whether its liberation is possible now or in the near future. Model-based brain research is rising to the central position in understanding the functional principle.

Early vocalization of preterm infants with extremely low birth weight (ELBW), Part I: From birth to expansion stage.

The vocalization of preterm infants with extremely low birth weight (ELBW) up to the expansion stage was systematically described and compared with those of healthy full-term infants. The sample consisted of 18 preterm ELBW infants and the control group of 11 full-term infants. The follow-up was performed intensively using video-recordings. The vocalization of the preterm and full-term infants was analyzed quantitatively according to the categorical stages created by Oller. A descriptive analysis of all the vocalizations produced by the infants was performed. The preterm infants entered the primitive articulation stage later than the full-term infants and failed to produce more skills during that stage. According to this sample, there was no difference in entering the expansion stage, but the preterm infants failed to produce more skills than the full-term infants. The number of vocalization acts varied differently by age between the groups.

Early vocalization of preterm infants with extremely low birth weight (ELBW), Part II: From canonical babbling up to the appearance of the first word.

The aim of this study was to systematically describe the preverbal development of preterm infants from canonical babbling up to the first word and to compare it with that of healthy full-term infants. In addition, the amount of vocalization between the preterm and full-term groups was compared. The sample consisted of 18 preterm infants with extremely low birth weight and 11 full-term infants. The development of preverbal vocalization before variegated babbling did not differ between the groups. Instead, the preterm infants failed to produce more different kinds of canonical syllable types than the full-term infants. However, they showed a larger variance of variegated babbling skills and remained in the babbling phase longer before reaching the first meaningful word compared with the full-term infants. Following the onset of canonical babbling, the preterm infants produced fewer vocalizations than the full-term infants and they reached the first word later than the full-term infants.

Screening for potential undiagnosed Gaucher disease patients: Utilisation of the Gaucher earlier diagnosis consensus point-scoring system (GED-C PSS) in conjunction with electronic health record data, tissue specimens, and small nucleotide polymorphism (SNP) genotype data available in Finnish biobanks.

Background: Autosomal recessive Gaucher disease (GD) is likely underdiagnosed in many countries. Because the number of diagnosed GD patients in Finland is relatively low, and the true prevalence is currently not known, it was hypothesized that undiagnosed GD patients may exist in Finland. Our previous study demonstrated the applicability of Gaucher Earlier Diagnosis Consensus point-scoring system (GED-C PSS; Mehta et al., 2019) and Finnish biobank data and specimens in the automated point scoring of large populations. An indicative point-score range for Finnish GD patients was determined, but undiagnosed patients were not identified partly due to high number of high-score subjects in combination with a lack of suitable samples for diagnostics in the assessed biobank population. The current study extended the screening to another biobank and evaluated the feasibility of utilising the automated GED-C PSS in conjunction with small nucleotide polymorphism (SNP) chip genotype data from the FinnGen study of biobank sample donors in the identification of undiagnosed GD patients in Finland. Furthermore, the applicability of FFPE tissues and DNA restoration in the next-generation sequencing (NGS) of the GBA gene were tested. Methods: Previously diagnosed Finnish GD patients eligible to the study, and up to 45,100 sample donors in Helsinki Biobank (HBB) were point scored. The GED-C point scoring, adjusted to local data, was automated, but also partly manually verified for GD patients. The SNP chip genotype data for rare GBA variants was visually assessed. FFPE tissues of GD patients were obtained from HBB and Biobank Borealis of Northern Finland (BB). Results: Three previously diagnosed GD patients and one patient previously treated for GD-related features were included. A genetic diagnosis was confirmed for the patient treated for GD-related features. The GED-C point score of the GD patients was 12.5-22.5 in the current study. The score in eight Finnish GD patients of the previous and the current study is thus 6-22.5 points per patient. In the automated point scoring of the HBB subpopulation (N ≈ 45,100), the overall scores ranged from 0 to 17.5, with 0.77% (346/45,100) of the subjects having ≥10 points. The analysis of SNP chip genotype data was able to identify the diagnosed GD patients, but potential undiagnosed patients with the GED-C score and/or the GBA genotype indicative of GD were not discovered. Restoration of the FFPE tissue DNA improved the quality of the GBA NGS, and pathogenic GBA variants were confirmed in five out of six unrestored and in all four restored FFPE DNA samples. Discussion: These findings imply that the prevalence of diagnosed patients (~1:325,000) may indeed correspond the true prevalence of GD in Finland. The SNP chip genotype data is a valuable tool that complements the screening with the GED-C PSS, especially if the genotyping pipeline is tuned for rare variants. These proof-of-concept biobank tools can be adapted to other rare genetic diseases.

Contextual Modulation is Related to Efficiency in a Spiking Network Model of Visual Cortex.

In the visual cortex, stimuli outside the classical receptive field (CRF) modulate the neural firing rate, without driving the neuron by themselves. In the primary visual cortex (V1), such contextual modulation can be parametrized with an area summation function (ASF): increasing stimulus size causes first an increase and then a decrease of firing rate before reaching an asymptote. Earlier work has reported increase of sparseness when CRF stimulation is extended to its surroundings. However, there has been no clear connection between the ASF and network efficiency. Here we aimed to investigate possible link between ASF and network efficiency. In this study, we simulated the responses of a biomimetic spiking neural network model of the visual cortex to a set of natural images. We varied the network parameters, and compared the V1 excitatory neuron spike responses to the corresponding responses predicted from earlier single neuron data from primate visual cortex. The network efficiency was quantified with firing rate (which has direct association to neural energy consumption), entropy per spike and population sparseness. All three measures together provided a clear association between the network efficiency and the ASF. The association was clear when varying the horizontal connectivity within V1, which influenced both the efficiency and the distance to ASF, DAS. Given the limitations of our biophysical model, this association is qualitative, but nevertheless suggests that an ASF-like receptive field structure can cause efficient population response.

Effectiveness of Facebook-Delivered Lifestyle Counselling and Physical Activity Self-Monitoring on Physical Activity and Body Mass Index in Overweight and Obese Adolescents: A Randomized Controlled Trial.

Background. The aim was to evaluate the effects of a 12-week, Facebook-delivered lifestyle counselling intervention, with or without physical activity self-monitoring, on physical activity and body mass index (BMI) in overweight and obese 13-16-year-old adolescents. Methods. Three-arm randomized controlled trial. Participants (n = 46) were randomly assigned to intervention and control groups: one group received Facebook-delivered lifestyle counselling and monitoring of their physical activity (Fb + Act, n = 15), whereas a second experimental group received the same Facebook-delivered lifestyle counselling without self-monitoring (Fb, n = 16) and a third group served as the control group (n = 15). Objective and self-reported physical activity assessment were used. Nonparametric statistical tests were used. Results. There were no significant intervention effects in terms of changes in physical activity levels or BMI from baseline to the 12-week postintervention measurements between the intervention and control groups. The Fb + Act group had lower sedentary time on weekdays compared to the control group during postintervention measurements (p = 0.021), but there was no interaction between time and group. Conclusions. Interventions were not effective at increasing physical activity in overweight and obese adolescents. Before implementing such interventions, more evaluations on their effectiveness are needed. This trial is registered with ClinicalTrials.gov identifier NCT02295761 (2014-11-17).

A novel Ca2+-feedback mechanism extends the operating range of mammalian rods to brighter light.

Sensory cells adjust their sensitivity to incoming signals, such as odor or light, in response to changes in background stimulation, thereby extending the range over which they operate. For instance, rod photoreceptors are extremely sensitive in darkness, so that they are able to detect individual photons, but remain responsive to visual stimuli under conditions of bright ambient light, which would be expected to saturate their response given the high gain of the rod transduction cascade in darkness. These photoreceptors regulate their sensitivity to light rapidly and reversibly in response to changes in ambient illumination, thereby avoiding saturation. Calcium ions (Ca2+) play a major role in mediating the rapid, subsecond adaptation to light, and the Ca2+-binding proteins GCAP1 and GCAP2 (or guanylyl cyclase-activating proteins [GCAPs]) have been identified as important mediators of the photoreceptor response to changes in intracellular Ca2+. However, mouse rods lacking both GCAP1 and GCAP2 (GCAP-/-) still show substantial light adaptation. Here, we determined the Ca2+ dependency of this residual light adaptation and, by combining pharmacological, genetic, and electrophysiological tools, showed that an unknown Ca2+-dependent mechanism contributes to light adaptation in GCAP-/- mouse rods. We found that mimicking the light-induced decrease in intracellular [Ca2+] accelerated recovery of the response to visual stimuli and caused a fourfold decrease of sensitivity in GCAP-/- rods. About half of this Ca2+-dependent regulation of sensitivity could be attributed to the recoverin-mediated pathway, whereas half of it was caused by the unknown mechanism. Furthermore, our data demonstrate that the feedback mechanisms regulating the sensitivity of mammalian rods on the second and subsecond time scales are all Ca2+ dependent and that, unlike salamander rods, Ca2+-independent background-induced acceleration of flash response kinetics is rather weak in mouse rods.

The effects of a counselling intervention on lifestyle change in people at risk of cardiovascular disease.

BACKGROUND: The study assessed the effects of a counselling intervention on lifestyle changes in certain-aged people at risk of cardiovascular disease. DESIGN AND METHODS: This was an intervention study at baseline and six- and 12-month follow-ups. The participants were 40 years old (n= 53 at baseline, n=33 at six months and n=34 at 12 months). The main outcomes were cardiovascular health parameters, such as weight, BMI, waist circumference, blood pressure, cholesterol (total, high density lipoprotein, low density lipoprotein), blood glucose, and self-assessed and reported lifestyle and adherence to lifestyle changes. The counselling intervention was Internet-based and carried out via Skype or face-to-face in small groups (on average, six participants). RESULTS: There were statistically significant differences between the baseline and the 12-month follow-up with respect to the consumption of fat and snacks. Some positive cardiovascular health improvements were detected between baseline and six months, but not as clearly between baseline and 12 months. The participants reported having a healthier diet at 12 months than at baseline. At 12 months, BMI measurements indicated that all participants were overweight (mean BMI 29.8), but according to the self-assessed data, only 25% considered themselves to be so. CONCLUSIONS: Changes in lifestyle were detected as a result of the intervention. These lifestyle changes may improve cardiovascular health in the long term. Discrepancies were found between the measured indicators of cardiovascular health and information obtained from questionnaires and diary records. In order to achieve sustainable lifestyle changes, long-term support is required.

Flash responses of mouse rod photoreceptors in the isolated retina and corneal electroretinogram: comparison of gain and kinetics.

PURPOSE: To examine the amplification and kinetics of murine rod photoresponses by recording ERG flash responses in vivo and ex vivo from the same retina. We also aimed to evaluate the two available methods for isolating the rod signal from the ERG flash response, that is, pharmacology and paired flash method on the isolated retina. METHODS: Dark-adapted ERG responses to full-field flashes of green light were recorded from anesthetized (ketamine/xylazine) C57BL/6N mice. ERG flash responses to homogenous light stimuli arriving from the photoreceptor side were then recorded transretinally from the same retinas, isolated and perfused with Ringer's or Ames' solution at 37°C. The responses were analyzed to determine the a-wave kinetics as well as the estimated flash sensitivity and kinetics of the full rod responses derived with the paired flash protocol. The analysis was complemented with pharmacologic blockade of glutamatergic transmission in the isolated retina. RESULTS: The a-waves were of comparable size, sensitivity and kinetics in vivo and in the isolated retina, but the onset of the b-wave was delayed in the isolated retina. The Lamb-Pugh activation constants determined for the a-waves were similar in both preparations. The kinetics of the derived photoreceptor responses were similar in both conditions, although the responses were consistently slightly slower ex vivo. This was not explicable as a direct effect of ketamine or xylazine on the photoreceptors or as their indirect effect through hyperglycemia, as tested on the isolated retina. CONCLUSIONS: Through comparison to the corneal ERG, the transretinal ERG is a valuable tool for assaying the physiologic state of isolated retinal tissue. The rod photoreceptor responses of the intact isolated retina correspond well to those recorded in vivo. The origin of their faster kinetics compared to single cell recordings remains to be determined.

The association between parental images and satisfaction in intimate relationships in a Northern Finland sample.

OBJECTIVES: Experiences in one's family of origin, especially the relationship to one's parents, supposedly form the basis of relationships in adulthood. The connection between traumatic childhood events and later life has been studied intensively, whereas average childhood growth experiences have been given less attention. The aim of this study was to find out the association between images of the mother and father and the psychosocial well-being of young adults from the perspective of satisfaction in intimate relationships. STUDY DESIGN: Cross-sectional study. METHODS: The research is a part of the Oulu University Hospital Mother-Child Follow-up Study 1971-1972. The follow-up data were collected from the young adults (n=337) in 2000 by way of mailed questionnaires, which included 17 questions about the participants' images of their parents and 18 questions about their intimate relationship satisfaction. In this study we used attachment theory as a theoretical frame of reference. RESULTS: Mental images of dominating parents were associated with quarrelsome intimate relationships, and the image of a dominating father, with repressive/submissive and less balanced relationships. Mental images of diligent and sociable parents were associated with a loving and balanced relationship, and the image of supportive parents, with a balanced relationship. Parental diligence was associated with a less quarrelsome relationship. CONCLUSION: The young adults' mental images of their parents were associated with their intimate relationship satisfaction. Positive mental images of the father, in particular, seemed to protect young adults from a quarrelsome and repressive/submissive intimate relationship.