Effects of verum acupuncture compared to placebo acupuncture on quantitative EEG and heart rate variability in healthy volunteers

OBJECTIVES: The aim of this single-blind randomized crossover study was to evaluate specific effects of manual acupuncture on central and vegetative nervous system activity measured by quantitative electroencephalography (qEEG) and heart rate variability (HRV). DESIGN: Twenty (20) healthy volunteers (mean: 25.2 +/- 3.6 years) were monitored simultaneously using a qEEG system and a 12-channel electrocardiogram recorder during verum acupuncture (VA) at acupuncture point Large Intestine 4 (Hegu) (LI4) or placebo acupuncture (PA) at a sham point. RESULTS: In the EEG conduction of the occipital area, needle stimulation in VA increased alpha1-frequency significantly, and the ratio alpha1/theta was shifted to the benefit of alpha1 over all electrodes. The HRV parameters showed a significant increase of the low frequency/high frequency (HF) ratio during the first minute of stimulation in VA, indicating an initial increase of sympathetic activation. However, an increase of HF power in the minute after stimulation followed by a decrease in heart rate suggests delayed vagal activation. De qi (a sensation that is typical of acupuncture needling) occurred in 16 subjects during VA and in 9 volunteers during PA (80% versus 45%). CONCLUSIONS: Manual stimulation on LI4 seems to lead to specific changes in alpha EEG-frequency and in HRV parameters. A linear relationship between the HRV parameters and the alpha EEG band might point to a specific modulation of cerebral function by vegetative effects during acupuncture.

Infection of organotypic slice cultures from rat central nervous tissue with Neospora caninum: an alternative approach to study host-parasite interactions

Neospora caninum is an apicomplexan parasite which has emerged as an important cause of bovine abortion worldwide. Abortion is usually triggered by reactivation of dormant bradyzoites during pregnancy and subsequent congenital infection of the foetus, where the central nervous system appears to be most frequently affected. We here report on an organotypic tissue culture model for Neospora infection which can be used to study certain aspects of the cerebral phase of neosporosis within the context of a three-dimensionally organised neuronal network. Organotypic slice cultures of rat cortical tissue were infected with N. caninum tachyzoites, and the kinetics of parasite proliferation, as well as the proliferation-inhibitory effect of interferon-gamma (IFN-gamma), were monitored by either immunofluorescence, transmission electron microscopy, and a quantitative PCR-assay using the LightCycler instrument, respectively. In addition, the neuronal cytoskeletal elements, namely glial acidic protein filaments as well as actin microfilament bundles were shown to be largely colocalising with the pseudocyst periphery. This organotypic culture model for cerebral neosporosis provides a system, which is useful to study the proliferation, ultrastructural characteristics, development, and the interactions of N. caninum within the context of neuronal tissue, which at the same time can be modulated and influenced under controlled conditions, and will be useful in the future to gain more information on the cerebral phase of neosporosis.

Influence of transrectal and transabdominal ultrasound examination on salivary cortisol, heart rate, and heart rate variability in mares

Pregnancy diagnostics in equine reproduction are routinely performed using transrectal ultrasonography, although it is also possible to visualize the fetus by transabdominal ultrasound examinations from the 90th day of gestation onward. We hypothesized that ultrasound examinations may stress the mare and that the gestational stage status and lactation may influence the mare's stress reaction. To investigate the stress reaction, 25 thoroughbred mares of different age, pregnancy and lactational status underwent a transrectal examination. In pregnant mares, an additional transabdominal examination was performed. Salivary cortisol concentration, mean heart rate, and heart rate variability of mares were assessed to evaluate the reactions of hypothalamic–pituitary–adrenal (HPA) axis and of the autonomic nervous system. Significant differences were observed between lactating and nonlactating mares; with a lower responsiveness to stress in lactating mares. The transrectal ultrasound examination in nonlactating mares induced a significant increase in salivary cortisol (P < 0.05), and in the heart rate variability parameter, ratio of low to high frequencies (P < 0.05). This reflects an activation of the HPA axis and a shift to more sympathetic dominance. In contrast, a transabdominally performed pregnancy check did not induce an activation of the HPA axis over basal level but increased the mean heart rate and low to high frequency ratio. The results of this study indicate that checks of advanced pregnancies can be easily performed by transabdominal ultrasonography. With regard to animal welfare, this technique should be preferred during midgestation in nonlactating mares.

Sex differences in heart rate variability: a longitudinal study in international elite cross-country skiers

PURPOSE: Exercise-related sudden cardiac deaths (SCD) occur with a striking male predominance. A higher sympathetic tone in men has been suggested as risk factor for SCD. Elite athletes have the highest risk for exercise-related SCD. We aimed to analyze the autonomic nervous system of elite cross-country skiers from Norway, Russia and Switzerland in supine position and after orthostatic challenge in various training periods (TP). METHOD: Measurements of heart rate variability (HRV) were performed on a weekly basis over 1 year using an orthostatic challenge test with controlled breathing. Main outcome parameters were the high-frequency power in supine position (HFsupine) as marker of cardiac parasympathetic activity and the low-frequency/high-frequency power ratio after orthostatic challenge (LF/HFstand) as marker of cardiac sympathetic activation. Training intensity and duration were recorded daily and expressed as training strain. The training year was divided into three TPs. An average of weekly HRV measurements was calculated for each TP. RESULT: Female (n = 19, VO2max 62.0 +/- 4.6 ml kg(-1) min(-1), age 25.8 +/- 4.3 years) and male (n = 16, VO2max 74.3 +/- 6.3 ml kg(-1) min(-1), age 24.4 +/- 4.2 years) athletes were included. Training strain was comparable between sexes (all p > 0.05) and changed between TPs (all p < 0.05) while no HRV parameters changed over time. There were no sex differences in HFsupine while the LF/HFstand was significantly higher in male athletes in all TPs. CONCLUSION: For a comparable amount of training, male athletes showed constantly higher markers of sympathetic activity after a provocation maneuver. This may explain part of the male predominance in sports-related SCD.

A novel motion tracking system for evaluation of functional rehabilitation of the upper limbs

Upper limb function impairment is one of the most common sequelae of central nervous system injury, especially in stroke patients and when spinal cord injury produces tetraplegia. Conventional assessment methods cannot provide objective evaluation of patient performance and the tiveness of therapies. The most common assessment tools are based on rating scales, which are inefficient when measuring small changes and can yield subjective bias. In this study, we designed an inertial sensor-based monitoring system composed of five sensors to measure and analyze the complex movements of the upper limbs, which are common in activities of daily living. We developed a kinematic model with nine degrees of freedom to analyze upper limb and head movements in three dimensions. This system was then validated using a commercial optoelectronic system. These findings suggest that an inertial sensor-based motion tracking system can be used in patients who have upper limb impairment through data integration with a virtual reality-based neuroretation system.

The oculomotor system as a model for the study of neuronal interaction processes

Identified neurons that control eye movements offer an excellent experimental target for the study of Information coding and neuronal interaction processes wíthin the central nervous system. Here are presented some prelimínary results of the motoneuron behaviour during steady eye fíxation, obtained by regressíon and analysis of variance techniques. A flexible information system intended for the systematic acquisitíon and analysis of simultaneous records of neuronal activity and both eyes angular position in a great amount of cells, oriented to the defínition of mathematical models, is also briefly outlíned.

Activity-dependent regulation of synaptic clustering in a hippocampal culture system

Currently, there is a limited understanding of the factors that influence the localization and density of individual synapses in the central nervous system. Here we have studied the effects of activity on synapse formation between hippocampal dentate granule cells and CA3 pyramidal neurons in culture, taking advantage of FM1–43 as a fluorescent marker of synaptic boutons. We observed an early tendency for synapses to group together, quickly followed by the appearance of synaptic clusters on dendritic processes. These events were strongly influenced by N-methyl-d-aspartic acid receptor- and cyclic AMP-dependent signaling. The microstructure and localization of the synaptic clusters resembled that found in hippocampus, at mossy fiber synapses of stratum lucidum. Activity-dependent clustering of synapses represents a means for synaptic targeting that might contribute to synaptic organization in the brain.

Endothelin-B receptor is expressed by neural crest cells in the avian embryo.

Disruptions of the genes encoding endothelin 3 (EDN3) and its receptor endothelin-B receptor (EDNRB) in the mouse result in defects of two neural crest (NC)-derived lineages, the melanocytes, and the enteric nervous system. To assess the mechanisms through which the EDN3/EDNRB signaling pathway can selectively act on these NC derivatives, we have studied the spatiotemporal expression pattern of the EDNRB gene in the avian embryo, a model in which NC development has been extensively studied. For this purpose, we have cloned the quail homologue of the mammalian EDNRB cDNA. EDNRB transcripts are present in NC cells before and during their emigration from the neural tube at all levels of the neuraxis. At later developmental stages, the receptor remains abundantly expressed in the peripheral nervous system including the enteric nervous system. In a previous study, we have shown that EDN3 enhances dramatically the proliferation of NC cells when they are at the pluripotent stage. We propose that the selective effect of EDN3 or EDNRB gene inactivation is due to the fact that both melanocytes and enteric nervous system precursors have to colonize large embryonic areas (skin and bowel) from a relatively small population of precursors that have to expand considerably in number. It is therefore understandable that a deficit in one of the growth-promoting pathways of NC cells has more deleterious effects on long-range migrating cells than on the NC derivatives which develop close to the neural primordium like the sensory and sympathetic ganglia.

Reconstitution of the hippocampal mossy fiber and associational-commissural pathways in a novel dissociated cell culture system.

Synapses of the hippocampal mossy fiber pathway exhibit several characteristic features, including a unique form of long-term potentiation that does not require activation of the N-methyl-D-aspartate receptor by glutamate, a complex postsynaptic architecture, and sprouting in response to seizures. However, these connections have proven difficult to study in hippocampal slices because of their relative paucity (<0.4%) compared to commissural-collateral synapses. To overcome this problem, we have developed a novel dissociated cell culture system in which we have enriched mossy fiber synapses by increasing the ratio of granule-to-pyramidal cells. As in vivo, mossy fiber connections are composed of large dynorphin A-positive varicosities contacting complex spines (but without a restricted localization). The elementary synaptic connections are glutamatergic, inhibited by dynorphin A, and exhibit N-methyl-D-aspartate-independent long-term potentiation. Thus, the simplicity and experimental accessibility of this enriched in vitro mossy fiber pathway provides a new perspective for studying nonassociative plasticity in the mammalian central nervous system.

Nonlinear control of heart rate variability in human infants.

Nonlinear analyses of infant heart rhythms reveal a marked rise in the complexity of the electrocardiogram with maturation. We find that normal mature infants (gestation greater than or equal to 35 weeks) have complex and distinctly nonlinear heart rhythms (consistent with recent reports for healthy adults) but that such nonlinearity is lacking in preterm infants (gestation > or = to 27 weeks) where parasympathetic-sympathetic interaction and function are presumed to be less well developed. Our study further shows that infants with clinical brain death and those treated with atropine exhibit a similar lack of nonlinear feedback control. These three lines of evidence support the hypothesis championed by Goldberger et al. [Goldberger, A.L., Rigney, D.R. & West, B.J. (1990) Sci. Am. 262, 43-49] that autonomic nervous system control underlies the nonlinearity and possible chaos of normal heart rhythms. This report demonstrates the acquisition of nonlinear heart rate dynamics and possible chaos in developing human infants and its loss in brain death and with the administration of atropine. It parallels earlier work documenting changes in the variability of heart rhythms in each of these cases and suggests that nonlinearity may provide additional power in characterizing physiological states.

Emergence of order in visual system development.

Neural connections in the adult central nervous system are highly precise. In the visual system, retinal ganglion cells send their axons to target neurons in the lateral geniculate nucleus (LGN) in such a way that axons originating from the two eyes terminate in adjacent but nonoverlapping eye-specific layers. During development, however, inputs from the two eyes are intermixed, and the adult pattern emerges gradually as axons from the two eyes sort out to form the layers. Experiments indicate that the sorting-out process, even though it occurs in utero in higher mammals and always before vision, requires retinal ganglion cell signaling; blocking retinal ganglion cell action potentials with tetrodotoxin prevents the formation of the layers. These action potentials are endogenously generated by the ganglion cells, which fire spontaneously and synchronously with each other, generating "waves" of activity that travel across the retina. Calcium imaging of the retina shows that the ganglion cells undergo correlated calcium bursting to generate the waves and that amacrine cells also participate in the correlated activity patterns. Physiological recordings from LGN neurons in vitro indicate that the quasiperiodic activity generated by the retinal ganglion cells is transmitted across the synapse between ganglion cells to drive target LGN neurons. These observations suggest that (i) a neural circuit within the immature retina is responsible for generating specific spatiotemporal patterns of neural activity; (ii) spontaneous activity generated in the retina is propagated across central synapses; and (iii) even before the photoreceptors are present, nerve cell function is essential for correct wiring of the visual system during early development. Since spontaneously generated activity is known to be present elsewhere in the developing CNS, this process of activity-dependent wiring could be used throughout the nervous system to help refine early sets of neural connections into their highly precise adult patterns.

bcl-x is expressed in embryonic and postnatal neural tissues and functions to prevent neuronal cell death.

Previous studies have implicated the bcl-2 protooncogene as a potential regulator of neuronal survival. However, mice lacking functional bcl-2 exhibited normal development and maintenance of the central nervous system (CNS). Since bcl-2 appears dispensable for neuronal survival, we have examined the expression and function of bcl-x, another member of the bcl-2 family of death regulatory genes. Bcl-2 is expressed in neuronal tissues during embryonic development but is down-regulated in the adult CNS. In contrast, Bcl-xL expression is retained in neurons of the adult CNS. Two different forms of bcl-x mRNA and their corresponding products, Bcl-xL and Bcl-x beta, were expressed in embryonic and adult neurons of the CNS. Microinjection of bcl-xL and bcl-x beta cDNAs into primary sympathetic neurons inhibited their death induced by nerve growth factor withdrawal. Thus, Bcl-x proteins appear to play an important role in the regulation of neuronal survival in the adult CNS.

Multi-agent system for control of robots inspired on the distributed activity and hormonal regulation of humans

Robotics is an emerging field with great activity. Robotics is a field that presents several problems because it depends on a large number of disciplines, technologies, devices and tasks. Its expansion from perfectly controlled industrial environments toward open and dynamic environment presents a many new challenges. New uses are, for example, household robots or professional robots. To facilitate the low cost, rapid development of robotic systems, reusability of code, its medium and long term maintainability and robustness are required novel approaches to provide generic models and software systems who develop paradigms capable of solving these problems. For this purpose, in this paper we propose a model based on multi-agent systems inspired by the human nervous system able to transfer the control characteristics of the biological system and able to take advantage of the best properties of distributed software systems. Specifically, we model the decentralized activity and hormonal variation.

The ubiquitin-proteasome system in retinal health and disease

The ubiquitin–proteasome system (UPS) is the main intracellular pathway for modulated protein turnover, playing an important role in the maintenance of cellular homeostasis. It also exerts a protein quality control through degradation of oxidized, mutant, denatured, or misfolded proteins and is involved in many biological processes where protein level regulation is necessary. This system allows the cell to modulate its protein expression pattern in response to changing physiological conditions and provides a critical protective role in health and disease. Impairments of UPS function in the central nervous system (CNS) underlie an increasing number of genetic and idiopathic diseases, many of which affect the retina. Current knowledge on the UPS composition and function in this tissue, however, is scarce and dispersed. This review focuses on UPS elements reported in the retina, including ubiquitinating and deubiquitinating enzymes (DUBs), and alternative proteasome assemblies. Known and inferred roles of protein ubiquitination, and of the related, SUMO conjugation (SUMOylation) process, in normal retinal development and adult homeostasis are addressed, including modulation of the visual cycle and response to retinal stress and injury. Additionally, the relationship between UPS dysfunction and human neurodegenerative disorders affecting the retina, including Alzheimer's, Parkinson's, and Huntington's diseases, are dealt with, together with numerous instances of retina-specific illnesses with UPS involvement, such as retinitis pigmentosa, macular degenerations, glaucoma, diabetic retinopathy (DR), and aging-related impairments. This information, though still basic and limited, constitutes a suitable framework to be expanded in incoming years and should prove orientative toward future therapy design targeting sight-affecting diseases with a UPS underlying basis.

Neurological bulletin. Clinical studies of nervous and mental diseases in the Neurological Department of Columbia University.

Editor: Frederick Tilney.