Precuneus functioning differentiates first-episode psychosis patients during the fantasy movie Alice in Wonderland.

BACKGROUND: While group-level functional alterations have been identified in many brain regions of psychotic patients, multivariate machine-learning methods provide a tool to test whether some of such alterations could be used to differentiate an individual patient. Earlier machine-learning studies have focused on data collected from chronic patients during rest or simple tasks. We set out to unravel brain activation patterns during naturalistic stimulation in first-episode psychosis (FEP). METHOD: We recorded brain activity from 46 FEP patients and 32 control subjects viewing scenes from the fantasy film Alice in Wonderland. Scenes with varying degrees of fantasy were selected based on the distortion of the 'sense of reality' in psychosis. After cleaning the data with a novel maxCorr method, we used machine learning to classify patients and healthy control subjects on the basis of voxel- and time-point patterns. RESULTS: Most (136/194) of the voxels that best classified the groups were clustered in a bilateral region of the precuneus. Classification accuracies were up to 79.5% (p = 5.69 × 10-8), and correct classification was more likely the higher the patient's positive-symptom score. Precuneus functioning was related to the fantasy content of the movie, and the relationship was stronger in control subjects than patients. CONCLUSIONS: These findings are the first to show abnormalities in precuneus functioning during naturalistic information processing in FEP patients. Correlational findings suggest that these alterations are associated with positive psychotic symptoms and processing of fantasy. The results may provide new insights into the neuronal basis of reality distortion in psychosis.

Uncovering cortical MEG responses to listened audiobook stories.

Naturalistic stimuli, such as normal speech and narratives, are opening up intriguing prospects in neuroscience, especially when merging neuroimaging with machine learning methodology. Here we propose a task-optimized spatial filtering strategy for uncovering individual magnetoencephalographic (MEG) responses to audiobook stories. Ten subjects listened to 1-h-long recording once, as well as to 48 repetitions of a 1-min-long speech passage. Employing response replicability as statistical validity and utilizing unsupervised learning methods, we trained spatial filters that were able to generalize over datasets of an individual. For this blind-signal-separation (BSS) task, we derived a version of multi-set similarity-constrained canonical correlation analysis (SimCCA) that theoretically provides maximal signal-to-noise ratio (SNR) in this setting. Irrespective of significant noise in unaveraged MEG traces, the method successfully uncovered feasible time courses up to ~120 Hz, with the most prominent signals below 20 Hz. Individual trial-to-trial correlations of such time courses reached the level of 0.55 (median 0.33 in the group) at ~0.5 Hz, with considerable variation between subjects. By this filtering, the SNR increased up to 20 times. In comparison, independent component analysis (ICA) or principal component analysis (PCA) did not improve SNR notably. The validity of the extracted brain signals was further assessed by inspecting their associations with the stimulus, as well as by mapping the contributing cortical signal sources. The results indicate that the proposed methodology effectively reduces noise in MEG recordings to that extent that brain responses can be seen to nonrecurring audiobook stories. The study paves the way for applications aiming at accurately modeling the stimulus-response-relationship by tackling the response variability, as well as for real-time monitoring of brain signals of individuals in naturalistic experimental conditions.

The 3D topography of MEG source localization accuracy: effects of conductor model and noise.

OBJECTIVE: To evaluate the effect that different head conductor models have on the source estimation accuracy of magnetoencephalography (MEG) under realistic conditions. METHODS: Magnetic fields evoked by current dipoles were simulated using a highly refined 3-layer realistically shaped conductor model. Noise from a real MEG measurement was added to the simulated fields. Source parameters (location, strength, orientation) were estimated from the noisy signals using 3 spherically symmetric models and several one- and 3-layer realistically shaped boundary-element models. The effect of different measurement sensors (gradiometers, magnetometers) was also tested. RESULTS: The noise typically present in brain signals masked the errors due to the different conductor models so that in most situations the models gave comparable results. Active cortical areas around the vertex and in the temporal, frontoparietal, and occipital regions were typically found with 2-4 mm accuracy, whereas source localization in several anterior frontal lobe and deep brain structures yielded errors exceeding 2 cm. Localization in anterior frontal regions may benefit most from the use of realistically shaped models. CONCLUSIONS: The traditionally used sphere model is an adequate model for most research purposes. Any means that increase the signal-to-noise ratio are of highest importance in attempting to improve the source estimation accuracy.

Chick ciliary neurotrophic factor is secreted via a nonclassical pathway.

In contrast to mammalian ciliary neurotrophic factors (CNTFs), chick CNTF is secreted, although it lacks an N-terminal signal. We determined that a 52 aa region of chick CNTF containing an internal hydrophobic domain could direct secretion of rat CNTF. Using a stable cell line that overexpressed chick CNTF, we found that chick CNTF immunoreactivity was punctate throughout the cytosol. Cellular fractionation confirmed chick CNTF to be protected by vesicles. Chick CNTF did not colocalize with fibronectin, calreticulin, wheat germ agglutinin binding sites, or with transferrin receptor. The distribution of chick CNTF was altered neither by brefeldin A nor by chloroquine treatment. Although the punctate pattern of chick CNTF immunoreactivity was not due to reuptake, chick CNTF could be found in a cellular compartment labeled after a brief incubation with dextran microbeads. When synthesized in vitro, chick CNTF did not translocate into microsomes. We conclude that chick CNTF is secreted via a nonclassical pathway.

Coinciding early activation of the human primary visual cortex and anteromedial cuneus.

Proper understanding of processes underlying visual perception requires information on the activation order of distinct brain areas. We measured dynamics of cortical signals with magnetoencephalography while human subjects viewed stimuli at four visual quadrants. The signals were analyzed with minimum current estimates at the individual and group level. Activation emerged 55-70 ms after stimulus onset both in the primary posterior visual areas and in the anteromedial part of the cuneus. Other cortical areas were active after this initial dual activation. Comparison of data between species suggests that the anteromedial cuneus either comprises a homologue of the monkey area V6 or is an area unique to humans. Our results show that visual stimuli activate two cortical areas right from the beginning of the cortical response. The anteromedial cuneus has the temporal position needed to interact with the primary visual cortex V1 and thereby to modify information transferred via V1 to extrastriate cortices.

Three-dimensional integration of brain anatomy and function to facilitate intraoperative navigation around the sensorimotor strip.

We studied 12 patients with brain tumors in the vicinity of the sensorimotor region to provide a preoperative three-dimensional visualization of the functional anatomy of the rolandic cortex. We also evaluated the role of cortex-muscle coherence analysis and anatomical landmarks in identifying the sensorimotor cortex. The functional landmarks were based on neuromagnetic recordings with a whole-scalp magnetometer, coregistred with magnetic resonance images. Evoked fields to median and tibial nerve and lip stimuli were recorded to identify hand, foot and face representations in the somatosensory cortex. Oscillatory cortical activity, coherent with surface electromyogram during isometric muscle contraction, was analyzed to reveal the hand and foot representations in the precentral motor cortex. The central sulcus was identified also by available anatomical landmarks. The source locations, calculated from the neuromagnetic data, were displayed on 3-D surface reconstructions of the individual brains, including the veins. The preoperative data were verified during awake craniotomy by cortical stimulation in 7 patients and by cortical somatosensory evoked potentials in 5 patients. Sources of somatosensory evoked fields identified correctly the postcentral gyrus in all patients. Useful corroborative information was obtained from anatomical landmarks in 11 patients and from cortex-muscle correlograms in 8 patients. The preoperative visualization of the functional anatomy of the sensorimotor strip assisted in designing the operational strategy, facilitated orientation of the neurosurgeon during the operation, and speeded up the selection of sites for intraoperative stimulation or mapping, thereby helping to prevent damage of eloquent brain areas during surgery.

Three hands: fragmentation of human bodily awareness.

We describe patient E.P. who occasionally perceives a 'ghost' hand which copies the previous positions of the left hand with a 0.5-1 min time lag, but follows the movement patterns of the right hand. The symptoms started after an operation of a ruptured aneurysm, followed by an infarction of the right frontal lobe; E.P. also has a previously lesioned corpus callosum. Neuromagnetic recordings revealed that activity of the left secondary somatosensory cortex was strongly suppressed during the ghost arm percept, thereby providing an objective correlate for E.P.'s sensations. We conclude that simultaneous mental contents about body scheme may be based on neural information extracted at considerably different times, resulting in fragmentation of bodily awareness.

Dynamical organisation of the human visual system revealed by lifetimes of activation traces.

Magnetic source imaging reveals a dynamical organisation of visual cortical areas suggesting that the participation of local memories is an essential component of visual information processing. Response recovery studies provide evidence that each responding cortical area supports a memory function with a well-defined lifetime. The areas fell into two groups, the earliest in occipital lobes with lifetimes ranging from 0.1 to 0.6 s, and the later ones in temporal, parietal, and frontal areas with lifetimes ranging from 7 to 30 s. Also, within each group the areas responding later tended to have longer lifetimes.

Supplemented gamma-linolenic acid and eicosapentaenoic acid influence bone status in young male rats: effects on free urinary collagen crosslinks, total urinary hydroxyproline, and bone calcium content.

The effect of different ratios of the prostaglandin precursors gamma-linolenic (GLA) and eicosapentaenoic (EPA) acids on bone status in growing rats measured as a function of free urinary pyridinium crosslinks and hydroxyproline levels was investigated. Male Sprague-Dawley rats were weaned onto an essential fatty acid deficient diet and from their fifth week, different groups of rats received a balanced, semisynthetic diet, supplemented with different ratios of GLA:EPA supplied as a mixture of evening primrose oil (EPO) and fish oil (FO). Controls were supplemented with linoleic (LA; sunflower oil) and alpha-linolenic (ALA; linseed oil) acids (3:1) or a commercially available rat chow. Animals were terminated at 84 days and femur length, ash weight, calcium content, free urinary pyridinium crosslinks (Pyd and Dpyd), total hydroxyproline (Hyp), and creatinine levels measured. Free urinary Pyd and Dpyd are good indicators of bone status and they correlated well with Hyp. Pyd and Dpyd excretion were significantly decreased in the higher GLA:EPA dietary groups and correlated well (r = 0.7) with Hyp levels. Concomitantly, bone calcium content increased significantly in the same dietary groups. These results suggest that diet supplementation with relatively high GLA:EPA ratios are more effective in inhibiting bone resorption than LA:ALA.