Activity-related Changes Research Articles

Aerobic glycolysis in the primate brain: reconsidering the implications for growth and maintenance

Glucose metabolism produces, by oxidative phosphorylation, more than 15 times the amount of energy generated by aerobic glycolysis. Nonetheless, aerobic glycolysis remains a prevalent metabolic pathway in the brain. Here we review evidence suggesting that this pathway contributes essential molecules to the biomass of the brain. Aerobic metabolism is the dominant metabolic pathway during early postnatal development when lipids and proteins are needed for the processes of axonal elongation, synaptogenesis, and myelination. Furthermore, aerobic metabolism may continue into adulthood to supply biomolecules for activity-related changes at the synapse and turnover of constituent structural components of neurons. Conversely, oxidative phosphorylation appears to be the main metabolic support for synaptic transmission, and, therefore, this pathway seems to be more dominant in brain structures and at time points in the lifespan that are characterized by increased synaptic density. We present the case for differing relationships between aerobic glycolysis and oxidative phosphorylation across primates in association with species-specific variation in neurodevelopmental trajectories. In doing so, we provide an alternative interpretation for the assessment of radiolabeled glucose positron emission tomography studies that regularly attribute increases in glucose uptake to neural activity alone, and propose a new model for the contribution of metabolic pathways for energetic demand and neural tissue growth. We conclude that comparative studies of metabolic appropriation in the brain may contribute to the discussion of human cognitive evolution and to the understanding of human-specific aging and the etiology of neuropsychiatric diseases.

X-ray activity cycle on the active ultra-fast rotator AB Doradus A?

Although chromospheric activity cycles have been studied in a larger number of late-type stars for quite some time, very little is known about coronal activity-cycles in other stars and their similarities or dissimilarities with the solar activity cycle. While it is usually assumed that cyclic activity is present only in stars of low to moderate activity, we investigate whether the ultra-fast rotator AB Dor, a K dwarf exhibiting signs of substantial magnetic activity in essentially all wavelength bands, exhibits a X-ray activity cycle in analogy to its photospheric activity cycle of about 17 years and possible correlations between these bands. We analysed the combined optical photometric data of AB Dor A, which span ~35 years. Additionally, we used ROSAT and XMM-Newton X-ray observations of AB Dor A to study the long-term evolution of magnetic activity in this active K dwarf over nearly three decades and searched for X-ray activity cycles and related photometric brightness changes. AB Dor A exhibits photometric brightness variations ranging between 6.75 < Vmag < 7.15 while the X-ray luminosities range between 29.8 < log LX [erg/s] < 30.2 in the 0.3-2.5 keV. As a very active star, AB Dor A shows frequent X-ray flaring, but, in the long XMM-Newton observations a kind of basal state is attained very often. This basal state probably varies with the photospheric activity-cycle of AB Dor A which has a period of ~17 years, but, the X-ray variability amounts at most to a factor of ~2, which is, much lower than the typical cycle amplitudes found on the Sun.

Dendritic Generation of mGluR-Mediated Slow Afterdepolarization in Layer 5 Neurons of Prefrontal Cortex

Many prefrontal cortex (PFC)-dependent tasks require individual neurons to fire persistently in response to brief stimuli. Persistent activity is proposed to involve changes in intrinsic properties, resulting in an increased sensitivity to inputs. The dendrite is particularly relevant to this hypothesis because it receives the majority of synaptic inputs and is enriched for conductances implicated in persistent firing. We provide evidence that dendritic conductances contribute to persistent activity-related changes in intrinsic properties. The effects of Group 1 metabotropic glutamate receptor (mGluR) activation on persistent activity-related properties were tested in two classes of rat L5 neurons with distinct membrane properties: those projecting to the pons (CPn) and those projecting across the commissure to the contralateral cortex (COM). mGluR activation produced long-term changes in the subthreshold properties of CPn, but not COM neurons. These changes were indicative of a decrease in hyperpolarization-activated cation nonselective current (I(h)) at the soma and dendrite. mGluR activation also transiently increased the amplitude of the postburst slow afterdepolarization potential (sADP) at the soma of both neuron types. Interestingly, the sADP occurred along the extent of the apical dendrite in CPn and COM neurons. Simultaneous somatic/dendritic recordings revealed that the dendritic sADP does not result solely from passive propagation of the somatic sADP. Focal mGluR activation in L5, near the soma or at the border of L1/L2, near the tuft, generates a local sADP. This dendritic depolarization may act synergistically with synaptic input to regulate mnemonic activity in PFC.

Age and activity-related changes in the respiratory motor system

The ability of the respiratory motor system to adapt to various functional demands is very important for maintaining human lifestyles. Age-related changes in the system have been studied in several animals. Furthermore, many kinds of models of altered use have been developed to examine activity-related changes in the system. In this review, the plasticity of the respiratory motor system, including spinal phrenic motoneurons and endplates on muscle fibers are discussed, mainly relating to inactivity and over-activity models in rat diaphragm muscle.

Hard Labor and Hostile Encounters: What Human Remains Reveal about Institutional Violence and Chinese Immigrants Living in Carlin, Nevada (1885–1923)

This article identifies activity-related changes to, traumatic injuries on, and pathological conditions of the human remains of the Chinese immigrants from Carlin, Nevada, who were interred between 1885 and 1923. Chinese males came to the Americas to work as railroad laborers and miners, and when the railroad was completed many went home, but some found work in small towns. In Carlin, Chinese immigrants were employed as merchants, shopkeepers, cooks, laundry workers, and a variety of other occupations. Within this immigrant group, there were differences in the degree of physical labor each individual experienced. According to historical records, this was a time of increasing anti-Chinese sentiments, and there are accounts of intergroup conflict with the politically dominant settlers. However, little is known about the biological correlates of this sociopolitical inequality. An analysis of these correlates is assessed as a means for understanding patterns of social, economic, and political inequality between these immigrants and the local population. The findings demonstrate that socioeconomic and political inequality experienced by the Carlin individuals resulted in high rates of activity-induced changes, trauma, and pathological conditions. Furthermore, examination of the relationship between cranial trauma and other types of skeletal injuries supports research that has shown trauma to the head can predispose people to other types of trauma (accidental or deliberate). The results support the historical accounts of the time that indicate hard physical labor, accidental or deliberate trauma, and interpersonal conflict were part of the life history of this group of Chinese immigrants.

Development of integrative autonomic nervous system function: an investigation based on time correlation in fetal heart rate patterns

To describe the development of the integrative capacity of the fetal autonomic nervous system (ANS) according to gestational age and emerging behavioral states, assuming that developing integrative ANS functions are reflected in increasing autocorrelation of fetal heart rate and fetal heart rate variability markers. Magnetocardiograms of 114 healthy fetuses (21-40 weeks of gestation) were recorded. Level of fetal activity (quiet/active sleep) was estimated according to characteristic heart rate patterns. Autocorrelation functions of (i) fetal heart rate and (ii) time patterns of SDNN (standard deviation of normal-to-normal intervals) and RMSSD (root mean square of successive differences in normal-to-normal intervals) were calculated and autocorrelation was determined over different time scales. Age and activity related changes were examined using linear regression and non-parametric tests. During pregnancy, autocorrelation increased in fetal heart rate signals and time patterns of SDNN and RMSSD. Short-time correlation (0-20 s) changed between 21 and 31 gestational weeks. Long-time correlation (75-300 s) accelerated later in pregnancy and did not increase in quiet heart rate patterns. Strong state-dependent changes were found with time patterns of SDNN. Emerging integrative ANS functions are reflected in increasing autocorrelation of fetal heart rate fluctuations over increasing time scales. The period from 21 to 31 gestational weeks seems to be critical to ANS development. Increasing long-time correlation is specific to active sleep states.

Coronal activity cycles in nearby G and K stars

We use X-ray observations of the nearby binaries 61 Cyg A/B (K5V and K7V) and Alpha Cen A/B (G2V and K1V) to study the long-term evolution of magnetic activity in weakly to moderately active G + K dwarfs over nearly a decade. Specifically we search for X-ray activity cycles and related coronal changes and compare them to the solar behavior. For 61 Cyg A we find a regular coronal activity cycle analog to its 7.3 yr chromospheric cycle. The X-ray brightness variations are with a factor of three significantly lower than on the Sun, yet the changes of coronal properties resemble the solar behavior with larger variations occurring in the respective hotter plasma components. 61 Cyg B does not show a clear cyclic coronal trend so far, but the X-ray data matches the more irregular chromospheric cycle. Both Alpha Cen stars exhibit significant long-term X-ray variability. Alpha Cen A shows indications for cyclic variability of an order of magnitude with a period of about 12-15 years; the Alpha Cen B data suggests an X-ray cycle with an amplitude of about six to eight and a period of 8-9 years. The sample stars exhibit X-ray luminosities ranging between Lx < 1x10^26 - 3x10^27 erg s^-1 in the 0.2-2.0 keV band and have coronae dominated by cool plasma with variable average temperatures of around 1.0-2.5 MK. We find that coronal activity cycles are apparently a common phenomenon in older, slowly rotating G and K stars. The spectral changes of the coronal X-ray emission over the cycles are solar-like in all studied targets.

Solar activity–climate relations: A different approach

The presentation of solar activity–climate relations is extended with the most recent sunspot and global temperature data series. The extension of data series shows clearly that the changes in terrestrial temperatures are related to sources different from solar activity after ∼1985. Based on analyses of data series for the years 1850–1985 it is demonstrated that, apart from an interval of positive deviation followed by a similar negative excursion in Earth's temperatures between ∼1923 and 1965, there is a strong correlation between solar activity and terrestrial temperatures delayed by 3 years, which complies with basic causality principles. A regression analysis between solar activity represented by the cycle-average sunspot number, SSN A , and global temperature anomalies, Δ T A , averaged over the same interval lengths, but delayed by 3 years, provides the relation Δ T A ∼0.009 (±0.002) SSN A . Since the largest ever observed SSN A is ∼90 (in 1954–1965), the solar activity-related changes in global temperatures could amount to no more than ±0.4 °C over the past ∼400 years where the sunspots have been recorded. It is demonstrated that the small amplitudes of cyclic variations in the average global temperatures over the ∼11 year solar cycle excludes many of the various driver processes suggested in published and frequently quoted solar activity–climate relations. It is suggested that the in-cycle variations and also the longer term variations in global temperatures over the examined 135 years are mainly caused by corresponding changes in the total solar irradiance level representing the energy output from the core, but further modulated by varying energy transmission properties in the active outer regions of the Sun.

A physiological systems approach to modeling and resetting of mouse thermoregulation under heat stress

Heat stroke (HS) is a serious civilian and military health issue. Due to the limited amount of experimental data available in humans, this study was conducted on a mouse mathematical model fitted on experimental data collected from mice under HS conditions, with the assumption there is good agreement among mammals. Core temperature (T(c)) recovery responses in a mouse model consist of hypothermia and delayed fever during 24 h of recovery that represent potential biomarkers of HS severity. The objective of this study was to develop a simulation model of mouse T(c) responses and identify optimal treatment windows for HS recovery using a three-dimensional predictive heat transfer simulation model. Several bioenergetic simulation variables, including nonlinear metabolic heat production (W/m³), temperature-dependent convective heat transfer through blood mass perfusion (W/m³), and activity-related changes in circadian T(c) were used for model simulation. The simulation results predicted the experimental data with few disparities. Using this simulation model, we tested a series of ambient temperature treatment strategies to minimize hypothermia and delayed fever to accelerate HS recovery. Using a genetic algorithm, we identified eight time segments (ambient temperature = 27, 30, 31, 29, 28, 28, 27, 26°C) of 110 min total duration that optimized HS recovery in our model simulation.

Excitatory synaptic activity is associated with a rapid structural plasticity of inhibitory synapses on hippocampal CA1 pyramidal cells

Synaptic activity, such as long-term potentiation (LTP), has been shown to induce morphological plasticity of excitatory synapses on dendritic spines through the spine head and postsynaptic density (PSD) enlargement and reorganization. Much less, however, is known about activity-induced morphological modifications of inhibitory synapses. Using an in vitro model of rat organotypic hippocampal slice cultures and electron microscopy, we studied activity-related morphological changes of somatic inhibitory inputs triggered by a brief oxygen–glucose deprivation (OGD) episode, a condition associated with a synaptic enhancement referred to as anoxic LTP and a structural remodeling of excitatory synapses. Three-dimensional reconstruction of inhibitory axo-somatic synapses at different times before and after brief OGD revealed important morphological changes. The PSD area significantly and markedly increased at synapses with large and complex PSDs, but not at synapses with simple, macular PSDs. Activity-related changes of PSD size and presynaptic bouton volume developed in a strongly correlated manner. Analyses of single and serial sections further showed that the density of inhibitory synaptic contacts on the cell soma did not change within 1 h after OGD. In contrast, the proportion of the cell surface covered with inhibitory PSDs, as well as the complexity of these PSDs significantly increased, with less macular PSDs and more complex, segmented shapes. Together, these data reveal a rapid activity-related restructuring of somatic inhibitory synapses characterized by an enlargement and increased complexity of inhibitory PSDs, providing a new mechanism for a quick adjustment of the excitatory–inhibitory balance. This article is part of a Special Issue entitled ‘Synaptic Plasticity & Interneurons’.

Optical Imaging: A New Window to the Adult Brain

Noninvasive optical imaging is an emerging method of functional neuroimaging that has major advantages that make it particularly suited to both basic and clinical neuroscience research as well as to clinical practice.2–7 It has great promise for contributing to neuropsychiatry.2 The required equipment is compact and portable, it is relatively easy to use, and the method is relatively tolerant of subject movement. Studies can be performed in almost any location including at the bedside and in natural settings. Patients who are not good candidates for more traditional functional imaging methods (e.g., functional MRI [fMRI] and positron emission tomography [PET]) often do well with optical imaging, as it does not require absolute stillness or confinement and has no associated loud noises. It is also safe to use in the presence of metal (e.g., plates, pins, pacemakers), an important consideration for some populations of interest. It has much faster time resolution than most other functional imaging techniques and can easily provide repeated within-subject measures. Other major advantages are low cost and high safety. Like surface electroencephalography (EEG), optical imaging captures activation-related changes only from the cerebral cortex. Historically, the major disadvantages of optical imaging have been its lower spatial resolution and smaller regions of coverage, areas of major improvement over the last decade. Use of optical imaging for monitoring of cerebral state in high-risk situations (e.g., neurosurgery, intensive care unit), while an important clinical application, is outside the scope of this review.8–10

Understanding Community and Family Barriers and Supports to Physical Activity in American Indian Children

Increasing physical activity (PA) in children and adults is necessary to prevent or ameliorate chronic diseases such as obesity, type 2 diabetes and cardiovascular disease. Interventions designed to increase PA at the individual and community level through policy and environmental change are essential. American Indian (AI) communities face a disproportionate burden of chronic disease and are eager to work on multi-level methods for disease prevention. 1 Over the past 10 years our research group has been partnering with multiple AI communities in northern Wisconsin on research to understand barriers and supports to healthy lifestyles and PA. Methods have included the WINGS epidemiological work and parental questionnaires 2 (see this issue), key informant interviews and focus groups 3-4 , PhotoVoice/GIS mapping, accelerometry/direct observation 5 , and environmental assessment. An intervention, Healthy Children, Strong Families, and Supportive Communities, is underway and focuses both on the family environment and aiding individuals in making healthy choices. 6 The intervention also assists communities in making community level changes to support healthy lifestyles. Our journey with these communities to understand the prevalence of obesity and cardiovascular disease and the role of attitude and environment in order to aid intervention design has taught us many valuable lessons. The framework of our work has been community based participatory research 7-8 , and tribal members were involved at all stages of the research whenever possible. In this commentary, discussion of the lessons learned from each of these methods is divided into 3 realms: community views and suggestions, objective measurement, and environmental assessment. Some methods cross more than one realm. These notes from the field may help other communities as they travel a similar journey toward wellness. Community Views and Suggestions During the WINGS study, the parent survey for parents of 3-8 year old children included an open ended question seeking suggestions for changes in the community that might encourage healthier lifestyles. 2 Caregivers provided 90 suggestions of how to promote healthy lifestyles in their community. Fifty-six of those suggestions specifically mentioned physical activity related changes. Common themes noted by caregivers were the desire for more family oriented activities, more activities and sports directed at younger children, parents needing to spend more time with children in activities, and needing more facilities for younger children/families. Our key informant and focus group work showed the importance of understanding parental views of health in order to intervene in increasing PA. Parents had a view of health

Amaranthus leucocarpus lectin (ALL) Enhances anti-CD3-Dependent Activation of Murine T Cells and Promotes Cell Survival

The Galβ1,3GalNAc-specific lectin from Amaranthus leucocarpus (ALL) shows a differential binding pattern on murine thymocytes, peripheral and activated CD4+ and CD8+ T cells. Although ALL detects activation-related changes in T cell surface carbohydrate moieties, no study has been performed to examine the effect of ALL on T cell activation. In this study, we analyzed the anti-CD3-dependent activation of murine T cells in the presence of ALL by measuring proliferation, surface activation marker expression, and IL-2 secretion using total cells from the lymph node. The results showed that ALL did not significantly induce T cell activation but did enhance anti-CD3-dependent activation of both CD4+ and CD8+ T cells. In addition, ALL protected T cells from spontaneous apoptosis and increased cell survival in serum-free culture conditions. Our findings indicate that ALL alone does not affect T cell activation, but do suggest that ALL has an anti-CD3-dependent co-stimulatory-like effect on T cell activation. Moreover, ALL promotes cell survival in regular and serum-free culture conditions. This study is the first report of a non-mitogenic T cell-binding lectin that can induce a possible costimulatory-like effect and provides a new tool for understanding how glycosylation impacts the T cell response.

Laser capture microdissection of spinally‐projecting RVLM neurons: Analysis of NMDA receptor subunit gene expression.

Spinally‐projecting neurons in the rostral ventrolateral medulla (RVLM) are important in blood pressure regulation. Functional and anatomical studies suggest that N‐methyl‐D‐aspartate receptors (NMDARs) are located in the RVLM and play important roles in cardiovascular reflexes. Since NMDARs are also associated with neuroplasticity, we determined the feasibility of comparing NMDAR subunit gene expression in the RVLM. To test this, Fluorogold (FG) was injected into the intermediolateral cell column of Sprague Dawley rats (n=4) to label spinally‐projecting neurons. After 1–2 wks, FG‐labeled cells were obtained under RNAase free conditions from fresh, frozen sections (8 μm) using laser capture microdissection (Arcturus PixCell II). Total mRNA was isolated, and NMDAR subunits (NR1 and NR2A) and GAPDH were quantified by real time PCR (qRT‐PCR) using Taqman probes. Preliminary findings suggest that we are able to detect NMDAR subunit gene expression in spinally‐projecting RVLM neurons. Alterations in NMDAR number or subunit composition may influence the excitability of RVLM neurons and contribute to changes in sympathetic outflow in physiological and pathophysiological states. Future studies will compare physical activity‐related changes in gene and protein expression levels of NMDAR subunits. (AHA# 09PRE2050230 and HL‐089364)

Peatland records of solar activity

Rainwater-fed Holocene raised bog deposits in temperate climate zones are valuable archives of solar activity fluctuations and related climate changes.

Relationship between circulating progenitor cells, vascular function and oxidative stress with long-term training and short-term detraining in older men

Exercise may contribute to the maintenance of vascular function via enhanced liberation and action of bone-marrow-derived progenitor cells. Activity related changes in oxidative stress may also influence the number and function of these cells. In the present study, we sought to determine (i) whether adaptations in reactive hyperaemic FBF (forearm blood flow) response associated with long-term endurance exercise and short-term detraining were related to resting putative progenitor cell number and function, and (ii) whether oxidative stress affected these factors. Participants included men with a history of more than 30 years of moderate-to-high intensity exercise (HI group) and healthy low-active age- and BMI (body mass index)-matched control subjects (LO group). Vascular reactive hyperaemic FBF response, resting CD34+ and CD34+/VEGFR2+ (vascular endothelial growth factor receptor 2+] cell number, CFU-EC (colony forming unit-endothelial cell) count and CFU-EC senescence were evaluated. Oxidative stress measures included OxLDL (oxidized low-density lipoprotein) and TAC (total antioxidant capacity).These measures were assessed following 10 days of detraining in the HI group. The HI group had greater peak reactive hyperaemic FBF responses compared with the LO group, despite no difference in resting CD34+ cell number, CD34+/VEGFR2+ cell number, CFU-EC colonies or CFU-EC senescence. With detraining in the HI group, CD34+ cells declined 44 %, and the percentage change in CD34+/VEGFR2+ cells was positively correlated with the change in FBF response to reactive hyperaemia. The percentage change in CD34+/VEGFR2+ cells and the percentage change in EPC (endothelial progenitor cell) senescence with detraining were related to the percentage change in TAC. These results reveal that changes in reactive hyperaemic FBF are closely related to activity dependent dynamic changes in CD34+/VEGFR2+ cell number, which may be influenced by alterations in oxidative stress.

Correcting Fan-Beam Magnification in Clinical Densitometry Scans of Growing Subjects

As children grow, body and limb girths increase. For serial densitometric measurements, growth increases the distance between the bone region of interest and X-ray source over time, thereby increasing fan-beam magnification. To isolate bone accrual from magnification error in growing subjects, we developed a correction method based on waist girth, a common anthropometric measure. This correction was applied to dual-energy X-ray absorptiometry output obtained in a cohort of premenarcheal gymnasts and nongymnasts. After correcting for magnification, results for projected area and bone mineral content (BMC) increased by 0.4–1.1% at the lumbar spine and 8–16% at the femoral neck, decreasing areal bone mineral density (aBMD) by 0.4–2.3% at both sites. The effects of magnification correction were similar in magnitude to BMC and aBMD gains previously reported in longitudinal studies of normoactive children. Because of body size differences, the effect of correction for BMC and aBMD was 10–20% greater in nongymnasts than in gymnasts, which increased the observed aBMD differential between gymnasts and nongymnasts. Fan-beam magnification distorts true changes in bone mineral measures in growing premenarcheal girls and, therefore, may obscure additional activity-related changes during growth. Our correction technique may enhance detection of skeletal adaptation, particularly in pediatric populations.

Simulation of the Electrically Stimulated Cochlear Neuron: Modeling Adaptation to Trains of Electric Pulses

The Hodgkin-Huxley (HH) model does not simulate the significant changes in auditory nerve fiber (ANF) responses to sustained stimulation that are associated with neural adaptation. Given that the electric stimuli used by cochlear prostheses can result in adapted responses, a computational model incorporating an adaptation process is warranted if such models are to remain relevant and contribute to related research efforts. In this paper, we describe the development of a modified HH single-node model that includes potassium ion ( K(+)) concentration changes in response to each action potential. This activity-related change results in an altered resting potential, and hence, excitability. Our implementation of K(+)-related changes uses a phenomenological approach based upon K(+) accumulation and dissipation time constants. Modeled spike times were computed using repeated presentations of modeled pulse-train stimuli. Spike-rate adaptation was characterized by rate decrements and time constants and compared against ANF data from animal experiments. Responses to relatively low (250 pulse/s) and high rate (5000 pulse/s) trains were evaluated and the novel adaptation model results were compared against model results obtained without the adaptation mechanism. In addition to spike-rate changes, jitter and spike intervals were evaluated and found to change with the addition of modeled adaptation. These results provide one means of incorporating a heretofore neglected (although important) aspect of ANF responses to electric stimuli. Future studies could include evaluation of alternative versions of the adaptation model elements and broadening the model to simulate a complete axon, and eventually, a spatially realistic model of the electrically stimulated nerve within extracochlear tissues.

Diabetes NetPLAY: A physical activity website and linked email counselling randomized intervention for individuals with type 2 diabetes

Background -This pilot study evaluated the feasibility (recruitment, retention, adherence and satisfaction) and preliminary efficacy of a 12-week website and email-linked counselling intervention on physical activity behaviour change in individuals with type 2 diabetes.Methods -A total of 49 individuals with type 2 diabetes (59% female, average age 54.1 years) were randomized to the Diabetes NetPLAY intervention or control condition. The intervention condition received information grounded in the Social Cognitive Theory (SCT), personalized weekly emails, an on-line logbook and message board. Key outcomes included physical activity behaviour and related cognition changes. The control condition was provided links to the Canadian Diabetes Association's Clinical Practice Guidelines for Physical Activity and Canada's Guide to Physical Activity.Results -Intervention participants indicated high levels of satisfaction for this mode of delivery and study results demonstrated the feasibility of web-based mediums for the delivery of physical activity information in this population. The intervention group demonstrated a significant improvement in total vigorous and moderate minutes of physical activity (p = 0.05) compared to the control group over the 12-week study. Among the SCT variables, behavioural capacity, showed a significant increase (p < 0.001) among intervention participants.Conclusion -Web-based interventions for individuals with type 2 diabetes are feasible and show promise for improving positive physical activity outcomes.

3D single-shot VASO using a maxwell gradient compensated GRASE sequence

The vascular space occupancy (VASO) method was recently proposed as a functional MRI (fMRI) method that is capable of detecting activation-related changes in blood volume (CBV), without the need for a blood-pool contrast agent. In the present work we introduce a new whole-brain VASO technique that is based on a parallel-accelerated single-shot 3D GRASE (gradient and spin echo) readout. The GRASE VASO sequence employs a flow-compensated correction scheme for concomitant Maxwell gradients which is necessary to avoid smearing artifacts that may occur due to violation of the Carr-Purcell-Meiboom-Gill (CPMG) condition for off-resonance excitation. Experiments with 6 min of visual-motor stimulation were performed on eight subjects. At P < 0.01, average percent signal change and t-score for visual stimulation were -3.11% and -8.42, respectively; activation in left and right motor cortices and supplementary motor area was detected with -2.75% and -6.70, respectively. Sensitivity and signal changes are comparable to those of echo-planar imaging (EPI)-based single-slice VASO, as indicated by additional visual-task experiments (-3.39% and -6.93). The method makes it possible to perform whole-brain cognitive activation studies based on CBV contrast.