Estimation of brain network ictogenicity predicts outcome from epilepsy surgery.

Surgery is a valuable option for pharmacologically intractable epilepsy. However, significant post-operative improvements are not always attained. This is due in part to our incomplete understanding of the seizure generating (ictogenic) capabilities of brain networks. Here we introduce an in silico, model-based framework to study the effects of surgery within ictogenic brain networks. We find that factors conventionally determining the region of tissue to resect, such as the location of focal brain lesions or the presence of epileptiform rhythms, do not necessarily predict the best resection strategy. We validate our framework by analysing electrocorticogram (ECoG) recordings from patients who have undergone epilepsy surgery. We find that when post-operative outcome is good, model predictions for optimal strategies align better with the actual surgery undertaken than when post-operative outcome is poor. Crucially, this allows the prediction of optimal surgical strategies and the provision of quantitative prognoses for patients undergoing epilepsy surgery.

Rapid intra-adrenal feedback regulation of glucocorticoid synthesis.

The hypothalamic-pituitary-adrenal axis is a vital neuroendocrine system that regulates the secretion of glucocorticoid hormones from the adrenal glands. This system is characterized by a dynamic ultradian hormonal oscillation, and in addition is highly responsive to stressful stimuli. We have recently shown that a primary mechanism generating this ultradian rhythm is a systems-level interaction where adrenocorticotrophin hormone (ACTH) released from the pituitary stimulates the secretion of adrenal glucocorticoids, which in turn feedback at the level of the pituitary to rapidly inhibit ACTH secretion. In this study, we combine experimental physiology and mathematical modelling to investigate intra-adrenal mechanisms regulating glucocorticoid synthesis. Our modelling results suggest that glucocorticoids can inhibit their own synthesis through a very rapid (within minutes), presumably non-genomic, intra-adrenal pathway. We present further evidence for the existence of a short time delay in this intra-adrenal inhibition, and also that at the initiation of each ACTH stimulus, this local feedback mechanism is rapidly antagonized, presumably via activation of the specific ACTH receptor (MC2R) signalling pathway. This mechanism of intra-adrenal inhibition enables the gland to rapidly release glucocorticoids while at the same time preventing uncontrolled release of glucocorticoids in response to large surges in ACTH associated with stress.

Knockout reactions from p-shell nuclei: tests of ab initio structure models.

Absolute cross sections have been determined following single neutron knockout reactions from 10Be and 10C at intermediate energy. Nucleon density distributions and bound-state wave function overlaps obtained from both variational Monte Carlo (VMC) and no core shell model (NCSM) ab initio calculations have been incorporated into the theoretical description of knockout reactions. Comparison to experimental cross sections demonstrates that the VMC approach, with the inclusion of 3-body forces, provides the best overall agreement while the NCSM and conventional shell-model calculations both overpredict the cross sections by 20% to 30% for 10Be and by 40% to 50% for 10C, respectively. This study gains new insight into the importance of 3-body forces and continuum effects in light nuclei and provides a sensitive technique to assess the accuracy of ab initio calculations for describing these effects.

Encoding and decoding mechanisms of pulsatile hormone secretion.

Ultradian pulsatile hormone secretion underlies the activity of most neuroendocrine systems, including the hypothalamic-pituitary adrenal (HPA) and gonadal (HPG) axes, and this pulsatile mode of signalling permits the encoding of information through both amplitude and frequency modulation. In the HPA axis, glucocorticoid pulse amplitude increases in anticipation of waking, and, in the HPG axis, changing gonadotrophin-releasing hormone pulse frequency is the primary means by which the body alters its reproductive status during development (i.e. puberty). The prevalence of hormone pulsatility raises two crucial questions: how are ultradian pulses encoded (or generated) by these systems, and how are these pulses decoded (or interpreted) at their target sites? We have looked at mechanisms within the HPA axis responsible for encoding the pulsatile mode of glucocorticoid signalling that we observe in vivo. We review evidence regarding the 'hypothalamic pulse generator' hypothesis, and describe an alternative model for pulse generation, which involves steroid feedback-dependent endogenous rhythmic activity throughout the HPA axis. We consider the decoding of hormone pulsatility by taking the HPG axis as a model system and focussing on molecular mechanisms of frequency decoding by pituitary gonadotrophs.

Mechanisms in knockout reactions.

We report the first detailed study of the relative importance of the stripping and diffraction mechanisms involved in nucleon knockout reactions, by the use of a coincidence measurement of the residue and fast proton following one-proton knockout reactions. The measurements used the S800 spectrograph in combination with the HiRA detector array at the NSCL. Results for the reactions 9Be(9C,8B+X)Y and 9Be(8B,7Be+X)Y are presented and compared with theoretical predictions for the two reaction mechanisms calculated using the eikonal model. The data show a clear distinction between the stripping and diffraction mechanisms and the measured relative proportions are very well reproduced by the reaction theory. This agreement adds support to the results of knockout reaction analyses and their applications to the spectroscopy of rare isotopes.

Z = 50 shell gap near 100Sn from intermediate-energy Coulomb excitations in even-mass 106-112Sn isotopes.

Rare isotope beams of neutron-deficient 106,108,110Sn from the fragmentation of 124Xe were employed in an intermediate-energy Coulomb excitation experiment. The measured B(E2,0(1)(+)-->2(1)(+)) values for 108Sn and 110Sn and the results obtained for the 106Sn show that the transition strengths for these nuclei are larger than predicted by current state-of-the-art shell-model calculations. This discrepancy might be explained by contributions of the protons from within the Z = 50 shell to the structure of low-energy excited states in this region.

Spectroscopy of 36Mg: interplay of normal and intruder configurations at the neutron-rich boundary of the "island of inversion".

We report on the first spectroscopy study of the very neutron-rich nucleus (36)(12)Mg24 using the direct two-proton knockout reaction 9Be(38Si,36Mg+gamma)X at 83 MeV/nucleon. The energy of the first excited 2+ state of 36Mg, E(2+(1)=660(6) keV, was measured. The magnitude of the partial cross sections to the ground state and the 2+(1) state is indicative of strong intruder admixtures in the lowest-lying states as suggested by Monte Carlo shell-model calculations.

Measurement of excited states in (40)Si and evidence for weakening of the N=28 shell gap.

Excited states in (40)Si have been established by detecting gamma rays coincident with inelastic scattering and nucleon removal reactions on a liquid hydrogen target. The low excitation energy, 986(5) keV, of the 2(1)(+) state provides evidence of a weakening in the N=28 shell closure in a neutron-rich nucleus devoid of deformation-driving proton collectivity.

Probing shell structure and shape changes in neutron-rich sulfur isotopes through transient-field g-factor measurements on fast radioactive beams of 38S and 40S.

The shell structure underlying shape changes in neutron-rich nuclei near N = 28 has been investigated by a novel application of the transient-field technique to measure the first-excited-state g factors in 38S and 40S produced as fast radioactive beams. There is a fine balance between proton and neutron contributions to the magnetic moments in both nuclei. The g factor of deformed 40S does not resemble that of a conventional collective nucleus because spin contributions are more important than usual.

A unifying explanation of primary generalized seizures through nonlinear brain modeling and bifurcation analysis.

The aim of this paper is to explain critical features of the human primary generalized epilepsies by investigating the dynamical bifurcations of a nonlinear model of the brain's mean field dynamics. The model treats the cortex as a medium for the propagation of waves of electrical activity, incorporating key physiological processes such as propagation delays, membrane physiology, and corticothalamic feedback. Previous analyses have demonstrated its descriptive validity in a wide range of healthy states and yielded specific predictions with regards to seizure phenomena. We show that mapping the structure of the nonlinear bifurcation set predicts a number of crucial dynamic processes, including the onset of periodic and chaotic dynamics as well as multistability. Quantitative study of electrophysiological data supports the validity of these predictions. Hence, we argue that the core electrophysiological and cognitive differences between tonic-clonic and absence seizures are predicted and interrelated by the global bifurcation diagram of the model's dynamics. The present study is the first to present a unifying explanation of these generalized seizures using the bifurcation analysis of a dynamical model of the brain.

Quadrupole deformation of the self-conjugate nucleus 72Kr.

We report on the first determination of the absolute B(E2;0+(1)-->2+(1)) excitation strength in the N=Z nucleus 72Kr. 72Kr is the heaviest N=Z nucleus for which this quantity has been measured and provides a benchmark in a region of the nuclear chart dominated by rapidly changing deformations and shapes mediated by the interplay of strongly oblate and prolate-driving orbitals. The deduced quadrupole deformation strength is in agreement with a variety of self-consistent models that predict an oblate shape for the ground state of 72Kr. Large-scale shell-model Monte Carlo calculations reproduce the experimental B(E2) value and link the result to the occupation of the deformation-driving g9/2 orbit.

'Magic' nucleus 42Si.

Nuclear shell structures--the distribution of the quantum states of individual protons and neutrons--provide one of our most important guides for understanding the stability of atomic nuclei. Nuclei with 'magic numbers' of protons and/or neutrons (corresponding to closed shells of strongly bound nucleons) are particularly stable. Whether the major shell closures and magic numbers change in very neutron-rich nuclei (potentially causing shape deformations) is a fundamental, and at present open, question. A unique opportunity to study these shell effects is offered by the 42Si nucleus, which has 28 neutrons--a magic number in stable nuclei--and 14 protons. This nucleus has a 12-neutron excess over the heaviest stable silicon nuclide, and has only one neutron fewer than the heaviest silicon nuclide observed so far. Here we report measurements of 42Si and two neighbouring nuclei using a technique involving one- and two-nucleon knockout from beams of exotic nuclei. We present strong evidence for a well-developed proton subshell closure at Z = 14 (14 protons), the near degeneracy of two different (s(1/2) and d(3/2)) proton orbits in the vicinity of 42Si, and a nearly spherical shape for 42Si.

Reduced occupancy of the deeply bound 0d(5/2) neutron state in 32Ar.

The 9Be(32Ar, 31Ar)X reaction, leading to the 5/2+ ground state of a nucleus at the proton drip line, has a cross section of 10.4(13) mb at a beam energy of 65.1 MeV/nucleon. This translates into a spectroscopic factor that is only 24(3)% of that predicted by the many-body shell-model theory. We introduce refinements to the eikonal reaction theory used to extract the spectroscopic factor to clarify that this very strong reduction represents an effect of nuclear structure. We suggest that it reflects correlation effects linked to the high neutron separation energy (22.0 MeV) for this state.

A disturbance of nonlinear interdependence in scalp EEG of subjects with first episode schizophrenia.

It has been proposed that schizophrenia arises through a disturbance of coupling between large-scale cortical systems. This "disconnection hypothesis" is tested by applying a measure of dynamical interdependence to scalp EEG data. EEG data were collected from 40 subjects with a first episode of schizophrenia and 40 matched healthy controls. An algorithm for the detection of dynamical interdependence was applied to six pairs of bipolar electrodes in each subject. The topographic organization of the interdependence was calculated and served as the principle measure of cortical integration. The rate of occurrence of dynamical interdependence did not statistically differ between subject groups at any of the sites. However, the topography across the scalp was significantly different between the two groups. Specifically, nonlinear interdependence tended to occur in larger concurrent "clusters" across the scalp in schizophrenia than in the healthy subjects. This disturbance was reflected most strongly in left intrahemispheric coupling and did not differ significantly according to symptomatology. Medication dose and subject arousal were not observed to be confounding factors. The study of dynamical interdependence in scalp EEG data does not support a straightforward interpretation of the disconnection hypothesis-that there is a decrease in the strength of functional coupling between adjacent cortical regions. Rather, it suggests a dysregulation in the organization of dynamical interactions across supraregional brain systems.

New direct reaction: two-proton knockout from neutron-rich nuclei.

The reaction 9Be(28Mg,26Ne+gamma)X has been studied at 82 MeV/nucleon together with two similar cases, 30Mg and 34Si. Strong evidence that the reactions are direct is offered by the parallel-momentum distributions of the reaction residues and by the inclusive cross sections. The pattern of the partial cross sections for 28Mg suggests the presence of correlations. A preliminary theoretical discussion based on eikonal reaction theory and the many-body shell model is presented. The reaction holds great promise for the study of neutron-rich nuclei.

Topographic organization of nonlinear interdependence in multichannel human EEG.

This paper investigates the spatial organization of nonlinear interactions between different brain regions in healthy human subjects. This is achieved by studying the topography of nonlinear interdependence in multichannel EEG data, acquired from 40 healthy human subjects at rest. An algorithm for the detection and quantification of nonlinear interdependence is applied to four pairs of bipolar electrode derivations to detect posterior and anterior interhemispheric and left and right intrahemispheric interdependences. Multivariate surrogate data sets are constructed to control for linear coherence and finite sample size. Nonlinear interdependence is shown to occur in a small but statistically robust number of epochs. The occurrence of nonlinear interdependence in any region is correlated with the concurrent presence of nonlinear interdependence in other regions at high levels of significance. The strength, direction and topography of the interdependences are also correlated. For example, posterior interhemispheric interdependence from right-to-left is strongly correlated with right intrahemispheric interdependence from back-to-front. There is a subtle change in these correlations when subjects open their eyes. These results suggest that nonlinear interdependence in the human brain has a specific topographic organization which reflects simple cognitive changes. It sometimes occurs as an isolated phenomenon between two brain regions, but often involves concurrent interdependences between multiple brain regions.

Detection and description of non-linear interdependence in normal multichannel human EEG data.

OBJECTIVES: This study examines human scalp electroencephalographic (EEG) data for evidence of non-linear interdependence between posterior channels. The spectral and phase properties of those epochs of EEG exhibiting non-linear interdependence are studied. METHODS: Scalp EEG data was collected from 40 healthy subjects. A technique for the detection of non-linear interdependence was applied to 2.048 s segments of posterior bipolar electrode data. Amplitude-adjusted phase-randomized surrogate data was used to statistically determine which EEG epochs exhibited non-linear interdependence. RESULTS: Statistically significant evidence of non-linear interactions were evident in 2.9% (eyes open) to 4.8% (eyes closed) of the epochs. In the eyes-open recordings, these epochs exhibited a peak in the spectral and cross-spectral density functions at about 10 Hz. Two types of EEG epochs are evident in the eyes-closed recordings; one type exhibits a peak in the spectral density and cross-spectrum at 8 Hz. The other type has increased spectral and cross-spectral power across faster frequencies. Epochs identified as exhibiting non-linear interdependence display a tendency towards phase interdependencies across and between a broad range of frequencies. CONCLUSIONS: Non-linear interdependence is detectable in a small number of multichannel EEG epochs, and makes a contribution to the alpha rhythm. Non-linear interdependence produces spatially distributed activity that exhibits phase synchronization between oscillations present at different frequencies. The possible physiological significance of these findings are discussed with reference to the dynamical properties of neural systems and the role of synchronous activity in the neocortex.

Nonlinear interdependence in neural systems: motivation, theory, and relevance.

In this article, we motivate models of medium to large-scale neural activity that place an emphasis on the modular nature of neocortical organization and discuss the occurrence of nonlinear interdependence in such models. On the basis of their functional, anatomical, and physiological properties, it is argued that cortical columns may be treated as the basic dynamical modules of cortical systems. Coupling between these columns is introduced to represent sparse long-range cortical connectivity. Thus, neocortical activity can be modeled as an array of weakly coupled dynamical subsystems. The behavior of such systems is represented by dynamical attractors, which may be fixed point, limit cycle, or chaotic in nature. If all the subsystems are perfectly identical, then the state of identical chaotic synchronization is a possible attractor for the array. Following the introduction of parameter variation across the array, such a state is not possible, although two other important nonlinear interdependences--generalized and phase synchronized--are possible. We suggest that an understanding of nonlinear interdependence may assist advances in models of neural activity and neuroscience time series analysis.