Selective homonuclear polarization transfer for spectroscopic imaging of GABA at 7T.

We develop and implement a selective homonuclear polarization transfer method for the detection of 3.0 ppm C-4 GABA resonance by spectroscopic imaging in the human brain at 7T. This single shot method is demonstrated with simulations and phantoms, which achieves comparable efficiency of detection to that of J-difference editing. The macromolecule resonance that commonly co-edits with GABA is suppressed at 7T through use of a narrow band preacquisition suppression pulse. This technique is implemented in humans with an eight channel transceiver array and high degree B(0) shimming to measure supplementary motor area and thalamic GABA in controls (n = 8) and epilepsy patients (n = 8 total). We find that the GABA/N-acetyl aspartate ratio in the thalamus of control volunteers, well controlled and poorly controlled epilepsy patients are 0.053 ± 0.012 (n = 8), 0.090 ± 0.012 (n = 2), and 0.038 ± 0.009 (n = 6), respectively.

Metabolic networks in epilepsy by MR spectroscopic imaging.

OBJECTIVE: The concept of an epileptic network has long been suggested from both animal and human studies of epilepsy. Based on the common observation that the MR spectroscopic imaging measure of NAA/Cr is sensitive to neuronal function and injury, we use this parameter to assess for the presence of a metabolic network in mesial temporal lobe epilepsy (MTLE) patients. MATERIALS AND METHODS: A multivariate factor analysis is performed with controls and MTLE patients, using NAA/Cr measures from 12 loci: the bilateral hippocampi, thalami, basal ganglia, and insula. The factor analysis determines which and to what extent these loci are metabolically covarying. RESULTS: We extract two independent factors that explain the data's variability in control and MTLE patients. In controls, these factors characterize a 'thalamic' and 'dominant subcortical' function. The MTLE patients also exhibit a 'thalamic' factor, in addition to a second factor involving the ipsilateral insula and bilateral basal ganglia. CONCLUSIONS: These data suggest that MTLE patients demonstrate a metabolic network that involves the thalami, also seen in controls. The MTLE patients also display a second set of metabolically covarying regions that may be a manifestation of the epileptic network that characterizes limbic seizure propagation.

Coherence of the electroencephalogram during the first sleep cycle.

OBJECTIVE: The increasing amplitude of the electroencephalogram (EEG) during non-rapid eye movement sleep implies a progressive synchronization of neuronal activity. We sought to characterize the spatial relationship of cortical activity at different frequencies during the first sleep cycle, focusing on sleep stages 3 and 4 (slow wave sleep). METHODS: Sleep EEGs were obtained at home from six adults using a portable recorder. Signal power and magnitude squared coherence were measured during the first sleep cycle. Spectra obtained from bipolar and common reference derivations were compared. RESULTS: During slow wave sleep, signal power is highest in the delta frequency band and regional coherence below 5 Hz is broadly distributed. Although signal power in the alpha and sigma frequency bands is lower, peaks of regional coherence in those bands are similar to or higher than delta-band coherence. Regional coherence during slow wave sleep is differentially distributed with a 14 Hz component in central and posterior regions and a 10 Hz component in frontal and central regions. CONCLUSIONS: Ten and 14 Hz rhythms are an essential component of slow wave sleep. SIGNIFICANCE: The interpretation of scalp EEG power and coherence spectra is limited by the lack of a satisfactory recording reference. However, conclusions can be made by comparing and contrasting results from both bipolar and common reference recordings.

Regional cerebral blood flow during spreading cortical depression in conscious rats.

Spreading cortical depression (SCD) of EEG activity was induced in one cerebral hemisphere of conscious restrained rats by direct current stimulation of the lateral frontal cortex. Regional CBF was measured using [14C]iodoantipyrine and brain dissection. An early phase of increased CBF was not measured in conscious rats, but an early relative hyperperfusion was measured if the resting CBF was first reduced by treatment with pentobarbital or indomethacin. A long-lasting reduction in CBF was measured in conscious rats following the passage of SCD. This flow reduction resolved after 3 h. In conscious rats, CBF decreased in the striatum and thalamus ipsilateral to the SCD, paralleling the CBF changes occurring in the cortex. The CBF change in these deep structures was abolished by pentobarbital. An early transient increase in regional CBF was measured in the cerebral cortex contralateral to the hemisphere involved with SCD in conscious rats. This early contralateral hyperperfusion was also abolished by pentobarbital or indomethacin but not by atropine or propranolol. The vascular response to SCD in conscious rats differs from that which occurs in anesthetized rats.

Regional optic nerve blood flow and its autoregulation.

An autoradiographic method (14C-iodoantipyrine autoradiography) was used to measure regional optic nerve blood flow (ONBF) under basal conditions in 11 adult female cats. Flow was measured in six regions of the optic nerve: (1) prelaminar, (2) laminar, (3) 1 mm post-laminar, (4) 4 mm post-laminar, (5) 6 mm post-laminar, and (6) intracranial optic nerve and chiasm. A gradient of flow rates was found with relatively high flow in the prelaminar, laminar, and 1-mm post-laminar optic nerve, and significantly lower flow in the 4- and 6-mm post-laminar nerve and in the intracranial optic nerve and chiasm. Blood flow in the 4- and 6-mm post-laminar nerve and in the intracranial nerve and chiasm was comparable to previously reported values for cerebral white matter in the cat. With alteration of mean arterial blood pressure (MABP), optic nerve blood flow demonstrated autoregulatory compensation in all areas.

Localization of muscarinic receptor subtypes in brain stem areas regulating sleep.

Muscarinic cholinergic receptors (mAChRs) within the pontine brain stem play a key role in generating rapid eye movement (REM) sleep. Using an in vitro autoradiographic technique that permits selective labeling of mAChR subtypes by radioligand binding, this study provides the first quantitative map of mAChR subtypes in cat brain stem areas important for REM sleep generation. M1, M2 and M3 mAChR subtypes were distributed heterogeneously throughout the brain stem. For all 3 mAChR subtypes, the greatest levels of binding were found in the dorsal raphe and locus coeruleus, and the least amount of binding was in the reticular formation. These findings are consistent with data from in vivo studies showing that multiple mAChR subtypes are involved in REM sleep generation.

A simplified method for computerized densitometry of complex shapes in 2-deoxyglucose autoradiographs.

A simple, computerized densitometer is described which can be used to measure densities of photographic prints by means of a fiber-optic reflectance densitometric probe coupled to the movable cursor of a digitizing tablet. The cursor, with its attached probe, is moved by hand along a scan trajectory determined by the operator. In its configuration for use with 2-deoxyglucose autoradiographs, the histological section from which the autoradiograph was derived provides architectonic landmarks for guiding the path of the scan. The X, Y and density values taken along a scan line are sequentially stored in the computer memory. Algorithms are presented for plotting densities along unfolded scan lines within layers of structures with complicated shapes, for normalizing non-linearities introduced during photographic processing, for standardizing the data sets with reference to the density of average gray matter in different animals, for calculating total integrated density within defined boundaries along the scan line, for generating averages of multiple scans, and for stacking sequential scans to form pseudo-3-dimensional plots. This system allows densitometric measures to be made from autoradiographs in anatomically defined regions, thereby permitting precise correlation between isotope concentration and histological structure.

Computer simulation of the blood-brain barrier: a model including two membranes, blood flow, facilitated and non-facilitated diffusion.

A mathematical model of blood-brain barrier (BBB) transport was developed to assist in experimental design and data analysis. The model includes the luminal and antiluminal endothelial cell membranes, each with separate transport systems. Substrate movement between 3 compartments can be calculated: the capillary lumen, the endothelial cell cytoplasm, and the brain parenchyma. Blood flow, substrate concentration and competition in each compartment, concentration gradients along the capillary, and non-steady-state conditions are considered. The utility of the model is demonstrated by predicting: (1) complex concentration profiles along the length of the capillary lumen under different circumstances, (2) the permeability-surface area products along the capillary lumen, (3) the time course of events during brain-uptake index (BUI) experiments, (4) the accuracy of the BUI in measuring glucose transport over a range of endogenous glucose concentrations, (5) the influence of 2 membranes in series with different kinetic constants, and (6) a comparison of kinetic constants expected from high-flow infusion and BUI experiments.

Regional cerebral blood flow and glucose utilization during hyperinsulinemia.

Regional cerebral blood flow and glucose utilization were measured in awake-restrained rats during euglycemic hyperinsulinemia and were found to be normal. This indicates that elevated plasma insulin does not alter cerebral blood flow and cannot explain decreases in cerebral blood flow measured during acute hyperglycemia.

A brief hypoperfusion precedes spreading depression if nitric oxide synthesis is inhibited.

Spreading cortical depression (SCD) alters cerebral blood flow by mechanisms that are not well understood. To investigate the role of the likely endothelium-derived relaxing factor, nitric oxide, in the blood flow changes occurring during SCD in awake rats, nitric oxide synthesis was blocked using N omega-nitro-L-arginine methyl ester (L-NAME). During SCD there is an initial hyperperfusion followed by a longer-lasting hypoperfusion. Treatment with L-NAME, 30 mg/kg, reduced resting cerebral blood flow globally. During SCD, L-NAME treatment produced an additional brief phase of hypoperfusion which preceded the initial hyperperfusion. The magnitude of the initial hyperperfusion was less than expected. The subsequent longer-lasting hypoperfusion was unchanged. Nitric oxide plays an important role in the regulation of cerebral blood flow during SCD.

Decreased cerebral blood flow during acute hyperglycemia.

Cerebral blood flow (CBF) decreases during acute hyperglycemia but the mechanism of this change is unknown. The role that plasma osmolality plays in this effect was reexamined in pentobarbital-anesthetized rats using a continuous measure of CBF, laser-Doppler flowmetry. CBF decreased 25% during acute elevation of plasma osmolality induced by intraperitoneal injection of concentrated solutions of glucose or mannitol. In addition there were brief transient increases of CBF with peak magnitude 2-4-times the baseline level that were not accompanied by transient depression of electroencephalographic activity. These transient CBF increases may explain why discontinuous methods of CBF measurement fail to detect flow decreases after mannitol injection. Decreased CBF measured during acute hyperglycemia may be the result of increased plasma osmolality.

Cortical hypoperfusion following spreading depression is not altered by tirilazad mesylate (U-74006F) in awake rats.

The 21-aminosteroid antioxidant tirilazad mesylate (U-74006F) blocks the delayed hypoperfusion associated with spreading cortical depression (SCD) in anesthetized rats. Because the resting vascular tone influences the blood flow response to SCD, the effect of this drug was reassessed in awake rats. In this state, tirilazad mesylate did not eliminate cerebral hypoperfusion following SCD. Oxygen radical-induced lipid peroxidation may not mediate cerebral hypoperfusion after SCD in awake rats.

The effect of a scalp reference signal on coherence measurements of intracranial electroencephalograms.

OBJECTIVE: To determine the effect of a scalp reference signal, such as that recorded from the mastoid or ear, on the coherence of referential intracranial electroencephalograms (EEGs). METHODS: The relationship between reference signal power and magnitude squared coherence (MSC) was determined from the theoretical expression of the coherence of referential recordings, obtained under the assumption that the reference signal is not correlated with the signals being studied. The effect of a contaminated reference signal on the coherence of intracranial EEGs was determined by measuring the MSC of both a recording of background EEGs with a simulated contaminated reference signal and a contaminated recording of a seizure. RESULTS: The MSC of referential intracranial EEGs is inflated due to the reference signal. This inflation is a function of the true MSC of the intracranial signals and the power of the reference and intracranial signals. The inflation is limited where reference signal power is smaller than the power of the intracranial signals; maximum inflation <0.1 when reference signal power=0.2xpower of intracranial EEGs and

Stance perturbation-evoked potentials in old people with poor gait and balance.

OBJECTIVE: Cerebral cortical potentials can be evoked by stance perturbation, and there is speculation that they represent the activation of supraspinal centers in preparation for the control and coordination of motor movements that maintain balance. We sought to determine if these potentials differed in old people at risk of falls. METHODS: Cortical potentials were generated by the sudden forward translation of a weight-bearing platform in 8 healthy young subjects and in 33 old subjects stratified by their functional capacity. Dependent measures were compared with non-parametric tests of significance. RESULTS: Perturbing the stance of young subjects produced a biphasic scalp potential centered at the vertex with an early positive peak at 60 ms and a larger, 45 microV, negative peak at 123 ms. In old subjects the response was delayed and the vertex-negative component was smaller and bifid. The interval between the two components of the negative peak was prolonged in a subgroup of old subjects with reduced mobility. CONCLUSIONS: Delays in sensory conduction may play a role in subsequent maladaptive motor responses to stance perturbation that can result in falls and injury in old people.

Measuring the coherence of intracranial electroencephalograms.

OBJECTIVE: Previous coherence studies of human intracranial electroencephalograms (EEGs) can be faulted on two methodological issues: (1) coherence estimates in a majority were formed from a very small number of independent sample spectra, and (2) the statistical significance of coherence estimates was either not reported or was poorly evaluated. Coherence estimator performance may be poor when a small number of independent sample spectra are employed, and the coupling of poor estimation and statistical testing can result in inaccuracy in the measurement of coherence. The performance characteristics of the coherence estimator and statistical testing of coherence estimates are described in this manuscript. METHODS: The bias, variance, probability density functions, and confidence intervals of the estimate of magnitude squared coherence (MSC); and power analysis for the test of zero MSC were developed from the exact analytic form of the probability density function of the estimate of MSC for Gaussian random processes. The coherence of a single epoch of background EEG, recorded from a patient with intractable seizures, was evaluated with different parameter values to aid in the exposition of the concepts developed here. RESULTS: The statistical characteristics of WOSA coherence estimates are a function of a single estimator parameter, the number of independent sample spectra employed in the estimation. Bias and variance are high, confidence intervals may be large, and the probability of Type II errors is high if a small number of independent sample spectra are employed. A considerable improvement in measurement accuracy is possible with careful selection of estimator parameter values. CONCLUSIONS: Coherence measurement accuracy can be improved over previous applications by attention to estimator performance and accurate statistical testing of coherence estimates.

Oxidative metabolic activity of cerebral cortex after fluid-percussion head injury in the cat.

To assess the metabolic and vascular effects of head trauma, fluid-percussion pressure waves were transmitted to the brains of anesthetized, paralyzed, and artificially ventilated cats. Changes in the redox state of cytochrome a,a3, and relative local blood volume were measured in situ by dual-wavelength reflection spectrophotometry of the cortical surface viewed through an acrylic cranial window implanted within the closed skull. Initial fluid-percussion impacts of 0.5 to 2.8 atm peak pressure produced consistent transient oxidation of cytochrome a,a3 and increases of cortical blood volume. These changes occurred despite the presence of transient posttraumatic hypotension i some cases. Also, impact-induced alterations of vascular tone occurred, independent of the presence or absence of transient hypertension in the posttraumatic period. These data demonstrate that hypoxia does not play a role in the immediate posttraumatic period in cerebral cortex, and are consistent with the idea that after injury there is increased cortical energy conservation. These data also support the concept that head trauma alters the relationship of metabolism and cerebral circulation in the period immediately after injury.

Brain mitochondrial redox state, tissue haemodynamic and extracellular ion responses to four-vessel occlusion and spreading depression in the rat.

Fibre-optic surface fluorometer reflectrometry was used to monitor the NADH (nicotine adenine dinucleotide) redox state from rat brain during three- or four-vessel occlusion. To compare the completeness of the electrocauterization of the vertebral arteries and the effectiveness of the anterior cerebral arteries, two light guides were implanted above the cerebral hemispheres. The NADH level was measured and correlated with the changes in the intensity of the reflected light at the excitation wavelength (366 nm) and to the ECoG (electrocorticogram). In the present study, we used ten rats in which unilateral and bilateral carotid occlusion were performed. In a second group of rats we tested the effects of four-vessel occlusion on the metabolic and extracellular K+ and Ca2+ activities as compared with those recorded under spreading depression conditions. These experiments were done by using the multiprobe assembly (MPA) approach. The results could be summarized as follows: (1) in the four-vessel occlusion model, the level of cerebral ischaemia could be estimated quantitatively, in real-time, by monitoring the NADH redox state; (2) unilateral carotid occlusion (after vertebral coagulation) led to a variable level of ipsilateral ischaemia, depending upon the blood flow compensation between the two hemispheres; (3) fibre-optic fluorometry enabled the correlation of NADH redox state with other physiological parameters as well as during after-brain ischaemia; (4) using the MPA in rats exposed to four-vessel occlusion as well as spreading depression, we identified the differences between the two pathological states, although there were some similarities in the ion homeostasis responses.

Comment on "Performance of different synchronization measures in real data: a case study on electroencephalographic signals".

Quian Quiroga et al. [Phys. Rev. E 65, 041903 (2002)] reported a similar performance of several linear and nonlinear measures of synchronization when applied to the rat electrocorticogram (ECoG). However, they found that the mutual information measure did not produce robust estimates of synchronization when compared to other measures. We reexamined their data using a histogram method with adaptive partitioning and found the mutual information to be a useful measure of regional ECoG interdependence.

Temporal distributions of seizure occurrence from various epileptogenic regions.

OBJECTIVE: The aim of this study was to determine whether seizure occurrence in partial epilepsy is under the influence of circadian rhythms and rhythmic exogenous factors, and how this influence varies according to cortical brain region. For these ends, we determined and analyzed detailed temporal distributions of seizures arising from the frontal, parietal, occipital, neocortical temporal, and mesial temporal lobes. METHODS: We retrospectively analyzed intracranial EEG recordings from 131 consecutive adult subjects whose partial epilepsy was sufficiently localized for surgical resection. In all, 669 seizures were analyzed: 132 frontal, 77 parietal, 83 occipital, 217 mesial temporal, and 160 neocortical temporal. RESULTS: Seizure distribution was dependent on brain region (p < 10(-9)). Nonuniform seizure distributions were observed in the parietal (p < 10(-4)), occipital (p < 10(-7)), mesial temporal (p < 0.02), and neocortical temporal lobes (p < 0.04). Occipital and parietal seizures occurred in strong gaussian-like distributions, 180 degrees out of phase relative to each other; occipital seizure occurrence peaked between 16:00 and 19:00, whereas parietal seizures peaked between 4:00 and 7:00. Frontal lobe seizures followed a unimodal distribution, peaking between 4:00 and 7:00. Seizures from the mesial temporal lobe were distributed bimodally, with the primary peak in the late afternoon between 16:00 and 19:00 and secondary peak in the morning between 7:00 and 10:00. Neocortical temporal seizures peaked slightly before the primary peak observed in the mesial temporal lobe; however, these distributions did not differ significantly. CONCLUSIONS: Seizure occurrence in partial epilepsy is not random. Endogenous circadian rhythms and rhythmic exogenous factors likely play substantial roles in seizure occurrence. These roles vary considerably according to brain region. Frontal and parietal lobe seizures seem most likely to occur nocturnally, whereas occipital and temporal lobe seizures seem to have strong afternoon preferences.