Comparing neural correlates of configural processing in faces and objects:An ERP study of the thatcher illusion

In the Thatcher illusion, a face with inverted eyes and mouth looks abnormal when upright but not when inverted. Behavioral studies have shown that thatcherization of an upright face disrupts perceptual processing of the local configuration. We recorded high-density EEG from normal observers to study ERP correlates of the illusion during the perception of faces and nonface objects, to determine whether inversion and thatcherization affect similar neural mechanisms. Observers viewed faces and houses in four conditions (upright vs. inverted, and normal vs. thatcherized) while detecting an oddball category (chairs). Thatcherization delayed the N170 component over occipito-temporal cortex to faces, but not to houses. This modulation matched the illusion as it was larger for upright than inverted faces. The P1 over medial occipital regions was delayed by face inversion but unaffected by thatcherization. Finally, face thatcherization delayed P2 over occipito-temporal but not over parietal regions, while inversion affected P2 across categories. All effects involving thatcherization were face-specific. These results indicate that effects of face inversion and feature inversion (in thatcherized faces) can be distinguished on a functional as well as neural level, and that they affect configural processing of faces in different time windows. © 2006 Elsevier Inc.

Neurophysiologic assessment of esophageal sensory processing in noncardiac chest pain

Background & Aims: Esophageal hypersensitivity is thought to be important in the generation and maintenance of symptoms in noncardiac chest pain (NCCP). In this study, we explored the neurophysiologic basis of esophageal hypersensitivity in a cohort of NCCP patients. Methods: We studied 12 healthy controls (9 women; mean age, 37.1 ± 8.7 y) and 32 NCCP patients (23 women; mean age, 47.2 ± 10 y). All had esophageal manometry, esophageal evoked potentials to electrical stimulation, and NCCP patients had 24-hour ambulatory pH testing. Results: The NCCP patients had reduced pain thresholds (PT) (72.1 ± 19.4 vs 54.2 ± 23.6, P = .02) and increased P1 latencies (P1 = 105.5 ± 11.1 vs 118.1 ± 23.4, P = .02). Subanalysis showed that the NCCP group could be divided into 3 distinct phenotypic classifications. Group 1 had reduced pain thresholds in conjunction with normal/reduced latency P1 latencies (n = 9). Group 2 had reduced pain thresholds in conjunction with increased (>2.5 SD) P1 latencies (n = 7), and group 3 had normal pain thresholds in conjunction with either normal (n = 10) or increased (>2.5 SD, n = 3) P1 latencies. Conclusions: Normal esophageal evoked potential latencies with reduced PT, as seen in group 1 patients, is indicative of enhanced afferent transmission and therefore increased esophageal afferent pathway sensitivity. Increased esophageal evoked potential latencies with reduced PT in group 2 patients implies normal afferent transmission to the cortex but heightened secondary cortical processing of this information, most likely owing to psychologic factors such as hypervigilance. This study shows that NCCP patients with esophageal hypersensitivity may be subclassified into distinct phenotypic subclasses based on sensory responsiveness and objective neurophysiologic profiles. © 2006 by the American Gastroenterological Association.

Real-time imaging of human cortical activity evoked by painful esophageal stimulation

Background & Aims: Current models of visceral pain processing derived from metabolic brain imaging techniques fail to differentiate between exogenous (stimulus-dependent) and endogenous (non-stimulus-specific) neural activity. The aim of this study was to determine the spatiotemporal correlates of exogenous neural activity evoked by painful esophageal stimulation. Methods: In 16 healthy subjects (8 men; mean age, 30.2 ± 2.2 years), we recorded magnetoencephalographic responses to 2 runs of 50 painful esophageal electrical stimuli originating from 8 brain subregions. Subsequently, 11 subjects (6 men; mean age, 31.2 ± 1.8 years) had esophageal cortical evoked potentials recorded on a separate occasion by using similar experimental parameters. Results: Earliest cortical activity (P1) was recorded in parallel in the primary/secondary somatosensory cortex and posterior insula (∼85 ms). Significantly later activity was seen in the anterior insula (∼103 ms) and cingulate cortex (∼106 ms; P = .0001). There was no difference between the P1 latency for magnetoencephalography and cortical evoked potential (P = .16); however, neural activity recorded with cortical evoked potential was longer than with magnetoencephalography (P = .001). No sex differences were seen for psychophysical or neurophysiological measures. Conclusions: This study shows that exogenous cortical neural activity evoked by experimental esophageal pain is processed simultaneously in somatosensory and posterior insula regions. Activity in the anterior insula and cingulate - brain regions that process the affective aspects of esophageal pain - occurs significantly later than in the somatosensory regions, and no sex differences were observed with this experimental paradigm. Cortical evoked potential reflects the summation of cortical activity from these brain regions and has sufficient temporal resolution to separate exogenous and endogenous neural activity. © 2005 by the American Gastroenterological Association.

Characterising the central mechanisms of sensory modulation in human swallowing motor cortex

Objective: Pharyngeal stimulation can induce remarkable increases in the excitability of swallowing motor cortex, which is associated with short-term improvements in swallowing behaviour in dysphagic stroke patients. However, the mechanism by which this input induces cortical change remains unclear. Our aims were to explore the stimulus-induced facilitation of the cortico-bulbar projections to swallowing musculature and examine how input from the pharynx interacts with swallowing motor cortex. Methods: In 8 healthy subjects, a transcranial magnetic stimulation (TMS) paired-pulse investigation was performed comprising a single conditioning electrical pharyngeal stimulus (pulse width 0.2 ms, 240 V) followed by cortical TMS at inter-stimulus intervals (ISI) of 10-100 ms. Pharyngeal sensory evoked potentials (PSEP) were also measured over the vertex. In 6 subjects whole-brain magnetoencephalography (MEG) was further acquired following pharyngeal stimulation. Results: TMS evoked pharyngeal motor evoked potentials were facilitated by the pharyngeal stimulus at ISI between 50 and 80 ms (Δ mean increase: 47±6%, P<0.05). This correlated with the peak latency of the P1 component of the PSEP (mean 79.6±8.5 ms). MEG confirmed that the equivalent P1 peak activities were localised to caudolateral sensory and motor cortices (BA 4, 1, 2). Conclusions: Facilitation of the cortico-bulbar pathway to pharyngeal stimulation relates to coincident afferent input to sensorimotor cortex. Significance: These findings have mechanistic importance on how pharyngeal stimulation may increase motor excitability and provide guidance on temporal windows for future manipulations of swallowing motor cortex. © 2004 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Cortical processing of human gut sensation: an evoked potential study

The rectum has a unique physiological role as a sensory organ and differs in its afferent innervation from other gut organs that do not normally mediate conscious sensation. We compared the central processing of human esophageal, duodenal, and rectal sensation using cortical evoked potentials (CEP) in 10 healthy volunteers (age range 21-34 yr). Esophageal and duodenal CEP had similar morphology in all subjects, whereas rectal CEP had two different but reproducible morphologies. The rectal CEP latency to the first component P1 (69 ms) was shorter than both duodenal (123 ms; P = 0.008) and esophageal CEP latencies (106 ms; P = 0.004). The duodenal CEP amplitude of the P1-N1 component (5.0 µV) was smaller than that of the corresponding esophageal component (5.7 µV; P = 0.04) but similar to that of the corresponding rectal component (6.5 µV; P = 0.25). This suggests that rectal sensation is either mediated by faster-conducting afferent pathways or that there is a difference in the orientation or volume of cortical neurons representing the different gut organs. In conclusion, the physiological and anatomic differences between gut organs are reflected in differences in the characteristics of their afferent pathways and cortical processing.

The Effect of nutritional supplementation on subjective and objective measures of visual and retinal function:a random controlled trial

In industrialised countries age-related macular disease (ARMD) is the leading cause of visual loss in older people. Because oxidative stress is purported to be associated with an increased risk of disease development the role of antioxidant supplementation is of interest. Lutein is a carotenoid antioxidant that accumulates within the retina and is thought to filter blue light. Increased levels of lutein have been associated with reduced risk of developing ARMD and improvements in visual and retinal function in eyes with ARMD. The aim of this randomised controlled trial (RCT) was to investigate the effect of a lutein-based nutritional supplement on subjective and objective measures of visual function in healthy eyes and in eyes with age-related maculopathy (ARM) – an early form of ARMD. Supplement withdrawal effects were also investigated. A sample size of 66 healthy older (HO), healthy younger (HY), and ARM eyes were randomly allocated to receive a lutein-based supplement or no treatment for 40 weeks. The supplemented group then stopped supplementation to look at the effects of withdrawal over a further 20 weeks. The primary outcome measure was multifocal electroretinogram (mfERG) N1P1 amplitude. Secondary outcome measures were mfERG N1, P1 and N2 latency, contrast sensitivity (CS), Visual acuity (VA) and macular pigment optical density (MPOD). Sample sizes were sufficient for the RCT to have an 80% power to detect a significant clinical effect at the 5% significance level for all outcome measures when the healthy eye groups were combined, and CS, VA and mfERG in the ARM group. This RCT demonstrates significant improvements in MPOD in HY and HO supplemented eyes. When HY and HO supplemented groups were combined, MPOD improvements were maintained, and mfERG ring 2 P1 latency became shorter. On withdrawal of the supplement mfERG ring 1 N1P1 amplitude reduced in HO eyes. When HO and HY groups were combined, mfERG ring 1 and ring 2 N1P1 amplitudes were reduced. In ARM eyes, ring 3 N2 latency and ring 4 P1 latency became longer. These statistically significant changes may not be clinically significant. The finding that a lutein-based supplement increases MPOD in healthy eyes, but does not increase mfERG amplitudes contrasts with the CARMIS study and contributes to the debate on the use of nutritional supplementation in ARM.

The separation of secondary oil-water dispersions in particulate beds

The literature relating to haze formation, methods of separation, coalescence mechanisms, and models by which droplets <100 μm are collected, coalesced and transferred, have been reviewed with particular reference to particulate bed coalescers. The separation of secondary oil-water dispersions was studied experimentally using packed beds of monosized glass ballotini particles. The variables investigated were superficial velocity, bed depth, particle size, and the phase ratio and drop size distribution of inlet secondary dispersion. A modified pump loop was used to generate secondary dispersions of toluene or Clairsol 350 in water with phase ratios between 0.5-6.0 v/v%.Inlet drop size distributions were determined using a Malvern Particle Size Analyser;effluent, coalesced droplets were sized by photography. Single phase flow pressure drop data were correlated by means of a Carman-Kozeny type equation. Correlations were obtained relating single and two phase pressure drops, as (ΔP2/μc)/ΔP1/μd) = kp Ua Lb dcc dpd Cine A flow equation was derived to correlate the two phase pressure drop data as, ΔP2/(ρcU2) = 8.64*107 [dc/D]-0.27 [L/D]0.71 [dp/D]-0.17 [NRe]1.5 [e1]-0.14 [Cin]0.26  In a comparison between functions to characterise the inlet drop size distributions a modification of the Weibull function provided the best fit of experimental data. The general mean drop diameter was correlated by: q_p q_p p_q /β      Γ ((q-3/β) +1) d qp = d fr  .α        Γ ((P-3/β +1 The measured and predicted mean inlet drop diameters agreed within ±15%. Secondary dispersion separation depends largely upon drop capture within a bed. A theoretical analysis of drop capture mechanisms in this work indicated that indirect interception and London-van der Waal's mechanisms predominate. Mathematical models of dispersed phase concentration m the bed were developed by considering drop motion to be analogous to molecular diffusion.The number of possible channels in a bed was predicted from a model in which the pores comprised randomly-interconnected passage-ways between adjacent packing elements and axial flow occured in cylinders on an equilateral triangular pitch. An expression was derived for length of service channels in a queuing system leading to the prediction of filter coefficients. The insight provided into the mechanisms of drop collection and travel, and the correlations of operating parameters, should assist design of industrial particulate bed coalescers.

The chromatic visual evoked response as an indication of visual development

In an endeavour to provide further insight into the maturation of the cortical visual system in human infants, chromatic transient pattern reversal visual evoked potentials to red/green stimuli, were studied in a group of normal full term infants between the ages of 1 and 14 weeks post term in both cross sectional and longitudinal studies. In order to produce stimuli in which luminance cues had been eliminated with an aim to eliciting a chromatic response, preliminary studies of isoluminance determination in adults and infants were undertaken using behavioural and electrophysiological techniques. The results showed close similarity between the isoluminant ratio for adults and infants and all values were close to photometric isoluminance. Pattern reversal VEPs were recorded to stimuli of a range of red/green luminance ratios and an achromatic checkerboard. No transient VEP could be elicited with an isoluminant chromatic pattern reversal stimulus from any infant less than 7 weeks post term and similarly, all infants more than 7 weeks post term showed clear chromatic VEPs. The chromatic response first appeared at that age as a major positive component (P1) of long latency. This was delayed and reduced in comparison to the achromatic response. As the infant grew older, the latency of the P1 component decreased with the appearance of N1 and N by the 10th week post term. This finding was consistent throughout all infants assessed. In a behavioural study, no infant less than 7 weeks post term demonstrated clear discrimination of the chromatic stimulus, while those infants older than 7 weeks could do so. These findings are reviewed with respect to current neural models of visual development.

The development of the visual system in pre-term infants as assessed by electrophysiological techniques

In an endeavour to provide further insight into the maturation of the human visual system, the contiguous development of the pattern reversal VEP, flash VEP and flash ERG was studied in a group of neurologically normal pre-term infants, born between 28 and 35 weeks gestation. Maturational changes were observed in all the evoked electrophysiological responses recorded, these were mainly characterised by an increase in the complexity of the waveform and a shortening in the latency of the response. Initially the ERG was seen to consist of a broad b-wave only, with the a-wave emerging at an average age of 40 weeks PMA. The a-wave showed only a slight reduction in latency and a modest increase in amplitude as the infant grows older, whereas the changes seen in the ERG b-wave were much more dramatic. Pattern reversal VEPs were successfully recorded for the first time during the pre-term period. Flash VEPs were also recorded for comparison. The neonatal pattern reversal VEP consistently showed a major positive component (P1) of long latency. As the infant grew older, the latency of the P1 component decreased and was found to be negatively correlated with PMA at recording. The appearance of the N1 and N2 components became more frequent as the infant matured. The majority of infants were found to be myopic at birth and refractive error was correlated with PMA, with emmetropisation occurring at about 45 weeks PMA. The pattern reversal VEP in response to 2o checks was apparently unaffected by refractive error.

The investigation of the primary response of the flash visual evoked response

The topographical distribution of the early components of the flash visual evoked response (VER) were investigated using a twenty channel brain mapping system. Thirty subjects, ranging in age from 21 to 84 years, had flash VERs recorded using the standard 10-20 electrode system to a balanced non-cephalic reference. The subjects were divided into three age groups: a young group, a middle group and an older group. The P2 component (positive component around 100-120 msec) of the flash VER was recorded consistently over the occipital region throughout the age range, as was a frontal negative component (N120) of about the same latency. Only the young age group had this single negative component on the frontage channels, whilst the middle age group showed an additional negative component at around 75 msec (N75). Neither group had a recordable P1 component (positive component around 60-75 msec) over the occipital region. The older age group showed both P1 and P2 components over the occipital region with the distribution of the P1 component being more widespread anteriorly. The frontal channels showed both the negative N75 and the later N120 components. The frontal negative components were shown not to be related to the electroretinogram or the balanced non-cephalic reference, but were affected by the type of stimulation. Responses recorded to both pattern reversal and onset/offset stimulation did not show the frontal negative potentials seen with flash stimulation. It was shown that the P1 component is more readily recordable in the elderly and is preceded during middle age by the development of a frontal negative component at around the same latency. The changing morphology of the negative activity in the frontal region across the age range suggests that the use of an Fz reference would produce an artificial P1 component in the middle age group and an enhancement of this component in the elderly, as well as enhance the P2 component in all ages.

Study of neutral Fe(III) complexes of pyridoxal-N-substituted thiosemicarbazone with desolvation induced spin-state transformation above room temperature

The preparation and characterization of two new neutral ferric complexes with desolvation-induced discontinuous spin-state transformation above room temperature are reported. The compounds, Fe(Hthpy)(thpy).CH3OH.3H2O (1) and Fe(Hmthpy)(mthpy).2H2O (2), are low-spin (LS) at room temperature and below, whereas their nonsolvated forms are high-spin (HS), exhibiting zero-field splitting. In these complexes, Hthpy, Hmthpy, and thpy, mthpy are the deprotonated forms of pyridoxal thiosemicarbazone and pyridoxal methylthiosemicarbazone, respectively; each is an O,N,S-tridentate ligand. The molecular structures have been determined at 100(1) K using single-crystal X-ray diffraction techniques and resulted in a triclinic system (space group P1) and monoclinic unit cell (space group P21/c) for 1 and 2, respectively. Structures were refined to the final error indices, where RF = 0.0560 for 1 and RF = 0.0522 for 2. The chemical inequivalence of the ligands was clearly established, for the "extra" hydrogen atom on the monodeprotonated ligands (Hthpy, Hmthpy) was found to be bound to the nitrogen of the pyridine ring. The ligands are all of the thiol form; the doubly deprotonated chelates (thpy, mthpy) have C-S bond lengths slightly longer than those of the singly deprotonated forms. There is a three-dimensional network of hydrogen bonds in both compounds. The discontinuous spin-state transformation is accompanied with liberation of solvate molecules. This is evidenced also from DSC analysis. Heat capacity data for the LS and HS phases are tabulated at selected temperatures, the values of the enthalpy and entropy changes connected with the change of spin state were reckoned at DeltaH = 12.5 0.3 kJ mol-1 and DeltaS = 33.3 0.8 J mol-1 K-1, respectively, for 1 and DeltaH = 6.5 0.3 kJ mol-1 and DeltaS = 17.6 0.8 J mol-1 K-1, respectively, for 2

Tuning of the charge in octahedral ferric complexes based on pyridoxal-N substituted thiosemicarbazone ligands

Four novel mononuclear coordination compounds namely: [Fe(Hthpy)2](SO4)1/2·3.5H2O 1, [Fe(Hthpy)2]NO3·3H2O 2, [Fe(H2mthpy)2](CH3C6H4SO3)3·CH3CH2OH 3 and [Fe(Hethpy)(ethpy)]·8H2O 4, (H2thpy = pyridoxalthiosemicarbazone, H2mthpy = pyridoxal-4-methylthiosemicarbazone, H2ethpy = pyridoxal-4-ethylthiosemicarbazone), were synthesized in the absence or presence of organic base, Et3N and NH3. Compounds 1 and 2 are monocationic, and were prepared using the singly deprotonated form of pyridoxalthiosemicarbazone. Both compounds crystallise in the monoclinic system, C2/c and P21/c space group for 1 and 2, respectively. Complex 3 is tricationic, it is formed with neutral bis(ligand) complex and possesses an interesting 3D channel architecture, the unit cell is triclinic, P1 space group. For complex 4, the pH value plays an important role during its synthesis; 4 is neutral and crystallises with two inequivalent forms of the ligand: the singly and the doubly deprotonated chelate of H2ethpy, the unit cell is monoclinic, C2/c space group. Notably, in 1 and 4, there is an attractive infinite three dimensional hydrogen bonding network in the crystal lattice. Magnetic measurements of 1 and 4 revealed that a rather steep spin transition from the low spin to high spin Fe(III) states occurs above 300 K in the first heating step. This transition is accompanied by the elimination of solvate molecules and thus, stabilizes the high spin form due to the breaking of hydrogen bonding networks; compared to 2 and 3, which keep their low spin state up to 400 K.

The effects of a lutein-based supplement on objective and subjective measures of retinal and visual function in eyes with age-related maculopathy - a randomised controlled trial

Lutein and zeaxanthin are lipid-soluble antioxidants found within the macula region of the retina. Links have been suggested between increased levels of these carotenoids and reduced risk for age-related macular disease (ARMD). Therefore, the effect of lutein-based supplementation on retinal and visual function in people with early stages of ARMD (age-related maculopathy, ARM) was assessed using multi-focal electroretinography (mfERG), contrast sensitivity and distance visual acuity. A total of fourteen participants were randomly allocated to either receive a lutein-based oral supplement (treated group) or no supplement (non-treated group). There were eight participants aged between 56 and 81 years (65·50 (sd 9·27) years) in the treated group and six participants aged between 61 and 83 years (69·67 (sd 7·52) years) in the non-treated group. Sample sizes provided 80 % power at the 5 % significance level. Participants attended for three visits (0, 20 and 40 weeks). At 60 weeks, the treated group attended a fourth visit following 20 weeks of supplement withdrawal. No changes were seen between the treated and non-treated groups during supplementation. Although not clinically significant, mfERG ring 3 N2 latency (P= 0·041) and ring 4 P1 latency (P= 0·016) increased, and a trend for reduction of mfERG amplitudes was observed in rings 1, 3 and 4 on supplement withdrawal. The statistically significant increase in mfERG latencies and the trend for reduced mfERG amplitudes on withdrawal are encouraging and may suggest a potentially beneficial effect of lutein-based supplementation in ARM-affected eyes. Copyright © 2012 The Authors.

Grading and disease management in national screening for diabetic retinopathy in England and Wales

Aims - A National Screening Programme for diabetic eye disease in the UK is in development. We propose a grading and early disease management protocol to detect sight-threatening diabetic retinopathy and any retinopathy, which will allow precise quality assurance at all steps while minimizing false-positive referral to the hospital eye service. Methods - Expert panel structured discussions between 2000 and 2002 with review of existing evidence and grading classifications. Proposals - Principles of the protocol include: separate grading of retinopathy and maculopathy, minimum number of steps, compatible with central monitoring, expandable for established more complex systems and for research, no lesion counting, no ‘questionable’ lesions, attempt to detect focal exudative, diffuse and ischaemic maculopathy and fast track referral from primary or secondary graders. Sight-threatening diabetic retinopathy is defined as: preproliferative retinopathy or worse, sight-threatening maculopathy and/or the presence of photocoagulation. In the centrally reported minimum data set retinopathy is graded into four levels: none (R0), background (R1), preproliferative (R2), proliferative (R3). Maculopathy and photocoagulation are graded as absent (M0, P0) or present (M1, P1). Discussion - The protocol developed by the Diabetic Retinopathy Grading and Disease Management Working Party represents a new consensus upon which national guidelines can be based leading to the introduction of quality-assured screening for people with diabetes.

One- and two-step spin-crossover behavior of [Fe(II)(isoxazole)6]2+ and the structure and magnetic properties of triangular [Fe(III)3O(OAc)6(isoxazole)3][ClO4)]

The structure and spin-crossover magnetic behavior of [FeII16][BF4]2 (1 = isoxazole) and [FeII16][ClO4]2 have been studied. [FeII16][BF4]2 undergoes two reversible spin-crossover transitions at 91 and 192 K, and is the first two-step spin transition to undergo a simultaneous crystallographic phase transition, but does not exhibit thermal hysteresis. The single-crystal structure determinations at 260 [space group P3̄, a = 17.4387(4) Å, c = 7.6847(2) Å] and at 130 K [space group P1̄, a = 17.0901(2) Å, b = 16.7481(2) Å, c = 7.5413(1) Å, α = 90.5309(6)°, β = 91.5231(6)°, γ = 117.8195(8)°] reveal two different iron sites, Fe1 and Fe2, in a 1:2 ratio. The room-temperature magnetic moment of 5.0 μB is consistent with high-spin Fe(II). A plateau in μ(T) having a moment of 3.3 μB centered at 130 K suggests a mixed spin system of some high-spin and some low-spin Fe(II) molecules. On the basis of the Fe−N bond distances at the two temperatures, and the molar fraction of high-spin molecules at the transition plateau, Fe1 and Fe2 can be assigned to the 91 and 192 K transitions, respectively. [FeII16][ClO4]2 [space group P3̄, a = 17.5829(3) Å, c = 7.8043(2) Å, β = 109.820 (3)°, T = 295 K] also possesses Fe1:Fe2 in a 1:2 ratio, and magnetic measurements show a single spin transition at 213 K, indicating that both Fe1 and Fe2 undergo a simultaneous spin transition. [FeII16][ClO4]2 slowly decomposes in solutions containing acetic anhydride to form [FeIII3O(OAc)613][ClO4] [space group I2, a = 10.1547(7) Å, b = 16.5497(11) Å, c = 10.3205(9) Å, β = 109.820 (3)°, T = 200 K]. The isosceles Fe3 unit contains two Fe···Fe distances of 3.2844(1) Å and a third Fe···Fe distance of 3.2857(1) Å. The magnetic data can be fit to a trinuclear model with ℋ = −2J(S1·S2 + S2·S3) − 2J13(S1·S3), where J = −27.1 and J13 = −32.5 cm-1.