A mesenchymal glioma stem cell profile is related to clinical outcome.

Recent studies have demonstrated a relationship between the expression of stem cell-associated genes and relapses in glioblastoma (GBM), suggesting a key role for tumor stem cells in this process. Although there is increasing interest in this field, glioma stem cells (GSCs) are still poorly characterized, their 'stemness' state and factors maintaining these properties remain largely unknown. We performed an expression profiling analysis of pluripotency in gliomaspheres derived from 11 patients. Comparative analysis between GSCs and H1 and H9 human embryonic stem cells as well as H9-derived neural stem cells indicates major variations in gene expression of pluripotency factors Nanog and OCT4, but a stable pattern for SOX2 suggesting its important function in maintaining pluripotency in GSCs. Our results also showed that all GSC lines have the capacity to commit to neural differentiation and express mesenchymal or endothelial differentiation markers. In addition, hierarchical clustering analysis revealed two groups of GSCs reflecting their heterogeneity and identified COL1A1 and IFITM1 as the most discriminating genes. Similar patterns have been observed in tumors from which gliomaspheres have been established. To determine whether this heterogeneity could be clinically relevant, the expression of both genes was further analyzed in an independent cohort of 30 patients with GBM and revealed strong correlation with overall survival. In vitro silencing of COL1A1 and IFTM1 confirmed the effect of these mesenchymal-associated genes on cell invasion and gliomasphere initiation. Our results indicate that COL1A1 and IFITM1 genes could be considered for use in stratifying patients with GBM into subgroups for risk of recurrence at diagnosis, as well as for prognostic and therapeutic evolution.

Feasibility of matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) networking in university hospitals in Brussels.

The mutualisation of analytical platforms might be used to address rising healthcare costs. Our study aimed to evaluate the feasibility of networking a unique matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) system for common use in several university hospitals in Brussels, Belgium. During a one-month period, 1,055 successive bacterial isolates from the Brugmann University Hospital were identified on-site using conventional techniques; these same isolates were also identified using a MALDI-TOF MS system at the Porte de Hal Laboratory by sending target plates and identification projects via transportation and the INFECTIO_MALDI software (Infopartner, Nancy, France), respectively. The occurrence of transmission problems (<2 %) and human errors (<1 %) suggested that the system was sufficiently robust to be implemented in a network. With a median time-to-identification of 5 h and 11 min (78 min, min-max: 154-547), MALDI-TOF MS networking always provided a faster identification result than conventional techniques, except when chromogenic culture media and oxidase tests were used (p < 0.0001). However, the limited clinical benefits of the chromogenic culture media do not support their extra cost. Our financial analysis also suggested that MALDI-TOF MS networking could lead to substantial annual cost savings. MALDI-TOF MS networking presents many advantages, and few conventional techniques (optochin and oxidase tests) are required to ensure the same quality in patient care from the distant laboratory. Nevertheless, such networking should not be considered unless there is a reorganisation of workflow, efficient communication between teams, qualified technologists and a reliable IT department and helpdesk to manage potential connectivity problems.

Cell transplantation in the damaged adult brain.

Parkinson's disease (PD) is the most common movement disorder in Europe, affecting more than two million people between 50 and 70 years of age. The current therapeutic approaches are of symptomatic nature and fail to halt the progressive neurodegenerative course of the disease. The development of innovative and complementary approaches to promote cellular repair may pave the way for disease-modifying therapies which may lead to less suffering for the patients and their families and finally to more cost-effective therapies. To date, cell replacement trials in PD aiming at replacing lost dopamine neurons were mainly focused on placing the transplanted cells within the target site, the striatum, and not within the lesioned site, the substantia nigra (SN). This was based on the misconception that the adult brain constitutes a non-permissive barrier not allowing the outgrowth of long distance axons originating from transplanted embryonic neurons. A growing body of evidence is challenging this concept and proposing instead to place the graft within its ontogenic site. This has been performed in several lesional animal models for various traumatic or neurodegenerative pathologies of the brain. For instance, transplanted neurons within the lesioned motor cortex were shown to be able to send distant and appropriate projections to target areas including the spinal cord. Similarly, in an animal model of PD, mesencephalic embryonic cells transplanted within the lesioned SN send massive projections to the striatum and, to a lesser extent, the frontal cortex and the nucleus accumbens. This has lead to the proposal that homotopic transplantation may be an alternative in cell-based therapies as transplanted neurons can integrate within the host brain, send projections to target areas, restore the damaged circuitry, increase neurotransmitter levels and ameliorate behavior. We will discuss also the potential of replacing embryonic neuronal cells by stem cell derived neurons as the use of embryonic cells is not without an ethical and logistical burden; in this line many have thrived to derive neurons from embryonic stem cells (ESC) in order to use them for cell transplantation. These studies are already yielding important information for future approaches in the field of cell therapies in PD but also in other neurodegenerative disorders where cell transplantation therapy may be considered. While the field of cell replacement therapies has been recently called into question with contrasting results in transplanted PD patients, these new sets of findings are raising new hopes and opening new avenues in this rejuvenated field.

Refined methodology for implantation of a head fixation device and chronic recording chambers in non-human primates.

The present study was aimed at developing a new strategy to design and anchor custom-fitted implants, consisting of a head fixation device and a chronic recording chamber, on the skull of adult macaque monkeys. This was done without the use of dental resin or orthopedic cement, as these modes of fixation exert a detrimental effect on the bone. The implants were made of titanium or tekapeek and anchored to the skull with titanium screws. Two adult macaque monkeys were initially implanted with the head fixation device several months previous to electrophysiological investigation, to allow optimal osseous-integration, including growth of the bone above the implant's footplate. In a second step, the chronic recording chamber was implanted above the brain region of interest. The present study proposes two original approaches for both implants. First, based on a CT scan of the monkey, a plastic replicate of the skull was obtained in the form of a 3D print, used to accurately shape and position the two implants. This would ensure a perfect match with the skull surface. Second, the part of the implants in contact with the bone was coated with hydroxyapatite, presenting chemical similarity to natural bone, thus promoting excellent osseous-integration. The longevity of the implants used here was 4 years for the head fixation device and 1.5 years for the chronic chamber. There were no adverse events and daily care was easy. This is clear evidence that the present implanting strategy was successful and provokes less discomfort to the animals.

A model to predict image formation in Atom probe Tomography.

A model devoted to the modelling of the field evaporation of a tip is presented in this paper. The influence of length scales from the atomic scale to the macroscopic scale is taken into account in this approach. The evolution of the tip shape is modelled at the atomic scale in a three dimensional geometry with cylindrical symmetry. The projection law of ions is determined using a realistic representation of the tip geometry including the presence of electrodes in the surrounding area of the specimen. This realistic modelling gives a direct access to the voltage required to field evaporate, to the evolving magnification in the microscope and to the understanding of reconstruction artefacts when the presence of phases with different evaporation fields and/or different dielectric permittivity constants are modelled. This model has been applied to understand the field evaporation behaviour in bulk dielectric materials. In particular the role of the residual conductivity of dielectric materials is addressed.

[Case report: electroconvulsive therapy in a 33-year-old man with hysterical quadriplegia]. / Traitement par électroconvulsivothérapie d'une tétraplégie par conversion hystérique : à propos d'un cas.

UNLABELLED: Conversion disorder refers to the occurrence of neurological-like symptoms or deficits that are neither intentionally produced nor simulated. While it cannot be explained by an organic disease, it is often related to psychological events. CASE REPORT: We report the case of a 33-year-old patient with a fluctuating hysterical tetraplegia, which had started three years earlier. After the failure or the exhaustion of several biological (psychotropic medication, transcranial magnetic stimulation) and psychotherapeutic strategies, treatment with electroconvulsive therapy (ECT) was conducted. A total of thirty-five ECT sessions were performed. Whereas the patient's clinical state was initially characterized by a complete quadriplegia and an uncontrollable muscular hypertonia, we noted that the ECT sessions were associated with a slow, though remarkable, progress. At first, the sessions were followed by moments of altered consciousness during which the patient would be relaxed and could make simple movements. Secondarily, not only was our patient able to consciously move his four limbs, but he was also able to walk. However, those improvements remained partial and fluctuating, sometimes allowing the symptom to return temporarily secondary to frustrations or annoyances. Finally, our patient relapsed. Nevertheless, his clinical state presently remains better than that in which we first knew him. DISCUSSION: The treatment of conversion disorders has been the subject of few studies and predominantly remains symptomatic. Its main goals are: to lessen secondary gains impact by adopting a neutral behaviour towards the symptom and by encouraging physical rehabilitation; to lower the symptom by allowing the patient to understand the normal functioning of the diseased organ, and; to help the patient to deal with stressful situations. There is no evidence that hypnosis is superior to medical and other psychotherapeutic approaches. Pharmacological treatments may be helpful in the case of anxiety, impulsivity or depression, albeit delivered with caution. According to some case reports, transcranial magnetic stimulation has also been associated with clinical remission. Although the use of ECT in motor conversion disorders constitutes an uncommon procedure, and even if no clinical trial has evaluated its impact on such a pathological condition, several case reports suggest that electroconvulsive therapy can be efficient in the treatment of motor conversion disorders. This efficacy may rely on several hypotheses. ECT could induce neural modifications, and participate in the suppression of an active inhibition, which is responsible for hysterical symptoms. Indeed, conversion cerebral disorder correlates can be explored with the help of functional neuro-imaging techniques, which could therefore also identify ECT neural effects. ECT adverse effects on memory could lead to a new relationship with the symptom, and modulate the psychological conflict which has participated in its emergence. Narcoanalysis, ECT sessions could have an impact on consciousness by means of some dissolution and reorganization phenomenon. It could therefore participate in the ending of an emotional block, the psychic integration of traumatic events and the recovery of a voluntary motor control. Finally, ECT could be efficient thanks to its antidepressant properties, especially its ability to stimulate triaminergic, and particularly dopaminergic transmission. This case report reminds us how difficult it can be to deal with severe conversion disorders, and to navigate between two reefs, which are abstention, and therapeutic escalation.

Neuropeptide Y modifies the disease course in the R6/2 transgenic model of Huntington's disease.

Huntington's disease (HD) is an inherited neurodegenerative disorder characterized by progressive neuronal dysfunction and cell loss, especially striatal GABAergic neurons, generating motor, cognitive and affective problems. Although the disease-causing gene is known, the exact mechanism by which it induces its pathological effect remains unknown, and no cure is currently available for this disease. Interestingly, striatal neurons that express neuropeptide Y (NPY) are preferentially spared in HD and the number of such cells is increased in the striatum of HD patients. Furthermore, neurogenesis in the subventricular zone (SVZ) also appears to be up-regulated in HD patients, and previously we also demonstrated in wild-type mice that intracerebroventricular (ICV) NPY promotes SVZ neurogenesis with migration of the newborn cells towards the striatum where they differentiate into GABAergic neurons. Therefore, we sought to determine whether NPY could be of therapeutic benefit in a transgenic mouse model of HD (R6/2) through an action on SVZ neurogenesis. We found that a single ICV injection of NPY in R6/2 mice increased survival time through reduced weight loss as well as having a beneficial effect on motor function as evidenced by improving rotarod performance and reducing paw-clasping. We also demonstrated that the degree of cerebral and striatal atrophy was reduced following such a single NPY injection and that whilst the peptide also increased the number of BrdU-positive cells in the SVZ (but not in the dentate gyrus) of R6/2 mice, this was not sufficient to account for the changes in anatomy and function that we found.. These results suggest that NPY may be of some therapeutic interest in patients with HD, although further work is needed to ascertain exactly how it mediates its beneficial effects.

Expression of ephrinA5 during development and potential involvement in the guidance of the mesostriatal pathway.

Identifying guidance cues that direct axon growth to their final connections during development is of crucial interest if we aim to repair circuits damaged in adulthood following neurodegenerative disorders or common traumatic injuries. In this work, we set out to determine the ephrinA5 guidance molecule involvement in the establishment of the mouse mesostriatal pathway during development. We showed, in vitro and in vivo, that a proportion of mesencephalic dopaminergic cells express the ephrinA5 receptor, EphA5. Moreover, we observed, using stripe assays, that ephrinA5 purified protein has a repulsive effect on most of the mesencephalic dopaminergic projections. In vivo, we detected rostro-caudal and ventro-dorsal ephrinA5 protein expression gradients in the vicinity of the dopaminergic axons in the ventral telencephalon and in the striatum, during the embryonic and early postnatal development. In addition, other EphA5 ligands were also detected in the mesostriatal pathway. Together, these expression patterns suggest that, ephrinAs and more specifically ephrinA5, may be actors in the guidance of dopaminergic projections. Further studies will focus on identifying the molecular specificity of these guidance cues, taking into account the mesencephalic dopaminergic heterogeneous neuronal population. This may help increase the integration of neuronal transplants in the mature lesioned brain or provide tools to re-establish mesostriatal circuits in vivo.

Fetal cortical allografts project massively through the adult cortex.

Allogeneic embryonic CNS tissue grafts placed in the mature brain are classically considered to lack significant long-range efferents. This problem was reexamined using 'green' cells from mice expressing ubiquitously an 'enhanced' green fluorescent protein as an alternative to classical tract tracing methods. The present study shows that fetal cortical neurons (E15; occipital origin) grafted in the occipitoparietal region of the adult cortex project massively throughout ipsilateral telencephalic structures. Two out of the nine grafted subjects had additional but sparse efferents in the visual thalamus, superior colliculus and pons.

Co-digestion of concentrated black water and kitchen refuse in an accumulation system within the DESAR (decentralized sanitation and reuse) concept.

Co-digestion of concentrated black water and kitchen refuse within the DESAR concept was the objective of this pilot research. The digestion took place in two, non-mixed accumulation reactors (AC1 and AC2) inoculated with digested primary sludge from a WWTP at a temperature of 20 degrees C for a period of around 150 days. Reactor AC1 was fed with a mixture of faeces, urine and kitchen refuse in the equivalent amount that one individual generates per day. The AC2 was fed with a mixture of faeces and kitchen refuse in the equivalent amount that two individuals produce per day. Some contribution of urine to AC2 was not to be avoided. Detailed characterisation of waste(water) was performed. The performance of the stratified reactor was followed by monitoring the reactor content for several reactors' heights as well as being based on the biogas production. In general the system exposed good process stability. The methanisation of 34 and 61% was obtained for AC1 and AC2 respectively. The biogas yield was 26.5 and 50.8 L/p/d for the respective reactors. Proper choice of inoculum as well as good buffering capacity did not lead to accumulation of VFA and an inhibitive effect due to relatively high ammonium concentration. The chosen process is a promising technology showing good process stability especially for high strength influent.

The influence of mental fatigue on facial EMG activity during a simulated workday.

The present study investigated whether facial EMG measures are sensitive to the effects of fatigue. EMG activity of the corrugator and frontalis muscles was recorded during and after a simulated workday. Fatigue was evaluated in four ways: (a) the building up of fatigue effects during the workday, (b) the building up of fatigue during a test period, (c) examination of after-effects of the workday in two test sessions in the evening, and (d) comparison of subjects with a high-and low-score on an Emotional Exhaustion questionnaire. EMG activity decreased during the workday and increased again in the evening. EMG activity also increased during a test period, reflecting increased mobilization to maintain performance. High-score subjects showed a lower level of EMG activity throughout the entire workday. They reported a higher need for recovery, experienced the workday as more fatiguing, and were less well rested when getting up. EMG measures seem to reflect that high-score subjects have problems with investing sufficient energy to maintain performance during a workday.

Attraction exerted in vivo by grafts of embryonic neocortex on developing thalamic axons.

In a previous study we provided evidence that embryonic (E) day 16 frontal cortical cells grafted into the occipital cortex of newborn rats receive inputs from the ventrolateral (VL) and ventromedial (VM) thalamic nuclei which, normally, project to the frontal cortex (25). The present study was designed to examine further the conditions of development of the thalamic innervation of heterotopic neocortical grafts. We demonstrate that VL/VM axons do not provide transitory aberrant input to the occipital cortex either in intact newborn animals or in rats having received neonatal occipital lesion and subsequent graft of E16 occipital cells. These findings indicate, therefore, that the VL/VM projection to the graft does not result from the stabilization of an initial widespread cortical projection from these thalamic nuclei occurring either spontaneously or in response to the lesion and homotopic transplantation procedures. We also show that the VL/VM projection to frontal-to-occipital grafts develops within a few days posttransplantation and is maintained in adulthood. Finally, this study establishes that most VL/VM axons which enter the grafts are not collaterals of thalamofrontal axons. After having reached the cortex, they proceed caudally primarily within the infragranular layers. The findings of this and previous (25) in vivo studies for the first time provide evidence that developing thalamic axons have the capacity to respond to signals from grafts of E16 cortical cells and are capable of deviating their trajectory to establish contact with the grafts. Only those axons arising from thalamic nuclei appropriate for the cortical locus of origin of the grafted cells respond to the guidance signals. The mechanisms by which the thalamic axons find their way to the graft probably rely on cell-contact signaling and/or long-range attraction exerted by diffusible molecules.

Flagellar radial spoke protein 3 is an A-kinase anchoring protein (AKAP).

Previous physiological and pharmacological experiments have demonstrated that the Chlamydomonas flagellar axoneme contains a cAMP-dependent protein kinase (PKA) that regulates axonemal motility and dynein activity. However, the mechanism for anchoring PKA in the axoneme is unknown. Here we test the hypothesis that the axoneme contains an A-kinase anchoring protein (AKAP). By performing RII blot overlays on motility mutants defective for specific axonemal structures, two axonemal AKAPs have been identified: a 240-kD AKAP associated with the central pair apparatus, and a 97-kD AKAP located in the radial spoke stalk. Based on a detailed analysis, we have shown that AKAP97 is radial spoke protein 3 (RSP3). By expressing truncated forms of RSP3, we have localized the RII-binding domain to a region between amino acids 144-180. Amino acids 161-180 are homologous with the RII-binding domains of other AKAPs and are predicted to form an amphipathic helix. Amino acid substitution of the central residues of this region (L to P or VL to AA) results in the complete loss of RII binding. RSP3 is located near the inner arm dyneins, where an anchored PKA would be in direct position to modify dynein activity and regulate flagellar motility.

Stage of specification of the spinal cord and tectal projections from cortical grafts.

In order to determine the embryonic age at which the hodological phenotype developed by neocortical cells is specified, we have examined the spinal or tectal projections developed by embryonic (E) grafts of presumptive frontal or occipital neocortex placed into the frontal or occipital neocortex of newborn host rats. Grafts of E13, E14 and E16 cells of the frontal cortex transplanted into the occipital cortex of newborns are capable of developing and maintaining in adulthood a spinal cord axon. Grafts of E12 cells do not project to the spinal cord but send fibres to the superficial layers of the tectum. In addition, following transplantation into the frontal cortex, early embryonic (E12) cells from the presumptive occipital cortex are capable of differentiating into neurons with spinal cord projection but are practically incapable of developing a tectal projection. When grafted at E14 into the frontal cortex, occipital cells lose the capacity to project to the spinal cord but become able to send fibres to the tectum. Taken together, these findings indicate that young (E12) embryonic frontal and occipital cortical cells are competent to subsequently differentiate into neurons projecting to the spinal cord or tectum according to instructive signals available in the cortical territory where they complete their development. By E13/E14, some cortical cells are specified and their capacity to contact targets that are not appropriate to their embryonic origin is much reduced. These findings are consistent with the notion that cortical specification involves progressive restriction in cell multipotentiality and fate specification toward region-specific phenotypes.

Early commitment of embryonic neocortical cells to develop area-specific thalamic connections.

In this study we examined the thalamic connectivity developed by grafts of embryonic (E16) parietal or occipital cortex placed homo- or heterotopically into the neocortex of newborn rats. We also examined the cytoarchitectonic organization developed by the grafts. Our findings indicate that E16 parietal cortex grafted into the parietal cortex of newborn recipients develops reciprocal connections with the host thalamic ventrobasal complex (VB) but does not establish connections with the host dorsal lateral geniculate nucleus (DLG). When implanted into the occipital cortex, these grafts are still able to establish connections with the VB. In contrast, E16 occipital cortex grafted into the parietal cortex establishes only a few connections with the VB. These grafts are, however, able to develop a substantial system of connections with the host DLG. At 16 days of embryonic age, graft cells are committed to establish thalamic connections appropriate to their tangential locus of origin. In addition, our results show that E16 parietal or occipital cortical cells do not possess the capacity to differentiate and maintain barrel organization even though they are grafted into the terminal field of developing VB axons.

Laminar distribution of isocortical neurons projecting to occipital grafts in neonate and adult rats.

Physiologically responsive grafts of embryonic (E16) occipital neurons placed into the visual cortex of adult rats were shown previously (Gaillard et al., 1998, Restor. Neurol. Neurosci. 12: 13-25) to receive a predominant (93-97%) cortical input from the infragranular layers V-VI. The present paper examines whether this specific pattern of connections is related to some process of maturation of the host cortex. Pieces of embryonic (E16) occipital cortical tissue were grafted into the visual cortex of neonate (P0), 1-week-old (P7), and adult (P120) subjects. Four months later, graft responsiveness was assessed through field potential recordings and host-to-graft afferents were labeled with a retrograde tracer (cholera toxin subunit B). The data show first that afferents to physiologically active grafts originate about equally from both supra- and infragranular cortical layers in newborn subjects and second that supragranular neurons contribute only 20 and 1.5% of these inputs in P7 and P120 recipients, respectively. This strong upside-down laminar shift of afferents may correlate with the layout of subsets of host neurons that at a given developmental stage would have the intrinsic capacity to regrow an axon. Substantial axogenesis and synaptic stabilization of host-to-graft cortical afferents appear possible only within the critical period for the supragranular neurons but may occur throughout life for the infragranular neurons.

Transplants of fetal frontal cortex grafted into the occipital cortex of newborn rats receive a substantial thalamic input from nuclei normally projecting to the frontal cortex.

A number of molecular and hodological experiments have provided evidence that there is an early commitment of neocortical neurons to express features unique to a certain cortical area. However, the findings of several transplantation experiments have indicated that late embryonic cortical tissue heterotopically grafted into the neocortex of newborn rats receives a set of thalamic projections appropriate for the host cortical locus within which it develops. To provide further information on the extent to which neocortical neurons are predetermined to develop area-specific systems of connections, in this study we have compared the pattern of thalamic afferents to grafts of embryonic day 16 occipital or frontal neocortex transplanted into the occipital cortex of newborn rats. Two months after grafting, a retrograde neurotracer (cholera toxin, subunit b) was injected into the grafts to precisely assess the number of cells in the visual- and/or motor-related nuclei of the host thalamus projecting to each category of transplants (occipital-to-occipital or frontal-to-occipital). Transplants of embryonic occipital cortex received significant input from several visual-related thalamic nuclei, i.e. the lateral posterior and lateral dorsal nuclei, and no input from motor-related thalamic nuclei. However, only few labeled cells were found in the dorsal lateral geniculate nucleus, which was systematically affected by a severe atrophy, probably in response to the lesion of the occipital cortex performed prior to the transplantation. By comparison, transplants of frontal origin received a substantial input from the ventrolateral and ventromedial thalamic nuclei, which normally project to the frontal cortex, but received a weak input from the lateral posterior and lateral dorsal nuclei. Neocortical neurons grafted heterotopically into the neocortex of newborn hosts are not only able to contact cortical and subcortical targets appropriate for their embryonic site of origin, but are also susceptible to derive thalamic inputs closely related to their embryonic origin.

Social loafing under fatigue.

In 2 experiments, 64 male students worked almost continuously for 20 hr without sleep under varying social conditions. In Experiment 1, participants worked either individually or as a group. As hypothesized, performance deteriorated over time, especially in the group condition, which allowed participants to loaf. In Experiment 2, all participants worked in groups. They were instructed that public feedback would be provided either on the group result only or on the individual results of all group members. As expected, when individual results were made public, performance deteriorated less. Overall, the data suggest that fatigue increases social loafing. However, both individualizing the task and providing public individual feedback seem to counteract these effects.

Influence of drive and timing mechanisms on breathing pattern and ventilation during mental task performance.

Assessment of multiple respiratory measures may provide insight into how behavioral demands affect the breathing pattern. This is illustrated by data from a study among 44 subjects, in which tidal volume, respiration rate, minute ventilation and indices of central drive and timing mechanisms were assessed via inductive plethysmography, in addition to end-tidal PCO2. After a baseline, three conditions of a memory comparison task were presented. The first two conditions differed only with regard to the presence or absence of feedback of performance (NFB and FB). In the third 'all-or-nothing' (AON) condition, subjects only received a monetary bonus, if their performance exceeded that of the previous two conditions. Minute ventilation increased from baseline to all task conditions, and from NFB and FB to AON. Respiration rate increased in all task conditions, but there were no differences between task conditions. Tidal volume decreased during NFB, but was equal to baseline during FB and AON. Of the respiratory control indices, inspiratory flow rate covaried much more closely with minute ventilation than duty cycle. The task performance induced a minor degree of hyperventilation. The discussion focusses on how behavioral demands affect respiratory control processes to produce alterations in breathing pattern and ventilation.