Prediction of functional outcome 18 months after a first psychotic episode: a proton magnetic resonance spectroscopy study.

CONTEXT: Recent magnetic resonance imaging studies have attempted to relate volumetric brain measurements in early schizophrenia to clinical and functional outcome some years later. These studies have generally been negative, perhaps because gray and white matter volumes inaccurately assess the underlying dysfunction that might be predictive of outcome. OBJECTIVE: To investigate the predictive value of frontal and temporal spectroscopy measures for outcome in patients with first-episode psychoses. DESIGN: Left prefrontal cortex and left mediotemporal lobe voxels were assessed using proton magnetic resonance spectroscopy to provide the ratio of N-acetylaspartate (NAA) and choline-containing compounds to creatine and phosphocreatine (Cr) (NAA/Cr ratio). These data were used to predict outcome at 18 months after admission, as assessed by a systematic medical record audit. SETTING: Early psychosis clinic. PARTICIPANTS: Forty-six patients with first-episode psychosis. MAIN OUTCOME MEASURES: We used regression models that included age at imaging and duration of untreated psychosis to predict outcome scores on the Global Assessment of Functioning Scale, Clinical Global Impression scales, and Social and Occupational Functional Assessment Scale, as well as the number of admissions during the treatment period. We then further considered the contributions of premorbid function and baseline level of negative symptoms. RESULTS: The only spectroscopic predictor of outcome was the NAA/Cr ratio in the prefrontal cortex. Low scores on this variable were related to poorer outcome on all measures. In addition, the frontal NAA/Cr ratio explained 17% to 30% of the variance in outcome. CONCLUSIONS: Prefrontal neuronal dysfunction is an inconsistent feature of early psychosis; rather, it is an early marker of poor prognosis across the first years of illness. The extent to which this can be used to guide treatment and whether it predicts outcome some years after first presentation are questions for further research.

Neuropsychological outcome after extra-temporal epilepsy surgery.

BACKGROUND: The neuropsychological results of temporal lobe epilepsy surgery are well reported in the literature. The aim of this study was to analyse the neuropsychological outcome in a consecutive series of patients with extra-temporal epilepsy. METHODS: We retrospectively analysed the data of patients operated between 1996 and 2008 for extra-temporal epilepsy. Standard neuropsychological tests were applied. We assessed the neuropsychological outcome after surgery and the correlation of the neuropsychological outcome with (1) side and localisation of surgery, (2) Engel scale for seizure outcome and (3) timing of surgery. FINDINGS: Patients had a better neuropsychological outcome when undergoing non-frontal resection [χ2 (2) =6.66, p = 0.036]. Subjects who had undergone left or right resection showed no difference in outcome [χ2 (2) =0.533, p = 0.766]. The correlation between the Engel scale for seizure re-occurence and the neuropsychological scores showed only a tendency for better outcome (Spearman ρ = -0.437; p = 0.069). The global measure of change did not correlate significantly with delay of surgery (Spearman ρ = -0.163; p = 0.518). CONCLUSIONS: Resective epilepsy surgery improves neuropsychological status outcome in patients with extra-temporal epilepsy even if the patient did not become seizure free. The outcome is better for non-frontal localisation.

Immunodensity and mRNA expression of A2A adenosine, D2 dopamine, and CB1 cannabinoid receptors in postmortem frontal cortex of subjects with schizophrenia: effect of antipsychotic treatment.

RATIONALE: Dopamine D2 receptors are the main target of antipsychotic drugs. In the brain, D2 receptors coexpress with adenosine A2A and CB1 cannabinoid receptors, leading to functional interactions. OBJECTIVES: The protein and messenger RNA (mRNA) contents of A2A, D2, and CB1 receptors were quantified in postmortem prefrontal cortex of subjects with schizophrenia. MATERIALS AND METHODS: The study was performed in subjects suffering schizophrenia (n=31) who mainly died by suicide, matched with non-schizophrenia suicide victims (n=13) and non-suicide controls (n=33). The density of receptor proteins was evaluated by immunodetection techniques, and their relative mRNA expression was quantified by quantitative real-time polymerase chain reaction. RESULTS: In schizophrenia, the densities of A2A (90+/-6%, n=24) and D2-like receptors (95+/-5%, n=22) did not differ from those in controls (100%). Antipsychotic treatment did not induce changes in the protein expression. In contrast, the immunodensity of CB1 receptors was significantly decreased (71+/-7%, n=11; p<0.05) in antipsychotic-treated subjects with schizophrenia but not in drug-free subjects (104+/-13%, n=11). The relative mRNA amounts encoding for A2A, D2, and CB1 receptors were similar in brains of drug-free, antipsychotic-treated subjects with schizophrenia and controls. CONCLUSIONS: The findings suggest that antipsychotics induce down-regulation of CB1 receptors in brain. Since A2A, D2, and CB1 receptors coexpress on brain GABAergic neurons and reductions in markers of GABA neurotransmission have been identified in schizophrenia, a lower density of CB1 receptor induced by antipsychotics could represent an adaptative mechanism that reduces the endocannabinoid-mediated suppression of GABA release, contributing to the normalization of cognitive functions in the disorder.

Voyages astraux et hors du corps. Héautoscopie, extase et hallucinations expérientielles d'origine épileptique [Astral and out-of-body voyages. Heautoscopy, ecstasis and experimental hallucinations of epileptic origin]

We report a 38 year-old patient who had temporoparietal epilepsy and unusual ictal "out of body" experiences that remained undiagnosed for more than ten years, until her admission for a motor seizure of the left hemibody. Out of body episodes were experienced as intense and ecstatic astral journeys. EEG showed a bilateral extension of epileptiform abnormalities to the parietal regions, predominantly on the right side. We discuss the various forms of heautoscopy and their putative mechanisms. We suggest that a disturbance in representing space in independent extrapersonal and personal coordinates might be as crucial as the elusive hypothesis of a body schema disorder. Combined involvement of the parietal neocortex and temporolimbic structures might allow those experiences to gain a subjective vividness which appears to be indissociable from normal conscious experiences.

Three-dimensional magnetic resonance myocardial motion tracking from a single image plane.

Three-dimensional imaging for the quantification of myocardial motion is a key step in the evaluation of cardiac disease. A tagged magnetic resonance imaging method that automatically tracks myocardial displacement in three dimensions is presented. Unlike other techniques, this method tracks both in-plane and through-plane motion from a single image plane without affecting the duration of image acquisition. A small z-encoding gradient is subsequently added to the refocusing lobe of the slice-selection gradient pulse in a slice following CSPAMM acquisition. An opposite polarity z-encoding gradient is added to the orthogonal tag direction. The additional z-gradients encode the instantaneous through plane position of the slice. The vertical and horizontal tags are used to resolve in-plane motion, while the added z-gradients is used to resolve through-plane motion. Postprocessing automatically decodes the acquired data and tracks the three-dimensional displacement of every material point within the image plane for each cine frame. Experiments include both a phantom and in vivo human validation. These studies demonstrate that the simultaneous extraction of both in-plane and through-plane displacements and pathlines from tagged images is achievable. This capability should open up new avenues for the automatic quantification of cardiac motion and strain for scientific and clinical purposes.

Statistical analysis and modelling of weather radar beam propagation conditions in the Po Valley (Italy)

Ground clutter caused by anomalous propagation (anaprop) can affect seriously radar rain rate estimates, particularly in fully automatic radar processing systems, and, if not filtered, can produce frequent false alarms. A statistical study of anomalous propagation detected from two operational C-band radars in the northern Italian region of Emilia Romagna is discussed, paying particular attention to its diurnal and seasonal variability. The analysis shows a high incidence of anaprop in summer, mainly in the morning and evening, due to the humid and hot summer climate of the Po Valley, particularly in the coastal zone. Thereafter, a comparison between different techniques and datasets to retrieve the vertical profile of the refractive index gradient in the boundary layer is also presented. In particular, their capability to detect anomalous propagation conditions is compared. Furthermore, beam path trajectories are simulated using a multilayer ray-tracing model and the influence of the propagation conditions on the beam trajectory and shape is examined. High resolution radiosounding data are identified as the best available dataset to reproduce accurately the local propagation conditions, while lower resolution standard TEMP data suffers from interpolation degradation and Numerical Weather Prediction model data (Lokal Model) are able to retrieve a tendency to superrefraction but not to detect ducting conditions. Observing the ray tracing of the centre, lower and upper limits of the radar antenna 3-dB half-power main beam lobe it is concluded that ducting layers produce a change in the measured volume and in the power distribution that can lead to an additional error in the reflectivity estimate and, subsequently, in the estimated rainfall rate.

An Adeno-Associated Virus-Based Intracellular Sensor of Pathological Nuclear Factor-κB Activation for Disease-Inducible Gene Transfer.

Stimulation of resident cells by NF-κB activating cytokines is a central element of inflammatory and degenerative disorders of the central nervous system (CNS). This disease-mediated NF-κB activation could be used to drive transgene expression selectively in affected cells, using adeno-associated virus (AAV)-mediated gene transfer. We have constructed a series of AAV vectors expressing GFP under the control of different promoters including NF-κB -responsive elements. As an initial screen, the vectors were tested in vitro in HEK-293T cells treated with TNF-α. The best profile of GFP induction was obtained with a promoter containing two blocks of four NF-κB -responsive sequences from the human JCV neurotropic polyoma virus promoter, fused to a new tight minimal CMV promoter, optimally distant from each other. A therapeutical gene, glial cell line-derived neurotrophic factor (GDNF) cDNA under the control of serotype 1-encapsidated NF-κB -responsive AAV vector (AAV-NF) was protective in senescent cultures of mouse cortical neurons. AAV-NF was then evaluated in vivo in the kainic acid (KA)-induced status epilepticus rat model for temporal lobe epilepsy, a major neurological disorder with a central pathophysiological role for NF-κB activation. We demonstrate that AAV-NF, injected in the hippocampus, responded to disease induction by mediating GFP expression, preferentially in CA1 and CA3 neurons and astrocytes, specifically in regions where inflammatory markers were also induced. Altogether, these data demonstrate the feasibility to use disease-activated transcription factor-responsive elements in order to drive transgene expression specifically in affected cells in inflammatory CNS disorders using AAV-mediated gene transfer.

Main-Channel Slopes of Selected Streams in Iowa for Estimation of Flood-Frequency Discharges, November 2004

This report describes a statewide study conducted to develop main-channel slope (MCS) curves for 138 selected streams in Iowa with drainage areas greater than 100 square miles. MCS values determined from the curves can be used in regression equations for estimating flood frequency discharges. Multi-variable regression equations previously developed for two of the three hydrologic regions defined for Iowa require the measurement of MCS. Main-channel slope is a difficult measurement to obtain for large streams using 1:24,000-scale topographic maps. The curves developed in this report provide a simplified method for determining MCS values for sites located along large streams in Iowa within hydrologic Regions 2 and 3. The curves were developed using MCS values quantified for 2,058 selected sites along 138 selected streams in Iowa. A geographic information system (GIS) technique and 1:24,000-scale topographic data were used to quantify MCS values for the stream sites. The sites were selected at about 5-mile intervals along the streams. River miles were quantified for each stream site using a GIS program. Data points for river-mile and MCS values were plotted and a best-fit curve was developed for each stream. An adjustment was applied to all 138 curves to compensate for differences in MCS values between manual measurements and GIS quantification. The multi-variable equations for Regions 2 and 3 were developed using manual measurements of MCS. A comparison of manual measurements and GIS quantification of MCS indicates that manual measurements typically produce greater values of MCS compared to GIS quantification. Median differences between manual measurements and GIS quantification of MCS are 14.8 and 17.7 percent for Regions 2 and 3, respectively. Comparisons of percentage differences between flood-frequency discharges calculated using MCS values of manual measurements and GIS quantification indicate that use of GIS values of MCS for Region 3 substantially underestimate flood discharges. Mean and median percentage differences for 2- to 500-year recurrence-interval flood discharges ranged from 5.0 to 5.3 and 4.3 to 4.5 percent, respectively, for Region 2 and ranged from 18.3 to 27.1 and 12.3 to 17.3 percent for Region 3. The MCS curves developed from GIS quantification were adjusted by 14.8 percent for streams located in Region 2 and by 17.7 percent for streams located in Region 3. Comparisons of percentage differences between flood discharges calculated using MCS values of manual measurements and adjusted-GIS quantification for Regions 2 and 3 indicate that the flood-discharge estimates are comparable. For Region 2, mean percentage differences for 2- to 500-year recurrence-interval flood discharges ranged between 0.6 and 0.8 percent and median differences were 0.0 percent. For Region 3, mean and median differences ranged between 5.4 to 8.4 and 0.0 to 0.3 percent, respectively. A list of selected stream sites presented with each curve provides information about the sites including river miles, drainage areas, the location of U.S. Geological Survey stream flowgage stations, and the location of streams Abstract crossing hydro logic region boundaries or the Des Moines Lobe landforms region boundary. Two examples are presented for determining river-mile and MCS values, and two techniques are presented for computing flood-frequency discharges.

In vivo evaluation of the anti-tumoral effect of sunitinib eluting beads in the rabbit VX2 tumor model

Purpose: To study the anti-tumoral effect of sunitinib eluting beads in the rabbit VX2 tumor modelMaterials: VX2 tumor were implanted in the left liver lobe of New-Zealand white rabbits. Seven animals received 0.2ml of DC Beads loaded with 6mg of sunitinb (group 1), 6 animals received 0.2ml of DC Beads (group 2) and 6 animals received NaCl 0.9% intra arterially in the left hepatic artery. One animal in each group was sacrificed at 24 hours and the others were left to survive. Liver enzyme were measured daily. In group 1 plasmatic sunitinib concentration were measured daily by LC MS/MS tandem mass spectroscopy. At day 15 all living animals were sacrficed. After sacrifice, or premature euthanasia the livers were harvested for determination of the VEGF receptor tyrosine kinase activity by western blot and histopathological examination.Results: In group 1, no animal died during follow-up. In group 2 and 3, respectively 2 and 3 animals died during follow-up. In group 1 plasmatic sunitinib level remained under therapeutic concentration during the whole experiment. There was an evident lack of phosphorylation of the RTK In group 1 and there was an augmentation of the RTK phosphorylation in group 2 at 24 hours. No difference in RTK activity was noticable at 15 days. From the histopathological point of view it was unpossible to differentiate treatment induced from spontaneous necrosis of tumors.Conclusions: Administration of sunitinib eluting Beads in VX2 carrying rabbits inhibits the activation of RTK's triggered by ischemia. It also seems to prolong survival of the treated animals.

Etude de Nkx5-3, un facteur de transcription impliqué dans le développement de l'oeil

Résumé :Une famille souffrant d'un nouveau syndrome oculo-auriculaire, appelé syndrome de Schorderet-Munier, a été identifiée. Ce syndrome est caractérisé par une déformation du lobe de l'oreille et des anomalies ophtalmiques, notamment une microphtalmie, une cataracte, un colobome et une dégénérescence rétinienne. Le gène impliqué dans ce syndrome est NKX5-3 codant un facteur de transcription contenant un homéodomaine. Chez les patient atteints, le gène comporte une délétion de 26 nucléotides provoquant probablement l'apparition d'un codon stop précoce. Ce gène n'est exprimé que dans certains organes dont les testicules et les ganglions cervicaux supérieurs, ainsi que dans les organes touchés par ce syndrome, à savoir le pavillon de l'oreille et l'oeil, surtout lors du développement embryonnaire. Au niveau de la rétine, NKX5-3 est présent dans la couche nucléaire interne et dans la couche dè cellules ganglionnaires et est exprimé de manière polarisée selon un axe temporal > nasal et ventral > dorsal. Son expression in vitro est régulée par Spl, un facteur de transcription exprimé durant le développement de l'oeil chez la souris. NKX5-3 semble lui-même provoquer une inhibition de l'expression de SHH et de EPHA6. Ces gènes sont tous les deux impliqués à leur manière dans le guidage des axones des cellules ganglionnaires de la rétine. Pris ensemble, ces résultats nous permettent donc d'émettre une hypothèse quant à un rôle potentiel de NKX5-3 dans ce processus.Abstract :A family with a new oculo-auricular syndrome, called syndrome of Schorderet-Munier, was identified. This disease is characterised by a deformation of the ear lobule and by several ophthalmic abnormalities, like microphthalmia, cataract, coloboma and a retinal degeneration. The gene, which causes this syndrome, is NKX5-3 coding for a transcription factor contaning a homeodomain. In the affectd patients, the defect consists of a deletion of 26 nucleotides probably producing a premature stop codon. This gene is only expressed in a few organs like testis and superior cervical ganglions, as well as in organs affected by this syndrome, namely the ear pinna and the eye, mainly during embryonic development. In the retina, NKX5-3 is present in the inner nuclear layer and in the ganglion cells layer. It is expressed along a gradient ranging from the temporal retina to nasal retina and from the ventral to the dorsal part. Its in vitro expression is regulated by Spl, a transcription factor expressed during the murine eye development. NKX5-3 seems to inhibit the expression of SHH and EPHA6. These genes are both implicated, in their own way, in the axon guidance of the retinal ganglion cells. Taken together, these results allow us to make an assumption about a potential role of NKX5-3 in this process.

An adeno-associated virus-based intracellular sensor of pathological nuclear factor-κB activation for disease-inducible gene transfer.

Stimulation of resident cells by NF-κB activating cytokines is a central element of inflammatory and degenerative disorders of the central nervous system (CNS). This disease-mediated NF-κB activation could be used to drive transgene expression selectively in affected cells, using adeno-associated virus (AAV)-mediated gene transfer. We have constructed a series of AAV vectors expressing GFP under the control of different promoters including NF-κB -responsive elements. As an initial screen, the vectors were tested in vitro in HEK-293T cells treated with TNF-α. The best profile of GFP induction was obtained with a promoter containing two blocks of four NF-κB -responsive sequences from the human JCV neurotropic polyoma virus promoter, fused to a new tight minimal CMV promoter, optimally distant from each other. A therapeutical gene, glial cell line-derived neurotrophic factor (GDNF) cDNA under the control of serotype 1-encapsidated NF-κB -responsive AAV vector (AAV-NF) was protective in senescent cultures of mouse cortical neurons. AAV-NF was then evaluated in vivo in the kainic acid (KA)-induced status epilepticus rat model for temporal lobe epilepsy, a major neurological disorder with a central pathophysiological role for NF-κB activation. We demonstrate that AAV-NF, injected in the hippocampus, responded to disease induction by mediating GFP expression, preferentially in CA1 and CA3 neurons and astrocytes, specifically in regions where inflammatory markers were also induced. Altogether, these data demonstrate the feasibility to use disease-activated transcription factor-responsive elements in order to drive transgene expression specifically in affected cells in inflammatory CNS disorders using AAV-mediated gene transfer.

Surgical treatment of temporoparietooccipital cortical dysplasia in infants: report of two cases.

PURPOSE: Extensive multilobar cortical dysplasia in infants commonly is first seen with catastrophic epilepsy and poses a therapeutic challenge with respect to control of epilepsy, brain development, and psychosocial outcome. Experience with surgical treatment of these lesions is limited, often not very encouraging, and holds a higher operative risk when compared with that in older children and adults. METHODS: Two infants were evaluated for surgical control of catastrophic epilepsy present since birth, along with a significant psychomotor developmental delay. Magnetic resonance imaging showed multilobar cortical dysplasia (temporoparietooccipital) with a good electroclinical correlation. They were treated with a temporal lobectomy and posterior (parietooccipital) disconnection. RESULTS: Both infants had excellent postoperative recovery and at follow-up (1.5 and 3.5 years) evaluation had total control of seizures with a definite "catch up" in their development, both motor and cognitive. No long-term complications have been detected to date. CONCLUSIONS: The incorporation of disconnective techniques in the surgery for extensive multilobar cortical dysplasia in infants has made it possible to achieve excellent seizure results by maximizing the extent of surgical treatment to include the entire epileptogenic zone. These techniques decrease perioperative morbidity, and we believe would decrease the potential for the development of long-term complications associated with large brain excisions.

Brain Connectivity Analysis in Children. Effects of Prematurity. and Prenatal Growth Restriction

Introduction: Survival of children born prematurely or with very low birth weight has increased dramatically, but the long term developmental outcome remains unknown. Many children have deficits in cognitive capacities, in particular involving executive domains and those disabilities are likely to involve a central nervous system deficit. To understand their neurostructural origin, we use DTI. Structurally segregated and functionally regions of the cerebral cortex are interconnected by a dense network of axonal pathways. We noninvasively map these pathways across cortical hemispheres and construct normalized structural connection matrices derived from DTI MR tractography. Group comparisons of brain connectivity reveal significant changes in fiber density in case of children with poor intrauterine grown and extremely premature children (gestational age<28 weeks at birth) compared to control subjects. This changes suggest a link between cortico-axonal pathways and the central nervous system deficit. Methods: Sixty premature born infants (5-6 years old) were scanned on clinical 3T scanner (Magnetom Trio, Siemens Medical Solutions, Erlangen, Germany) at two hospitals (HUG, Geneva and CHUV, Lausanne). For each subject, T1-weighted MPRAGE images (TR/TE=2500/2.91,TI=1100, resolution=1x1x1mm, matrix=256x154) and DTI images (30 directions, TR/TE=10200/107, in-plane resolution=1.8x1.8x2mm, 64 axial, matrix=112x112) were acquired. Parent(s) provided written consent on prior ethical board approval. The extraction of the Whole Brain Structural Connectivity Matrix was performed following (Cammoun, 2009 and Hagmann, 2008). The MPARGE images were registered using an affine registration to the non-weighted-DTI and WM-GM segmentation performed on it. In order to have equal anatomical localization among subjects, 66 cortical regions with anatomical landmarks were created using the curvature information, i.e. sulcus and gyrus (Cammoun et al, 2007; Fischl et al, 2004; Desikan et al, 2006) with freesurfer software (http://surfer.nmr.mgh.harvard.edu/). Tractography was performed in WM using an algorithm especially designed for DTI/DSI data (Hagmann et al., 2007) and both information were then combined in a matrix. Each row and column of the matrix corresponds to a particular ROI. Each cell of index (i,j) represents the fiber density of the bundle connecting the ROIs i and j. Subdividing each cortical region, we obtained 4 Connectivity Matrices of different resolution (33, 66, 125 and 250 ROI/hemisphere) for each subject . Subjects were sorted in 3 different groups, namely (1) control, (2) Intrauterine Growth Restriction (IUGR), (3) Extreme Prematurity (EP), depending on their gestational age, weight and percentile-weight score at birth. Group-to-group comparisons were performed between groups (1)-(2) and (1)-(3). The mean age at examination of the three groups were similar. Results: Quantitative analysis were performed between groups to determine fibers density differences. For each group, a mean connectivity matrix with 33ROI/hemisphere resolution was computed. On the other hand, for all matrix resolutions (33,66,125,250 ROI/hemisphere), the number of bundles were computed and averaged. As seen in figure 1, EP and IUGR subjects present an overall reduction of fibers density in both interhemispherical and intrahemispherical connections. This is given quantitatively in table 1. IUGR subjects presents a higher percentage of missing fiber bundles than EP when compared to control subjects (~16% against 11%). When comparing both groups to control subjects, for the EP subjects, the occipito-parietal regions seem less interhemispherically connected whilst the intrahemispherical networks present lack of fiber density in the lymbic system. Children born with IUGR, have similar reductions in interhemispherical connections than the EP. However, the cuneus and precuneus connections with the precentral and paracentral lobe are even lower than in the case of the EP. For the intrahemispherical connections the IUGR group preset a loss of fiber density between the deep gray matter structures (striatum) and the frontal and middlefrontal poles, connections typically involved in the control of executive functions. For the qualitative analysis, a t-test comparing number of bundles (p-value<0.05) gave some preliminary significant results (figure 2). Again, even if both IUGR and EP appear to have significantly less connections comparing to the control subjects, the IUGR cohort seems to present a higher lack of fiber density specially relying the cuneus, precuneus and parietal areas. In terms of fiber density, preliminary Wilcoxon tests seem to validate the hypothesis set by the previous analysis. Conclusions: The goal of this study was to determine the effect of extreme prematurity and poor intrauterine growth on neurostructural development at the age of 6 years-old. This data indicates that differences in connectivity may well be the basis for the neurostructural and neuropsychological deficit described in these populations in the absence of overt brain lesions (Inder TE, 2005; Borradori-Tolsa, 2004; Dubois, 2008). Indeed, we suggest that IUGR and prematurity leads to alteration of connectivity between brain structures, especially in occipito-parietal and frontal lobes for EP and frontal and middletemporal poles for IUGR. Overall, IUGR children have a higher loss of connectivity in the overall connectivity matrix than EP children. In both cases, the localized alteration of connectivity suggests a direct link between cortico-axonal pathways and the central nervous system deficit. Our next step is to link these connectivity alterations to the performance in executive function tests.

Influence of magnetic field strength and image registration strategy on voxel-based morphometry in a study of Alzheimer's disease.

Multi-centre data repositories like the Alzheimer's Disease Neuroimaging Initiative (ADNI) offer a unique research platform, but pose questions concerning comparability of results when using a range of imaging protocols and data processing algorithms. The variability is mainly due to the non-quantitative character of the widely used structural T1-weighted magnetic resonance (MR) images. Although the stability of the main effect of Alzheimer's disease (AD) on brain structure across platforms and field strength has been addressed in previous studies using multi-site MR images, there are only sparse empirically-based recommendations for processing and analysis of pooled multi-centre structural MR data acquired at different magnetic field strengths (MFS). Aiming to minimise potential systematic bias when using ADNI data we investigate the specific contributions of spatial registration strategies and the impact of MFS on voxel-based morphometry in AD. We perform a whole-brain analysis within the framework of Statistical Parametric Mapping, testing for main effects of various diffeomorphic spatial registration strategies, of MFS and their interaction with disease status. Beyond the confirmation of medial temporal lobe volume loss in AD, we detect a significant impact of spatial registration strategy on estimation of AD related atrophy. Additionally, we report a significant effect of MFS on the assessment of brain anatomy (i) in the cerebellum, (ii) the precentral gyrus and (iii) the thalamus bilaterally, showing no interaction with the disease status. We provide empirical evidence in support of pooling data in multi-centre VBM studies irrespective of disease status or MFS.

Different colors of light lead to different adaptation and activation as determined by high-density EEG.

Light adaptation is crucial for coping with the varying levels of ambient light. Using high-density electroencephalography (EEG), we investigated how adaptation to light of different colors affects brain responsiveness. In a within-subject design, sixteen young participants were adapted first to dim white light and then to blue, green, red, or white bright light (one color per session in a randomized order). Immediately after both dim and bright light adaptation, we presented brief light pulses and recorded event-related potentials (ERPs). We analyzed ERP response strengths and brain topographies and determined the underlying sources using electrical source imaging. Between 150 and 261ms after stimulus onset, the global field power (GFP) was higher after dim than bright light adaptation. This effect was most pronounced with red light and localized in the frontal lobe, the fusiform gyrus, the occipital lobe and the cerebellum. After bright light adaptation, within the first 100ms after light onset, stronger responses were found than after dim light adaptation for all colors except for red light. Differences between conditions were localized in the frontal lobe, the cingulate gyrus, and the cerebellum. These results indicate that very short-term EEG brain responses are influenced by prior light adaptation and the spectral quality of the light stimulus. We show that the early EEG responses are differently affected by adaptation to different colors of light which may contribute to known differences in performance and reaction times in cognitive tests.