scholarly journals Aerobic glycolysis, the efficiency tradeoff hypothesis, and the biological basis of neuroimaging: A solution to a metabolic mystery at the heart of neuroscience.

2021 ◽  
Author(s):  
Jordan E. Theriault ◽  
Clare Shaffer ◽  
Gerald A. Dienel ◽  
Christin Y. Sander ◽  
Jacob M. Hooker ◽  
...  

Aerobic glycolysis is a form of glucose-inefficient metabolism that occurs when cells metabolize glucose without oxygen, despite oxygen being abundant; the result is less energy per glucose molecule and increased glucose consumption. Aerobic glycolysis in the brain is a metabolic paradox: this inefficient metabolic process is a hallmark of neural activity, yet brains supposedly evolved to be energy-efficient. We discuss this paradox and introduce a possible solution, formalized as the efficiency tradeoff hypothesis: aerobic glycolysis, despite using glucose inefficiently, allows for energy-efficient communication. It allows axon diameter to be minimized (decreasing energy costs of communication) while allowing energy production to closely adhere to unpredictable, rapid-on/rapid-off energy demands. We expand on this hypothesis—linking observations across levels of analysis, from cognitive function to its biological implementation in the brain—culminating in a novel interpretation of the blood-oxygen level-dependent (BOLD) signal, which is closely related to localized metabolic changes caused by aerobic glycolysis. We hypothesize that the BOLD signal indexes bottom-up sensory encoding, or more specifically, prediction error in predictive processing models. This implies that much of a brain’s function, which is implemented with predictive signaling, is not indexed by BOLD fMRI. We then elaborate on the implications of our account for (a) how the evolution of human cytoarchitecture may relate to metabolism and brain function, (b) how social behavior may depend on metabolic cost functions, and (c) how metabolism may play a fundamental role in mental illness. We conclude that aerobic glycolysis and the efficiency tradeoff hypothesis offer a generative foundation for future neuroscientific research.

2016 ◽  
Vol 371 (1705) ◽  
pp. 20150546 ◽  
Author(s):  
Anish Mitra ◽  
Marcus E. Raichle

Initially regarded as ‘noise’, spontaneous (intrinsic) activity accounts for a large portion of the brain's metabolic cost. Moreover, it is now widely known that infra-slow (less than 0.1 Hz) spontaneous activity, measured using resting state functional magnetic resonance imaging of the blood oxygen level-dependent (BOLD) signal, is correlated within functionally defined resting state networks (RSNs). However, despite these advances, the temporal organization of spontaneous BOLD fluctuations has remained elusive. By studying temporal lags in the resting state BOLD signal, we have recently shown that spontaneous BOLD fluctuations consist of remarkably reproducible patterns of whole brain propagation. Embedded in these propagation patterns are unidirectional ‘motifs’ which, in turn, give rise to RSNs. Additionally, propagation patterns are markedly altered as a function of state, whether physiological or pathological. Understanding such propagation patterns will likely yield deeper insights into the role of spontaneous activity in brain function in health and disease. This article is part of the themed issue ‘Interpreting blood oxygen level-dependent: a dialogue between cognitive and cellular neuroscience’.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Young-Bo Kim ◽  
Nambeom Kim ◽  
Jae Jun Lee ◽  
Seo-Eun Cho ◽  
Kyoung-Sae Na ◽  
...  

AbstractSubjective–objective discrepancy of sleep (SODS) might be related to the distorted perception of sleep deficit and hypersensitivity to insomnia-related stimuli. We investigated differences in brain activation to insomnia-related stimuli among insomnia patients with SODS (SODS group), insomnia patients without SODS (NOSODS group), and healthy controls (HC). Participants were evaluated for subjective and objective sleep using sleep diary and polysomnography. Functional magnetic resonance imaging was conducted during the presentation of insomnia-related (Ins), general anxiety-inducing (Gen), and neutral (Neu) stimuli. Brain reactivity to the contrast of Ins vs. Neu and Gen vs. Neu was compared among the SODS (n = 13), NOSODS (n = 15), and HC (n = 16) groups. In the SODS group compared to other groups, brain areas including the left fusiform, bilateral precuneus, right superior frontal gyrus, genu of corpus callosum, and bilateral anterior corona radiata showed significantly increased blood oxygen level dependent (BOLD) signal in the contrast of Ins vs. Neu. There was no brain region with significantly increased BOLD signal in the Gen vs. Neu contrast in the group comparisons. Increased brain activity to insomnia-related stimuli in several brain regions of the SODS group is likely due to these individuals being more sensitive to sleep-related threat and negative cognitive distortion toward insomnia.


2019 ◽  
Vol 40 (10) ◽  
pp. 2066-2080
Author(s):  
Yaoyu Zhang ◽  
Yayan Yin ◽  
Huanjie Li ◽  
Jia-Hong Gao

Cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) are physiological parameters that not only reflect brain health and disease but also jointly contribute to blood oxygen level-dependent (BOLD) signals. Nevertheless, unsolved issues remain concerning the CBF–CMRO2 relationship in the working brain under various oxygen conditions. In particular, the CMRO2 responses to functional tasks in hypoxia are less studied. We extended the calibrated BOLD model to incorporate CMRO2 measurements in hypoxia. The extended model, which was cross-validated with a multicompartment BOLD model, considers the influences of the reduced arterial saturation level and increased baseline cerebral blood volume (CBV) and deoxyhemoglobin concentration on the changes of BOLD signals in hypoxia. By implementing a pulse sequence to simultaneously acquire the CBV-, CBF- and BOLD-weighted signals, we investigated the effects of mild hypoxia on the CBF and CMRO2 responses to graded visual stimuli. Compared with normoxia, mild hypoxia caused significant alterations in both the amplitude and the trend of the CMRO2 responses but did not impact the corresponding CBF responses. Our observations suggested that the flow-metabolism coupling strategies in the brain during mild hypoxia were different from those during normoxia.


2006 ◽  
Vol 96 (1) ◽  
pp. 259-275 ◽  
Author(s):  
Maria G. Knyazeva ◽  
Eleonora Fornari ◽  
Reto Meuli ◽  
Philippe Maeder

The early visual system processes different spatial frequencies (SFs) separately. To examine where in the brain the scale-specific information is integrated, we mapped the neural assemblies engaged in interhemispheric coupling with electroencephalographic (EEG) coherence and blood-oxygen-level dependent (BOLD) signal. During similar EEG and functional magnetic resonance imaging (fMRI) experiments, our subjects viewed centrally presented bilateral gratings of different SF (0.25–8.0 cpd), which either obeyed Gestalt grouping rules (iso-oriented, IG) or violated them (orthogonally oriented, OG). The IG stimuli (0.5–4.0 cpd) synchronized EEG at discrete beta frequencies (beta1, beta2) and increased BOLD (0.5 and 2.0 cpd tested) in ventral (around collateral sulcus) and dorsal (parieto-occipital fissure) regions compared with OG. At both SF, the beta1 coherence correlated with the ventral activations, whereas the beta2 coherence correlated with the dorsal ones. Thus distributed neural substrates mediated interhemispheric integration at single SF. The relative impact of the ventral versus dorsal networks was modulated by the SF of the stimulus.


2016 ◽  
Vol 25 (4) ◽  
pp. 517-522
Author(s):  
Alex J. Koefman ◽  
Melissa Licari ◽  
Michael Bynevelt ◽  
Christopher R. P. Lind

OBJECTIVE An objective biomarker for pain is yet to be established. Functional MRI (fMRI) is a promising neuroimaging technique that may reveal an objective radiological biomarker. The purpose of this study was to evaluate fMRI technology in the setting of lumbosacral radiculopathy and discuss its application in revealing a biomarker for pain in the future. METHODS A prospective, within-participant control study was conducted. Twenty participants with painful lumbosacral radiculopathy from intervertebral disc pathology were recruited. Functional imaging of the brain was performed during a randomly generated series of nonprovocative and provocative straight leg raise maneuvers. RESULTS With a statistical threshold set at p < 0.000001, 3 areas showed significant blood oxygen level–dependent (BOLD) signal change: right superior frontal gyrus (x = 2, y = 13, z = 48, k = 29, Brodmann area 6 [BA6]), left supramarginal cortex (x = −37, y = −44, z = 33, k = 1084, BA40), and left parietal cortex (x = −19, y = −41, z = 63, k = 354, BA5). With a statistical threshold set at p < 0.0002, 2 structures showed significant BOLD signal change: right putamen (x = 29, y = −11, z = 6, k = 72) and bilateral thalami (right: x = 23, y = −11, z = 21, k = 29; x = 8, y = −11, z = 9, k = 274; and left: x = −28, y = −32, z = 6, k = 21). CONCLUSIONS The results in this study compare with those in previous studies and suggest that fMRI technology can provide an objective assessment of the pain experience.


2021 ◽  
Author(s):  
Paul F. Hill ◽  
Sarah E. Seger ◽  
Hye Bin Yoo ◽  
Danielle R. King ◽  
Bradley C. Lega ◽  
...  

AbstractFunctional magnetic resonance imaging (fMRI) is among the foremost methods for mapping human brain function but provides only an indirect measure of underlying neural activity. Recent findings suggest that the neurophysiological correlates of the fMRI blood-oxygen-level-dependent (BOLD) signal might be regionally specific. We examined the neurophysiological correlates of the fMRI BOLD signal in the hippocampus and neocortex, where differences in neural architecture might result in a different relationship between the respective signals. Fifteen human neurosurgical patients (10 female, 5 male) implanted with depth electrodes performed a verbal free recall task while electrophysiological activity was recorded simultaneously from hippocampal and neocortical sites. The same patients subsequently performed a similar version of the task during a later fMRI session. Subsequent memory effects (SMEs) were computed for both imaging modalities as patterns of encoding-related brain activity predictive of later free recall. Linear mixed-effects modelling revealed that the relationship between BOLD and gamma-band SMEs was moderated by the lobar location of the recording site. BOLD and high gamma (70-150 Hz) SMEs positively covaried across much of the neocortex. This relationship was reversed in the hippocampus, where a negative correlation between BOLD and high gamma SMEs was evident. We also observed a negative relationship between BOLD and low gamma (30-70 Hz) SMEs in the medial temporal lobe more broadly. These results suggest that the neurophysiological correlates of the BOLD signal in the hippocampus differ from those observed in the neocortex.Significance StatementThe blood-oxygen-level-dependent (BOLD) signal forms the basis of fMRI but provides only an indirect measure of neural activity. Task-related modulation of BOLD signals are typically equated with changes in gamma-band activity; however, relevant empirical evidence comes largely from the neocortex. We examined neurophysiological correlates of the BOLD signal in the hippocampus, where the differing neural architecture might result in a different relationship between the respective signals. We identified a positive relationship between encoding-related changes in BOLD and gamma-band activity in frontal, temporal, and parietal cortex. This effect was reversed in the hippocampus, where BOLD and gamma-band effects negatively covaried. These results suggest regional variability in the transfer function between neural activity and the BOLD signal in the hippocampus and neocortex.


2013 ◽  
Vol 203 (3) ◽  
pp. 209-214 ◽  
Author(s):  
Eva R. Kenny ◽  
John T. O'Brien ◽  
Michael J. Firbank ◽  
Andrew M. Blamire

BackgroundResting-state functional magnetic resonance imaging (fMRI) can be used to measure correlations in spontaneous low-frequency fluctuations in the blood oxygen level-dependent (BOLD) signal which represent functional connectivity between key brain areas.AimsTo investigate functional connectivity with regions hypothesised to be differentially affected in dementia with Lewy bodies (DLB) compared with Alzheimer's disease and controls.MethodFifteen participants with probable DLB, 16 with probable Alzheimer's disease and 16 controls were scanned in the resting-state using a 3T scanner. The BOLD signal time-series of fluctuations in seed regions were correlated with all other voxels to measure functional connectivity.ResultsParticipants with DLB and Alzheimer's disease showed greater caudate and thalamic connectivity compared with controls. Those with DLB showed greater putamen connectivity compared with those with Alzheimer's disease and the controls. No regions showed less connectivity in DLB or Alzheimer's disease v. controls, or in DLB v. Alzheimer's disease.ConclusionsAltered connectivity in DLB and Alzheimer's disease provides new insights into the neurobiology of these disorders and may aid in earlier diagnosis.


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