5,688 research outputs found

    Interpreting Oxygenation-Based Neuroimaging Signals: The Importance and the Challenge of Understanding Brain Oxygen Metabolism

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    Functional magnetic resonance imaging is widely used to map patterns of brain activation based on blood oxygenation level dependent (BOLD) signal changes associated with changes in neural activity. However, because oxygenation changes depend on the relative changes in cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2), a quantitative interpretation of BOLD signals, and also other functional neuroimaging signals related to blood or tissue oxygenation, is fundamentally limited until we better understand brain oxygen metabolism and how it is related to blood flow. However, the positive side of the complexity of oxygenation signals is that when combined with dynamic CBF measurements they potentially provide the best tool currently available for investigating the dynamics of CMRO2. This review focuses on the problem of interpreting oxygenation-based signals, the challenges involved in measuring CMRO2 in general, and what is needed to put oxygenation-based estimates of CMRO2 on a firm foundation. The importance of developing a solid theoretical framework is emphasized, both as an essential tool for analyzing oxygenation-based multimodal measurements, and also potentially as a way to better understand the physiological phenomena themselves. The existing data, integrated within a simple theoretical framework of O2 transport, suggests the hypothesis that an important functional role of the mismatch of CBF and CMRO2 changes with neural activation is to prevent a fall of tissue pO2. Future directions for better understanding brain oxygen metabolism are discussed

    Post-stimulus fMRI and EEG responses: evidence for a neuronal origin hypothesised to be inhibitory

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    Post-stimulus undershoots, negative responses following cessation of stimulation, are widely observed in functional magnetic resonance (fMRI) blood oxygenation level dependent (BOLD) data. However, the debate surrounding whether the origin of this response phase is neuronal or vascular, and whether it provides functionally relevant information, that is additional to what is contained in primary response, means that undershoots are widely overlooked. We simultaneously recorded electroencephalography (EEG), BOLD and cerebral blood-flow (CBF) [obtained from arterial spin labelled (ASL) fMRI] fMRI responses to hemifield checkerboard stimulation to test the potential neural origin of the fMRI post-stimulus undershoot. The post-stimulus BOLD and CBF signal amplitudes in both contralateral and ipsilateral visual cortex depended on the post-stimulus power of the 8-13 Hz (alpha) EEG neuronal activity, such that trials with highest EEG power showed largest fMRI undershoots in contralateral visual cortex. This correlation in post-stimulus EEG-fMRI responses was not predicted by the primary response amplitude. In the contralateral visual cortex we observed a decrease in both cerebral rate of oxygen metabolism (CMRO2) and CBF during the post-stimulus phase. In addition, the coupling ratio (n) between CMRO2 and CBF was significantly lower during the positive contralateral primary response phase compared with the post-stimulus phase and we propose that this reflects an altered balance of excitatory and inhibitory neuronal activity. Together our data provide strong evidence that the post-stimulus phase of the BOLD response has a neural origin which reflects, at least partially, an uncoupling of the neuronal responses driving the primary and post-stimulus responses, explaining the uncoupling of the signals measured in the two response phases. We suggest our results are consistent with inhibitory processes driving the post-stimulus EEG and fMRI responses. We therefore propose that new methods are required to model the post-stimulus and primary responses independently, enabling separate investigation of response phases in cognitive function and neurological disease

    Pericyte-mediated regulation of capillary diameter: a component of neurovascular coupling in health and disease

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    Because regional blood flow increases in association with the increased metabolic demand generated by localised increases in neural activity, functional imaging researchers often assume that changes in blood flow are an accurate read-out of changes in underlying neural activity. An understanding of the mechanisms that link changes in neural activity to changes in blood flow is crucial for assessing the validity of this assumption, and for understanding the processes that can go wrong during disease states such as ischaemic stroke. Many studies have investigated the mechanisms of neurovascular regulation in arterioles but other evidence suggests that blood flow regulation can also occur in capillaries, because of the presence of contractile cells, pericytes, on the capillary wall. Here we review the evidence that pericytes can modulate capillary diameter in response to neuronal activity and assess the likely importance of neurovascular regulation at the capillary level for functional imaging experiments. We also discuss evidence suggesting that pericytes are particularly sensitive to damage during pathological insults such as ischaemia, Alzheimer’s disease and diabetic retinopathy, and consider the potential impact that pericyte dysfunction might have on the development of therapeutic interventions and on the interpretation of functional imaging data in these disorders

    Reduced haemodynamic response in the ageing visual cortex measured by absolute fNIRS

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    The effect of healthy ageing on visual cortical activation is still to be fully explored. This study aimed to elucidate whether the haemodynamic response (HDR) of the visual cortex altered as a result of ageing. Visually normal (healthy) participants were presented with a simple visual stimulus (reversing checkerboard). Full optometric screening was implemented to identify two age groups: younger adults (n = 12, mean age 21) and older adults (n = 13, mean age 71). Frequency-domain Multi-distance (FD-MD) functional Near-Infrared Spectroscopy (fNIRS) was used to measure absolute changes in oxygenated [HbO] and deoxygenated [HbR] haemoglobin concentrations in the occipital cortices. Utilising a slow event-related design, subjects viewed a full field reversing checkerboard with contrast and check size manipulations (15 and 30 minutes of arc, 50% and 100% contrast). Both groups showed the characteristic response of increased [HbO] and decreased [HbR] during stimulus presentation. However, older adults produced a more varied HDR and often had comparable levels of [HbO] and [HbR] during both stimulus presentation and baseline resting state. Younger adults had significantly greater concentrations of both [HbO] and [HbR] in every investigation regardless of the type of stimulus displayed (p<0.05). The average variance associated with this age-related effect for [HbO] was 88% and [HbR] 91%. Passive viewing of a visual stimulus, without any cognitive input, showed a marked age-related decline in the cortical HDR. Moreover, regardless of stimulus parameters such as check size, the HDR was characterised by age. In concurrence with present neuroimaging literature, we conclude that the visual HDR decreases as healthy ageing proceeds

    The BOLD signal and neurovascular coupling in autism

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    BOLD (blood oxygen level dependent) fMRI (functional magnetic resonance imaging) is commonly used to study differences in neuronal activity between human populations. As the BOLD response is an indirect measure of neuronal activity, meaningful interpretation of differences in BOLD responses between groups relies upon a stable relationship existing between neuronal activity and the BOLD response across these groups. However, this relationship can be altered by changes in neurovascular coupling or energy consumption, which would lead to problems in identifying differences in neuronal activity. In this review, we focus on fMRI studies of people with autism, and comparisons that are made of their BOLD responses with those of control groups. We examine neurophysiological differences in autism that may alter neurovascular coupling or energy use, discuss recent studies that have used fMRI to identify differences between participants with autism and control participants, and explore experimental approaches that could help attribute between-group differences in BOLD signals to either neuronal or neurovascular factors

    Oxygen Polarography in the Awake Macaque: Bridging BOLD fMRI and Electrophysiology

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    Blood oxygen level dependent (BOLD) fMRI is the predominant method for evaluating human brain activity. This technique identifies brain activity by measuring blood oxygen changes associated with neural activity. Although clearly related, the nature of the relationship between BOLD fMRI identified brain activity and electrophysiologically measured neural activity remains unclear. Direct comparison of BOLD fMRI and electrophysiology has been severely limited by the technical challenges of combining the two techniques. Microelectrode electrophysiology in non-human primates is an excellent model for studying neural activity related to high order brain function similar to that commonly studied with BOLD fMRI in humans, i.e. attention, working memory, engagement. This thesis discusses the development of, validation of, and first results obtained using a new multi-site oxygen polarographic recording system in the awake macaques as a surrogate for BOLD fMRI. Oxygen polarography measures tissue oxygen which is coupled to blood oxygen. This tool offers higher resolution than BOLD fMRI and can be more readily combined with electrophysiology. Using this new tool we evaluated local field potential and oxygen responses to an engaging visual stimulus in two distinct brain systems. In area V3, a key region in the visual system and representative of stimulus driven sensory cortex, we show increased tissue oxygen and local field potential power in response to visual stimulus. In area 23 of the posterior cingulate cortex (PCC), a hub of the default-mode network we show decreased oxygen and local field potential in response to the same stimulus. The default-mode network is a set of brain regions identified in humans whose BOLD fMRI activity is higher at rest than during external engagement, arguing that they sub-serve a function that is engaged as the default-mode in humans. Our results provide new evidence of default-mode network activity in the macaque similar to that seen in humans, provide evidence that the BOLD identified default-mode suppression reflects neural suppression and overall support a strong relationship between neural activity and BOLD fMRI. However, we also note that the LFP responses in both regions show substantial nuances that cannot be seen in the oxygen response and suggest response complexity that is invisible with fMRI. Further the nature of the relationship between LFP and oxygen differs between regions. Our multi-site technique also allows us to evaluate inter-regional interaction of ongoing oxygen fluctuations. Inter-regional correlation of BOLD fMRI fluctuations is commonly used as an index of functional connectivity and has provided new insight into behaviorally relevant aspects of the brains organization and its disruption in disease. Here we demonstrate that we can measure the same inter-regional correlation using oxygen polarography. We utilize the increased resolution of our technique to investigate the frequency structure of the signals driving the correlation and find that inter-regional correlation of oxygen fluctuations appears to depend on a rhythmic mechanism operating at ~0.06 Hz
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