Can quantitative EEG measures predict clinical outcome in subjects at Clinical High Risk for psychosis? A prospective multicenter study

BACKGROUND Prediction studies in subjects at Clinical High Risk (CHR) for psychosis are hampered by a high proportion of uncertain outcomes. We therefore investigated whether quantitative EEG (QEEG) parameters can contribute to an improved identification of CHR subjects with a later conversion to psychosis. METHODS This investigation was a project within the European Prediction of Psychosis Study (EPOS), a prospective multicenter, naturalistic field study with an 18-month follow-up period. QEEG spectral power and alpha peak frequencies (APF) were determined in 113 CHR subjects. The primary outcome measure was conversion to psychosis. RESULTS Cox regression yielded a model including frontal theta (HR=1.82; [95% CI 1.00-3.32]) and delta (HR=2.60; [95% CI 1.30-5.20]) power, and occipital-parietal APF (HR=.52; [95% CI .35-.80]) as predictors of conversion to psychosis. The resulting equation enabled the development of a prognostic index with three risk classes (hazard rate 0.057 to 0.81). CONCLUSIONS Power in theta and delta ranges and APF contribute to the short-term prediction of psychosis and enable a further stratification of risk in CHR samples. Combined with (other) clinical ratings, EEG parameters may therefore be a useful tool for individualized risk estimation and, consequently, targeted prevention.

The Effects of Flowline Length Evolution on Chemistry-Delta O-18 Profiles from Penny Ice Cap, Baffin Island, Canada

The isotopic and chemical signatures for ice-age and Holocene ice from Summit, Greenland and Penny Ice Cap, Baffin Island, Canada, arc compared. The usual pattern of low delta(18)O, high Ca2+ and high Cl- is presented in the Summit records, but Penny Ice Cap has lower than present Cl- in its ice-age ice. A simple extension of the Hansson model (Hansson, 1994) is developed and used to simulate these signatures. The low ice-age Cl- from Penny Ice Cap is explained by having the ice-age ice originating many thousands of km inland near the centre of the Laurentide ice sheet and much further from the marine sources. Summit's flowlines all start close to the present site. The Penny Ice Cap early-Holocene delta(18)O's had to be corrected to offset the Laurentide meltwater distortion. The analysis suggests that presently the Summit and Penny Ice Cap marine impurity originates about,500 km away, and that presently Penny Ice Cap receives a significant amount of local continental impurity.

The Frontal Eye Field Is Involved in Visual Vector Inversion in Humans – A Theta Burst Stimulation Study

In the antisaccade task, subjects are requested to suppress a reflexive saccade towards a visual target and to perform a saccade towards the opposite side. In addition, in order to reproduce an accurate saccadic amplitude, the visual saccade vector (i.e., the distance between a central fixation point and the peripheral target) must be exactly inverted from one visual hemifield to the other. Results from recent studies using a correlational approach (i.e., fMRI, MEG) suggest that not only the posterior parietal cortex (PPC) but also the frontal eye field (FEF) might play an important role in such a visual vector inversion process. In order to assess whether the FEF contributes to visual vector inversion, we applied an interference approach with continuous theta burst stimulation (cTBS) during a memory-guided antisaccade task. In 10 healthy subjects, one train of cTBS was applied over the right FEF prior to a memory-guided antisaccade task. In comparison to the performance without stimulation or with sham stimulation, cTBS over the right FEF induced a hypometric gain for rightward but not leftward antisaccades. These results obtained with an interference approach confirm that the FEF is also involved in the process of visual vector inversion.

Professional musicians listen differently to music

INTRODUCTION: Experience-based adaptation of emotional responses is an important faculty for cognitive and emotional functioning. Professional musicians represent an ideal model in which to elicit experience-driven changes in the emotional processing domain. The changes of the central representation of emotional arousal due to musical expertise are still largely unknown. The aim of the present study was to investigate the electroencephalogram (EEG) correlates of experience-driven changes in the domain of emotional arousal. Therefore, the differences in perceived (subjective arousal via ratings) and physiologically measured (EEG) arousal between amateur and professional musicians were examined. PROCEDURE: A total of 15 professional and 19 amateur musicians listened to the first movement of Ludwig van Beethoven's 5th symphony (duration=∼7.4min), during which a continuous 76-channel EEG was recorded. In a second session, the participants evaluated their emotional arousal during listening. In a tonic analysis, we examined the average EEG data over the time course of the music piece. For a phasic analysis, a fast Fourier transform was performed and covariance maps of spectral power were computed in association with the subjective arousal ratings. RESULTS: The subjective arousal ratings of the professional musicians were more consistent than those of the amateur musicians. In the tonic EEG analysis, a mid-frontal theta activity was observed in the professionals. In the phasic EEG, the professionals exhibited an increase of posterior alpha, central delta, and beta rhythm during high arousal. DISCUSSION: Professionals exhibited different and/or more intense patterns of emotional activation when they listened to the music. The results of the present study underscore the impact of music experience on emotional reactions.

Combined systemic and local morpholino treatment rescues the phenotype of the SMA Delta 7 mouse model

Spinal muscular atrophy (SMA) is a childhood fatal motor neuron disease caused by mutations in the Survival Motor Neuron 1 (SMN1) gene, currently without effective treatment. One possible therapeutic approach is the use of antisense oligonucleotides (ASOs) to redirect the splicing of a paralogous gene, SMN2, to increase the production of functional SMN protein. A range of ASOs with different chemical properties is suitable for these applications, including a morpholino (MO) variant, which has a particularly excellent safety, and efficacy profile. We used a 25- nt MO oligomer sequence against the ISS-N1 region of SMN2 (HSMN2Ex7D(-10-34)) with superior efficacy to previously described sequences also in transgenic SMA Δ7 mice. The combined local and systemic administration of MO (bare or conjugated to octa-guanidine) is necessary to increase full-length SMN expression, leading to robust neuropathological features improvement and survival rescue. Additionally, several snRNA levels that are dysregulated in SMA mice could be restored by MO treatment. These results demonstrate that MO therapy is efficacious and can result in phenotypic rescue. These data provide important insights for the development of therapeutic strategies in SMA patients.

Measurement of the Azimuthal Angle Dependence of Inclusive Jet Yields in Pb+Pb Collisions at sqrts_NN= 2.76 TeV with the ATLAS detector

Measurements of the variation of inclusive jet suppression as a function of relative azimuthal angle, Delta phi, with respect to the elliptic event plane provide insight into the path-length dependence of jet quenching. ATLAS has measured the Delta phi dependence of jet yields in 0.14 nb(-1) of root s(NN) = 2.76 TeV Pb + Pb collisions at the LHC for jet transverse momenta p(T) > 45 GeV in different collision centrality bins using an underlying event subtraction procedure that accounts for elliptic flow. The variation of the jet yield with Delta phi was characterized by the parameter, nu(jet)(2), and the ratio of out-of-plane (Delta phi similar to pi/2) to in-plane (Delta phi similar to 0) yields. Nonzero nu(jet)(2) values were measured in all centrality bins for p(T) < 160 GeV. The jet yields are observed to vary by as much as 20% between in-plane and out-of-plane directions.

Search for νμ→νe oscillations with the OPERA experiment in the CNGS beam

A first result of the search for nu(mu)->nu(e) oscillations in the OPERA experiment, located at the Gran Sasso Underground Laboratory, is presented. The experiment looked for the appearance of nu(e) in the CNGS neutrino beam using the data collected in 2008 and 2009. Data are compatible with the non-oscillation hypothesis in the three-flavour mixing model. A further analysis of the same data constrains the non-standard oscillation parameters theta(new) and Delta m(new)(2) suggested by the LSND and MiniBooNE experiments. For large Delta m(new)(2) values (>0.1 eV(2)), the OPERA 90% C.L. upper limit on sin(2)(2 theta(new)) based on a Bayesian statistical method reaches the value 7.2 x 10(-3).

Evidence of Electron Neutrino Appearance in a Muon Neutrino Beam

The T2K Collaboration reports evidence for electron neutrino appearance at the atmospheric mass splitting, vertical bar Delta m(32)(2)vertical bar approximate to 2.4 X 10(-3) eV(2). An excess of electron neutrino interactions over background is observed from a muon neutrino beam with a peak energy of 0.6 GeV at the Super-Kamiokande (SK) detector 295 km from the beam's origin. Signal and background predictions are constrained by data from near detectors located 280 m from the neutrino production target. We observe 11 electron neutrino candidate events at the SK detector when a background of 3.3 +/- 0.4(syst) events is expected. The background-only hypothesis is rejected with a p value of 0.0009 (3.1 sigma), and a fit assuming nu(mu) -> nu(e) oscillations with sin (2)2 theta(23) = 1, delta(CP) = 0 and vertical bar Delta m(32)(2)vertical bar = 2.4 X 10(-3) eV(2) yields sin (2)2 theta(13) = 0.088(-0.039)(+0.049)(stat + syst).

Simultaneous quantification of delta-9-THC, THC-acid A, CBN and CBD in seized drugs using HPLC-DAD

An HPLC-DAD method for the quantitative analysis of Δ(9)-tetrahydrocannabinol (THC), Δ(9)-tetrahydrocannabinolic acid-A (THCA-A), cannabidiol (CBD), and cannabinol (CBN) in confiscated cannabis products has been developed, fully validated and applied to analyse seized cannabis products. For determination of the THC content of plant material, this method combines quantitation of THCA-A, which is the inactive precursor of THC, and free THC. Plant material was dried, homogenized and extracted with methanol by ultrasonication. Chromatographic separation was achieved with a Waters Alliance 2695 HPLC equipped with a Merck LiChrospher 60 RP-Select B (5μm) precolumn and a Merck LiChroCart 125-4 LiChrospher 60 RP-Select B (5μm) analytical column. Analytes were detected and quantified using a Waters 2996 photo diode array detector. This method has been accepted by the public authorities of Switzerland (Bundesamt für Gesundheit, Federal Office of Public Health), and has been used to analyse 9092 samples since 2000. Since no thermal decarboxylation of THCA-A occurs, the method is highly reproducible for different cannabis materials. Two calibration ranges are used, a lower one for THC, CBN and CBD, and a higher one for THCA-A, due to its dominant presence in fresh plant material. As provider of the Swiss proficiency test, the robustness of this method has been tested over several years, and homogeneity tests even in the low calibration range (1%) show high precision (RSD≤4.3%, except CBD) and accuracy (bias≤4.1%, except CBN).

Rivastigmine effects on EEG spectra and three-dimensional LORETA functional imaging in Alzheimer's disease

OBJECTIVE The objective of the study is to investigate the electrocortical and the global cognitive effects of 3 months rivastigmine medication in a group of mild to moderate Alzheimer's disease patients. MATERIALS AND METHODS Multichannel EEG and cognitive performances measured with the Mini Mental State Examination in a group of 16 patients with mild to moderate Alzheimer's Disease were collected before and 3 months after the onset of rivastigmine medication. RESULTS Spectral analysis of the EEG data showed a significant power decrease in the delta and theta frequency bands during rivastigmine medication, i.e., a shift of the power spectrum towards 'normalization'. Three-dimensional low resolution electromagnetic tomography (LORETA) functional imaging localized rivastigmine effects in a network that includes left fronto-parietal regions, posterior cingulate cortex, bilateral parahippocampal regions, and the hippocampus. Moreover, a correlation analysis between differences in the cognitive performances during the two recordings and LORETA-computed intracortical activity showed, in the alpha1 frequency band, better cognitive performance with increased cortical activity in the left insula. CONCLUSION The results point to a 'normalization' of the EEG power spectrum due to medication, and the intracortical localization of these effects showed an increase of cortical activity in frontal, parietal, and temporal regions that are well-known to be affected in Alzheimer's disease. The topographic convergence of the present results with the memory network proposed by Vincent et al. (J. Neurophysiol. 96:3517-3531, 2006) leads to the speculation that in our group of patients, rivastigmine specifically activates brain regions that are involved in memory functions, notably a key symptom in this degenerative disease.

Correlation between disease severity and brain electric LORETA tomography in Alzheimer's disease

OBJECTIVE To compare EEG power spectra and LORETA-computed intracortical activity between Alzheimer's disease (AD) patients and healthy controls, and to correlate the results with cognitive performance in the AD group. METHODS Nineteen channel resting EEG was recorded in 21 mild to moderate AD patients and in 23 controls. Power spectra and intracortical LORETA tomography were computed in seven frequency bands and compared between groups. In the AD patients, the EEG results were correlated with cognitive performance (Mini Mental State Examination, MMSE). RESULTS AD patients showed increased power in EEG delta and theta frequency bands, and decreased power in alpha2, beta1, beta2 and beta3. LORETA specified that increases and decreases of power affected different cortical areas while largely sparing prefrontal cortex. Delta power correlated negatively and alpha1 power positively with the AD patients' MMSE scores; LORETA tomography localized these correlations in left temporo-parietal cortex. CONCLUSIONS The non-invasive EEG method of LORETA localized pathological cortical activity in our mild to moderate AD patients in agreement with the literature, and yielded striking correlations between EEG delta and alpha1 activity and MMSE scores in left temporo-parietal cortex. SIGNIFICANCE The present data support the hypothesis of an asymmetrical progression of the Alzheimer's disease.

Coherence and phase locking in the scalp EEG and between LORETA model sources, and microstates as putative mechanisms of brain temporo-spatial functional organization

Brain electric mechanisms of temporary, functional binding between brain regions are studied using computation of scalp EEG coherence and phase locking, sensitive to time differences of few milliseconds. However, such results if computed from scalp data are ambiguous since electric sources are spatially oriented. Non-ambiguous results can be obtained using calculated time series of strength of intracerebral model sources. This is illustrated applying LORETA modeling to EEG during resting and meditation. During meditation, time series of LORETA model sources revealed a tendency to decreased left-right intracerebral coherence in the delta band, and to increased anterior-posterior intracerebral coherence in the theta band. An alternate conceptualization of functional binding is based on the observation that brain electric activity is discontinuous, i.e., that it occurs in chunks of up to about 100 ms duration that are detectable as quasi-stable scalp field configurations of brain electric activity, called microstates. Their functional significance is illustrated in spontaneous and event-related paradigms, where microstates associated with imagery- versus abstract-type mentation, or while reading positive versus negative emotion words showed clearly different regions of cortical activation in LORETA tomography. These data support the concept that complete brain functions of higher order such as a momentary thought might be incorporated in temporal chunks of processing in the range of tens to about 100 ms as quasi-stable brain states; during these time windows, subprocesses would be accepted as members of the ongoing chunk of processing.

Enhancing treatment effects by combining continuous theta burst stimulation with smooth pursuit training

Continuous theta burst stimulation (cTBS) represents a promising approach in the treatment of neglect syndrom. However, it is not known whether cTBS in conjunction with another technique may enhance the therapeutic effects. In the present sham-controlled study, we aimed to combine cTBS with smooth pursuit training (SPT), another method known to effectively improve neglect symptoms, and to evaluate whether this combination would result in a stronger effect than SPT alone. Eighteen patients with left spatial neglect after right-hemispheric stroke were included in the study and performed a cancellation task on a large 54.6" touchscreen monitor. A sequential application of cTBS and SPT induced a significantly greater improvement of neglect than SPT alone. After the combined application of these two methods, patients detected significantly more targets and their cancellation behaviour presented a significantly greater shift towards the contralesional hemispace. We suggest that a combined, sequential application of cTBS and SPT is a promising new approach to treat neglect.

The differential production cross section of the phi (1020) meson in sqrts = 7 TeV pp collisions measured with the ATLAS detector

Ameasurement is presented of the φ×BR(φ → K+K−) production cross section at √s = 7 TeV using pp collision data corresponding to an integrated luminosity of 383 μb−1, collected with theATLAS experiment at the LHC. Selection of φ(1020) mesons is based on the identification of charged kaons by their energy loss in the pixel detector. The differential cross section ismeasured as a function of the transverse momentum, pT,φ , and rapidity, yφ, of the φ(1020) meson in the fiducial region 500< pT,φ <1200MeV, |yφ| < 0.8, kaon pT,K > 230 MeV and kaon momentum pK < 800 MeV. The integrated φ(1020)-meson production cross section in this fiducial range is measured to be σφ×BR(φ → K+K−) = 570 ± 8 (stat) ± 66 (syst) ± 20 (lumi) μb.