Task induced modulation of neural oscillations in electrophysiological brain networks.

In recent years, one of the most important findings in systems neuroscience has been the identification of large scale distributed brain networks. These networks support healthy brain function and are perturbed in a number of neurological disorders (e.g. schizophrenia). Their study is therefore an important and evolving focus for neuroscience research. The majority of network studies are conducted using functional magnetic resonance imaging (fMRI) which relies on changes in blood oxygenation induced by neural activity. However recently, a small number of studies have begun to elucidate the electrical origin of fMRI networks by searching for correlations between neural oscillatory signals from spatially separate brain areas in magnetoencephalography (MEG) data. Here we advance this research area. We introduce two methodological extensions to previous independent component analysis (ICA) approaches to MEG network characterisation: 1) we show how to derive pan-spectral networks that combine independent components computed within individual frequency bands. 2) We show how to measure the temporal evolution of each network with millisecond temporal resolution. We apply our approach to ~10h of MEG data recorded in 28 experimental sessions during 3 separate cognitive tasks showing that a number of networks could be identified and were robust across time, task, subject and recording session. Further, we show that neural oscillations in those networks are modulated by memory load, and task relevance. This study furthers recent findings on electrodynamic brain networks and paves the way for future clinical studies in patients in which abnormal connectivity is thought to underlie core symptoms.

Inferring task-related networks using independent component analysis in magnetoencephalography.

A novel framework for analysing task-positive data in magnetoencephalography (MEG) is presented that can identify task-related networks. Techniques that combine beamforming, the Hilbert transform and temporal independent component analysis (ICA) have recently been applied to resting-state MEG data and have been shown to extract resting-state networks similar to those found in fMRI. Here we extend this approach in two ways. First, we systematically investigate optimisation of time-frequency windows for connectivity measurement. This is achieved by estimating the distribution of functional connectivity scores between nodes of known resting-state networks and contrasting it with a distribution of artefactual scores that are entirely due to spatial leakage caused by the inverse problem. We find that functional connectivity, both in the resting-state and during a cognitive task, is best estimated via correlations in the oscillatory envelope in the 8-20 Hz frequency range, temporally down-sampled with windows of 1-4s. Second, we combine ICA with the general linear model (GLM) to incorporate knowledge of task structure into our connectivity analysis. The combination of ICA with the GLM helps overcome problems of these techniques when used independently: namely, the interpretation and separation of interesting independent components from those that represent noise in ICA and the correction for multiple comparisons when applying the GLM. We demonstrate the approach on a 2-back working memory task and show that this novel analysis framework is able to elucidate the functional networks involved in the task beyond that which is achieved using the GLM alone. We find evidence of localised task-related activity in the area of the hippocampus, which is difficult to detect reliably using standard methods. Task-positive ICA, coupled with the GLM, has the potential to be a powerful tool in the analysis of MEG data.

Cardiovascular responses to heat stress in late gestation fetal sheep.

Heat stress during pregnancy in sheep is associated with respiratory alkalosis in both the mother and fetus, and, if prolonged, fetal growth is retarded. In seven pregnant sheep at 130-137 days gestation we used 15 microns diameter radioactive microspheres to determine the effect of raising the environmental temperature from 20 to 43 degrees C for 8 h on uteroplacental blood flows and the distribution of cardiac output in the ewe and fetus. Fetal cardiac output increased slightly from 47.0 +/- 3.2 (mean +/- S.E.M.) to 54.0 +/- 3.6 ml min-1 (100 g tissue)-1, fetal arterial pressure and heart rate were unchanged, and total vascular conductance in the fetus increased significantly from 12397 +/- 1111 to 14732 +/- 1569 ml min-1 kg-1 mmHg-1 (P < 0.01). Tissue blood flows (in ml min-1 (100 g)-1) increased significantly (P < 0.05) in the fetal body (e.g. nasal mucosa, torso and foreleg skin, adrenal, thyroid and thymus glands, brown and omental fats, heart, urinary bladder and carcass) and the fetal brain (e.g. cerebellum, cerebral grey matter, cervical spinal cord and pituitary gland). These regional vasodilatations occurred despite a significant fall (P < 0.01) in fetal arterial O2 saturation (55.2 +/- 1.8 vs. 38.6 +/- 2.4%), PO2 (18.1 +/- 0.7 vs. 13.5 +/- 0.8 mmHg) and PCO2 (51.0 +/- 1.8 vs. 36.1 +/- 2.3 mmHg); under normothermic conditions hypoxia is associated with peripheral vasoconstriction. Because hypocapnia would also be expected to cause cerebral vasoconstriction it is suggested that during hyperthermia, hypoxia- and hypocapnia-induced vasoconstrictions are reduced by the release of vasodilator substances, or a decrease of sympathoadrenal effector responses. Blood flow to the fetal and maternal sides of the placenta did not change during the heat stress, suggesting that perfusion-dependent transfer of heat from fetus to mother across the placenta does not increase under hyperthermic conditions.

Magnetic microspheres as drug carriers: factors influencing localization at different anatomical sites in rats.

Factors of practical expediency influencing magnetic fixation of circulating microspheres, known to be capable of carrying therapeutically effective drugs, were studied in three different anatomic sites in rats: the tail, the hind leg, and the head (including both soft tissues and brain). Specific localization of magnetic microspheres was achieved at these three sites, but only with varying degrees of success. Specific targeting of the microspheres within brain tissue could not be accomplished. Factors influencing and tending to restrict specific retention of circulating microspheres by an external magnetic force include: complex vasculature networks, subsurface depth, and tissue-vascular barriers. Even with magnets producing high magnetic field gradients, effective localization of microspheres would appear to be restricted to tissues relatively close to body surfaces.

A new magnetic technique for the treatment of giant retinal tears.

Using surgical techniques similar to those for closed vitreous surgery, we introduced a small magnetic sphere into the intraocular cavity of experimental animals. The sphere was subsequently maneuvered gently over the retina to unfold and reposition it with a small external permanent magnet probe. We used 68 enucleated canine eyes; eight eyes were operated in vivo and then examined microscopically. Retinal damage was caused by friction and excessive pressure when we used external magnets that were too strong or spheres that were too large. When small intraocular magnetic spheres coated with silicone or teflon or encased in a hollow oversize epoxy sphere were used the damage to the retina was minimal, or absent. We suggest using this same technique to treat retinal tumors through the introduction of radioactive material or antitumoral drugs. The intraocular magnetic sphere of this type would be left inside the eye in contact with the lesion for an extended period (seven days to three months) by suturing a small magnet to the sclera over the lesion.

High-pouch imperforate anus treated by electromagnetic bougienage and subsequent perineal repair.

Four male infants with imperforate anus were treated by electromagnetic bougienage and subsequent perineal anoplasty with division of rectourethral fistula. Each had high-pouch imperforate anus of the supralevator type, with rectourethral fishtula at or above the level of the membranous urethra. Perineal anoplasty was accomplished in all four, with division of the rectourethral fistula, avoiding the need to do a sacral-abdominal-perineal procedure, as had been customary previously in similar cases.

Electromagnetic bougienage to lengthen esophageal segments in congenital esophageal atresia.

Some cases of esophageal atresia, either with or without tracheoesophageal fistula, are not suited for primary anastomosis. To avert the need for colon interposition in two such infants, intermittent electromagnetic force was used to pull together "bullets" placed in the esophageal ends. This method elongated and enlarged the esophageal segments enough to accomplish their anastomosis later. This approach appears feasible to use for infants whose esophageal malformation does not permit primary repair. It may also be applicable to cases of imperforate anus with a hight pouch.