Comparing MEG and high-density EEG for intrinsic functional connectivity mapping.

Magnetoencephalography (MEG) has been used in conjunction with resting-state functional connectivity (rsFC) based on band-limited power envelope correlation to study the intrinsic human brain network organization into resting-state networks (RSNs). However, the limited availability of current MEG systems hampers the clinical applications of electrophysiological rsFC. Here, we directly compared well-known RSNs as well as the whole-brain rsFC connectome together with its state dynamics, obtained from simultaneously-recorded MEG and high-density scalp electroencephalography (EEG) resting-state data. We also examined the impact of head model precision on EEG rsFC estimation, by comparing results obtained with boundary and finite element head models. Results showed that most RSN topographies obtained with MEG and EEG are similar, except for the fronto-parietal network. At the connectome level, sensitivity was lower to frontal rsFC and higher to parieto-occipital rsFC with MEG compared to EEG. This was mostly due to inhomogeneity of MEG sensor locations relative to the scalp and significant MEG-EEG differences disappeared when taking relative MEG-EEG sensor locations into account. The default-mode network was the only RSN requiring advanced head modeling in EEG, in which gray and white matter are distinguished. Importantly, comparison of rsFC state dynamics evidenced a poor correspondence between MEG and scalp EEG, suggesting sensitivity to different components of transient neural functional integration. This study therefore shows that the investigation of static rsFC based on the human brain connectome can be performed with scalp EEG in a similar way than with MEG, opening the avenue to widespread clinical applications of rsFC analyses.

Individual response of humans to ionising radiation: governing factors and importance for radiological protection.

Tissue reactions and stochastic effects after exposure to ionising radiation are variable between individuals but the factors and mechanisms governing individual responses are not well understood. Individual responses can be measured at different levels of biological organization and using different endpoints following varying doses of radiation, including: cancers, non-cancer diseases and mortality in the whole organism; normal tissue reactions after exposures; and, cellular endpoints such as chromosomal damage and molecular alterations. There is no doubt that many factors influence the responses of people to radiation to different degrees. In addition to the obvious general factors of radiation quality, dose, dose rate and the tissue (sub)volume irradiated, recognized and potential determining factors include age, sex, life style (e.g., smoking, diet, possibly body mass index), environmental factors, genetics and epigenetics, stochastic distribution of cellular events, and systemic comorbidities such as diabetes or viral infections. Genetic factors are commonly thought to be a substantial contributor to individual response to radiation. Apart from a small number of rare monogenic diseases such as ataxia telangiectasia, the inheritance of an abnormally responsive phenotype among a population of healthy individuals does not follow a classical Mendelian inheritance pattern. Rather it is considered to be a multi-factorial, complex trait.

Radiation protection in mammography for breast cancer screening: not covered by the French press.

BACKGROUND: In the context of major exposure to medical-based ionizing radiation (IR), French health institutions agree that adopting a precautionary approach is essential. A number of scientific studies have highlighted the risk of developing breast cancer after exposure to IR, even from low doses. However, the information circulating on the subject is varied. OBJECTIVES: A study of the mainstream press was performed to better understand the elements constituting women's representations of IR in mammography for breast cancer screening. STUDY DESIGN: The data used came from a corpus created with the mainstream press database 'Europresse.' The keyword 'mammography' was chosen. The software package Iramuteq was used to perform a statistical analysis of textual data using the Reinert method. RESULTS: This study highlights a paradox between the social principle of prevention and the discourse elements on mammography screening present in the mainstream press. CONCLUSION: The general French press does not take into account radiation protection in cancer screening discourses. A greater effort to provide information on this subject is needed.

Neuromagnetic Cerebellar Activity Entrains to the Kinematics of Executed Finger Movements.

This magnetoencephalography (MEG) study aims at characterizing the coupling between cerebellar activity and the kinematics of repetitive self-paced finger movements. Neuromagnetic signals were recorded in 11 right-handed healthy adults while they performed repetitive flexion-extensions of right-hand fingers at three different movement rates: slow (~ 1 Hz), medium (~ 2 Hz), and fast (~ 3 Hz). Right index finger acceleration was monitored with an accelerometer. Coherence analysis was used to index the coupling between right index finger acceleration and neuromagnetic signals. Dynamic imaging of coherent sources was used to locate coherent sources. Coupling directionality between primary sensorimotor (SM1), cerebellar, and accelerometer signals was assessed with renormalized partial directed coherence. Permutation-based statistics coupled with maximum statistic over the entire brain volume or restricted to the cerebellum were used. At all movement rates, maximum coherence peaked at SM1 cortex contralateral to finger movements at movement frequency (F0) and its first harmonic (F1). Significant (statistics restricted to the cerebellum) coherence consistently peaked at the right posterior lobe of the cerebellum at F0 with no influence of movement rate. Coupling between Acc and cerebellar signals was significantly stronger in the afferent than in the efferent direction with no effective contribution of cortico-cerebellar or cerebello-cortical pathways. This study demonstrates the existence of significant coupling between finger movement kinematics and neuromagnetic activity at the posterior cerebellar lobe ipsilateral to finger movement at F0. This coupling is mainly driven by spinocerebellar, presumably proprioceptive, afferences.

Movement Kinematics Dynamically Modulates the Rolandic ~ 20-Hz Rhythm During Goal-Directed Executed and Observed Hand Actions.

This study investigates whether movement kinematics modulates similarly the rolandic α and ß rhythm amplitude during executed and observed goal-directed hand movements. It also assesses if this modulation relates to the corticokinematic coherence (CKC), which is the coupling observed between cortical activity and movement kinematics during such motor actions. Magnetoencephalography (MEG) signals were recorded from 11 right-handed healthy subjects while they performed or observed an actor performing the same repetitive hand pinching action. Subjects' and actor's forefinger movements were monitored with an accelerometer. Coherence was computed between acceleration signals and the amplitude of α (8-12 Hz) or ß (15-25 Hz) oscillations. The coherence was also evaluated between source-projected MEG signals and their ß amplitude. Coherence was mainly observed between acceleration and the amplitude of ß oscillations at movement frequency within bilateral primary sensorimotor (SM1) cortex with no difference between executed and observed movements. Cross-correlation between the amplitude of ß oscillations at the SM1 cortex and movement acceleration was maximal when acceleration was delayed by ~ 100 ms, both during movement execution and observation. Coherence between source-projected MEG signals and their ß amplitude during movement observation and execution was not significantly different from that during rest. This study shows that observing others' actions engages in the viewer's brain similar dynamic modulations of SM1 cortex ß rhythm as during action execution. Results support the view that different neural mechanisms might account for this modulation and CKC. These two kinematic-related phenomena might help humans to understand how observed motor actions are actually performed.

Snakes elicit specific neural responses in the human infant brain.

Detecting predators is essential for survival. Given that snakes are the first of primates' major predators, natural selection may have fostered efficient snake detection mechanisms to allow for optimal defensive behavior. Here, we provide electrophysiological evidence for a brain-anchored evolved predisposition to rapidly detect snakes in humans, which does not depend on previous exposure or knowledge about snakes. To do so, we recorded scalp electrical brain activity in 7- to 10-month-old infants watching sequences of flickering animal pictures. All animals were presented in their natural background. We showed that glancing at snakes generates specific neural responses in the infant brain, that are higher in amplitude than those generated by frogs or caterpillars, especially in the occipital region of the brain. The temporal dynamics of these neural responses support that infants devote increased attention to snakes than to non-snake stimuli. These results therefore demonstrate that a single fixation at snakes is sufficient to generate a prompt and large selective response in the infant brain. They argue for the existence in humans of an inborn, brain-anchored mechanism to swiftly detect snakes based on their characteristic visual features.

Changes in electrophysiological static and dynamic human brain functional architecture from childhood to late adulthood.

This magnetoencephalography study aimed at characterizing age-related changes in resting-state functional brain organization from mid-childhood to late adulthood. We investigated neuromagnetic brain activity at rest in 105 participants divided into three age groups: children (6-9 years), young adults (18-34 years) and healthy elders (53-78 years). The effects of age on static resting-state functional brain integration were assessed using band-limited power envelope correlation, whereas those on transient functional brain dynamics were disclosed using hidden Markov modeling of power envelope activity. Brain development from childhood to adulthood came with (1) a strengthening of functional integration within and between resting-state networks and (2) an increased temporal stability of transient (100-300 ms lifetime) and recurrent states of network activation or deactivation mainly encompassing lateral or medial associative neocortical areas. Healthy aging was characterized by decreased static resting-state functional integration and dynamic stability within the primary visual network. These results based on electrophysiological measurements free of neurovascular biases suggest that functional brain integration mainly evolves during brain development, with limited changes in healthy aging. These novel electrophysiological insights into human brain functional architecture across the lifespan pave the way for future clinical studies investigating how brain disorders affect brain development or healthy aging.

Tissue-engineered bone regeneration.

Bone lesions above a critical size become scarred rather than regenerated, leading to nonunion. We have attempted to obtain a greater degree of regeneration by using a resorbable scaffold with regeneration-competent cells to recreate an embryonic environment in injured adult tissues, and thus improve clinical outcome. We have used a combination of a coral scaffold with in vitro-expanded marrow stromal cells (MSC) to increase osteogenesis more than that obtained with the scaffold alone or the scaffold plus fresh bone marrow. The efficiency of the various combinations was assessed in a large segmental defect model in sheep. The tissue-engineered artificial bone underwent morphogenesis leading to complete recorticalization and the formation of a medullary canal with mature lamellar cortical bone in the most favorable cases. Clinical union never occurred when the defects were left empty or filled with the scaffold alone. In contrast, clinical union was obtained in three out of seven operated limbs when the defects were filled with the tissue-engineered bone.

[The enigma of the biological interpretation of the linear-quadratic model finally resolved? A summary for non-mathematicians]. / L'énigme de l'interprétation biologique du modèle linéaire-quadratique enfin résolue ? Une synthèse pour les non-mathématiciens.

The linear-quadratic (LQ) model is the only mathematical formula linking cellular survival and radiation dose that is sufficiently consensual to help radiation oncologists and radiobiologists in describing the radiation-induced events. However, this formula proposed in the 1970s and α and ß parameters on which it is based remained without relevant biological meaning. From a collection of cutaneous fibroblasts with different radiosensitivity, built over 12 years by more than 50 French radiation oncologists, we recently pointed out that the ATM protein, major actor of the radiation response, diffuses from the cytoplasm to the nucleus after irradiation. The evidence of this nuclear shuttling of ATM allowed us to provide a biological interpretation of the LQ model in its mathematical features, validated by a hundred of radiosensitive cases. A mechanistic explanation of the radiosensitivity of syndromes caused by the mutation of cytoplasmic proteins and of the hypersensitivity to low-dose phenomenon has been proposed, as well. In this review, we present our resolution of the LQ model in the most didactic way.

[Repeated radiation dose effect and DNA repair: Importance of the individual factor and the time interval between the doses]. / Effets de répétitions de doses d'irradiation et réparation de l'ADN : importance du facteur individuel et de l'intervalle de temps entre les doses.

The dose fractionation effect is a recurrent question of radiation biology research that remains unsolved since no model predicts the clinical effect only with the cumulated dose and the radiobiology of irradiated tissues. Such an important question is differentially answered in radioprotection, radiotherapy, radiology or epidemiology. A better understanding of the molecular response to radiation makes possible today a novel approach to identify the parameters that condition the fractionation effect. Particularly, the time between doses appears to be a key factor since it will permit, or not, the repair of certain radiation-induced DNA damages whose repair rates are of the order of seconds, minutes or hours: the fractionation effect will therefore vary according to the functionality of the different repair pathways, whatever for tumor or normal tissues.

Evaluation of radionuclide angiography in diagnosis of arrhythmogenic right ventricular cardiomyopathy.

OBJECTIVES: The accuracy of Fourier analysis of radionuclide angiography for the diagnosis of arrhythmogenic right ventricular cardiomyopathy was assessed versus X-ray right ventricular angiography. BACKGROUND: In patients with recurrent right ventricular tachycardia, the diagnosis of arrhythmogenic right ventricular cardiomyopathy is based on the presence of right ventricular wall motion abnormalities on conventional X-ray angiography without evidence of other heart disease. METHODS: X-ray and radionuclide angiography were prospectively compared in 73 patients with ventricular tachycardia. We analyzed the presence of a right ventricular enlargement, global hypokinesia and segmental wall motion abnormalities, using visual analysis for both techniques and Fourier analysis for radionuclide angiography. Disease was noted as absent or present and as diffuse or localized. The interobserver reproducibility of both techniques for the diagnosis of right ventricular wall motion abnormalities was tested in 27 randomly selected patients. RESULTS: According to X-ray angiography, 53 patients were considered to have arrhythmogenic right ventricular cardiomyopathy (22 diffuse, 31 localized forms) and 20 patients a normal right ventricle. The sensitivity of radionuclide angiography was 94.3%, specificity 90% and positive and negative predictive values 96% and 85.7%, respectively. Agreement for the location of the wall motion abnormalities was 60% for the apex, 76% for the outflow tract, 82% for the inferior wall and 74% for the free wall. The diagnostic interobserver reproducibility of X-ray and radionuclide angiography was 74% and 96.2%, respectively. CONCLUSIONS: In a selected cohort, Fourier analysis of radionuclide angiography is an accurate and reproducible tool for the diagnosis of arrhythmogenic right ventricular cardiomyopathy.

Effect of movement rate on corticokinematic coherence.

AIMS OF THE STUDY: This study investigates the effect of movement rate on the coupling between cortical magnetoencephalographic (MEG) signals and the kinematics of repetitive active finger movements, i.e., the corticokinematic coherence (CKC). MATERIAL AND METHODS: CKC was evaluated in ten right-handed healthy adults performing repetitive flexion-extension of the right-hand fingers in three different movement rate conditions: slow (∼1 Hz, duration: 11 min), medium (∼2 Hz, duration: 5 min) and fast (∼3 Hz, duration: 3 min). Neuromagnetic signals were recorded with a whole-scalp-covering MEG (Elekta Oy) and index acceleration was monitored with a 3-axis accelerometer. Coherent sources were estimated on the time-course of the cross-correlogram using equivalent current dipole (ECD) modeling. RESULTS: Significant coherence was found at movement frequency or its first harmonics in all subjects and movement conditions. ECDs clustered at the primary sensorimotor cortex contralateral to hand movements. Movement rate had no effect on the coherence levels and the location of coherent sources. CONCLUSIONS: This study demonstrates that the movement rate does not affect coherence levels and CKC source location during active finger movements. This finding has direct implications for CKC functional mapping applications and studies investigating the pathophysiology of central nervous disorders affecting proprioceptive pathways.

Changes in regional cerebral blood flow during brain maturation in children and adolescents.

Regional cerebral blood flow (rCBF) was studied by SPECT using 133Xe in 42 children, aged 2 days to 19 years, considered as neurologically normal. rCBF was measured on cortical regions and on the cerebellum and thalamus. Curves for reference values and standard deviation were defined for each region. At birth, cortical rCBFs were lower than those for adults; after birth they increased until 5 or 6 yr of age to values 50%-85% higher than those for adults and thereafter decreased, reaching adult levels between 15 and 19 yr. Neonatal values of rCBF on cerebellum and thalamus were slightly higher than adult level, but not significantly; after age 1, they followed the common pattern for cortical curves. When rCBFs were expressed in percent global CBF, they were lower at birth than adult levels in the cortex, then increased and reached a plateau corresponding to the adult value before the second year of age. The time needed to reach normal adult values differed for each cortical region. The shortest time was found on the primary cortex and the longest on the associative cortex. Cognitive development of the child seems to be related to changes in blood flow of the corresponding brain regions.

Prognostic value of cardiac metaiodobenzylguanidine imaging in patients with heart failure.

The prognostic value of 123I-metaiodobenzylguanidine (MIBG) imaging was compared with that of other noninvasive cardiac imaging indices in ninety patients (mean age = 52 +/- 7 yr) suffering from either ischemic (n = 24) or idiopathic (n = 66) cardiomyopathy. Patients had different measurements taken: cardiac MIBG uptake, radionuclide left ventricular ejection fraction, x-ray cardiothoracic ratio and echographic M-Mode data. Cardiac MIBG uptake was assessed as the heart-to-mediastinum activity ratio measured on the chest anterior view image obtained 4 hr after intravenous injection. The patients then had follow-up for 1-27 mo, at which time 10 patients had transplants, 22 had died and 58 were still alive. Data from patients with transplants were not used in the analysis, in which multivariate stepwise regression discriminant analysis showed that cardiac MIBG uptake was more potent to predict survival than other indices: H/M (p less than 0.0001), x-ray cardiothoracic ratio (p = 0.0017), echographic end-diastolic diameter (p = 0.0264) and radionuclide left ventricular ejection fraction (p = 0.0301). Moreover, multivariate life table analysis showed that cardiac MIBG uptake was also the best predictor for life duration: H/M (p = 0.0001), radionuclide left ventricular ejection fraction (p = 0.0098) and x-ray cardiothoracic ratio (p = 0.0139); echographic data were not useful. Thus, cardiac MIBG imaging may be helpful for heart transplantation decision making in patients with heart failure.

In-vivo SPECT imaging of D2 receptor with iodine-iodolisuride: results in supranuclear palsy.

We assessed the potential use of [123I]iodolisuride (ILIS), a new iodine ergolene derivative, to study human striatal D2 dopamine receptors with SPECT. In normal subjects, we found that the tracer accumulated preferentially in striatum. This was prevented by high doses of haloperidol. The striatal accumulation was maximal between 60 and 180 min after injection. The striatum-to-cerebellum radioactivity concentration ratio as an index of specific binding, measured 60 min after injection, was 1.52 +/- 0.19 (mean +/- s.d.) in controls and 1.36 +/- 0.11 in patients with supranuclear palsy (p less than 0.03). Our results show that ILIS may be used to study D2 receptors with SPECT. In-vivo changes of D2 receptors in human brain may be detected with this method.

Improved detection of anterior left ventricular aneurysm with multiharmonic fourier analysis.

Single and multiharmonic Fourier analysis of LAO 30-45 degrees gated blood-pool studies were performed in a selected group of 30 patients with a left ventricular anterior aneurysm proven by contrast angiography. The sensitivity of the first harmonic phase image for the diagnosis of ventricular aneurysm was 80%. The clear phase shift (greater than 110 degrees) between the normal and the aneurysmal areas was missing in six patients. Peak acceleration images (negative maximum of the second derivative of the Fourier series) were calculated for each pixel with the analytical Fourier formula using two or three harmonics. A clear phase shift (greater than 126 degrees) than appeared in all the patients. This improvement was related to the increased weight of the second and third harmonics in the aneurysmal area when compared to control patients or to patients with dilative cardiomyopathy. Multiharmonic Fourier analysis clearly improved the sensitivity of the diagnosis of anterior left ventricular aneurysm on LAO 30 degrees-45 degrees gated blood-pool images.

MIBG scintigraphic assessment of cardiac adrenergic activity in response to altitude hypoxia.

High altitude hypoxia induces a decrease in the cardiac chronotropic function at maximal exercise or in response to isoproterenol infusion, suggesting an alteration in the cardiac sympathetic activation. Iodine-123 metaiodobenzylguanidine [( 123I]MIBG) was used to map scintigraphically the cardiac sympathetic neuronal function in six male subjects (aged 32 +/- 7 yr) after an exposure to high altitude that created hypoxic conditions. Results obtained just after return to sea level (RSL) were compared with the normal values obtained after 2 or 3 mo of normoxia (N). A static image was created as the sum of the 16-EKG gated images recorded for 10 min in the anterior view of the chest at 20, 60, 120, and 240 min after injection. Regions of interest were located over the heart (H), lungs (L), and mediastinum (M) regions. There was a significant decrease in the H/M and the L/M ratios in RSL compared to N condition. Plasma norepinephrine concentration was elevated during the stay at altitude but not significantly different in RSL compared to N. In conclusion, cardiac [123I]MIBG uptake is reduced after an exposure to altitude hypoxia, supporting the hypothesis of an hypoxia-induced reduction of adrenergic neurotransmitter reserve in the myocardium. Furthermore, the observed significant decrease in pulmonary MIBG uptake suggests an alteration of endothelial cell function after exposure to chronic hypoxia.

Quantification of left to right cardiac shunts by multiple deconvolution analysis.

A new method for quantification of left to right cardiac shunts was studied in 17 patients scheduled for cardiac catheterization who had also undergone radionuclide angiocardiography. The observed pulmonary transit curve was deconvoluted in two different ways: (1) by the superior vena caval ("bolus") time-activity curve, to yield the deconvoluted pulmonary transit curve, which represented the theoretical pulmonary transit curve with a perfect bolus injection, and (2) by the right ventricular time-activity curve, to yield the pulmonary transfer function, which represented the theoretical pulmonary transit curve with a perfect bolus injection an with no intracardiac shunts. The pulmonary transfer function was superimposed on the deconvoluted pulmonary transit curve, and the area A under it obtained. The pulmonary transfer function was then subtracted from the deconvoluted pulmonary transit curve. The pulmonary transfer function was scaled to fit the resulting shunt recirculation peak in the difference curve, and the area B under this scaled pulmonary transfer function obtained. Shunt size was quantified as the pulmonary (QP) to systemic (QS) flow ration QP/QS = A/(A-B). The method correlated closely with oximetry (r = 0.93). Use of this multiple deconvolution analysis technique provides accurate shunt quantification and reduces subjective operator decisions.