Functional organization of the caudal part of the human superior parietal lobule

: Like in macaque, the caudal portion of the human superior parietal lobule (SPL) plays a key role in a series of perceptive, visuomotor and somatosensory processes. Here, we review the functional properties of three separate portions of the caudal SPL, i.e., the posterior parieto-occipital sulcus (POs), the anterior POs, and the anterior part of the caudal SPL. We propose that the posterior POs is mainly dedicated to the analysis of visual motion cues useful for object motion detection during self-motion and for spatial navigation, while the more anterior parts are implicated in visuomotor control of limb actions. The anterior POs is mainly involved in using the spotlight of attention to guide reach-to-grasp hand movements, especially in dynamic environments. The anterior part of the caudal SPL plays a central role in visually guided locomotion, being implicated in controlling leg-related movements as well as the four limbs interaction with the environment, and in encoding egomotion-compatible optic flow. Together, these functions reveal how the caudal SPL is strongly implicated in skilled visually-guided behaviors

A common neural substrate for processing scenes and egomotion-compatible visual motion

Neuroimaging studies have revealed two separate classes of category-selective regions specialized in optic flow (egomotion-compatible) processing and in scene/place perception. Despite the importance of both optic flow and scene/place recognition to estimate changes in position and orientation within the environment during self-motion, the possible functional link between egomotion- and scene-selective regions has not yet been established. Here we reanalyzed functional magnetic resonance images from a large sample of participants performing two well-known \u201clocalizer\u201d fMRI experiments, consisting in passive viewing of navigationally relevant stimuli such as buildings and places (scene/place stimulus) and coherently moving fields of dots simulating the visual stimulation during self-motion (flow fields). After interrogating the egomotion-selective areas with respect to the scene/place stimulus and the scene-selective areas with respect to flow fields, we found that the egomotion-selective areas V6+ and pIPS/V3A responded bilaterally more to scenes/places compared to faces, and all the scene-selective areas (parahippocampal place area or PPA, retrosplenial complex or RSC, and occipital place area or OPA) responded more to egomotion-compatible optic flow compared to random motion. The conjunction analysis between scene/place and flow field stimuli revealed that the most important focus of common activation was found in the dorsolateral parieto-occipital cortex, spanning the scene-selective OPA and the egomotion-selective pIPS/V3A. Individual inspection of the relative locations of these two regions revealed a partial overlap and a similar response profile to an independent low-level visual motion stimulus, suggesting that OPA and pIPS/V3A may be part of a unique motion-selective complex specialized in encoding both egomotion- and scene-relevant information, likely for the control of navigation in a structured environment

Aging is associated with increased clonogenic potential in rat liver in vivo

Summary Cancer increases with age and often arises from the selective clonal growth of altered cells. Thus, any environment favoring clonal growth per se poses a higher risk for cancer development. Using a genetically tagged animal model, we investigated whether aging is associated with increased clonogenic potential. Groups of 4-, 12-, 18-, and 24-month-old Fischer 344 rats were infused (via the portal vein) with 2 × 106 hepatocytes isolated from a normal syngenic 2-month-old donor. Animals deficient in dipeptidyl-peptidase type IV (DPP-IV–) enzyme were used as recipients, allowing for the histochemical detection of injected DPP-IV+ cells. Groups of animals were sacrificed at various times thereafter. No growth of DPP-IV+ transplanted hepatocytes was present after either 2 or 6 months in the liver of rats transplanted at young age, as expected. In striking contrast, significant expansion of donor-derived cells was seen in animals transplanted at the age of 18 months: clusters comprising 7–10 DPP-IV+ hepatocytes/cross-section were present after 2 months and were markedly enlarged after 6 months (mean of 88 ± 35 cells/cluster/cross-section). These results indicate that the microenvironment of the aged liver supports the clonal expansion of transplanted normal hepatocytes. Such clonogenic environments can foster the selective growth of pre-existing altered cells, thereby increasing the overall risk for cancer development associated with aging

Refractive error and vision correction in a general sports-playing population

Purpose: To evaluate, in an amateur sports-playing population, the prevalence of refractive error, the type of vision correction used during sport and attitudes toward different kinds of vision correction used in various types of sports. Method: A questionnaire was used for people engaging in sport and data was collected from sport centres, gyms and universities that focused on the motor sciences. Results: One thousand, five hundred and seventy-three questionnaires were collected (mean age 26.5 ± 12.9 years; 63.5 per cent male). Nearly all (93.8 per cent) subjects stated that their vision had been checked at least once. Fifty-three subjects (3.4 per cent) had undergone refractive surgery. Of the remainder who did not have refractive surgery (n = 1,519), 580 (38.2 per cent) reported a defect of vision, 474 (31.2 per cent) were myopic, 63 (4.1 per cent) hyperopic and 241 (15.9 per cent) astigmatic. Logistic regression analysis showed that the best predictors for myopia prevalence were gender (p < 0.001) and location of sport practice (p < 0.001). Sports that present higher prevalence of outdoor activity have lower prevalence of myopia. Contact lens penetration over the study sample was 18.7 per cent. Contact lenses were the favourite system of correction among people interviewed compared to spectacles and refractive surgery (p < 0.001). Conclusions: This study showed that sport was not associated with different levels of myopia prevalence in the adult population. However, subjects engaging in outdoor sports had lower rates of myopia prevalence. Penetration of contact lens use in sport was four times higher than the overall adult population. Contact lenses were the preferred system of correction in sports compared to spectacles or refractive surgery, but this preference was affected by the type of sport practised and by the age and level of sports activity for which the preference was required

An 8-week rehabilitation training using the HBP exoskeleton improves cognitive brain functions in multiple sclerosis patients

It has been showed that a single application of the exoskeleton (HBP) in multiple sclerosis patients is able to improve mobility and ambulation. These effects have been associated with brain changes in high-level executive functions decisive for improving patients’ motor control [1]. We applied an 8-weeks rehabilitation protocol in 12 MS patients, half of them randomly assigned to a standard protocol (control group, CG) and the other half to a protocol based on the HBP use (experimental group, EG). Patients were evaluated before and after rehabilitation training using multiple neurological, physiotherapeutic and cognitive testing. During the cognitive task, high-resolution EEG was also recorded for ERP analysis. Results showed that both groups improved their performance in the Barthel, Rivermead, 2-WT, 25-FWT, Tinetti and BBS tests. Only in the EG, other positive treatment effects were observed as measured by the EDSS disability scale and the FSS. Accordingly, in cognitive testing, only the EG showed significant benefits in response time (RT) and accuracy. At brain level the EG showed enhancement in task-related preparatory activity in frontal and prefrontal cortices and stronger post-stimulus activity in the anterior Insula, whose activity is related to more efficient decision making. The CG didn’t show enhanced performance in the cognitive task but only large activity in visual areas, as observed in EG. Concluding, both rehabilitation protocols brought substantial neurophysiological benefits to MS patients, however, the HBP protocol was particularly effective, boosting cognitive functions in prefrontal and frontal brain areas, it allowed improvements in RT and accuracy. The integration of HBP with standard rehabilitation procedure may considerably reduce disability in MS patients

What is involved and what is necessary for complex linguistic and nonlinguistic auditory processing: evidence from functional magnetic resonance imaging and lesion data

We used functional magnetic resonance imaging (fMRI) in conjunction with a voxel-based approach to lesion symptom mapping to quantitatively evaluate the similarities and differences between brain areas involved in language and environmental sound comprehension. In general, we found that language and environmental sounds recruit highly overlapping cortical regions, with cross-domain differences being graded rather than absolute. Within language-based regions of interest, we found that in the left hemisphere, language and environmental sound stimuli evoked very similar volumes of activation, whereas in the right hemisphere, there was greater activation for environmental sound stimuli. Finally, lesion symptom maps of aphasic patients based on environmental sounds or linguistic deficits [Saygin, A. P., Dick, F., Wilson, S. W., Dronkers, N. F., & Bates, E. Shared neural resources for processing language and environmental sounds: Evidence from aphasia. Brain, 126, 928–945, 2003] were generally predictive of the extent of blood oxygenation level dependent fMRI activation across these regions for sounds and linguistic stimuli in young healthy subjects

Concurrent Oral 9 - Rheumatoid Arthritis: Aetiopathogenesis [OP59-OP64]: OP59. The Value of Interleukin-17 Serum Level in Rheumatoid Arthritis Immunopathogenesis

Background: Interleukin (IL)-17 is the main Th-1 cytokine, produced by activated T-lymphocytes. The potential IL-17 value in rheumatoid arthritis (RA) pathogenesis consists of its independent inflammatory response induction and mediated stimulation of proinflammatory factors synthesis resulting in joint destruction. The aim of study was to determine the role of IL-17 in immuno-inflammatory/autoimmune reactions development and to reveal IL-17 serum level associations with clinical and immunological characteristics of RA. Methods: 50 patients with early RA (disease duration >, Russia), anti-CCP antibodies (Axies-Shield Diagnostic, UK) were revealed using ELISA immunoassay. Results: On the base of IL-17 serum level patients were divided in two groups: group1 (n = 28) were patients with normal IL-17 serum level and group2 (n = 22) were those with high IL-17 serum level. In the group2, the rate of patients' pain assessment by visual analogue scale (67.3 ± 7.2 vs 32.8 ± 4.6; P < 0.001), tender (16.7 ± 2.0 vs 8.4 ± 1.1; P < 0.01) and swollen (12.3 ± 2.3 vs 3.9 ± 0.8; P < 0.01) joint count, DAS28 (5.0 ± 0.4 vs 2.8 ± 0.2 P < 0.01) were significantly higher compare to group1. It was found that in group2 the higher T-lymphocyte amount (CD3) was due to CD4 higher quantity, at the same time CD8 amount was significantly lower (22.2 ± 1.5% vs 28.4 ± 1.7%, P < 0.05) compare to group1. This caused the immunoregulative index increasing and indicated in the lost of autoimmune process regulation, including B-lymphocytes (CD19) activation. The CD154 expression was significantly lower in the group2 (3.4 ± 0.4% vs 10.8 ± 2.8%, P < 0.05) compare to group1. The difference in autoimmune reaction indices wasn't significant between groups except antibody-producing B-lymphocytes (13.7 ± 1.5% vs 8.5 ± 1.0%, P < 0.05) and IgM RF serum level (2.9 ± 0.3 U/ml vs 1.6 ± 0.5 U/ml, P < 0.05), which were significantly higher in group1. The IL-17 level had a positive correlative connections with DAS28 (r = 0.7; P < 0.05), circulative immune complex level (r = 0.38; P < 0.05), anti-CCP antibodies (r = 0.4; P < 0.05), IgM RF (r = 0.41; P < 0.05), CD4 (r = 0.38; P < 0.05) and negative correlative connection with CD8 (r = -0.39; P < 0.05). Conclusions: The importance of IL-17 value in immuno-inflammatory and autoimmune reactions development through T-lymphocytes activation in RA pathogenesis was confirmed. Thus the influence on T-depended immuno-inflammatory reaction products synthesis could be a new therapeutic target of RA patients' management. Disclosure statement: All authors have declared no conflicts of interes

Spatio-Temporal Brain Mapping of Motion-Onset VEPs Combined with fMRI and Retinotopic Maps

Neuroimaging studies have identified several motion-sensitive visual areas in the human brain, but the time course of their activation cannot be measured with these techniques. In the present study, we combined electrophysiological and neuroimaging methods (including retinotopic brain mapping) to determine the spatio-temporal profile of motion-onset visual evoked potentials for slow and fast motion stimuli and to localize its neural generators. We found that cortical activity initiates in the primary visual area (V1) for slow stimuli, peaking 100 ms after the onset of motion. Subsequently, activity in the mid-temporal motion-sensitive areas, MT+, peaked at 120 ms, followed by peaks in activity in the more dorsal area, V3A, at 160 ms and the lateral occipital complex at 180 ms. Approximately 250 ms after stimulus onset, activity fast motion stimuli was predominant in area V6 along the parieto-occipital sulcus. Finally, at 350 ms (100 ms after the motion offset) brain activity was visible again in area V1. For fast motion stimuli, the spatio-temporal brain pattern was similar, except that the first activity was detected at 70 ms in area MT+. Comparing functional magnetic resonance data for slow vs. fast motion, we found signs of slow-fast motion stimulus topography along the posterior brain in at least three cortical regions (MT+, V3A and LOR)

Oral abstracts 3: RA Treatment and outcomesO13. Validation of jadas in all subtypes of juvenile idiopathic arthritis in a clinical setting

Background: Juvenile Arthritis Disease Activity Score (JADAS) is a 4 variable composite disease activity (DA) score for JIA (including active 10, 27 or 71 joint count (AJC), physician global (PGA), parent/child global (PGE) and ESR). The validity of JADAS for all ILAR subtypes in the routine clinical setting is unknown. We investigated the construct validity of JADAS in the clinical setting in all subtypes of JIA through application to a prospective inception cohort of UK children presenting with new onset inflammatory arthritis. Methods: JADAS 10, 27 and 71 were determined for all children in the Childhood Arthritis Prospective Study (CAPS) with complete data available at baseline. Correlation of JADAS 10, 27 and 71 with single DA markers was determined for all subtypes. All correlations were calculated using Spearman's rank statistic. Results: 262/1238 visits had sufficient data for calculation of JADAS (1028 (83%) AJC, 744 (60%) PGA, 843 (68%) PGE and 459 (37%) ESR). Median age at disease onset was 6.0 years (IQR 2.6-10.4) and 64% were female. Correlation between JADAS 10, 27 and 71 approached 1 for all subtypes. Median JADAS 71 was 5.3 (IQR 2.2-10.1) with a significant difference between median JADAS scores between subtypes (p < 0.01). Correlation of JADAS 71 with each single marker of DA was moderate to high in the total cohort (see Table 1). Overall, correlation with AJC, PGA and PGE was moderate to high and correlation with ESR, limited JC, parental pain and CHAQ was low to moderate in the individual subtypes. Correlation coefficients in the extended oligoarticular, rheumatoid factor negative and enthesitis related subtypes were interpreted with caution in view of low numbers. Conclusions: This study adds to the body of evidence supporting the construct validity of JADAS. JADAS correlates with other measures of DA in all ILAR subtypes in the routine clinical setting. Given the high frequency of missing ESR data, it would be useful to assess the validity of JADAS without inclusion of the ESR. Disclosure statement: All authors have declared no conflicts of interest. Table 1Spearman's correlation between JADAS 71 and single markers DA by ILAR subtype ILAR Subtype Systemic onset JIA Persistent oligo JIA Extended oligo JIA Rheumatoid factor neg JIA Rheumatoid factor pos JIA Enthesitis related JIA Psoriatic JIA Undifferentiated JIA Unknown subtype Total cohort Number of children 23 111 12 57 7 9 19 7 17 262 AJC 0.54 0.67 0.53 0.75 0.53 0.34 0.59 0.81 0.37 0.59 PGA 0.63 0.69 0.25 0.73 0.14 0.05 0.50 0.83 0.56 0.64 PGE 0.51 0.68 0.83 0.61 0.41 0.69 0.71 0.9 0.48 0.61 ESR 0.28 0.31 0.35 0.4 0.6 0.85 0.43 0.7 0.5 0.53 Limited 71 JC 0.29 0.51 0.23 0.37 0.14 -0.12 0.4 0.81 0.45 0.41 Parental pain 0.23 0.62 0.03 0.57 0.41 0.69 0.7 0.79 0.42 0.53 Childhood health assessment questionnaire 0.25 0.57 -0.07 0.36 -0.47 0.84 0.37 0.8 0.66 0.4

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes